Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome (LEOPARDS)

Children's Hospital of Philadelphia (CHOP)

Status: Completed

Conditions: Acute Respiratory Distress Syndrome

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04113434

R01HL148054 (U.S. NIH Grant/Contract)

19-016271

Details and patient eligibility

About

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.

Full 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).

Enrollment: 500 patients

Sex: All

Ages: 44 weeks to 17 years old

Volunteers: No Healthy Volunteers

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