Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome Clinical Trial

— LEOPARDS  

Official title:

Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04113434
• Other study ID #: 19-016271
• Secondary ID: R01HL148054
• Status: Active, not recruiting
• Start date: January 7, 2020
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 44 Weeks to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Children's Healthcare of Atlanta - Emory	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Texas Children's Hospital / Baylor College of Medicine	Houston	Texas
United States	Riley Children's at Indiana University Health	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Cooperman Barnabas Medical Center	Livingston	New Jersey
United States	Variety Children's Hospital D/B/A Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri

Sponsors (17)

Lead Sponsor

Collaborator

Children's Hospital of Philadelphia

Akron Children's Hospital, Arkansas Children's Hospital Research Institute, Baylor College of Medicine, Children's Healthcare of Atlanta, Children's Hospital and Health System Foundation, Wisconsin, Children's Hospital Colorado, Children's Hospital Medical Center, Cincinnati, Children's Mercy Hospital Kansas City, Columbia University, Cooperman Barnabas Medical Center, Indiana University, Milton S. Hershey Medical Center, National Heart, Lung, and Blood Institute (NHLBI), Nationwide Children's Hospital, Nicklaus Children's Hospital, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28 Day Mortality in Pediatric ARDS.	28 day all cause mortality.	28 days
Primary	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
Primary	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	ventilator-free days at 28 days.	composite endpoint of days alive and free of mechanical ventilation by day 28.	28 days