Acute Respiratory Distress Syndrome
Conditions
Keywords
Acute Respiratory Distress Syndrome, ARDS
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).
Interventions
None listed
Sponsors
Children's Hospital of Philadelphia
Akron Children's Hospital
Children's Hospital and Health System Foundation, Wisconsin
Children's Hospital Medical Center, Cincinnati
Children's Mercy Hospital Kansas City
Milton S. Hershey Medical Center
Nationwide Children's Hospital
Nicklaus Children's Hospital
Indiana University
Cooperman Barnabas Medical Center
Baylor College of Medicine
Columbia University
National Heart, Lung, and Blood Institute (NHLBI)
Arkansas Children's Hospital Research Institute
Children's Healthcare of Atlanta
Children's Hospital Colorado
Washington University School of Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
44 Weeks to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free Days at 28 Days. | 28 days | composite endpoint of days alive and free of mechanical ventilation by day 28. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNadir Yehya, M.D.
Children's Hospital of Philadelphia
Participant flow
Recruitment details
Recruitment Period: 1/7/2020 - 5/8/2024 Sites: 16 (PICU)
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 513 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 109 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 390 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 17 Participants |
| Race (NIH/OMB) Black or African American | 87 Participants |
| Race (NIH/OMB) More than one race | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 62 Participants |
| Race (NIH/OMB) White | 326 Participants |
| Sex: Female, Male Female | 238 Participants |
| Sex: Female, Male Male | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 67 / 500 |
| other Total, other adverse events | 0 / 500 |
| serious Total, serious adverse events | 0 / 500 |
Outcome results
None listed