Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Completed

• Conditions: Acute Respiratory Distress Syndrome

• Registration Number: NCT04113434
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2019-10-01
• Study First Submitted QC: 2019-10-01
• Study First Posted: 2019-10-02
• Study Start: 2020-01-07
• Primary Completion: 2025-02-15
• Status Verified: 2025-04
• Study Completion: 2025-04-01
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. acute (≤ 7 days of risk factor) respiratory failure requiring invasive mechanical ventilation
2. age > 44 weeks corrected gestational age and < 17.5 years
3. invasive mechanical ventilation via endotracheal tube
4. bilateral infiltrates on chest radiograph
5. oxygenation index (OI) ≥ 4; or oxygen saturation index (OSI) ≥ 5 on 2 consecutive measurements at least 4 hours apart but < 24 hours apart
6. invasively ventilated ≤ 7 days before meeting above radiographic and oxygenation criteria

Exclusion Criteria

1. weight < 3 kilograms
2. cyanotic congenital heart disease (other than Patent Foramen Ovale (PFO) or Patent Ductus Arteriosus (PDA))
3. tracheostomy at time of screening
4. invasively ventilated for > 7 days when meet ARDS criteria above
5. cardiac failure as predominant cause of respiratory failure
6. primary obstructive airway disease (asthma, bronchiolitis) by judgement of clinician as the primary cause of respiratory failure
7. alternative known chronic lung disease as cause of respiratory failure (cystic fibrosis, eosinophilic pneumonia, interstitial pneumonitis, pulmonary hemosiderosis, cryptogenic organizing pneumonia)
8. severe neurologic morbidity not expected to survive > 72 hours
9. any limitations of care at time of screening
10. previous enrollment in this study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
ventilator-free days at 28 days.	28 days	composite endpoint of days alive and free of mechanical ventilation by day 28.

Trial Locations

Locations (16)

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Variety Children's Hospital D/B/A Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States

Children's Healthcare of Atlanta - Emory; 🇺🇸 Atlanta, Georgia, United States

Riley Children's at Indiana University Health; 🇺🇸 Indianapolis, Indiana, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Cooperman Barnabas Medical Center; 🇺🇸 Livingston, New Jersey, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States

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