| <!DOCTYPE html> |
| <html lang="en-US"> |
| <head> |
| <meta charset="UTF-8"> |
| <title>7661986c-6b35-485b-b687-3694b03da10f</title> |
| <meta name="viewport" content="width=device-width, initial-scale=1"> |
| <link rel="stylesheet" href="https://cdn.mathpix.com/fonts/cmu.css"/> |
| <style>html,body { |
| width: 100%; |
| height: 100%; |
| } |
| *, *::before,*::after { |
| box-sizing: border-box; |
| } |
| body { |
| margin: 0; |
| color: #1E2029; |
| font-size: 14px; |
| line-height: normal; |
| } |
| hr { |
| box-sizing: content-box; |
| height: 0; |
| overflow: visible; |
| } |
| h1, h2, h3, h4, h5, h6 { |
| margin-top: 0; |
| margin-bottom: 0.5em; |
| color: rgba(0, 0, 0, 0.85); |
| font-weight: 500; |
| } |
| p { |
| margin-top: 0; |
| margin-bottom: 1em; |
| } |
| ol, ul, dl { |
| margin-top: 0; |
| margin-bottom: 1em; |
| } |
| ol ol, ul ul, ol ul, ul ol { |
| margin-bottom: 0; |
| } |
| dt { |
| font-weight: 500; |
| } |
| dd { |
| margin-bottom: 0.5em; |
| margin-left: 0; |
| } |
| blockquote { |
| margin: 0 0 1em; |
| } |
| dfn { |
| font-style: italic; |
| } |
| b, strong { |
| font-weight: bolder; |
| } |
| small { |
| font-size: 80%; |
| } |
| sub, sup { |
| position: relative; |
| font-size: 75%; |
| line-height: 0; |
| vertical-align: baseline; |
| } |
| sub { |
| bottom: -0.25em; |
| } |
| sup { |
| top: -0.5em; |
| } |
| a { |
| color: #0B93ff; |
| text-decoration: none; |
| background-color: transparent; |
| outline: none; |
| cursor: pointer; |
| transition: color 0.3s; |
| } |
| a:hover { |
| color: #33aaff; |
| } |
| a:active { |
| color: #0070d9; |
| } |
| a:active, a:hover { |
| text-decoration: none; |
| outline: 0; |
| } |
| a[disabled] { |
| color: rgba(0, 0, 0, 0.25); |
| cursor: not-allowed; |
| pointer-events: none; |
| } |
| pre, code, kbd, samp { |
| font-size: 1em; |
| } |
| pre { |
| margin-top: 0; |
| margin-bottom: 1em; |
| overflow: auto; |
| } |
| figure { |
| margin: 0 0 1em; |
| } |
| img { |
| vertical-align: middle; |
| border-style: none; |
| } |
| svg:not(:root) { |
| overflow: hidden; |
| } |
| table { |
| border-collapse: collapse; |
| } |
| caption { |
| padding-top: 0.75em; |
| padding-bottom: 0.3em; |
| color: rgba(0, 0, 0, 0.45); |
| text-align: left; |
| caption-side: bottom; |
| } |
| th { |
| text-align: inherit; |
| } |
| mjx-container[jax="SVG"] { |
| direction: ltr; |
| } |
| |
| mjx-container[jax="SVG"] > svg { |
| overflow: visible; |
| min-height: 1px; |
| min-width: 1px; |
| } |
| |
| mjx-container[jax="SVG"] > svg a { |
| fill: blue; |
| stroke: blue; |
| } |
| |
| mjx-container[jax="SVG"][display="true"] { |
| display: block; |
| text-align: center; |
| margin: 1em 0; |
| } |
| |
| mjx-container[jax="SVG"][display="true"][width="full"] { |
| display: flex; |
| } |
| |
| mjx-container[jax="SVG"][justify="left"] { |
| text-align: left; |
| } |
| |
| mjx-container[jax="SVG"][justify="right"] { |
| text-align: right; |
| } |
| |
| g[data-mml-node="merror"] > g { |
| fill: red; |
| stroke: red; |
| } |
| |
| g[data-mml-node="merror"] > rect[data-background] { |
| fill: yellow; |
| stroke: none; |
| } |
| |
| g[data-mml-node="mtable"] > line[data-line], svg[data-table] > g > line[data-line] { |
| stroke-width: 70px; |
| fill: none; |
| } |
| |
| g[data-mml-node="mtable"] > rect[data-frame], svg[data-table] > g > rect[data-frame] { |
| stroke-width: 70px; |
| fill: none; |
| } |
| |
| g[data-mml-node="mtable"] > .mjx-dashed, svg[data-table] > g > .mjx-dashed { |
| stroke-dasharray: 140; |
| } |
| |
| g[data-mml-node="mtable"] > .mjx-dotted, svg[data-table] > g > .mjx-dotted { |
| stroke-linecap: round; |
| stroke-dasharray: 0,140; |
| } |
| |
| g[data-mml-node="mtable"] > g > svg { |
| overflow: visible; |
| } |
| |
| [jax="SVG"] mjx-tool { |
| display: inline-block; |
| position: relative; |
| width: 0; |
| height: 0; |
| } |
| |
| [jax="SVG"] mjx-tool > mjx-tip { |
| position: absolute; |
| top: 0; |
| left: 0; |
| } |
| |
| mjx-tool > mjx-tip { |
| display: inline-block; |
| padding: .2em; |
| border: 1px solid #888; |
| font-size: 70%; |
| background-color: #F8F8F8; |
| color: black; |
| box-shadow: 2px 2px 5px #AAAAAA; |
| } |
| |
| g[data-mml-node="maction"][data-toggle] { |
| cursor: pointer; |
| } |
| |
| mjx-status { |
| display: block; |
| position: fixed; |
| left: 1em; |
| bottom: 1em; |
| min-width: 25%; |
| padding: .2em .4em; |
| border: 1px solid #888; |
| font-size: 90%; |
| background-color: #F8F8F8; |
| color: black; |
| } |
| |
| foreignObject[data-mjx-xml] { |
| font-family: initial; |
| line-height: normal; |
| overflow: visible; |
| } |
| |
| mjx-container[jax="SVG"] path[data-c], mjx-container[jax="SVG"] use[data-c] { |
| stroke-width: 3; |
| } |
| #setText > div { |
| justify-content: inherit; |
| margin-top: 0; |
| margin-bottom: 1em; |
| |
| |
| } |
| #setText div:last-child { |
| margin-bottom: 0 !important; |
| } |
| #setText > br, #preview-content br { |
| line-height: 1.2; |
| } |
| #preview-content > div { |
| margin-top: 0; |
| margin-bottom: 1em; |
| |
| } |
| .proof > div, |
| #preview-content .proof > div, #setText .proof > div, |
| .theorem > div, |
| #preview-content .theorem > div, #setText .theorem > div { |
| margin-top: 1rem; |
| } |
| mjx-container { |
| text-indent: 0; |
| overflow-y: hidden; |
| overflow-x: auto; |
| padding-top: 1px; |
| padding-bottom: 1px; |
| |
| } |
| .math-inline mjx-container { |
| display: inline-block !important; |
| page-break-inside: avoid; |
| max-width: 100%; |
| padding: 0; |
| line-height: 0; |
| } |
| .math-inline[data-overflow="visible"] mjx-container { |
| overflow: visible; |
| } |
| .math-inline mjx-container mjx-assistive-mml { |
| max-width: 100%; |
| } |
| .math-block { |
| align-items: center; |
| page-break-after: auto; |
| page-break-inside: avoid; |
| margin: 0; |
| display: block; |
| } |
| .math-inline { |
| display: inline-flex; |
| max-width: 100%; |
| } |
| .math-block[data-width="full"] { |
| overflow-x: auto; |
| display: flex; |
| } |
| .math-block[data-width="full"] mjx-container[jax=SVG][display=true] { |
| display: flex; |
| flex: 1 1; |
| justify-content: center; |
| } |
| svg .math-inline { |
| display: initial; |
| max-width: initial; |
| } |
| svg .math-inline mjx-container { |
| max-width: initial; |
| } |
| svg mjx-container { |
| overflow: visible; |
| padding: 0; |
| } |
| svg .math-block[data-width="full"] { |
| overflow: visible; |
| } |
| .math-block, .math-inline { |
| --mmd-highlight-color: rgba(0, 147, 255, 0.25); |
| --mmd-highlight-text-color: #1e2029; |
| } |
| .math-block[data-highlight-color] mjx-container[jax="SVG"] > svg { |
| background-color: var(--mmd-highlight-color); |
| } |
| .math-block[data-highlight-text-color] mjx-container[jax="SVG"] > svg { |
| color: var(--mmd-highlight-text-color); |
| } |
| .math-inline[data-highlight-color] mjx-container[jax="SVG"] { |
| background-color: var(--mmd-highlight-color); |
| } |
| .math-inline[data-highlight-text-color] mjx-container[jax="SVG"] { |
| color: var(--mmd-highlight-text-color); |
| } |
| .math-block p { |
| flex-shrink: 1; |
| } |
| .math-block mjx-container { |
| margin: 0 !important; |
| } |
| .math-error { |
| background-color: yellow; |
| color: red; |
| } |
| #preview-content img, #setText img { |
| max-width: 100%; |
| } |
| #preview-content blockquote, #setText blockquote { |
| page-break-inside: avoid; |
| color: #666; |
| margin: 0 0 1em 0; |
| padding-left: 3em; |
| border-left: .5em solid #eee; |
| } |
| #preview-content pre, #setText pre { |
| border: none; |
| padding: 0; |
| overflow: auto; |
| font-size: 85%; |
| line-height: 1.45; |
| border-radius: 6px; |
| box-sizing: border-box; |
| background: #f8f8fa; |
| } |
| #preview-content pre code, #setText pre code { |
| padding: 1rem; |
| display: block; |
| overflow-x: auto; |
| line-height: 24px; |
| } |
| #preview-content table, #setText table { |
| display: table; |
| overflow: auto; |
| max-width: 100%; |
| border-collapse: collapse; |
| page-break-inside: avoid; |
| margin-bottom: 1em; |
| } |
| #preview-content table th, #setText table th { |
| text-align: center; |
| font-weight: bold; |
| } |
| #preview-content table td, #setText table td, |
| #preview-content table th, #setText table th { |
| border: 1px solid #dfe2e5; |
| padding: 6px 13px; |
| } |
| #preview-content table tr, #setText table tr { |
| background-color: #fff; |
| border-top: 1px solid #c6cbd1; |
| } |
| #preview-content table tr:nth-child(2n), #setText table tr:nth-child(2n) { |
| background-color: #f6f8fa; |
| } |
| .main-title, |
| #preview-content .main-title, #setText .main-title { |
| text-align: center; |
| line-height: 1.2; |
| margin: 0 auto 1em auto; |
| } |
| .author, |
| #preview-content .author, #setText .author { |
| text-align: center; |
| margin: 0 auto; |
| display: flex; |
| justify-content: center; |
| flex-wrap: wrap; |
| } |
| .author p, |
| #preview-content .author p, #setText .author p { |
| min-width: 30%; |
| max-width: 50%; |
| padding: 0 7px; |
| } |
| .author > p > span, |
| #preview-content .author > p > span, #setText .author > p > span { |
| display: block; |
| text-align: center; |
| } |
| .section-title, |
| #preview-content .section-title, #setText .section-title { |
| margin-top: 1.5em; |
| } |
| .abstract, |
| #preview-content .abstract, #setText .abstract { |
| text-align: justify; |
| margin-bottom: 1em; |
| } |
| .abstract p, |
| #preview-content .abstract p, #setText .abstract p { |
| margin-bottom: 0; |
| } |
| #preview-content sup, #setText sup { |
| top: -.5em; |
| position: relative; |
| font-size: 75%; |
| line-height: 0; |
| vertical-align: baseline; |
| } |
| .text-url, |
| #preview-content .text-url, #setText .text-url { |
| color: #0B93ff; |
| cursor: text; |
| pointer-events: none; |
| } |
| .text-url a:hover, |
| #preview-content .text-url a:hover, #setText .text-url a:hover { |
| color: #0B93ff; |
| } |
| mark, |
| #preview-content mark, #setText mark { |
| background-color: #feffe6; |
| } |
| span[data-underline-type] mark, |
| #preview-content span[data-underline-type] mark, |
| #setText span[data-underline-type] mark { |
| background: inherit; |
| background-color: #feffe6; |
| padding-top: 0; |
| padding-bottom: 0; |
| } |
| *[data-has-dotfill] { |
| position: relative; |
| overflow: hidden; |
| } |
| *[data-has-dotfill] .dotfill::after { |
| position: absolute; |
| padding-left: .25ch; |
| content: " . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . " |
| ". . . . . . . . . . . . . . . . . . . . . . . "; |
| text-align: right; |
| } |
| .smiles, |
| #preview-content .smiles, #setText .smiles { |
| text-align: center; |
| } |
| div.svg-container, |
| #preview-content > div.svg-container, |
| #setText > div.svg-container { |
| display: flex; |
| justify-content: center; |
| } |
| @media print { |
| #preview { |
| font-size: 10pt !important; |
| } |
| .math-block svg, .math-inline svg { |
| shape-rendering: crispEdges; |
| margin-top: 1px; |
| } |
| #preview-content img, #setText img { |
| display: block; |
| } |
| #preview-content .figure_img img, #setText .figure_img img { |
| display: inline; |
| } |
| #preview-content h1, #preview-content h2, #preview-content h3, |
| #preview-content h4, #preview-content h5, #preview-content h6, |
| #setText h1, #setText h2, #setText h3, |
| #setText h4, #setText h5, #setText h6 { |
| page-break-inside: avoid; |
| position: relative; |
| border: 2px solid transparent; |
| } |
| #preview-content h1::after, #preview-content h2::after, #preview-content h3::after, |
| #preview-content h4::after, #preview-content h5::after, #preview-content h6::after, |
| #setText h1::after, #setText h2::after, #setText h3::after, |
| #setText h4::after, #setText h5::after, #setText h6::after { |
| content: ""; |
| display: block; |
| height: 100px; |
| margin-bottom: -100px; |
| position: relative; |
| } |
| } |
| #preview-content code, #setText code { |
| font-family: Inconsolata; |
| font-size: inherit; |
| display: initial; |
| background: #f8f8fa; |
| } |
| #preview-content .mmd-highlight code, #setText .mmd-highlight code, |
| #preview-content pre.mmd-highlight code, #setText pre.mmd-highlight code { |
| background-color: transparent; |
| } |
| #preview-content pre code, #setText pre code { |
| font-family: 'DM Mono', Inconsolata, monospace; |
| color: #333; |
| font-size: 15px; |
| } |
| .hljs-comment, .hljs-quote, |
| #preview-content .hljs-comment, #setText .hljs-comment, |
| #preview-content .hljs-quote, #setText .hljs-quote { |
| color: #998; |
| font-style: italic; |
| } |
| .hljs-command, |
| #preview-content .hljs-command, #setText .hljs-command { |
| color: #005cc5; |
| } |
| .hljs-keyword, .hljs-selector-tag, .hljs-subst, |
| #preview-content .hljs-keyword, #setText .hljs-keyword, |
| #preview-content .hljs-selector-tag, #setText .hljs-selector-tag, |
| #preview-content .hljs-subst, #setText .hljs-subst { |
| color: #d73a49; |
| font-weight: bold; |
| } |
| .hljs-number, .hljs-literal, .hljs-variable, |
| .hljs-template-variable, .hljs-tag .hljs-attr, |
| #preview-content .hljs-number, #setText .hljs-number, |
| #preview-content .hljs-literal, #setText .hljs-literal, |
| #preview-content .hljs-variable, #setText .hljs-variable, |
| #preview-content .hljs-template-variable, #setText .hljs-template-variable, |
| #preview-content .hljs-tag .hljs-attr, #setText .hljs-tag .hljs-attr { |
| color: #005cc5; |
| } |
| .hljs-string, .hljs-doctag, |
| #preview-content .hljs-string, #setText .hljs-string, |
| #preview-content .hljs-doctag, #setText .hljs-doctag { |
| color: #24292e; |
| } |
| .hljs-title, .hljs-section, .hljs-selector-id, |
| #preview-content .hljs-title, #setText .hljs-title, |
| #preview-content .hljs-section, #setText .hljs-section, |
| #preview-content .hljs-selector-id, #setText .hljs-selector-id { |
| color: #6f42c1; |
| font-weight: bold; |
| } |
| .hljs-subst, |
| #preview-content .hljs-subst, #setText .hljs-subst { |
| font-weight: normal; |
| } |
| .hljs-type, .hljs-class .hljs-title, |
| #preview-content .hljs-type, #setText .hljs-type, |
| #preview-content .hljs-class .hljs-title, #setText .hljs-class .hljs-title { |
| color: #458; |
| font-weight: bold; |
| } |
| .hljs-tag, .hljs-name, .hljs-attribute, |
| #preview-content .hljs-tag, #setText .hljs-tag, |
| #preview-content .hljs-name, #setText .hljs-name, |
| #preview-content .hljs-attribute, #setText .hljs-attribute { |
| color: #000080; |
| font-weight: normal; |
| } |
| .hljs-regexp, .hljs-link, |
| #preview-content .hljs-regexp, #setText .hljs-regexp, |
| #preview-content .hljs-link, #setText .hljs-link { |
| color: #009926; |
| } |
| .hljs-symbol, .hljs-bullet, |
| #preview-content .hljs-symbol, #setText .hljs-symbol, |
| #preview-content .hljs-bullet, #setText .hljs-bullet { |
| color: #990073; |
| } |
| .hljs-built_in, .hljs-builtin-name, |
| #preview-content .hljs-built_in, #setText .hljs-built_in, |
| #preview-content .hljs-builtin-name, #setText .hljs-builtin-name { |
| color: #24292e; |
| } |
| .hljs-meta, |
| #preview-content .hljs-meta, #setText .hljs-meta { |
| color: #999; |
| font-weight: bold; |
| } |
| .hljs-meta-keyword, |
| #preview-content .hljs-meta-keyword, #setText .hljs-meta-keyword { |
| color: #d73a49; |
| } |
| .hljs-meta-string, |
| #preview-content .hljs-meta-string, #setText .hljs-meta-string { |
| color: #032f62; |
| } |
| .hljs-deletion, |
| #preview-content .hljs-deletion, #setText .hljs-deletion { |
| background: #fdd; |
| } |
| .hljs-addition, |
| #preview-content .hljs-addition, #setText .hljs-addition { |
| background: #dfd; |
| } |
| .hljs-emphasis, |
| #preview-content .hljs-emphasis, #setText .hljs-emphasis { |
| font-style: italic; |
| } |
| .hljs-strong, |
| #preview-content .hljs-strong, #setText .hljs-strong { |
| font-weight: bold; |
| } |
| .table_tabular, |
| #preview-content .table_tabular, #setText .table_tabular { |
| overflow-x: auto; |
| padding: 0 2px 0.5em 2px; |
| } |
| .tabular, |
| #preview-content .tabular, #setText .tabular { |
| display: inline-table !important; |
| width: auto; |
| table-layout: auto; |
| border-collapse: collapse; |
| border-spacing: 0; |
| margin: 0 0 1em; |
| font-size: inherit; |
| height: fit-content; |
| } |
| .tabular th, |
| #preview-content .tabular th, #setText .tabular th { |
| border: none !important; |
| padding: 6px 13px; |
| background-color: transparent; |
| font-weight: bold; |
| } |
| .tabular tr, |
| #preview-content .tabular tr, #setText .tabular tr { |
| border-top: none !important; |
| border-bottom: none !important; |
| background-color: transparent; |
| } |
| .tabular td, |
| #preview-content .tabular td, #setText .tabular td { |
| border-style: none !important; |
| background-color: #fff; |
| border-color: #000 !important; |
| word-break: keep-all; |
| padding: 0.1em 0.5em !important; |
| } |
| .tabular td > p, |
| #preview-content .tabular td > p, #setText .tabular td > p { |
| margin-bottom: 0; |
| margin-top: 0; |
| } |
| .tabular td._empty, |
| #preview-content .tabular td._empty, #setText .tabular td._empty { |
| height: 1.3em; |
| } |
| .tabular td .f, |
| #preview-content .tabular td .f, #setText .tabular td .f { |
| opacity: 0; |
| } |
| #preview-content .sub-table table, #setText .sub-table table { |
| margin-bottom: 0; |
| } |
| html[data-theme="dark"] .tabular tr, |
| html[data-theme="dark"] #preview-content .tabular tr, html[data-theme="dark"] #setText .tabular tr, |
| html[data-theme="dark"] .tabular td, |
| html[data-theme="dark"] #preview-content .tabular td, html[data-theme="dark"] #setText .tabular td { |
| background-color: #202226; |
| border-color: #fff !important; |
| } |
| .figure_img, |
| #preview-content .figure_img, #setText .figure_img { |
| margin-bottom: 0.5em; |
| overflow-x: auto; |
| } |
| div.figure_img img, |
| #preview-content div.figure_img img, #setText div.figure_img img { |
| display: inline; |
| margin: 0; |
| } |
| ol.enumerate, ul.itemize, |
| #preview-content ol.enumerate, #setText ol.enumerate, |
| #preview-content ul.itemize, #setText ul.itemize { |
| padding-inline-start: 40px; |
| margin: 0 0 1em 0; |
| } |
| li > ol.enumerate, li > ul.itemize, |
| #preview-content li > ol.enumerate, #setText li > ol.enumerate, |
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| .enumerate > .li_enumerate, |
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| margin-bottom: 0; |
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| .enumerate > li > span.li_level .math-inline, |
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| </head> |
| <body> |
| <div id="preview" class="preview scrollEditor"> |
| <div id="container-ruller" /> |
| <div id="preview-content"> |
| <div><figure style="text-align: center"><img src="https://cdn.mathpix.com/cropped/7661986c-6b35-485b-b687-3694b03da10f-01.jpg?height=332&width=570&top_left_y=244&top_left_x=756" alt="" data-align="center"></figure></div> |
| <h1 type="title" class="main-title" id="the-randomized-clinical-trial"> |
| the <span class="math-inline "> |
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| Randomized Clinical Trial </h1> |
| <h1 type="title" class="main-title" id="a-randomized-multicenter-clinical-trial-to-determine-the-best-of-two-strategies-to-optimally-aerate-the-preterm-infant-lung"> |
| A Randomized Multicenter Clinical Trial to Determine the Best of Two Strategies to Optimally Aerate the Preterm Infant Lung </h1> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="data-analysis-and-monitoring-plan-(damp)"> |
| Data Analysis and Monitoring Plan (DAMP)</h2> |
| <div>Version 1.2, Monday, April 14, 2014</div> |
| <div><div class="author"> |
| <p><span>Sarah J. Ratcliffe, PhD</span><span>Russell Localio, PhD</span><span>Xiaoyan Han, MS</span><span>Department of Biostatistics and Epidemiology</span><span>University of Pennsylvania Perelman School of Medicine</span><span>Blockley Hall</span><span>423 Guardian Drive</span><span>Philadelphia, PA 19104</span></p> |
| </div></div> |
| <div>Sponsored by the<br> |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<br> |
| National Institutes of Health (NIH)</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="table-of-contents"> |
| Table of Contents</h2> |
| <ol> |
| <li>PURPOSE ..... 3</li> |
| <li>STUDY DESCRIPTION ..... 3<br> |
| 2.1 Study Design ..... 3<br> |
| 2.2 Study Objectives ..... 3<br> |
| 2.3 Study Endpoints ..... 5<br> |
| 2.3.1 Primary Efficacy Endpoint ..... 5<br> |
| 2.3.2 Secondary Efficacy Endpoints(12 weeks) ..... 5<br> |
| 2.3.3 Safety ..... 6</li> |
| <li>REGULAR MONITORING OF RECRUITMENT, DATA QUALITY, AND SAFETY ..... 7<br> |
| 3.1 Monthly Reporting of Participant Recruitment and Accrual ..... 7<br> |
| 3.2 Data Quality and Monitoring Reports ..... 8<br> |
| 3.3 Demographics and Other Baseline Data ..... 8<br> |
| 3.4 Adverse Events ..... 8<br> |
| 3.4.1 Serious Adverse Events ..... 8<br> |
| 3.4.2 Other Adverse Events ..... 9</li> |
| <li>INTERIM ANALYSIS PRESENTED TO EXTERNAL ADVISORY COMMITTEE ..... 9<br> |
| 4.1 Blinding ..... 10<br> |
| 4.2 Baseline Data ..... 11<br> |
| 4.3 Subject Accounting and Withdrawals ..... 11<br> |
| 4.4 Evaluation of Safety ..... 11</li> |
| <li>FINAL DATA ANALYSIS UPON COMPLETION OF TRIAL ..... 12<br> |
| 5.1 Examination of Baseline Characteristics ..... 12<br> |
| 5.2 Subject Accounting and Withdrawal Rates ..... 12<br> |
| 5.3 Analysis of Safety and Toxicity ..... 12<br> |
| 5.4 Analysis of Efficacy Endpoints ..... 12<br> |
| 5.4.1 Primary Endpoint ..... 12<br> |
| 5.4.2 Secondary Endpoints ..... 13<br> |
| 5.4.3 Group Sequential Boundary for Primary Endpoint ..... 13</li> |
| <li>INTENT-TO-TREAT ANALYSIS AND MISSING DATA ..... 13<br> |
| 6.1 Treatment and Study Withdrawals ..... 13<br> |
| 6.2 Other Missing Data Considerations ..... 14<br> |
| 6.3 Intent-to-Treat Analysis for the Primary Endpoint ..... 14<br> |
| 6.4 Potential Effects of Missing Data on Secondary Endpoints ..... 14</li> |
| <li>PRESENTATION AND FORMAT OF RESULTS ..... 15</li> |
| <li>REVISIONS TO THE DAMP ..... 15</li> |
| <li>APPENDIX A: SCHEDULE OF STUDY REPORTING ..... 16</li> |
| <li>APPENDIX B: DRAFT STUDY REPORT TABLES ..... 17</li> |
| <li>APPENDIX C: STANDARD MONITORING REPORTS ..... 23</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="1.-purpose"> |
| 1. Purpose</h2> |
| <div>The purpose of this document is to describe the methods to be used for data analysis for the Sustained Aeration of Infant Lungs (SAIL) randomized clinical trial. The methods described will cover the standard accrual, safety, and data quality reporting for presentation at SAIL Steering Committee meetings, as well as the interim and final analyses of safety and efficacy data specified in the study protocol. This plan will go into specific detail for each analysis including, where appropriate,<br> |
| The endpoints or data items to be evaluated<br> |
| The population or subset upon which the evaluation is being performed<br> |
| Rules for handling exceptional data<br> |
| The descriptive and statistical methods to be applied to each endpoint or data item<br> |
| The format to be used for presenting the results<br> |
| The frequency of analyses and other monitoring<br> |
| The parties to whom each report will be provided<br> |
| A summary of the types and frequencies of reports produced, the personnel responsible for each report, and distribution lists are given in Appendix A. Additional information regarding procedures to be followed by the SAIL Data Safety and Monitoring Committee (DSMC) are provided in the DSMC section of the SAIL Protocol.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="2.-study-description"> |
| 2. Study Description</h2> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.1-study-design"> |
| 2.1 Study Design</h3> |
| <div>This study is a 2 -arm randomized, controlled, multi-center clinical trial to determine which of two strategies at birth are best to optimally aerate the lung of preterm infants. Treatment allocation is blinded, though implementation of intervention is not blinded. Specifically we will determine in 600 infants of 23-26 weeks gestational age (GA) requiring respiratory support at birth which of two lung opening strategies - either a standard PEEP/CPAP of <span class="math-inline "> |
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61Q147 65 216 339T285 628Q285 635 228 637Z"></path></g><g data-mml-node="mn" transform="translate(4421.4,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g><g data-mml-node="mi" transform="translate(4921.4,0)"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g></g></g></svg></mjx-container></span> in the delivery room (DR), as compared to early lung recruitment using Sustained Inflation (SI) in the DR, will result in a lower rate of the combined endpoint of death or Bronchopulmonary Dysplasia (BPD) (using a standardized oxygen reduction test) at 36 weeks PMA. We will also compare which has the lower rate of other important secondary outcomes including rates of neurodevelopmental impairment at <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="7.291ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 3222.4 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(500,0)"></path></g><g data-mml-node="mo" transform="translate(1222.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(2222.4,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z" transform="translate(500,0)"></path></g></g></g></svg></mjx-container></span> months of corrected age in survivors. A full description of the study design is contained in the study protocol.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.2-study-objectives"> |
| 2.2 Study Objectives</h3> |
| <div>Hypotheses:</div> |
| <ol> |
| <li>Early lung recruitment with SI superimposed upon standard PEEP/CPAP in the DR will reduce the need for mechanical ventilation in the first seven days of life, and reduce need for surfactant use; and</li> |
| <li>A policy of DR SI on standard PEEP/CPAP recruitment will confer better outcomes at 36 weeks post-menstrual age (PMA) than standard PEEP/CPAP.</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="primary-aim%3A"> |
| Primary Aim:</h2> |
| <ol> |
| <li>To determine in 600 infants born at <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="7.291ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 3222.4 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z" transform="translate(500,0)"></path></g><g data-mml-node="mo" transform="translate(1222.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(2222.4,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z" transform="translate(500,0)"></path></g></g></g></svg></mjx-container></span> weeks GA requiring respiratory support at birth, which of two lung opening strategies - either a standard PEEP/CPAP of <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="7.994ex" height="1.715ex" role="img" focusable="false" viewBox="0 -676 3533.4 758"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="37" d="M55 458Q56 460 72 567L88 674Q88 676 108 676H128V672Q128 662 143 655T195 646T364 644H485V605L417 512Q408 500 387 472T360 435T339 403T319 367T305 330T292 284T284 230T278 162T275 80Q275 66 275 52T274 28V19Q270 2 255 -10T221 -22Q210 -22 200 -19T179 0T168 40Q168 198 265 368Q285 400 349 489L395 552H302Q128 552 119 546Q113 543 108 522T98 479L95 458V455H55V458Z"></path></g><g data-mml-node="mi" transform="translate(2222.4,0)"><path data-c="1D450" d="M34 159Q34 268 120 355T306 442Q362 442 394 418T427 355Q427 326 408 306T360 285Q341 285 330 295T319 325T330 359T352 380T366 386H367Q367 388 361 392T340 400T306 404Q276 404 249 390Q228 381 206 359Q162 315 142 235T121 119Q121 73 147 50Q169 26 205 26H209Q321 26 394 111Q403 121 406 121Q410 121 419 112T429 98T420 83T391 55T346 25T282 0T202 -11Q127 -11 81 37T34 159Z"></path></g><g data-mml-node="mi" transform="translate(2655.4,0)"><path data-c="1D45A" d="M21 287Q22 293 24 303T36 341T56 388T88 425T132 442T175 435T205 417T221 395T229 376L231 369Q231 367 232 367L243 378Q303 442 384 442Q401 442 415 440T441 433T460 423T475 411T485 398T493 385T497 373T500 364T502 357L510 367Q573 442 659 442Q713 442 746 415T780 336Q780 285 742 178T704 50Q705 36 709 31T724 26Q752 26 776 56T815 138Q818 149 821 151T837 153Q857 153 857 145Q857 144 853 130Q845 101 831 73T785 17T716 -10Q669 -10 648 17T627 73Q627 92 663 193T700 345Q700 404 656 404H651Q565 404 506 303L499 291L466 157Q433 26 428 16Q415 -11 385 -11Q372 -11 364 -4T353 8T350 18Q350 29 384 161L420 307Q423 322 423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 181Q151 335 151 342Q154 357 154 369Q154 405 129 405Q107 405 92 377T69 316T57 280Q55 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span> H2O in the DR, compared to early lung recruitment using SI in the DR, results in a lower rate of the combined endpoint of death or BPD (using a standardized oxygen reduction test) at 36 weeks PMA.</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="secondary-aims%3A"> |
| Secondary Aims:</h2> |
| <div>To compare the rates of other important secondary outcomes such as:</div> |
| <ol> |
| <li>Detailed outcomes of potential importance in the first 10 days of life:<br> |
| a. Heart rate in the DR<br> |
| b. Detailed status on departure from the DR<br> |
| c. Use of inotropes on arrival in NICU<br> |
| d. Chest X-ray reports showing pneumothorax or new chest drains in the first 48 hours of life;<br> |
| e. Need for new chest drains after NICU admission<br> |
| f. Duration of any chest drain in-situ post-DR<br> |
| g. Oxygen profile over first 48 hours post DR using hourly FiO 2 records<br> |
| h. Oxygen profile with highest FiO 2 up to 48 hours<br> |
| i. Head US and/or MRI findings of intraventricular hemorrhage grades 3 and 4 by 48 hour and by day 10, if clinically available<br> |
| j. CXR appearance between days 7-10, if clinically obtained</li> |
| <li>Components of the primary outcome (i.e. death by 36 weeks PMA or BPD at 36 weeks PMA</li> |
| <li>Need for intubation in DR or by 24 hours of age</li> |
| <li>Pressure-volume characteristics in the DR (at several but not all sites)</li> |
| <li>Death or need for positive pressure ventilation at 7 days</li> |
| <li>Highest FiO2 and Area under the curve FiO2 for first week of life</li> |
| <li>Survival to discharge home without BPD, retinopathy of prematurity (grades 3 & 4), or significant brain abnormalities on head ultrasound</li> |
| <li>Pneumothorax and pulmonary interstitial emphysema (PIE)</li> |
| <li>Duration of respiratory support (ventilation, CPAP, supplemental oxygen)</li> |
| <li>Retinopathy of prematurity (ROP) stage 3 or greater requiring treatment</li> |
| <li>Death before discharge</li> |
| <li>Use of postnatal steroids for treatment of BPD</li> |
| <li>Length of hospital stay</li> |
| <li>Neurodevelopmental and respiratory outcome at 22-26 months corrected GA</li> |
| </ol> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.3-study-endpoints"> |
| 2.3 Study Endpoints</h3> |
| <div>The primary endpoint for this study is both an efficacy and safety endpoint. Improved death / BPD rates suggest efficacy, while worse rates suggest a safety problem. As such, all comparisons are inherently two-sided. Interim and final analyses present the classic spectrum of decisions: superiority, non-inferiority, and inferiority.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.3.1-primary-efficacy-endpoint"> |
| 2.3.1 Primary Efficacy Endpoint</h3> |
| <div>To compare the rate of Death or BPD between the two intervention arms, with BPD being defined using a standardized oxygen reduction test. The primary endpoint will be recorded at 36 weeks PMA.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.3.2-secondary-efficacy-endpoints"> |
| 2.3.2 Secondary Efficacy Endpoints</h3> |
| <div>The secondary efficacy endpoints (and associated secondary aim) are defined below. Endpoints considered adverse events / safety endpoints are given in Section 2.3.3. The timing of evaluation of each endpoint is given in bolded font.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="delivery-room-(dr)%3A"> |
| Delivery Room (DR):</h2> |
| <ol> |
| <li>Heart rate in the DR (SA1a)</li> |
| </ol> |
| <div>Categorical variable with 3 levels: <span class="math-inline "> |
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46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1000,0)"></path></g></g></g></svg></mjx-container></span><br> |
| 2. Type of respiratory support (CPAP, PPV) on departure from DR (SA1b)<br> |
| 3. Fraction of Inspired Oxygen ( <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.339ex;" xmlns="http://www.w3.org/2000/svg" width="5.189ex" height="1.932ex" role="img" focusable="false" viewBox="0 -704 2293.6 854"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D439" d="M48 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q146 66 215 342T285 622Q285 629 281 629Q273 632 228 634H197Q191 640 191 642T193 659Q197 676 203 680H742Q749 676 749 669Q749 664 736 557T722 447Q720 440 702 440H690Q683 445 683 453Q683 454 686 477T689 530Q689 560 682 579T663 610T626 626T575 633T503 634H480Q398 633 393 631Q388 629 386 623Q385 622 352 492L320 363H375Q378 363 398 363T426 364T448 367T472 374T489 386Q502 398 511 419T524 457T529 475Q532 480 548 480H560Q567 475 567 470Q567 467 536 339T502 207Q500 200 482 200H470Q463 206 463 212Q463 215 468 234T473 274Q473 303 453 310T364 317H309L277 190Q245 66 245 60Q245 46 334 46H359Q365 40 365 39T363 19Q359 6 353 0H336Q295 2 185 2Q120 2 86 2T48 1Z"></path></g><g data-mml-node="mi" transform="translate(749,0)"><path data-c="1D456" d="M184 600Q184 624 203 642T247 661Q265 661 277 649T290 619Q290 596 270 577T226 557Q211 557 198 567T184 600ZM21 287Q21 295 30 318T54 369T98 420T158 442Q197 442 223 419T250 357Q250 340 236 301T196 196T154 83Q149 61 149 51Q149 26 166 26Q175 26 185 29T208 43T235 78T260 137Q263 149 265 151T282 153Q302 153 302 143Q302 135 293 112T268 61T223 11T161 -11Q129 -11 102 10T74 74Q74 91 79 106T122 220Q160 321 166 341T173 380Q173 404 156 404H154Q124 404 99 371T61 287Q60 286 59 284T58 281T56 279T53 278T49 278T41 278H27Q21 284 21 287Z"></path></g><g data-mml-node="msub" transform="translate(1094,0)"><g data-mml-node="mi"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g><g data-mml-node="TeXAtom" transform="translate(796,-150) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span> ) on departure from DR (SA1b)<br> |
| 4. Pressure-volume characteristics in the DR (at several but not all sites) (SA4)<br> |
| 5. Need for intubation in DR (SA3)</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="first-48-hours-of-life%3A"> |
| First 48 hours of life:</h2> |
| <ol start="6"> |
| <li>Use of inotropes (SA1c)</li> |
| </ol> |
| <div>Any use within first 48 hours of life<br> |
| 7. Pneumothorax (SA1d, SA8)</div> |
| <div>Source documentation needed for adjudicated yes/no variable<br> |
| 8. Need for new chest drains (SA1de)</div> |
| <div>Calculated as an increase in the number of chest drains recorded hourly.<br> |
| 9. Oxygen requirement of <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.339ex;" xmlns="http://www.w3.org/2000/svg" width="12.353ex" height="2.036ex" role="img" focusable="false" viewBox="0 -750 5460.1 900"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D439" d="M48 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q146 66 215 342T285 622Q285 629 281 629Q273 632 228 634H197Q191 640 191 642T193 659Q197 676 203 680H742Q749 676 749 669Q749 664 736 557T722 447Q720 440 702 440H690Q683 445 683 453Q683 454 686 477T689 530Q689 560 682 579T663 610T626 626T575 633T503 634H480Q398 633 393 631Q388 629 386 623Q385 622 352 492L320 363H375Q378 363 398 363T426 364T448 367T472 374T489 386Q502 398 511 419T524 457T529 475Q532 480 548 480H560Q567 475 567 470Q567 467 536 339T502 207Q500 200 482 200H470Q463 206 463 212Q463 215 468 234T473 274Q473 303 453 310T364 317H309L277 190Q245 66 245 60Q245 46 334 46H359Q365 40 365 39T363 19Q359 6 353 0H336Q295 2 185 2Q120 2 86 2T48 1Z"></path></g><g data-mml-node="mi" transform="translate(749,0)"><path data-c="1D456" d="M184 600Q184 624 203 642T247 661Q265 661 277 649T290 619Q290 596 270 577T226 557Q211 557 198 567T184 600ZM21 287Q21 295 30 318T54 369T98 420T158 442Q197 442 223 419T250 357Q250 340 236 301T196 196T154 83Q149 61 149 51Q149 26 166 26Q175 26 185 29T208 43T235 78T260 137Q263 149 265 151T282 153Q302 153 302 143Q302 135 293 112T268 61T223 11T161 -11Q129 -11 102 10T74 74Q74 91 79 106T122 220Q160 321 166 341T173 380Q173 404 156 404H154Q124 404 99 371T61 287Q60 286 59 284T58 281T56 279T53 278T49 278T41 278H27Q21 284 21 287Z"></path></g><g data-mml-node="msub" transform="translate(1094,0)"><g data-mml-node="mi"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g><g data-mml-node="TeXAtom" transform="translate(796,-150) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g><g data-mml-node="mo" transform="translate(2571.3,0)"><path data-c="2265" d="M83 616Q83 624 89 630T99 636Q107 636 253 568T543 431T687 361Q694 356 694 346T687 331Q685 329 395 192L107 56H101Q83 58 83 76Q83 77 83 79Q82 86 98 95Q117 105 248 167Q326 204 378 228L626 346L360 472Q291 505 200 548Q112 589 98 597T83 616ZM84 -118Q84 -108 99 -98H678Q694 -104 694 -118Q694 -130 679 -138H98Q84 -131 84 -118Z"></path></g><g data-mml-node="mn" transform="translate(3627.1,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(4627.1,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> for 2 hours or more (SA1g)<br> |
| 10. Highest <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.339ex;" xmlns="http://www.w3.org/2000/svg" width="5.189ex" height="1.932ex" role="img" focusable="false" viewBox="0 -704 2293.6 854"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D439" d="M48 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q146 66 215 342T285 622Q285 629 281 629Q273 632 228 634H197Q191 640 191 642T193 659Q197 676 203 680H742Q749 676 749 669Q749 664 736 557T722 447Q720 440 702 440H690Q683 445 683 453Q683 454 686 477T689 530Q689 560 682 579T663 610T626 626T575 633T503 634H480Q398 633 393 631Q388 629 386 623Q385 622 352 492L320 363H375Q378 363 398 363T426 364T448 367T472 374T489 386Q502 398 511 419T524 457T529 475Q532 480 548 480H560Q567 475 567 470Q567 467 536 339T502 207Q500 200 482 200H470Q463 206 463 212Q463 215 468 234T473 274Q473 303 453 310T364 317H309L277 190Q245 66 245 60Q245 46 334 46H359Q365 40 365 39T363 19Q359 6 353 0H336Q295 2 185 2Q120 2 86 2T48 1Z"></path></g><g data-mml-node="mi" transform="translate(749,0)"><path data-c="1D456" d="M184 600Q184 624 203 642T247 661Q265 661 277 649T290 619Q290 596 270 577T226 557Q211 557 198 567T184 600ZM21 287Q21 295 30 318T54 369T98 420T158 442Q197 442 223 419T250 357Q250 340 236 301T196 196T154 83Q149 61 149 51Q149 26 166 26Q175 26 185 29T208 43T235 78T260 137Q263 149 265 151T282 153Q302 153 302 143Q302 135 293 112T268 61T223 11T161 -11Q129 -11 102 10T74 74Q74 91 79 106T122 220Q160 321 166 341T173 380Q173 404 156 404H154Q124 404 99 371T61 287Q60 286 59 284T58 281T56 279T53 278T49 278T41 278H27Q21 284 21 287Z"></path></g><g data-mml-node="msub" transform="translate(1094,0)"><g data-mml-node="mi"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g><g data-mml-node="TeXAtom" transform="translate(796,-150) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span> level recorded during the first 48 hours post DR (SA1h)<br> |
| 11. Area under the hourly <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.339ex;" xmlns="http://www.w3.org/2000/svg" width="5.189ex" height="1.932ex" role="img" focusable="false" viewBox="0 -704 2293.6 854"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D439" d="M48 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q146 66 215 342T285 622Q285 629 281 629Q273 632 228 634H197Q191 640 191 642T193 659Q197 676 203 680H742Q749 676 749 669Q749 664 736 557T722 447Q720 440 702 440H690Q683 445 683 453Q683 454 686 477T689 530Q689 560 682 579T663 610T626 626T575 633T503 634H480Q398 633 393 631Q388 629 386 623Q385 622 352 492L320 363H375Q378 363 398 363T426 364T448 367T472 374T489 386Q502 398 511 419T524 457T529 475Q532 480 548 480H560Q567 475 567 470Q567 467 536 339T502 207Q500 200 482 200H470Q463 206 463 212Q463 215 468 234T473 274Q473 303 453 310T364 317H309L277 190Q245 66 245 60Q245 46 334 46H359Q365 40 365 39T363 19Q359 6 353 0H336Q295 2 185 2Q120 2 86 2T48 1Z"></path></g><g data-mml-node="mi" transform="translate(749,0)"><path data-c="1D456" d="M184 600Q184 624 203 642T247 661Q265 661 277 649T290 619Q290 596 270 577T226 557Q211 557 198 567T184 600ZM21 287Q21 295 30 318T54 369T98 420T158 442Q197 442 223 419T250 357Q250 340 236 301T196 196T154 83Q149 61 149 51Q149 26 166 26Q175 26 185 29T208 43T235 78T260 137Q263 149 265 151T282 153Q302 153 302 143Q302 135 293 112T268 61T223 11T161 -11Q129 -11 102 10T74 74Q74 91 79 106T122 220Q160 321 166 341T173 380Q173 404 156 404H154Q124 404 99 371T61 287Q60 286 59 284T58 281T56 279T53 278T49 278T41 278H27Q21 284 21 287Z"></path></g><g data-mml-node="msub" transform="translate(1094,0)"><g data-mml-node="mi"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g><g data-mml-node="TeXAtom" transform="translate(796,-150) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span> curve (SA6)<br> |
| 12. Need for intubation in DR or during first 48 hours of life (SA3)</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="first-7-days-of-life%3A"> |
| First 7 days of life:</h2> |
| <ol start="13"> |
| <li>Death or need for positive pressure ventilation at 7 days (SA5)</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="first-10-days-of-life%3A"> |
| First 10 days of life:</h2> |
| <ol start="14"> |
| <li>Need for new chest drains (SA1de)</li> |
| </ol> |
| <div>Calculated as an increase in the number of chest drains recorded hourly for the first 48 hours, and then daily up to 10 days of life.<br> |
| 15. Duration of any chest drain (SA1f)</div> |
| <div>Calculated as the amount of time the number of chest drains is <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.09ex;" xmlns="http://www.w3.org/2000/svg" width="3.52ex" height="1.597ex" role="img" focusable="false" viewBox="0 -666 1555.8 706"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="3E" d="M84 520Q84 528 88 533T96 539L99 540Q106 540 253 471T544 334L687 265Q694 260 694 250T687 235Q685 233 395 96L107 -40H101Q83 -38 83 -20Q83 -19 83 -17Q82 -10 98 -1Q117 9 248 71Q326 108 378 132L626 250L378 368Q90 504 86 509Q84 513 84 520Z"></path></g><g data-mml-node="mn" transform="translate(1055.8,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path></g></g></g></svg></mjx-container></span>. Since this will be measured hourly for 48 hours and then daily, the finest level possible will be calculated for each infant and then the data will be examined to determine the scale for analysis.<br> |
| 16. Highest <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.339ex;" xmlns="http://www.w3.org/2000/svg" width="5.189ex" height="1.932ex" role="img" focusable="false" viewBox="0 -704 2293.6 854"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D439" d="M48 1Q31 1 31 11Q31 13 34 25Q38 41 42 43T65 46Q92 46 125 49Q139 52 144 61Q146 66 215 342T285 622Q285 629 281 629Q273 632 228 634H197Q191 640 191 642T193 659Q197 676 203 680H742Q749 676 749 669Q749 664 736 557T722 447Q720 440 702 440H690Q683 445 683 453Q683 454 686 477T689 530Q689 560 682 579T663 610T626 626T575 633T503 634H480Q398 633 393 631Q388 629 386 623Q385 622 352 492L320 363H375Q378 363 398 363T426 364T448 367T472 374T489 386Q502 398 511 419T524 457T529 475Q532 480 548 480H560Q567 475 567 470Q567 467 536 339T502 207Q500 200 482 200H470Q463 206 463 212Q463 215 468 234T473 274Q473 303 453 310T364 317H309L277 190Q245 66 245 60Q245 46 334 46H359Q365 40 365 39T363 19Q359 6 353 0H336Q295 2 185 2Q120 2 86 2T48 1Z"></path></g><g data-mml-node="mi" transform="translate(749,0)"><path data-c="1D456" d="M184 600Q184 624 203 642T247 661Q265 661 277 649T290 619Q290 596 270 577T226 557Q211 557 198 567T184 600ZM21 287Q21 295 30 318T54 369T98 420T158 442Q197 442 223 419T250 357Q250 340 236 301T196 196T154 83Q149 61 149 51Q149 26 166 26Q175 26 185 29T208 43T235 78T260 137Q263 149 265 151T282 153Q302 153 302 143Q302 135 293 112T268 61T223 11T161 -11Q129 -11 102 10T74 74Q74 91 79 106T122 220Q160 321 166 341T173 380Q173 404 156 404H154Q124 404 99 371T61 287Q60 286 59 284T58 281T56 279T53 278T49 278T41 278H27Q21 284 21 287Z"></path></g><g data-mml-node="msub" transform="translate(1094,0)"><g data-mml-node="mi"><path data-c="1D442" d="M740 435Q740 320 676 213T511 42T304 -22Q207 -22 138 35T51 201Q50 209 50 244Q50 346 98 438T227 601Q351 704 476 704Q514 704 524 703Q621 689 680 617T740 435ZM637 476Q637 565 591 615T476 665Q396 665 322 605Q242 542 200 428T157 216Q157 126 200 73T314 19Q404 19 485 98T608 313Q637 408 637 476Z"></path></g><g data-mml-node="TeXAtom" transform="translate(796,-150) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span> level recorded from 48 hours to 10 days of life (SA6)<br> |
| 17. Air leak (SA8)</div> |
| <div>Defined as radiographic evidence of pneumothorax, pulmonary interstitial emphysema (PIE) or pneumopericardium.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="36-weeks-pma%3A"> |
| 36 weeks PMA:</h2> |
| <ol start="18"> |
| <li>Death (SA2)</li> |
| <li>BPD defined using a standardized oxygen reduction test (SA2)</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="discharge%3A"> |
| Discharge:</h2> |
| <ol start="20"> |
| <li>Retinopathy of prematurity (ROP) stage 3 or greater requiring treatment (SA10)</li> |
| <li>Death in hospital (SA11)</li> |
| <li>Survival to discharge home without BPD, retinopathy of prematurity (grades 3 & 4), or significant brain abnormalities on head ultrasound (SA7)</li> |
| <li>Length of hospital stay in days (SA13)</li> |
| <li>Use of postnatal steroids for treatment of BPD (SA12)</li> |
| <li>Duration of respiratory support (ventilation, CPAP, supplemental oxygen) in days (SA9)</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="22-26-months-corrected-gestational-age%3A"> |
| 22-26 Months corrected gestational age:</h2> |
| <ol start="26"> |
| <li>Neurodevelopmental outcomes (SA14)</li> |
| <li>Respiratory outcomes (SA14)</li> |
| </ol> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="2.3.3-safety"> |
| 2.3.3 Safety</h3> |
| <div>The primary safety endpoint is:</div> |
| <ul> |
| <li>Death or BPD at 36 weeks PMA.</li> |
| </ul> |
| <div>The secondary safety endpoints are:</div> |
| <ul> |
| <li>Death within 48 hours of delivery.</li> |
| <li>Oxygen requirement of Fi02 <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.312ex;" xmlns="http://www.w3.org/2000/svg" width="6.536ex" height="2.009ex" role="img" focusable="false" viewBox="0 -750 2888.8 888"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="2265" d="M83 616Q83 624 89 630T99 636Q107 636 253 568T543 431T687 361Q694 356 694 346T687 331Q685 329 395 192L107 56H101Q83 58 83 76Q83 77 83 79Q82 86 98 95Q117 105 248 167Q326 204 378 228L626 346L360 472Q291 505 200 548Q112 589 98 597T83 616ZM84 -118Q84 -108 99 -98H678Q694 -104 694 -118Q694 -130 679 -138H98Q84 -131 84 -118Z"></path></g><g data-mml-node="mn" transform="translate(1055.8,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(2055.8,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> for 2 hours or more within the first 48 hours post delivery.</li> |
| <li>Rate of pneumothorax, pulmonary interstitial emphysema (PIE), and pneumopericardium within the first 10 days of life. These will determined by radiographic evidence and supplemented by data on a) any chest tube in-situ post DR and b) need for new chest tube after arrival in NICU.</li> |
| <li>Grade 3 or 4 IVH within the first 10 days of life. Head ultrasound findings will be used to determine incidence of IVH.</li> |
| <li>Any other serious adverse events that have been adjudicated as potentially relating to the intervention. (See Protocol section 9.2.2)</li> |
| </ul> |
| <div>Adverse events will be compared between intervention arms. Adverse event data, including all serious adverse events, will also be descriptively summarized.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="3.-regular-monitoring-of-recruitment%2C-data-quality%2C-and-safety"> |
| 3. Regular Monitoring of Recruitment, Data Quality, and Safety</h2> |
| <div>Monitoring of the study will be performed by the DCC. The DCC consists of personnel from three groups: faculty biostatisticians, staff biostatisticians from the Biostatistics Analysis Center (BAC) and Clinical Data Management (CDM) staff from the CRCU.</div> |
| <div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Person</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Group</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Role</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Sarah Ratcliffe</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Faculty</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">MPI / DCC director</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Russ Localio</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Faculty</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Co-I</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Rosemary Madigan</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Project Manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Denise Cifelli</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Project Manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Steve Durborow</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Database Manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Chris Helker</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Database Manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Melissa Fernando</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Data manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Maria Blanco</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CRCU</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Data manager</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Sherry Han</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">BAC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Staff Statistician</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Min Du</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">BAC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Programmer</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| <div>Four types of standardized reports will be produced on a regular basis: participant recruitment and follow-up, data quality and monitoring reports, demographics, and adverse events. All of these reports will be done combining the intervention arms and presented both overall and by clinical site as appropriate. Selected examples of these reports will be provided when the database development has been completed.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.1-reporting-of-participant-recruitment-and-accrual"> |
| 3.1 Reporting of Participant Recruitment and Accrual</h3> |
| <div>Sites will enter all recruitment activity into the REDCap database, from which the weekly recruitment and accrual report will be generated. This includes information on reasons for ineligibility of subjects. The following reports will be produced by Clinical Data Management (CDM) staff in the DCC on Tuesday mornings, both overall and by clinical center (see Appendix B, Table 3 for example):</div> |
| <ul> |
| <li>Number of infants screened</li> |
| <li>Number of infants ineligible by reason</li> |
| <li>Number of infants randomized</li> |
| <li>Number of infants randomized versus established accrual targets</li> |
| <li>Number of infants completing each post-delivery evaluation</li> |
| </ul> |
| <div>Approximately every 3-4 months to correspond to full meetings of the SAIL Steering Committee, the staff biostatistician at BAC (Biostatistics Analysis Center) will produce a chart to display the cumulative number of infants successfully randomized at each site as compared to the targeted number, and a graph of overall cumulative accrual to date versus the targeted accrual based on the accrual goals. Reasons for withdrawal from follow-up and time to withdrawal will also be presented as data become available.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.2-data-quality-and-monitoring-reports"> |
| 3.2 Data Quality and Monitoring Reports</h3> |
| <div>CDM staff will produce the following reports to monitor overall data quality. These reports will be produced approximately every <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="5.028ex" height="1.717ex" role="img" focusable="false" viewBox="0 -677 2222.4 759"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path></g></g></g></svg></mjx-container></span> months to correspond to full meetings of the SAIL Steering Committee. These reports will include, but are not limited to:</div> |
| <ul> |
| <li>Missing post-delivery data</li> |
| <li>Missing forms</li> |
| <li>Missing values</li> |
| <li>Query rates</li> |
| <li>Timely entry and verification</li> |
| </ul> |
| <div>Additional monitoring reports that may be produced by CDM staff include incorrect opening of randomization envelopes, and query status updates.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.3-demographics-and-other-baseline-data"> |
| 3.3 Demographics and Other Baseline Data</h3> |
| <div>The staff biostatistician will prepare reports summarizing the distributions of demographic and clinical characteristics (Appendix B, Tables 1-2), both overall and by clinical center. These will be prepared approximately every <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="5.028ex" height="1.717ex" role="img" focusable="false" viewBox="0 -677 2222.4 759"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path></g></g></g></svg></mjx-container></span> months to correspond to full meetings of the SAIL Steering Committee.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.4-adverse-events"> |
| 3.4 Adverse Events</h3> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.4.1-serious-adverse-events"> |
| 3.4.1 Serious Adverse Events</h3> |
| <div>The serious adverse event (SAE) definitions are given in Protocol Section 9.2.2. These will include, for example:</div> |
| <ul> |
| <li>Death within the first 48 hours post delivery</li> |
| <li>Pneumothorax, pulmonary interstitial emphysema (PIE) and pneumopericardium determined by radiographic evidence within the first 10 days of life</li> |
| <li>Grade 3 or 4 IVH determined by head ultrasound findings within the first 10 days of life<br> |
| Based on the premature infant population studied, the SAE categories of events that result in congenital anomaly/birth defect or require intervention to prevent permanent impairment or damage (devices) do not apply when defining events.</li> |
| </ul> |
| <div>Serious adverse events (SAEs), regardless of whether they are unexpected or considered to be associated with the study, will be communicated immediately upon discovery of the event, by either telephone or fax. Reporting requirements are provided in the protocol and additional details will be provided in the Manual of Procedures (MOP) for the trial.</div> |
| <div>A description of all serious adverse events to date, without any intervention identifiers, will be presented at each meeting of the Steering Committee. This list will also be provided to the DSMC. The DSMC will ultimately adjudicate whether the reported adverse event is in fact an<br> |
| adverse event, and a serious AE, if the SAE could be attributed to the intervention, and unblind the intervention identifiers if they deem it necessary.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="3.4.2-other-adverse-events"> |
| 3.4.2 Other Adverse Events</h3> |
| <div>For Steering Committee Meetings, two types of summaries of adverse events will be produced. These data will also be provided to the DSMC.</div> |
| <ol> |
| <li>A listing of all adverse events will be produced by the CDM staff in the DCC directly from the AE/SAE form in the REDCap database. This listing will include a description, date of onset, grade, and relationship to study intervention, and whether or not the event was serious.</li> |
| <li>The study biostatistician will produce summaries of the observed adverse events combined into categories, as needed, using SAS or another similar statistical tool. All the events, regardless of the relationship to the study intervention, will be included in these reports. These reports will combine data across all interventions and clinical sites. An example of the type of table which will be produced for safety analysis is shown in Appendix B.</li> |
| </ol> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="4.-interim-analysis"> |
| 4. Interim Analysis</h2> |
| <div>Since neonatal safety is a consideration in this study, we have chosen to use a group sequential design. Thus, in addition to the final analysis, there will be two interim statistical analyses during the course of this study. The purpose of the interim analyses will be to determine whether or not there is sufficient evidence of a difference between the treatment arms in the primary endpoint such that the trial should be discontinued prior to reaching the target accrual goal.</div> |
| <div>Interim analyses will be performed after approximately <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.566ex;" xmlns="http://www.w3.org/2000/svg" width="3.394ex" height="2.262ex" role="img" focusable="false" viewBox="0 -750 1500 1000"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g><g data-mml-node="TeXAtom" data-mjx-texclass="ORD" transform="translate(500,0)"><g data-mml-node="mo"><path data-c="2F" d="M423 750Q432 750 438 744T444 730Q444 725 271 248T92 -240Q85 -250 75 -250Q68 -250 62 -245T56 -231Q56 -221 230 257T407 740Q411 750 423 750Z"></path></g></g><g data-mml-node="mn" transform="translate(1000,0)"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></svg></mjx-container></span> ( 200 subjects) and <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.566ex;" xmlns="http://www.w3.org/2000/svg" width="3.394ex" height="2.262ex" role="img" focusable="false" viewBox="0 -750 1500 1000"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g><g data-mml-node="TeXAtom" data-mjx-texclass="ORD" transform="translate(500,0)"><g data-mml-node="mo"><path data-c="2F" d="M423 750Q432 750 438 744T444 730Q444 725 271 248T92 -240Q85 -250 75 -250Q68 -250 62 -245T56 -231Q56 -221 230 257T407 740Q411 750 423 750Z"></path></g></g><g data-mml-node="mn" transform="translate(1000,0)"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></svg></mjx-container></span> ( 400 subjects) of the total required patients have completed their primary outcome. An additional safety review will be undertaken after 1/6 (100 subjects) have completed their primary outcome. The results of the interim analyses will be presented to the SAIL Data Safety and Monitoring Committee (DSMC). The primary outcome for the interim analyses will be the comparison of death/BPD between the treatment arms. This comparison will be accomplished by means of a simple generalized estimating equation (GEE) model for death/BPD versus treatment (since adjustment for deliveries with multiple babies will be needed). An approximate O'Brien-Fleming boundary will be used at each interim look to calculate the nominal significance level to which interim p-values are compared (O'Brien PC, 1979). Using the O'Brien Fleming spending function, the three analyses (2 interim + final) should use the following incremental <span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="1.448ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 640 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D6FC" d="M34 156Q34 270 120 356T309 442Q379 442 421 402T478 304Q484 275 485 237V208Q534 282 560 374Q564 388 566 390T582 393Q603 393 603 385Q603 376 594 346T558 261T497 161L486 147L487 123Q489 67 495 47T514 26Q528 28 540 37T557 60Q559 67 562 68T577 70Q597 70 597 62Q597 56 591 43Q579 19 556 5T512 -10H505Q438 -10 414 62L411 69L400 61Q390 53 370 41T325 18T267 -2T203 -11Q124 -11 79 39T34 156ZM208 26Q257 26 306 47T379 90L403 112Q401 255 396 290Q382 405 304 405Q235 405 183 332Q156 292 139 224T121 120Q121 71 146 49T208 26Z"></path></g></g></g></svg></mjx-container></span> values ( <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.439ex;" xmlns="http://www.w3.org/2000/svg" width="12.445ex" height="1.946ex" role="img" focusable="false" viewBox="0 -666 5500.7 860"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1278,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1778,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(2278,0)"></path></g><g data-mml-node="mo" transform="translate(2778,0)"><path data-c="2C" d="M78 35T78 60T94 103T137 121Q165 121 187 96T210 8Q210 -27 201 -60T180 -117T154 -158T130 -185T117 -194Q113 -194 104 -185T95 -172Q95 -168 106 -156T131 -126T157 -76T173 -3V9L172 8Q170 7 167 6T161 3T152 1T140 0Q113 0 96 17Z"></path></g><g data-mml-node="mn" transform="translate(3222.7,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z" transform="translate(1278,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(1778,0)"></path></g></g></g></svg></mjx-container></span>, and 0.038 ) in order to achieve an overall <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="8.488ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 3751.6 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D6FC" d="M34 156Q34 270 120 356T309 442Q379 442 421 402T478 304Q484 275 485 237V208Q534 282 560 374Q564 388 566 390T582 393Q603 393 603 385Q603 376 594 346T558 261T497 161L486 147L487 123Q489 67 495 47T514 26Q528 28 540 37T557 60Q559 67 562 68T577 70Q597 70 597 62Q597 56 591 43Q579 19 556 5T512 -10H505Q438 -10 414 62L411 69L400 61Q390 53 370 41T325 18T267 -2T203 -11Q124 -11 79 39T34 156ZM208 26Q257 26 306 47T379 90L403 112Q401 255 396 290Q382 405 304 405Q235 405 183 332Q156 292 139 224T121 120Q121 71 146 49T208 26Z"></path></g><g data-mml-node="mo" transform="translate(917.8,0)"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1973.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(1278,0)"></path></g></g></g></svg></mjx-container></span>.</div> |
| <div>There are four comparisons to warrant early stopping: (1) Clear superiority: Superiority of the intervention is sufficiently large that the study should be discontinued because equipoise is lost and randomization should no longer proceed. (2) Futility: The evidence in favor of the intervention is such that at the completion of the study, there is inadequate power to detect an improvement and the study should be dropped. (3) Inferiority: The evidence shows that the intervention is worse than the control and the study needs to be stopped. (4) Safety: Secondary safety outcomes that are considered serious adverse events possible related to the study are clinically higher in the intervention group. (See also section 4.4 for additional safety outcomes).<br> |
| (1) Clear superiority -- whether the experimental treatment is clearly inferior to standard therapy. For these calculations, we trade off the power to detect a difference and the size of that difference. Assuming <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="10.75ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 4751.6 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D6FC" d="M34 156Q34 270 120 356T309 442Q379 442 421 402T478 304Q484 275 485 237V208Q534 282 560 374Q564 388 566 390T582 393Q603 393 603 385Q603 376 594 346T558 261T497 161L486 147L487 123Q489 67 495 47T514 26Q528 28 540 37T557 60Q559 67 562 68T577 70Q597 70 597 62Q597 56 591 43Q579 19 556 5T512 -10H505Q438 -10 414 62L411 69L400 61Q390 53 370 41T325 18T267 -2T203 -11Q124 -11 79 39T34 156ZM208 26Q257 26 306 47T379 90L403 112Q401 255 396 290Q382 405 304 405Q235 405 183 332Q156 292 139 224T121 120Q121 71 146 49T208 26Z"></path></g><g data-mml-node="mo" transform="translate(917.8,0)"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1973.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1278,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1778,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(2278,0)"></path></g></g></g></svg></mjx-container></span> for boundaries for the initial interim analysis when 200 children have been followed to completion, power is limited except to detect large reductions in outcomes of death and BPD. For example, power is approximately 0.81 to detect a reduction from <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> in the conventional therapy to <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="5.907ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 2611 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(500,0)"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(1000,0)"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(1278,0)"></path></g><g data-mml-node="mi" transform="translate(1778,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> in the experimental therapy, a <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> relative reduction. For the second interim analysis, using <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="9.619ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 4251.6 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D6FC" d="M34 156Q34 270 120 356T309 442Q379 442 421 402T478 304Q484 275 485 237V208Q534 282 560 374Q564 388 566 390T582 393Q603 393 603 385Q603 376 594 346T558 261T497 161L486 147L487 123Q489 67 495 47T514 26Q528 28 540 37T557 60Q559 67 562 68T577 70Q597 70 597 62Q597 56 591 43Q579 19 556 5T512 -10H505Q438 -10 414 62L411 69L400 61Q390 53 370 41T325 18T267 -2T203 -11Q124 -11 79 39T34 156ZM208 26Q257 26 306 47T379 90L403 112Q401 255 396 290Q382 405 304 405Q235 405 183 332Q156 292 139 224T121 120Q121 71 146 49T208 26Z"></path></g><g data-mml-node="mo" transform="translate(917.8,0)"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1973.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z" transform="translate(1278,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(1778,0)"></path></g></g></g></svg></mjx-container></span>, power with 400 children followed is about 0.85 to detect an absolute reduction from <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> to <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> in the risk of death plus BPD. Thus, early or premature stopping for superiority is unlikely, without dramatic improvement from experimental treatment.<br> |
| (2) Futility. Early stopping based on futility of the primary outcome will not be considered independently of the secondary clinical and safety outcomes. In the event that the intervention arm has equivalent BPD/death rates to the standard care arm, it would still be clinically useful to know if the intervention improves any of the secondary outcomes (that are closer to the time of the intervention) or decreases the serious adverse event rate.<br> |
| (3) Inferiority. Power is limited to identify inferiority of the experimental treatment, with 0.8 power to demonstrate a <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> point increase in the risk of outcome from <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z"></path><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> in the standard therapy to <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="38" d="M70 417T70 494T124 618T248 666Q319 666 374 624T429 515Q429 485 418 459T392 417T361 389T335 371T324 363L338 354Q352 344 366 334T382 323Q457 264 457 174Q457 95 399 37T249 -22Q159 -22 101 29T43 155Q43 263 172 335L154 348Q133 361 127 368Q70 417 70 494ZM286 386L292 390Q298 394 301 396T311 403T323 413T334 425T345 438T355 454T364 471T369 491T371 513Q371 556 342 586T275 624Q268 625 242 625Q201 625 165 599T128 534Q128 511 141 492T167 463T217 431Q224 426 228 424L286 386ZM250 21Q308 21 350 55T392 137Q392 154 387 169T375 194T353 216T330 234T301 253T274 270Q260 279 244 289T218 306L210 311Q204 311 181 294T133 239T107 157Q107 98 150 60T250 21Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> in the intervention.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="(4)-safety."> |
| (4) Safety.</h2> |
| <div>(a) Early stopping based on inferior safety and non-inferior efficacy must be based largely on descriptive data and close examination of adverse events. With 200 subjects per group at a second early stopping review, and assuming that the experimental therapy is actually no worse than conventional care, observed risk in the experimental group would have to be at most 0.5 (risk of death and BPD) to have <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="38" d="M70 417T70 494T124 618T248 666Q319 666 374 624T429 515Q429 485 418 459T392 417T361 389T335 371T324 363L338 354Q352 344 366 334T382 323Q457 264 457 174Q457 95 399 37T249 -22Q159 -22 101 29T43 155Q43 263 172 335L154 348Q133 361 127 368Q70 417 70 494ZM286 386L292 390Q298 394 301 396T311 403T323 413T334 425T345 438T355 454T364 471T369 491T371 513Q371 556 342 586T275 624Q268 625 242 625Q201 625 165 599T128 534Q128 511 141 492T167 463T217 431Q224 426 228 424L286 386ZM250 21Q308 21 350 55T392 137Q392 154 387 169T375 194T353 216T330 234T301 253T274 270Q260 279 244 289T218 306L210 311Q204 311 181 294T133 239T107 157Q107 98 150 60T250 21Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> power to show non-inferior efficacy (with alpha <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="7.542ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 3333.8 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1055.8,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z" transform="translate(1278,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(1778,0)"></path></g></g></g></svg></mjx-container></span> ).<br> |
| (b) To justify stopping for non-inferior efficacy and superior safety again will require a substantial observed improvement in the experimental arm at the second early stopping time.</div> |
| <div>In summary, given the projected number of patients to be enrolled, early stopping will be unlikely unless the observed effect of experimental care is clearly better or worse than standard care at the planned early stopping assessment times.</div> |
| <div>All of the standard reports described in the previous section will be provided to the DSMC with this analysis. Additional measures to be considered at the interim analysis include baseline clinical factors and adverse events. The study population for all of the analyses provided to the DSMC is the intent-to-treat population, including all participants and time points for which data have been entered and verified in the study database. A summary of the analyses to be included in the interim report is outlined below. Additional details of the statistical methods to be used are given in the next section regarding the final analysis.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="4.1-blinding"> |
| 4.1 Blinding</h3> |
| <div>The study will be blinded in treatment allocation; patients, parents and clinicians will be unblinded once treatment is assigned; and then blinded analyses. All analyses provided to the DSMC will be provided by intervention, but with the individual interventions identified only as A and B. The same code will be used for each intervention throughout the report. A sealed envelope with the codes for these interventions will be provided to the chair of the DSMC, to allow the DSMC to unblind these results if needed for safety reasons. These codes are also maintained by a member of the DCC who is not involved in the group trials and are not made<br> |
| available to any other DCC members, including the statisticians. None of the personnel in the DCC, including the statisticians, will have access to these codes until the study has been completed, all data are entered and verified in the database, and the DSMC has approved unblinding of the intervention results.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="4.2-baseline%2Fdelivery-data"> |
| 4.2 Baseline/Delivery Data</h3> |
| <div>Selected baseline factors will be summarized and compared between intervention groups to evaluate the adequacy of randomization, the impact of any post-randomization dropout, and to identify any imbalances that may affect intervention comparisons (Appendix B, Table 1 and Table 2). Standard descriptive statistics will be used to describe baseline characteristics, both overall and within each intervention group. Baseline characteristics examined will include maternal and gestational age, race/ethnicity, Clinical Site, consenting procedure (antenatal vs. deferred consent), route of treatment (facemask vs. nasopharyngeal tube), and enrollment date (in 3 month increments). Baseline values of selected secondary outcomes will be included as part of that analysis (see below).</div> |
| <div>Summary statistics such as medians, ranges, minima and maxima, and percentages will be produced for all measured variables. Frequencies will be computed for all categorical and ordinal variables. Graphical methods including stem and leaf plots, histograms, scatterplots, and boxplots, will be used in order to understand aspects of data quality, examine assumptions (such as normality) underlying statistical models, identify potential influential points, and guide in the choice of transformations if warranted. The balance of baseline measures across the intervention groups will be compared by inspection and by standardized differences. Overall imbalance across several or all covariates will be examined using multivariable logistic regression with treatment assignment as the outcome. .</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="4.3-subject-accounting-and-withdrawals"> |
| 4.3 Subject Accounting and Withdrawals</h3> |
| <div>A detailed summary of subject accounting over the course of the study will be prepared for each treatment group (Appendix B, Table 3 & 4). A study flow diagram, derived from the one recommended by CONSORT, will also be provided (Appendix B, Figure 1). Withdrawal rates over time and reasons for withdrawal will be summarized. For the follow-up evaluation at 22-26 month corrected GA, withdrawal rates will be compared between arms using standard methods for dichotomous measures.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="4.4-evaluation-of-safety"> |
| 4.4 Evaluation of Safety</h3> |
| <div>In addition to the standard reports, statistical analyses will be performed to compare adverse event rates between treatments. In particular, the rate of pneumothorax, pulmonary interstitial emphysema (PIE), and/or other serious adverse events (that have been adjudicated as potentially relating to the intervention; see Protocol section 8.2.2). In order to minimize the risk, this safety outcome will be compared between treatment arms after <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.566ex;" xmlns="http://www.w3.org/2000/svg" width="3.394ex" height="2.262ex" role="img" focusable="false" viewBox="0 -750 1500 1000"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g><g data-mml-node="TeXAtom" data-mjx-texclass="ORD" transform="translate(500,0)"><g data-mml-node="mo"><path data-c="2F" d="M423 750Q432 750 438 744T444 730Q444 725 271 248T92 -240Q85 -250 75 -250Q68 -250 62 -245T56 -231Q56 -221 230 257T407 740Q411 750 423 750Z"></path></g></g><g data-mml-node="mn" transform="translate(1000,0)"><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z"></path></g></g></g></svg></mjx-container></span> ( 100 subjects) have completed the primary outcome, as well as at the two planned interim analyses for the primary outcome ( <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.566ex;" xmlns="http://www.w3.org/2000/svg" width="3.394ex" height="2.262ex" role="img" focusable="false" viewBox="0 -750 1500 1000"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g><g data-mml-node="TeXAtom" data-mjx-texclass="ORD" transform="translate(500,0)"><g data-mml-node="mo"><path data-c="2F" d="M423 750Q432 750 438 744T444 730Q444 725 271 248T92 -240Q85 -250 75 -250Q68 -250 62 -245T56 -231Q56 -221 230 257T407 740Q411 750 423 750Z"></path></g></g><g data-mml-node="mn" transform="translate(1000,0)"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></svg></mjx-container></span> and <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.566ex;" xmlns="http://www.w3.org/2000/svg" width="3.394ex" height="2.262ex" role="img" focusable="false" viewBox="0 -750 1500 1000"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g><g data-mml-node="TeXAtom" data-mjx-texclass="ORD" transform="translate(500,0)"><g data-mml-node="mo"><path data-c="2F" d="M423 750Q432 750 438 744T444 730Q444 725 271 248T92 -240Q85 -250 75 -250Q68 -250 62 -245T56 -231Q56 -221 230 257T407 740Q411 750 423 750Z"></path></g></g><g data-mml-node="mn" transform="translate(1000,0)"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></svg></mjx-container></span> ), since we would not expect any statistically significant differences in the rate after 100 subjects (with O'Brien-Fleming alpha 0.000002). Instead, we will look for a clinically meaningful double the risk in the intervention versus standard care arms. (Appendix B, Table 5)</div> |
| <div>All other adverse events not explicitly mentioned in the Protocol will also be included, regardless of their presumed relationship to the study intervention. Adverse events will be collapsed into groups based on body part depending on numbers seen. The proportion of subjects<br> |
| with any adverse event will be compared between groups using an exact Mantel-Haenszel test. Comparisons between interventions will be primarily descriptive</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="5.-final-data-analysis-upon-completion-of-trial"> |
| 5. Final Data Analysis upon Completion of Trial</h2> |
| <div>Upon completion of the primary outcome at 36 weeks PMA, after all data has been entered in the database and query resolution is complete, the primary statistical analysis and description of the data will be performed. The final analysis for the <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="7.291ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 3222.4 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(500,0)"></path></g><g data-mml-node="mo" transform="translate(1222.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(2222.4,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="36" d="M42 313Q42 476 123 571T303 666Q372 666 402 630T432 550Q432 525 418 510T379 495Q356 495 341 509T326 548Q326 592 373 601Q351 623 311 626Q240 626 194 566Q147 500 147 364L148 360Q153 366 156 373Q197 433 263 433H267Q313 433 348 414Q372 400 396 374T435 317Q456 268 456 210V192Q456 169 451 149Q440 90 387 34T253 -22Q225 -22 199 -14T143 16T92 75T56 172T42 313ZM257 397Q227 397 205 380T171 335T154 278T148 216Q148 133 160 97T198 39Q222 21 251 21Q302 21 329 59Q342 77 347 104T352 209Q352 289 347 316T329 361Q302 397 257 397Z" transform="translate(500,0)"></path></g></g></g></svg></mjx-container></span> month cGA secondary outcomes will be completed separately, after that data has been entered in the database and cleaned. The staff biostatistician under the direction of the faculty biostatisticians will produce a final report outlining all analyses and interpretation of the results. This report will be used as the basis of the primary manuscript to be prepared for publication. Details of the analyses and statistical methods to be included in the final report are outlined below. All statistical tests described below will be conducted using a two-sided level of significance.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.1-examination-of-baseline-characteristics"> |
| 5.1 Examination of Baseline Characteristics</h3> |
| <div>These will be reported as described above under the interim analysis.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.2-subject-accounting-and-withdrawal-rates"> |
| 5.2 Subject Accounting and Withdrawal Rates</h3> |
| <div>These will be reported as described above under the interim analysis.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.3-analysis-of-safety-and-toxicity"> |
| 5.3 Analysis of Safety and Toxicity</h3> |
| <div>These will be reported as described above under the interim analysis.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.4-analysis-of-efficacy-endpoints"> |
| 5.4 Analysis of Efficacy Endpoints</h3> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.4.1-primary-endpoint"> |
| 5.4.1 Primary Endpoint</h3> |
| <div>In addition to the two-sample comparison (Appendix B, Table 5), adjusted analyses of the primary endpoint (death/BPD rate) may be performed. These adjusted analyses of the primary endpoint will rely on logistic regression and generalized estimating equation (GEE, to control for clustering within multiple births) methods to evaluate whether observed differences, if any, are attributable to imbalances in prognostic factors such as gender, gestational age, initial heart rate, maternal corticosteriods use, and small for gestational age (SGA). Standard regression diagnostics will be used to assess model adequacy and examine potential outlying or influential data points for these analyses. If there are clinical or demographic characteristic imbalances between the two treatment arms, a propensity score analysis (via stratification into 5 subgroups, and via inverse propensity treatment weights) will be used to assess the sensitivity of the results to any treatment allocation biases.</div> |
| <div>Prior studies offer no basis for assuming a priori interactions between treatment arms and subgroups defined by sex, race/ethnicity, gestational age, site or a combination of these groups, beyond that already controlled for in the randomization. For that reason, preplanned tests for interactions with treatment assignment are not warranted, and not powered for. We propose, however, to table all results by subgroups for descriptive purposes and to explore in secondary analyses possible subgroup differences by treatment group, solely for purposes of generating hypotheses for future studies. In particular, there is interest in exploring subgroups defined by:</div> |
| <ul> |
| <li>Consenting procedure which may vary by site (antenatal vs. deferred consent). While consenting procedure differences may result in some selection bias, this will be implicity adjusted for with the already planned clinical site stratification factor. Additionally, the sample size still results in <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="4.147ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 1833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="38" d="M70 417T70 494T124 618T248 666Q319 666 374 624T429 515Q429 485 418 459T392 417T361 389T335 371T324 363L338 354Q352 344 366 334T382 323Q457 264 457 174Q457 95 399 37T249 -22Q159 -22 101 29T43 155Q43 263 172 335L154 348Q133 361 127 368Q70 417 70 494ZM286 386L292 390Q298 394 301 396T311 403T323 413T334 425T345 438T355 454T364 471T369 491T371 513Q371 556 342 586T275 624Q268 625 242 625Q201 625 165 599T128 534Q128 511 141 492T167 463T217 431Q224 426 228 424L286 386ZM250 21Q308 21 350 55T392 137Q392 154 387 169T375 194T353 216T330 234T301 253T274 270Q260 279 244 289T218 306L210 311Q204 311 181 294T133 239T107 157Q107 98 150 60T250 21Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(1000,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> power at <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="9.619ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 4251.6 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D6FC" d="M34 156Q34 270 120 356T309 442Q379 442 421 402T478 304Q484 275 485 237V208Q534 282 560 374Q564 388 566 390T582 393Q603 393 603 385Q603 376 594 346T558 261T497 161L486 147L487 123Q489 67 495 47T514 26Q528 28 540 37T557 60Q559 67 562 68T577 70Q597 70 597 62Q597 56 591 43Q579 19 556 5T512 -10H505Q438 -10 414 62L411 69L400 61Q390 53 370 41T325 18T267 -2T203 -11Q124 -11 79 39T34 156ZM208 26Q257 26 306 47T379 90L403 112Q401 255 396 290Q382 405 304 405Q235 405 183 332Q156 292 139 224T121 120Q121 71 146 49T208 26Z"></path></g><g data-mml-node="mo" transform="translate(917.8,0)"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1973.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z" transform="translate(1278,0)"></path><path data-c="38" d="M70 417T70 494T124 618T248 666Q319 666 374 624T429 515Q429 485 418 459T392 417T361 389T335 371T324 363L338 354Q352 344 366 334T382 323Q457 264 457 174Q457 95 399 37T249 -22Q159 -22 101 29T43 155Q43 263 172 335L154 348Q133 361 127 368Q70 417 70 494ZM286 386L292 390Q298 394 301 396T311 403T323 413T334 425T345 438T355 454T364 471T369 491T371 513Q371 556 342 586T275 624Q268 625 242 625Q201 625 165 599T128 534Q128 511 141 492T167 463T217 431Q224 426 228 424L286 386ZM250 21Q308 21 350 55T392 137Q392 154 387 169T375 194T353 216T330 234T301 253T274 270Q260 279 244 289T218 306L210 311Q204 311 181 294T133 239T107 157Q107 98 150 60T250 21Z" transform="translate(1778,0)"></path></g></g></g></svg></mjx-container></span> for the primary outcome even if the selection bias results in a reduced control arm rate.</li> |
| <li>Route of treatment (facemask vs. nasopharyngeal tube). While not expected to modify the intervention effectiveness, exploring this difference will be important for future study design and clinical practice.</li> |
| <li>Enrollment date. Clinical practices unrelated to this intervention, as well as increased intervention experience, could result in changes in the clinical effectiveness of the intervention over time (positively or negatively). We will explore graphically any temporal trends in the intervention effect, and will allow/test for a time-varying treatment effect via a functional logistic regression model, if needed (for which the original power calculations are conservative) (Ratcliffe SJ, et al., 2002).</li> |
| </ul> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.4.2-secondary-endpoints"> |
| 5.4.2 Secondary Endpoints</h3> |
| <div>Secondary outcomes will be analyzed using similar procedures to the primary outcome. Descriptive statistics for secondary outcome measures will be calculated. Outcomes will be compared between treatment groups using GEE methods (where needed to account for twins) with logistic regression (dichotomous outcomes), linear regression (continuous outcomes), or survival analysis (survival time outcomes), as appropriate. If indicated, these models will be expanded to include baseline covariates and potential interactions between baseline factors and intervention.</div> |
| <div>Standard data and regression diagnostics will be used to assess model adequacy and examine potential outlying or influential data points for all of the above analyses. If these analyses suggest significant skewness or other violations of parametric model assumptions, the comparisons above may be supplemented with non-parametric methods based on rank scores within the generalized Mantel-Haenszel testing framework, adjusting for clustering of multiple births.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="5.4.3-group-sequential-boundary-for-primary-endpoint"> |
| 5.4.3 Group Sequential Boundary for Primary Endpoint</h3> |
| <div>To avoid inflating the overall Type I error rate for the primary analysis of efficacy, an O'Brien-Fleming boundary will be used to calculate the nominal significance level to which the interim p-value for the primary endpoint is compared. The efficacy boundary is 0.038 at the final analysis.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="6.-intent-to-treat-analysis-and-missing-data"> |
| 6. Intent-to-Treat Analysis and Missing Data</h2> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="6.1-treatment-and-study-withdrawals"> |
| 6.1 Treatment and Study Withdrawals</h3> |
| <div>It is anticipated that there will be a small number of infants who, because of acute clinical deterioration are treated according to the preference of their medical team rather than by study protocol. However, their outcomes will be measured and analyzed according to original allocation by intention-to-treat principles.</div> |
| <div>It should be noted that infants who discontinue in the trial, particularly in the case of an adverse event, will not be considered withdrawals from the study unless their parent withdraws consent for further follow-up. The parents of such infants will be encouraged to continue in the study in order to provide complete follow-up information. The characteristics at time of randomization for those participants without complete follow-up will be examined; however, there will be limited statistical power to detect any but major differences between these infants and those with complete follow-up. As mentioned above, in order to assess the potential biases introduced by differential withdrawal among intervention arms, a comparison of withdrawal rates will be carried out using the exact conditional test (ECT) version of Mantel-Haenszel methods to adjust for within-center clustering.</div> |
| <div>Potential effects of withdrawals and other sources of missing data on the statistical analysis and interpretation of results are discussed further below.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="6.2-other-missing-data-considerations"> |
| 6.2 Other Missing Data Considerations</h3> |
| <div>In addition to data that is naturally missing from participants who withdraw from study, it is expected that there may be occasional missing values for other subjects. All attempts will be made to keep missing data to a minimum. Extensive procedures to minimize missing data during the data collection and entry process will be put in place, following standard operating procedures at the DCC. These procedures will be described further in the Manual of Procedures. In addition, since the infants are still hospitalized at 36 weeks PMA as part of routine clinical care, it has been our experience that this type of missing data is minimal. The number of subjects included with each individual analysis will be given with the results. In general, missing data will not be directly imputed in any way.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="6.3-intent-to-treat-analysis-for-the-primary-endpoint"> |
| 6.3 Intent-to-Treat Analysis for the Primary Endpoint</h3> |
| <div>An as randomized (formerly called "intent-to-treat") analysis, in which all available data on all randomized participants are included, will be used for the primary endpoint comparison between interventions.</div> |
| <h3 type="subsection" data-unnumbered="true" class="sub_section-title" id="6.4-potential-effects-of-missing-data-on-secondary-endpoints"> |
| 6.4 Potential Effects of Missing Data on Secondary Endpoints</h3> |
| <div>The possibility of missing data can have serious consequences for the interpretation of statistical analyses. This is particularly problematic if the probability of missing data is related to the intervention, the outcome, or both. There is a large statistical literature on the potential effects of missing data and also some proposed methods for analysis, although these methods often require assumptions that cannot be tested within the trial dataset itself. Some of the issues regarding the potential effects of missing data on the evaluation of secondary endpoints in this trial are briefly addressed below.</div> |
| <div>For measures recorded at 22-26 months corrected GA, some missing data due to loss-to-follow-up is to be expected, though minimal. Data for those subjects without 22-26 months data will be omitted from these analyses. Although these analyses will be conducted, it is important that the results be interpreted in light of the fact that they will only include a subgroup of the population ("completers"), and that the subgroup is based on outcomes such that the benefit of the original randomization may no longer hold. In the event that the analysis of the secondary endpoints at 22-26 months becomes an important issue for clinical decision-making, methods which directly model the outcomes and the withdrawal process may be considered.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="7.-presentation-and-format-of-results"> |
| 7. Presentation and Format of Results</h2> |
| <div>Examples of some of the tables described in the previous section are given in Appendix B. Additional tables and appropriate figures will be produced as needed. For general reporting, one decimal point for most efficacy and safety endpoints, p -values will be reported to two significant digits (following the ICJME conventions of <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="4.888ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 2160.7 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D465" d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path></g><g data-mml-node="mo" transform="translate(572,0)"><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z"></path></g><g data-mml-node="mi" transform="translate(1016.7,0)"><path data-c="1D465" d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path></g><g data-mml-node="mi" transform="translate(1588.7,0)"><path data-c="1D465" d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path></g></g></g></svg></mjx-container></span> for most, <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.439ex;" xmlns="http://www.w3.org/2000/svg" width="7.047ex" height="1.946ex" role="img" focusable="false" viewBox="0 -666 3114.6 860"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D45D" d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></g><g data-mml-node="mo" transform="translate(780.8,0)"><path data-c="3E" d="M84 520Q84 528 88 533T96 539L99 540Q106 540 253 471T544 334L687 265Q694 260 694 250T687 235Q685 233 395 96L107 -40H101Q83 -38 83 -20Q83 -19 83 -17Q82 -10 98 -1Q117 9 248 71Q326 108 378 132L626 250L378 368Q90 504 86 509Q84 513 84 520Z"></path></g><g data-mml-node="mn" transform="translate(1836.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(778,0)"></path></g></g></g></svg></mjx-container></span>, or <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.439ex;" xmlns="http://www.w3.org/2000/svg" width="9.309ex" height="1.946ex" role="img" focusable="false" viewBox="0 -666 4114.6 860"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D45D" d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></g><g data-mml-node="mo" transform="translate(780.8,0)"><path data-c="3C" d="M694 -11T694 -19T688 -33T678 -40Q671 -40 524 29T234 166L90 235Q83 240 83 250Q83 261 91 266Q664 540 678 540Q681 540 687 534T694 519T687 505Q686 504 417 376L151 250L417 124Q686 -4 687 -5Q694 -11 694 -19Z"></path></g><g data-mml-node="mn" transform="translate(1836.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z" transform="translate(500,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(778,0)"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(1278,0)"></path><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z" transform="translate(1778,0)"></path></g></g></g></svg></mjx-container></span> ), and no rounding in any intermediate data or analysis steps will be used.</div> |
| <div>Data will be primarily managed in REDCap. SAS will be used for secondary data management and descriptive statistics. SAS datasets will be downloaded at least weekly from the study database for analysis. Graphics will be prepared using Stata v13 (or later) (Stata Corp, San Antonio TX, 2009) and the R programming package v 3.0 or later (The R Foundation for Statistical Computing, Vienna, Austria, 2011). Analyses will be implemented in SAS, Stata, or R as needed. These programs will be documented according to the Standard Operating Procedures of the Biostatistics and Epidemiology Consulting Center (BECC) and will be made available to sponsoring and regulatory agencies during study close out (See Manual of Procedures).</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="8.-revisions-to-the-damp"> |
| 8. Revisions to the DAMP</h2> |
| <div>An attempt has been made to anticipate possible data problems and to pre-specify handling conventions. However, it is recognized that this DAMP may not have covered all possible issues related to data analysis and reporting. Blinded data reviews will be performed, and data problems found through such reviews will be handled according to the principles outlined in this DAMP and will be properly documented. Data problems found during final analysis will be handled in the same manner and will be clearly noted in study reports. Changes to these procedures that occur during the course of this study, will be incorporated as amendments to the DAMP and included in the protocol, if appropriate.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="9.-appendix-a%3A-schedule-of-study-reporting"> |
| 9. Appendix A: Schedule Of Study Reporting</h2> |
| <div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Type of Report</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Prepared By:</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Provided To:</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Frequency:</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Serious Adverse Events (SAEs)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Sites, DCC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">SC <span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0;" xmlns="http://www.w3.org/2000/svg" width="0.988ex" height="1.887ex" role="img" focusable="false" viewBox="0 -833.9 436.6 833.9"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="msup"><g data-mml-node="TeXAtom" data-mjx-texclass="ORD"></g><g data-mml-node="TeXAtom" transform="translate(33,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g></g></g></g></g></svg></mjx-container></span>, DSMC, IRBs</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Immediately</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Patient Recruitment/Targets</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.05ex;" xmlns="http://www.w3.org/2000/svg" width="7.081ex" height="1.937ex" role="img" focusable="false" viewBox="0 -833.9 3129.6 855.9"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D436" d="M50 252Q50 367 117 473T286 641T490 704Q580 704 633 653Q642 643 648 636T656 626L657 623Q660 623 684 649Q691 655 699 663T715 679T725 690L740 705H746Q760 705 760 698Q760 694 728 561Q692 422 692 421Q690 416 687 415T669 413H653Q647 419 647 422Q647 423 648 429T650 449T651 481Q651 552 619 605T510 659Q484 659 454 652T382 628T299 572T226 479Q194 422 175 346T156 222Q156 108 232 58Q280 24 350 24Q441 24 512 92T606 240Q610 253 612 255T628 257Q648 257 648 248Q648 243 647 239Q618 132 523 55T319 -22Q206 -22 128 53T50 252Z"></path></g><g data-mml-node="mi" transform="translate(760,0)"><path data-c="1D437" d="M287 628Q287 635 230 637Q207 637 200 638T193 647Q193 655 197 667T204 682Q206 683 403 683Q570 682 590 682T630 676Q702 659 752 597T803 431Q803 275 696 151T444 3L430 1L236 0H125H72Q48 0 41 2T33 11Q33 13 36 25Q40 41 44 43T67 46Q94 46 127 49Q141 52 146 61Q149 65 218 339T287 628ZM703 469Q703 507 692 537T666 584T629 613T590 629T555 636Q553 636 541 636T512 636T479 637H436Q392 637 386 627Q384 623 313 339T242 52Q242 48 253 48T330 47Q335 47 349 47T373 46Q499 46 581 128Q617 164 640 212T683 339T703 469Z"></path></g><g data-mml-node="msup" transform="translate(1588,0)"><g data-mml-node="mi"><path data-c="1D440" d="M289 629Q289 635 232 637Q208 637 201 638T194 648Q194 649 196 659Q197 662 198 666T199 671T201 676T203 679T207 681T212 683T220 683T232 684Q238 684 262 684T307 683Q386 683 398 683T414 678Q415 674 451 396L487 117L510 154Q534 190 574 254T662 394Q837 673 839 675Q840 676 842 678T846 681L852 683H948Q965 683 988 683T1017 684Q1051 684 1051 673Q1051 668 1048 656T1045 643Q1041 637 1008 637Q968 636 957 634T939 623Q936 618 867 340T797 59Q797 55 798 54T805 50T822 48T855 46H886Q892 37 892 35Q892 19 885 5Q880 0 869 0Q864 0 828 1T736 2Q675 2 644 2T609 1Q592 1 592 11Q592 13 594 25Q598 41 602 43T625 46Q652 46 685 49Q699 52 704 61Q706 65 742 207T813 490T848 631L654 322Q458 10 453 5Q451 4 449 3Q444 0 433 0Q418 0 415 7Q413 11 374 317L335 624L267 354Q200 88 200 79Q206 46 272 46H282Q288 41 289 37T286 19Q282 3 278 1Q274 0 267 0Q265 0 255 0T221 1T157 2Q127 2 95 1T58 0Q43 0 39 2T35 11Q35 13 38 25T43 40Q45 46 65 46Q135 46 154 86Q158 92 223 354T289 629Z"></path></g><g data-mml-node="TeXAtom" transform="translate(1138,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span>, DCC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">SC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">weekly</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Data Quality, Timeliness</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">CDM</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">SC, DSMC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">weekly quarterly <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="9.312ex" height="1.717ex" role="img" focusable="false" viewBox="0 -677 4116.1 759"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path></g><g data-mml-node="mi" transform="translate(2389.1,0)"><path data-c="6D" d="M41 46H55Q94 46 102 60V68Q102 77 102 91T102 122T103 161T103 203Q103 234 103 269T102 328V351Q99 370 88 376T43 385H25V408Q25 431 27 431L37 432Q47 433 65 434T102 436Q119 437 138 438T167 441T178 442H181V402Q181 364 182 364T187 369T199 384T218 402T247 421T285 437Q305 442 336 442Q351 442 364 440T387 434T406 426T421 417T432 406T441 395T448 384T452 374T455 366L457 361L460 365Q463 369 466 373T475 384T488 397T503 410T523 422T546 432T572 439T603 442Q729 442 740 329Q741 322 741 190V104Q741 66 743 59T754 49Q775 46 803 46H819V0H811L788 1Q764 2 737 2T699 3Q596 3 587 0H579V46H595Q656 46 656 62Q657 64 657 200Q656 335 655 343Q649 371 635 385T611 402T585 404Q540 404 506 370Q479 343 472 315T464 232V168V108Q464 78 465 68T468 55T477 49Q498 46 526 46H542V0H534L510 1Q487 2 460 2T422 3Q319 3 310 0H302V46H318Q379 46 379 62Q380 64 380 200Q379 335 378 343Q372 371 358 385T334 402T308 404Q263 404 229 370Q202 343 195 315T187 232V168V108Q187 78 188 68T191 55T200 49Q221 46 249 46H265V0H257L234 1Q210 2 183 2T145 3Q42 3 33 0H25V46H41Z"></path><path data-c="6F" d="M28 214Q28 309 93 378T250 448Q340 448 405 380T471 215Q471 120 407 55T250 -10Q153 -10 91 57T28 214ZM250 30Q372 30 372 193V225V250Q372 272 371 288T364 326T348 362T317 390T268 410Q263 411 252 411Q222 411 195 399Q152 377 139 338T126 246V226Q126 130 145 91Q177 30 250 30Z" transform="translate(833,0)"></path><path data-c="73" d="M295 316Q295 356 268 385T190 414Q154 414 128 401Q98 382 98 349Q97 344 98 336T114 312T157 287Q175 282 201 278T245 269T277 256Q294 248 310 236T342 195T359 133Q359 71 321 31T198 -10H190Q138 -10 94 26L86 19L77 10Q71 4 65 -1L54 -11H46H42Q39 -11 33 -5V74V132Q33 153 35 157T45 162H54Q66 162 70 158T75 146T82 119T101 77Q136 26 198 26Q295 26 295 104Q295 133 277 151Q257 175 194 187T111 210Q75 227 54 256T33 318Q33 357 50 384T93 424T143 442T187 447H198Q238 447 268 432L283 424L292 431Q302 440 314 448H322H326Q329 448 335 442V310L329 304H301Q295 310 295 316Z" transform="translate(1333,0)"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Demographics (combined)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Biostat <span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0;" xmlns="http://www.w3.org/2000/svg" width="0.988ex" height="1.885ex" role="img" focusable="false" viewBox="0 -833.2 436.6 833.2"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="msup"><g data-mml-node="TeXAtom" data-mjx-texclass="ORD"></g><g data-mml-node="TeXAtom" transform="translate(33,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">SC, DSMC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">quarterly <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="5.028ex" height="1.717ex" role="img" focusable="false" viewBox="0 -677 2222.4 759"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path></g></g></g></svg></mjx-container></span> mos</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Interim analysis:</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Biostat</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">DSMC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">After 100, 200, 400 subjects complete 36 weeks PMA</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Final analysis: Safety and Efficacy</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Biostat</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">DSMC</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">100% accrual, follow-up after randomization until 36 weeks PMA.</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| <div><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0;" xmlns="http://www.w3.org/2000/svg" width="0.988ex" height="1.887ex" role="img" focusable="false" viewBox="0 -833.9 436.6 833.9"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="msup"><g data-mml-node="TeXAtom" data-mjx-texclass="ORD"></g><g data-mml-node="TeXAtom" transform="translate(33,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g></g></g></g></g></svg></mjx-container></span> SC denotes the SAIL Steering Committee, consisting of all site Investigators, the Data Coordinating Center (DCC), and NICHD representatives.<br> |
| <span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0;" xmlns="http://www.w3.org/2000/svg" width="0.988ex" height="1.887ex" role="img" focusable="false" viewBox="0 -833.9 436.6 833.9"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="msup"><g data-mml-node="TeXAtom" data-mjx-texclass="ORD"></g><g data-mml-node="TeXAtom" transform="translate(33,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g></g></g></g></g></svg></mjx-container></span> CDM denotes clinical data management staff in the DCC.<br> |
| <span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0;" xmlns="http://www.w3.org/2000/svg" width="0.988ex" height="1.885ex" role="img" focusable="false" viewBox="0 -833.2 436.6 833.2"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="msup"><g data-mml-node="TeXAtom" data-mjx-texclass="ORD"></g><g data-mml-node="TeXAtom" transform="translate(33,363) scale(0.707)" data-mjx-texclass="ORD"><g data-mml-node="mn"><path data-c="33" d="M127 463Q100 463 85 480T69 524Q69 579 117 622T233 665Q268 665 277 664Q351 652 390 611T430 522Q430 470 396 421T302 350L299 348Q299 347 308 345T337 336T375 315Q457 262 457 175Q457 96 395 37T238 -22Q158 -22 100 21T42 130Q42 158 60 175T105 193Q133 193 151 175T169 130Q169 119 166 110T159 94T148 82T136 74T126 70T118 67L114 66Q165 21 238 21Q293 21 321 74Q338 107 338 175V195Q338 290 274 322Q259 328 213 329L171 330L168 332Q166 335 166 348Q166 366 174 366Q202 366 232 371Q266 376 294 413T322 525V533Q322 590 287 612Q265 626 240 626Q208 626 181 615T143 592T132 580H135Q138 579 143 578T153 573T165 566T175 555T183 540T186 520Q186 498 172 481T127 463Z"></path></g></g></g></g></g></svg></mjx-container></span> Biostat denotes staff biostatistician under the direction of the faculty biostatisticians in the DCC.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="10.-appendix-b%3A-draft-study-report-tables"> |
| 10. Appendix B: Draft Study Report Tables</h2> |
| <div>The following are examples of some of the tables that may be included in final report for this clinical trial. Selected tables may also be used for reporting the results of the interim analyses. Although the exact content and format may change, an attempt has been made to summarize the most important population, safety, and efficacy data.</div> |
| <div class="table" number="1"> |
| <div class="caption_table">Table 1. Summary of Baseline Demographic Characteristics by Intervention Group</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">A</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">B</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Total</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.439ex;" xmlns="http://www.w3.org/2000/svg" width="1.138ex" height="1.439ex" role="img" focusable="false" viewBox="0 -442 503 636"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D45D" d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></g></g></g></svg></mjx-container></span>-value</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Number of Subjects</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0.301ex;" xmlns="http://www.w3.org/2000/svg" width="1.76ex" height="0.529ex" role="img" focusable="false" viewBox="0 -367 778 234"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g></g></g></svg></mjx-container></span> n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Clinical Site</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">University of Pennsylvania</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n/a</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">University of Melbourne</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">etc.</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Consenting Procedure Used</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Antenatal</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Deferred</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Sex</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Male</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Female</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Race</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">White/Caucasian</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Black/African-American</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">etc.</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Gestational Age</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Median Range</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Maternal Age</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Median Range</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="5">Maternal Gravidity</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Median Range</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">xx.x xx to xx</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <div class="table" number="2"> |
| <div class="caption_table">Table 2. Summary of Baseline Clinical Characteristics by Intervention Group</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">A</td> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">B</td> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">Total</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">p-value</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Number of Subjects</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0.301ex;" xmlns="http://www.w3.org/2000/svg" width="1.76ex" height="0.529ex" role="img" focusable="false" viewBox="0 -367 778 234"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g></g></g></svg></mjx-container></span> n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Exposure to Antenatal Steroids</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">No</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Yes</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; vertical-align: top; width: auto; border-bottom-style: solid !important; border-bottom-width: 1px !important; " rowspan="3">Type of Antenatal Steroids (only in subset with exposure)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Exposure to Medications to Prolong Pregnancy</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">No</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Yes</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Placental Abruption</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">No</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Yes</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Chorioamnionitis</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">No</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Yes</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Membranes Rupture <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.312ex;" xmlns="http://www.w3.org/2000/svg" width="4.651ex" height="1.844ex" role="img" focusable="false" viewBox="0 -677 2055.8 815"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="2265" d="M83 616Q83 624 89 630T99 636Q107 636 253 568T543 431T687 361Q694 356 694 346T687 331Q685 329 395 192L107 56H101Q83 58 83 76Q83 77 83 79Q82 86 98 95Q117 105 248 167Q326 204 378 228L626 346L360 472Q291 505 200 548Q112 589 98 597T83 616ZM84 -118Q84 -108 99 -98H678Q694 -104 694 -118Q694 -130 679 -138H98Q84 -131 84 -118Z"></path></g><g data-mml-node="mn" transform="translate(1055.8,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z" transform="translate(500,0)"></path></g></g></g></svg></mjx-container></span> hours before Delivery</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">No</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Yes</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Mode of Delivery</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Vaginal</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">C-Section</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Route of Intervention Administration</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Facemask</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Nasopharyngeal Tube</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <div class="table" number="3"> |
| <div class="caption_table">Table 3: Screening and Eligibility</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Total</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Total Infants Screened</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: 0.301ex;" xmlns="http://www.w3.org/2000/svg" width="1.76ex" height="0.529ex" role="img" focusable="false" viewBox="0 -367 778 234"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g></g></g></svg></mjx-container></span> n</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Eligible</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Ineligible</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">Reasons for exclusion / ineligible:</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Baby was active, crying, HR>100bpm</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Considered non-viable</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Major anomaly (ies)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Mother unable to consent</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Parent refused consent</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Total Randomized</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Completed Study</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Completed 36 week PMA assessment</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Completed first month of life</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Completed 48 hours post delivery</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <div class="table" number="4"> |
| <div class="caption_table">Table 4: Subject Accounting by Intervention Arm</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">B</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Total</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Total Randomized</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Completed Study</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Still on Study</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Discontinued Study:</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Violation of protocol</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Withdrawal of consent</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Adverse event</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Other</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n (%)</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="flow-of-subjects-through-study-phases"> |
| Flow of Subjects Through Study Phases</h2> |
| <div class="table" number="1"> |
| <div class="figure_img" style="text-align: center;"><img src="https://cdn.mathpix.com/cropped/7661986c-6b35-485b-b687-3694b03da10f-20.jpg?height=1333&width=1531&top_left_y=466&top_left_x=354" alt="" style="max-width: 100%;"/></div><div class="caption_figure">Figure 1. Flow of Subjects Through Study Phases</div></div> |
| <div class="table" number="5"> |
| <div class="caption_table">Table 5. Cumulative Serious Adverse Events by Intervention Arm</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">A</td> |
| <td style="text-align: center; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">B</td> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-top-style: solid !important; border-top-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="2">Total</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">p-value</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Number of Subjects</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Within the first <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.05ex;" xmlns="http://www.w3.org/2000/svg" width="2.262ex" height="1.581ex" role="img" focusable="false" viewBox="0 -677 1000 699"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path></g><g data-mml-node="mn" transform="translate(500,0)"><path data-c="38" d="M70 417T70 494T124 618T248 666Q319 666 374 624T429 515Q429 485 418 459T392 417T361 389T335 371T324 363L338 354Q352 344 366 334T382 323Q457 264 457 174Q457 95 399 37T249 -22Q159 -22 101 29T43 155Q43 263 172 335L154 348Q133 361 127 368Q70 417 70 494ZM286 386L292 390Q298 394 301 396T311 403T323 413T334 425T345 438T355 454T364 471T369 491T371 513Q371 556 342 586T275 624Q268 625 242 625Q201 625 165 599T128 534Q128 511 141 492T167 463T217 431Q224 426 228 424L286 386ZM250 21Q308 21 350 55T392 137Q392 154 387 169T375 194T353 216T330 234T301 253T274 270Q260 279 244 289T218 306L210 311Q204 311 181 294T133 239T107 157Q107 98 150 60T250 21Z"></path></g></g></g></svg></mjx-container></span> hours post delivery</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Death</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Oxygen Requirement (Fi02 <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.312ex;" xmlns="http://www.w3.org/2000/svg" width="6.536ex" height="2.009ex" role="img" focusable="false" viewBox="0 -750 2888.8 888"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="2265" d="M83 616Q83 624 89 630T99 636Q107 636 253 568T543 431T687 361Q694 356 694 346T687 331Q685 329 395 192L107 56H101Q83 58 83 76Q83 77 83 79Q82 86 98 95Q117 105 248 167Q326 204 378 228L626 346L360 472Q291 505 200 548Q112 589 98 597T83 616ZM84 -118Q84 -108 99 -98H678Q694 -104 694 -118Q694 -130 679 -138H98Q84 -131 84 -118Z"></path></g><g data-mml-node="mn" transform="translate(1055.8,0)"><path data-c="34" d="M462 0Q444 3 333 3Q217 3 199 0H190V46H221Q241 46 248 46T265 48T279 53T286 61Q287 63 287 115V165H28V211L179 442Q332 674 334 675Q336 677 355 677H373L379 671V211H471V165H379V114Q379 73 379 66T385 54Q393 47 442 46H471V0H462ZM293 211V545L74 212L183 211H293Z"></path><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z" transform="translate(500,0)"></path></g><g data-mml-node="mi" transform="translate(2055.8,0)"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span> for 2 hours or more)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Within first 10 days of life:</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Pneumothorax</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Pulmonary Interstitial Eemphysema</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Pneumopericardium</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Grade 3 or 4 IVH</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Within first month of life:</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">BPD</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom: none !important; border-top: none !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; " colspan="8">Other:</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">XXX</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">0.xx</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="table-6.-assessment-of-si-intervention"> |
| Table 6. Assessment of SI Intervention</h2> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="total"> |
| Total</h2> |
| <div>Number of SI maneuvers performed</div> |
| <div><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.579ex;" xmlns="http://www.w3.org/2000/svg" width="5.58ex" height="2.88ex" role="img" focusable="false" viewBox="0 -1017 2466.5 1273"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path></g><g data-mml-node="mn" transform="translate(500,0)"><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z"></path></g><g data-mml-node="menclose" transform="translate(1000,0)"><g transform="translate(433.5, 0)"><g data-mml-node="mi"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g><path style="stroke-width: 67;" d="M 33.5 -222.5 a 183.3 502.5 0 0,1 0 1206 L 1433 983.5" stroke-linecap="round" stroke-linejoin="round" fill="none"></path></g></g></g></svg></mjx-container></span></div> |
| <div>2 SIs performed by Clinical Site</div> |
| <div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left: none !important; border-right: none !important; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">University of Pennsylvania</td> |
| <td style="text-align: left; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="1.885ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left: none !important; border-right: none !important; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">University of Melbourne</td> |
| <td style="text-align: left; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="1.885ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left: none !important; border-right: none !important; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">etc.</td> |
| <td style="text-align: left; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline " data-overflow="visible"> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.127ex;" xmlns="http://www.w3.org/2000/svg" width="1.885ex" height="1.824ex" role="img" focusable="false" viewBox="0 -750 833 806"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="25" d="M465 605Q428 605 394 614T340 632T319 641Q332 608 332 548Q332 458 293 403T202 347Q145 347 101 402T56 548Q56 637 101 693T202 750Q241 750 272 719Q359 642 464 642Q580 642 650 732Q662 748 668 749Q670 750 673 750Q682 750 688 743T693 726Q178 -47 170 -52Q166 -56 160 -56Q147 -56 142 -45Q137 -36 142 -27Q143 -24 363 304Q469 462 525 546T581 630Q528 605 465 605ZM207 385Q235 385 263 427T292 548Q292 617 267 664T200 712Q193 712 186 709T167 698T147 668T134 615Q132 595 132 548V527Q132 436 165 403Q183 385 203 385H207ZM500 146Q500 234 544 290T647 347Q699 347 737 292T776 146T737 0T646 -56Q590 -56 545 0T500 146ZM651 -18Q679 -18 707 24T736 146Q736 215 711 262T644 309Q637 309 630 306T611 295T591 265T578 212Q577 200 577 146V124Q577 -18 647 -18H651Z"></path></g></g></g></svg></mjx-container></span></td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| <div>Post SI intervention Respiratory Mode</div> |
| <div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left: none !important; border-right: none !important; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">CPAP</td> |
| <td style="text-align: left; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">%</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left: none !important; border-right: none !important; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">PPV</td> |
| <td style="text-align: left; border-bottom: none !important; border-top: none !important; width: auto; vertical-align: middle; ">%</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| <div>NB: Percentages only in SI arm to maintain blinding until study completion.</div> |
| <div class="table" number="6"> |
| <div class="caption_table">Table 7. Primary Endpoint: Death or BPD at 36 weeks PMA</div><div class="table_tabular" style="text-align: center"> |
| <div class="inline-tabular"><table class="tabular"> |
| <tbody> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">A</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">B</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top-style: solid !important; border-top-width: 1px !important; width: auto; vertical-align: middle; ">Total</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Number of Subjects Randomized</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; "><span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.025ex;" xmlns="http://www.w3.org/2000/svg" width="3.746ex" height="1.025ex" role="img" focusable="false" viewBox="0 -442 1655.8 453"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mo"><path data-c="223C" d="M55 166Q55 241 101 304T222 367Q260 367 296 349T362 304T421 252T484 208T554 189Q616 189 655 236T694 338Q694 350 698 358T708 367Q722 367 722 334Q722 260 677 197T562 134H554Q517 134 481 152T414 196T355 248T292 293T223 311Q179 311 145 286Q109 257 96 218T80 156T69 133Q55 133 55 166Z"></path></g><g data-mml-node="mi" transform="translate(1055.8,0)"><path data-c="1D45B" d="M21 287Q22 293 24 303T36 341T56 388T89 425T135 442Q171 442 195 424T225 390T231 369Q231 367 232 367L243 378Q304 442 382 442Q436 442 469 415T503 336T465 179T427 52Q427 26 444 26Q450 26 453 27Q482 32 505 65T540 145Q542 153 560 153Q580 153 580 145Q580 144 576 130Q568 101 554 73T508 17T439 -10Q392 -10 371 17T350 73Q350 92 386 193T423 345Q423 404 379 404H374Q288 404 229 303L222 291L189 157Q156 26 151 16Q138 -11 108 -11Q95 -11 87 -5T76 7T74 17Q74 30 112 180T152 343Q153 348 153 366Q153 405 129 405Q91 405 66 305Q60 285 60 284Q58 278 41 278H27Q21 284 21 287Z"></path></g></g></g></svg></mjx-container></span></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; " class="_empty"></td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">~n</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Death/BPD Rate ( <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.439ex;" xmlns="http://www.w3.org/2000/svg" width="8.881ex" height="1.946ex" role="img" focusable="false" viewBox="0 -666 3925.2 860"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mi"><path data-c="1D45D" d="M23 287Q24 290 25 295T30 317T40 348T55 381T75 411T101 433T134 442Q209 442 230 378L240 387Q302 442 358 442Q423 442 460 395T497 281Q497 173 421 82T249 -10Q227 -10 210 -4Q199 1 187 11T168 28L161 36Q160 35 139 -51T118 -138Q118 -144 126 -145T163 -148H188Q194 -155 194 -157T191 -175Q188 -187 185 -190T172 -194Q170 -194 161 -194T127 -193T65 -192Q-5 -192 -24 -194H-32Q-39 -187 -39 -183Q-37 -156 -26 -148H-6Q28 -147 33 -136Q36 -130 94 103T155 350Q156 355 156 364Q156 405 131 405Q109 405 94 377T71 316T59 280Q57 278 43 278H29Q23 284 23 287ZM178 102Q200 26 252 26Q282 26 310 49T356 107Q374 141 392 215T411 325V331Q411 405 350 405Q339 405 328 402T306 393T286 380T269 365T254 350T243 336T235 326L232 322Q232 321 229 308T218 264T204 212Q178 106 178 102Z"></path></g><g data-mml-node="mo" transform="translate(780.8,0)"><path data-c="3D" d="M56 347Q56 360 70 367H707Q722 359 722 347Q722 336 708 328L390 327H72Q56 332 56 347ZM56 153Q56 168 72 173H708Q722 163 722 153Q722 140 707 133H70Q56 140 56 153Z"></path></g><g data-mml-node="mn" transform="translate(1836.6,0)"><path data-c="30" d="M96 585Q152 666 249 666Q297 666 345 640T423 548Q460 465 460 320Q460 165 417 83Q397 41 362 16T301 -15T250 -22Q224 -22 198 -16T137 16T82 83Q39 165 39 320Q39 494 96 585ZM321 597Q291 629 250 629Q208 629 178 597Q153 571 145 525T137 333Q137 175 145 125T181 46Q209 16 250 16Q290 16 318 46Q347 76 354 130T362 333Q362 478 354 524T321 597Z"></path></g><g data-mml-node="mo" transform="translate(2336.6,0)"><path data-c="2E" d="M78 60Q78 84 95 102T138 120Q162 120 180 104T199 61Q199 36 182 18T139 0T96 17T78 60Z"></path></g><g data-mml-node="mi" transform="translate(2781.2,0)"><path data-c="1D465" d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path></g><g data-mml-node="mi" transform="translate(3353.2,0)"><path data-c="1D465" d="M52 289Q59 331 106 386T222 442Q257 442 286 424T329 379Q371 442 430 442Q467 442 494 420T522 361Q522 332 508 314T481 292T458 288Q439 288 427 299T415 328Q415 374 465 391Q454 404 425 404Q412 404 406 402Q368 386 350 336Q290 115 290 78Q290 50 306 38T341 26Q378 26 414 59T463 140Q466 150 469 151T485 153H489Q504 153 504 145Q504 144 502 134Q486 77 440 33T333 -11Q263 -11 227 52Q186 -10 133 -10H127Q78 -10 57 16T35 71Q35 103 54 123T99 143Q142 143 142 101Q142 81 130 66T107 46T94 41L91 40Q91 39 97 36T113 29T132 26Q168 26 194 71Q203 87 217 139T245 247T261 313Q266 340 266 352Q266 380 251 392T217 404Q177 404 142 372T93 290Q91 281 88 280T72 278H58Q52 284 52 289Z"></path></g></g></g></svg></mjx-container></span> )</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">Death</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| </tr> |
| <tr style="border-top: none !important; border-bottom: none !important;"> |
| <td style="text-align: left; border-left-style: solid !important; border-left-width: 1px !important; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">BPD</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">(%)</td> |
| <td style="text-align: left; border-right-style: solid !important; border-right-width: 1px !important; border-bottom-style: solid !important; border-bottom-width: 1px !important; border-top: none !important; width: auto; vertical-align: middle; ">n</td> |
| </tr> |
| </tbody> |
| </table> |
| </div></div> |
| </div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="11.-appendix-c%3A-standard-monitoring-reports"> |
| 11. Appendix C: Standard Monitoring Reports</h2> |
| <div>The following are examples of the standard reports on patient recruitment, data quality, and demographics that will be prepared for the regular full Steering Committee meetings. These reports will also be sent to the DSMC as noted in Appendix A. For details, please refer to the MOP (under development).</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="sail-accrual-and-data-reports-summary-generated-(mm%2Fdd%2Fyyyy)"> |
| SAIL Accrual and Data Reports Summary <br> |
| Generated (MM/DD/YYYY)</h2> |
| <div>Notation: Tables <span class="math-inline "> |
| <mjx-container class="MathJax" jax="SVG"><svg style="vertical-align: -0.186ex;" xmlns="http://www.w3.org/2000/svg" width="6.159ex" height="1.692ex" role="img" focusable="false" viewBox="0 -666 2722.4 748"><g stroke="currentColor" fill="currentColor" stroke-width="0" transform="scale(1,-1)"><g data-mml-node="math"><g data-mml-node="mn"><path data-c="35" d="M164 157Q164 133 148 117T109 101H102Q148 22 224 22Q294 22 326 82Q345 115 345 210Q345 313 318 349Q292 382 260 382H254Q176 382 136 314Q132 307 129 306T114 304Q97 304 95 310Q93 314 93 485V614Q93 664 98 664Q100 666 102 666Q103 666 123 658T178 642T253 634Q324 634 389 662Q397 666 402 666Q410 666 410 648V635Q328 538 205 538Q174 538 149 544L139 546V374Q158 388 169 396T205 412T256 420Q337 420 393 355T449 201Q449 109 385 44T229 -22Q148 -22 99 32T50 154Q50 178 61 192T84 210T107 214Q132 214 148 197T164 157Z"></path></g><g data-mml-node="mo" transform="translate(722.2,0)"><path data-c="2212" d="M84 237T84 250T98 270H679Q694 262 694 250T679 230H98Q84 237 84 250Z"></path></g><g data-mml-node="mn" transform="translate(1722.4,0)"><path data-c="31" d="M213 578L200 573Q186 568 160 563T102 556H83V602H102Q149 604 189 617T245 641T273 663Q275 666 285 666Q294 666 302 660V361L303 61Q310 54 315 52T339 48T401 46H427V0H416Q395 3 257 3Q121 3 100 0H88V46H114Q136 46 152 46T177 47T193 50T201 52T207 57T213 61V578Z"></path><path data-c="32" d="M109 429Q82 429 66 447T50 491Q50 562 103 614T235 666Q326 666 387 610T449 465Q449 422 429 383T381 315T301 241Q265 210 201 149L142 93L218 92Q375 92 385 97Q392 99 409 186V189H449V186Q448 183 436 95T421 3V0H50V19V31Q50 38 56 46T86 81Q115 113 136 137Q145 147 170 174T204 211T233 244T261 278T284 308T305 340T320 369T333 401T340 431T343 464Q343 527 309 573T212 619Q179 619 154 602T119 569T109 550Q109 549 114 549Q132 549 151 535T170 489Q170 464 154 447T109 429Z" transform="translate(500,0)"></path></g></g></g></svg></mjx-container></span> use only data that has been entered and verified. It may not include all infants that have completed a given time period assessment.</div> |
| <h2 type="section" data-unnumbered="true" class="section-title" id="list-of-reports"> |
| List of Reports</h2> |
| <div>Table 1: Number of Participants Randomized<br> |
| Table 2: Participant Randomization and Withdrawal Report<br> |
| Figure 1: Overall SAIL Randomization Profile<br> |
| Figure 2: SAIL Randomization Profiles by Clinical Center<br> |
| Table 3: Number of Participants With Completed Data - The Randomization column represents the delivery room phase. For follow-up assessments, this report is based on data verified in the database as of the date shown. Therefore, it may not include all patients who have data at the stated gestational age.</div> |
| <div>Table 4: Completion Rates Among Active Study Participants by Clinical Center<br> |
| Table 5: Age Distribution - Gestational and Maternal<br> |
| Table 6: Race Distribution<br> |
| Table 7: Gender Distribution<br> |
| Table 8: Missing Forms (Number of Missing Forms, by Type of Form)<br> |
| Table 9: Timely Entry and Verification (Mean Number of Days from Date of Birth/Randomization to First Entry in Database)</div> |
| <div>Table 10: Missing Values (Missing Fields Per Completed Forms, by Type of Form)<br> |
| Table 11: Query Rates (Fields Queried Per Completed Forms, by Type of Form)<br> |
| Table 12: Adverse Event Reporting</div> |
|
|
| </div> |
| </div> |
| </body> |
| </html> |
