Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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The overall goal of the study is to risk stratify pediatric Acute Respiratory Distress Syndrome (ARDS) patients and to identify sub-phenotypes with shared biology in order to appropriately target therapies in future trials. This is a prospective, multicenter study of 500 intubated children with ARDS, with planned blood collection within 24 hours of ARDS onset and subsequent measurement of plasma protein biomarkers and peripheral blood gene expression.

Detailed Description
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Investigators will measure pre-determined biomarkers with known or suspected association with ARDS severity or outcome. Simultaneously, investigators will measure gene expression of peripheral blood. Both plasma biomarkers and gene expression profiles will be analyzed using various machine learning techniques, including classification and regression tree, latent class analysis, and hierarchical clustering with the goal of identifying sub-phenotypes of ARDS. These sub-phenotypes will be examined for association with outcome (primary is 28-day mortality), and explicitly tested for variation in response to exogenous treatments (e.g., corticosteroids).

Official Title
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Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Conditions
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Acute Respiratory Distress Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute (≤ 7 days of risk factor) respiratory failure requiring invasive mechanical ventilation age > 44 weeks corrected gestational age and < 17.5 years invasive mechanical ventilation via endotracheal tube bilateral infiltrates on chest radiograph oxygenation index (OI) ≥ 4; or oxygen saturation index (OSI) ≥ 5 on 2 consecutive measurements at least 4 hours apart but < 24 hours apart invasively ventilated ≤ 7 days before meeting above radiographic and oxygenation criteria Exclusion Criteria: weight < 3 kilograms cyanotic congenital heart disease (other than Patent Foramen Ovale (PFO) or Patent Ductus Arteriosus (PDA)) tracheostomy at time of screening invasively ventilated for > 7 days when meet ARDS criteria above cardiac failure as predominant cause of respiratory failure primary obstructive airway disease (asthma, bronchiolitis) by judgement of clinician as the primary cause of respiratory failure alternative known chronic lung disease as cause of respiratory failure (cystic fibrosis, eosinophilic pneumonia, interstitial pneumonitis, pulmonary hemosiderosis, cryptogenic organizing pneumonia) severe neurologic morbidity not expected to survive > 72 hours any limitations of care at time of screening previous enrollment in this study

Ages Eligible for Study
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Minimum Age: 44 Weeks
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 Day Mortality in Pediatric ARDS. | 28 day all cause mortality. | 28 days | 
| Presence of two or more endotypes in Pediatric ARDS. | Stratify pediatric ARDS into sub-phenotypes using a known 100-gene expression-based classifier to group subjects according to shared underlying biology. | Within 24 hours of ARDS onset | 
| Occurrence of de novo sub-phenotypes in pediatric ARDS using biomarkers and whole genome transcriptomics of peripheral blood. | Occurrence of de novo sub-phenotypes in pediatric ARDS using 12 protein biomarkers and whole genome transcriptomics of peripheral blood. | Within 24 hours of ARDS onset. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ventilator-free days at 28 days. | composite endpoint of days alive and free of mechanical ventilation by day 28. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, ARDS