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LEOPARDS: Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

Sponsor
Children's Hospital of Philadelphia (Other)
Overall Status
Recruiting
CT.gov ID
NCT04113434
Collaborator
Akron Children's Hospital (Other), Children's Hospital and Health System Foundation, Wisconsin (Other), Children's Hospital Medical Center, Cincinnati (Other), Children's Mercy Hospital Kansas City (Other), Children's National Research Institute (Other), Milton S. Hershey Medical Center (Other), Nationwide Children's Hospital (Other), Nicklaus Children's Hospital (Other), Indiana University (Other), St. Barnabas Medical Center (Other), Baylor College of Medicine (Other), Columbia University (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Arkansas Children's Hospital Research Institute (Other), Children's Healthcare of Atlanta (Other), Children's Hospital Colorado (Other), Washington University School of Medicine (Other)
500
Enrollment
17
Locations
58.8
Anticipated Duration (Months)
29.4
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

    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 Design

    Study Type:
    Observational
    Anticipated Enrollment :
    500 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome
    Actual Study Start Date :
    Jan 7, 2020
    Anticipated Primary Completion Date :
    Jan 1, 2023
    Anticipated Study Completion Date :
    Dec 1, 2024

    Outcome Measures

    Primary Outcome Measures

    1. 28 Day Mortality in Pediatric ARDS. [28 days]

      28 day all cause mortality.

    2. 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.

    3. 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

    1. ventilator-free days at 28 days. [28 days]

      composite endpoint of days alive and free of mechanical ventilation by day 28.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    44 Weeks to 17 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    7. invasive blood drawing access (central venous catheter, arterial catheter, or blood-drawing IV)

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Hospital Little Rock Arkansas United States 72202
    2 Children's Hospital Colorado Aurora Colorado United States 80045
    3 Children's National Medical Center Washington District of Columbia United States 20010
    4 Variety Children's Hospital D/B/A Nicklaus Children's Hospital Miami Florida United States 33155
    5 Children's Healthcare of Atlanta - Emory Atlanta Georgia United States 30322
    6 Riley Children's at Indiana University Health Indianapolis Indiana United States 46202
    7 Children's Mercy Hospital Kansas City Missouri United States 64108
    8 Washington University Saint Louis Missouri United States 63110
    9 Saint Barnabas Medical Center Livingston New Jersey United States 07039
    10 Columbia University Medical Center New York New York United States 10032
    11 Akron Children's Hospital Akron Ohio United States 44308
    12 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    13 Nationwide Children's Hospital Columbus Ohio United States 43205
    14 Penn State Hershey Children's Hospital Hershey Pennsylvania United States 17033
    15 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    16 Texas Children's Hospital / Baylor College of Medicine Houston Texas United States 77030
    17 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • 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
    • Children's National Research Institute
    • Milton S. Hershey Medical Center
    • Nationwide Children's Hospital
    • Nicklaus Children's Hospital
    • Indiana University
    • St. 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

    Investigators

    • Principal Investigator: Nadir Yehya, M.D., Children's Hospital of Philadelphia

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Hospital of Philadelphia
    ClinicalTrials.gov Identifier:
    NCT04113434
    Other Study ID Numbers:
    • 19-016271
    • R01HL148054
    First Posted:
    Oct 2, 2019
    Last Update Posted:
    Feb 25, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Children's Hospital of Philadelphia
    Acute Respiratory Distress Syndrome
    ARDS
    Additional relevant MeSH terms:
    Respiratory Distress Syndrome
    Respiratory Distress Syndrome, Newborn
    Acute Lung Injury
    Syndrome

    Study Results

    No Results Posted as of Feb 25, 2022