Clinical trial NCT04113434: Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome
Official title: Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Respiratory Distress Syndrome
Keywords: Acute Respiratory Distress Syndrome
ARDS
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Akron Children's Hospital
name: Children's Hospital and Health System Foundation, Wisconsin
name: Children's Hospital Medical Center, Cincinnati
name: Children's Mercy Hospital Kansas City
name: Milton S. Hershey Medical Center
name: Nationwide Children's Hospital
name: Nicklaus Children's Hospital
name: Indiana University
name: Cooperman Barnabas Medical Center
name: Baylor College of Medicine
name: Columbia University
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Arkansas Children's Hospital Research Institute
name: Children's Healthcare of Atlanta
name: Children's Hospital Colorado
name: Washington University School of Medicine
First posted: 2019-10-02
Enrollment: 500
Sex: ALL
Minimum age (years): 44
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infants to adolescents between the ages of 44 weeks and 17.5 years, who are admitted to PICU for acute respiratory failure requiring invasive mechanical ventilation.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 28 Day Mortality in Pediatric ARDS.
timeFrame: 28 days
measure: Presence of two or more endotypes in Pediatric ARDS.
timeFrame: Within 24 hours of ARDS onset
measure: Occurrence of de novo sub-phenotypes in pediatric ARDS using biomarkers and whole genome transcriptomics of peripheral blood.
timeFrame: Within 24 hours of ARDS onset.
Secondary outcomes:
measure: ventilator-free days at 28 days.
timeFrame: 28 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Variety Children's Hospital D/B/A Nicklaus Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Emory
state: Georgia
city: Indianapolis
country: United States
facility: Riley Children's at Indiana University Health
state: Indiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Livingston
country: United States
facility: Cooperman Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital / Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Nadir Yehya, M.D.
role: PRINCIPAL_INVESTIGATOR
References: