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Completed

NCT Number: NCT04113434

Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

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.

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Key information

Age range

44 week–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Arkansas Children's Hospital, Little Rock, Arkansas, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • acute (≤ 7 days of risk factor) respiratory failure requiring invasive mechanical ventilation
  • age > 44 weeks corrected gestational age and < 17.5 years
  • invasive mechanical ventilation via endotracheal tube
  • bilateral infiltrates on chest radiograph
  • oxygenation index (OI) ≥ 4; or oxygen saturation index (OSI) ≥ 5 on 2 consecutive measurements at least 4 hours apart but < 24 hours apart
  • invasively ventilated ≤ 7 days before meeting above radiographic and oxygenation criteria

Exclusion criteria

  • weight < 3 kilograms
  • cyanotic congenital heart disease (other than Patent Foramen Ovale (PFO) or Patent Ductus Arteriosus (PDA))
  • tracheostomy at time of screening
  • invasively ventilated for > 7 days when meet ARDS criteria above
  • cardiac failure as predominant cause of respiratory failure
  • primary obstructive airway disease (asthma, bronchiolitis) by judgement of clinician as the primary cause of respiratory failure
  • alternative known chronic lung disease as cause of respiratory failure (cystic fibrosis, eosinophilic pneumonia, interstitial pneumonitis, pulmonary hemosiderosis, cryptogenic organizing pneumonia)
  • severe neurologic morbidity not expected to survive > 72 hours
  • any limitations of care at time of screening
  • previous enrollment in this study

Treatment and study plan

Primary outcomes

  1. 28 Day Mortality in Pediatric ARDS.

    Time frame: 28 days

    28 day all cause mortality.

  2. Presence of Two or More Endotypes in Pediatric ARDS.

    Time frame: 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.

    Time frame: 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 outcomes

  1. Ventilator-free Days at 28 Days.

    Time frame: 28 days

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

Sponsors and collaborators

Lead sponsor

Children's Hospital of Philadelphia

Other

Collaborators

  • Akron Children's Hospital
  • Arkansas Children's Hospital Research Institute
  • Baylor College of Medicine
  • Children's Healthcare of Atlanta
  • Children's Hospital Colorado
  • Children's Hospital Medical Center, Cincinnati
  • Children's Hospital and Health System Foundation, Wisconsin
  • 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

Registry information

Acronym: LEOPARDS

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Oct 2, 2019
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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