Acute Respiratory Distress SyndromeLEOPARDSNCT04113434
Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome
An observational study of Acute Respiratory Distress Syndrome, run by Children's Hospital of Philadelphia at 16 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 44 weeks to 17 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- How many people
- 513 participants
- Where
- 16 sitesUnited States
- Study dates
- 7 Jan 2020to 1 Apr 2025
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 44 weeks to 17 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Akron Children's Hospital
Akron, Ohio, 44308
Children's Healthcare of Atlanta - Emory
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033
Texas Children's Hospital / Baylor College of Medicine
Houston, Texas, 77030
Riley Children's at Indiana University Health
Indianapolis, Indiana, 46202
Children's Mercy Hospital
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Cooperman Barnabas Medical Center
Livingston, New Jersey, 07039
Variety Children's Hospital D/B/A Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Washington University
St Louis, Missouri, 63110
About this study
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.
Read the 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).
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute Respiratory Distress Syndrome, ARDS
- Medical subject headings
- Respiratory Distress Syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
28 Day Mortality in Pediatric ARDS.
28 day all cause mortality.
Measured: 28 days
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.
Measured: Within 24 hours of ARDS onset
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.
Measured: Within 24 hours of ARDS onset.
Secondary outcomes (1)
Ventilator-free Days at 28 Days.
composite endpoint of days alive and free of mechanical ventilation by day 28.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start7 Jan 2020
- Primary completion15 Feb 2025
- Study completion1 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 513 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Nadir Yehya, M.D., Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04113434
- Sponsor's protocol ID
- 19-016271
- Other IDs
- R01HL148054
- Acronym
- LEOPARDS
- Status last verified
- Apr 2026
- First submitted
- 1 Oct 2019
- Last updated
- 20 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Specific consent will be obtained to store blood and use data for future research. We will share data with the research community using the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) program at NHLBI, and we will follow suggested guidelines for de-identifying the data (coding of site IDs, conversion of dates to study days). Pursuant to the NIH policy, all data obtained from this proposal will be made available for research by qualified individuals within the scientific community after publication of the proposed studies. Gene expression data from Aims 2 and 3 will be made available simultaneous with publication of the results of these aims by uploading to the Gene Expression Omnibus. For dissemination of plasma biomarker results and the associated clinical dataset, we will use BioLINCC program at NHLBI, with release of a de-identified dataset with untraceable identifiers within 2 years of publication of the main manuscript.
Publications
Halstead ES, Umstead TM, Chroneos ZC, Riccio-Baum C, Allie SR, McKeone DJ, Spear D, Nofziger RA, Sanders RC Jr, Ahn D, Dowell JC, Wagner AF, Thomas NJ, Sendi P, Frazier WJ, Rowan CM, Jain PN, Bashir DA, Friess SH, Varisco BM, Grunwell J, Maddux AB, Famularo ST 3rd, Yehya N. Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS. Crit Care. 2026 Jul 1. doi: 10.1186/s13054-026-06174-8. Online ahead of print.
PubMed 42387347Whitney JE, Johnson GM, Varisco BM, Raby BA, Yehya N. Biomarker-Based Risk Stratification Tool in Pediatric Acute Respiratory Distress Syndrome: Single-Center, Longitudinal Validation in a 2014-2019 Cohort. Pediatr Crit Care Med. 2024 Jul 1;25(7):599-608. doi: 10.1097/PCC.0000000000003512. Epub 2024 Apr 9.
PubMed 38591949
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04113434
- Acronym / sponsor ID
- LEOPARDS / 19-016271
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Acute Respiratory Distress Syndrome, ARDS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 513 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- 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 start
- 7 Jan 2020 (actual)
- Primary completion
- 15 Feb 2025 (actual)
- Study completion
- 1 Apr 2025 (actual)
- First posted
- 2 Oct 2019 (actual)
- Results
- Posted 20 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 44 weeks to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
28 Day Mortality in Pediatric ARDS.
Time frame: 28 days
28 day all cause mortality.
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.
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.
1 secondary outcome
Ventilator-free Days at 28 Days.
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42387347Halstead ES, Umstead TM, Chroneos ZC, Riccio-Baum C, Allie SR, McKeone DJ, Spear D, Nofziger RA, Sanders RC Jr, Ahn D, Dowell JC, Wagner AF, Thomas NJ, Sendi P, Frazier WJ, Rowan CM, Jain PN, Bashir DA, Friess SH, Varisco BM, Grunwell J, Maddux AB, Famularo ST 3rd, Yehya N. Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS. Crit Care. 2026 Jul 1. doi: 10.1186/s13054-026-06174-8. Online ahead of print.
- Derived from this study: PubMed 38591949Whitney JE, Johnson GM, Varisco BM, Raby BA, Yehya N. Biomarker-Based Risk Stratification Tool in Pediatric Acute Respiratory Distress Syndrome: Single-Center, Longitudinal Validation in a 2014-2019 Cohort. Pediatr Crit Care Med. 2024 Jul 1;25(7):599-608. doi: 10.1097/PCC.0000000000003512. Epub 2024 Apr 9.
- Individual participant dataSharing planned: Yes. Specific consent will be obtained to store blood and use data for future research. We will share data with the research community using the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) program at NHLBI, and we will follow suggested guidelines for de-identifying the data (coding of site IDs, conversion of dates to study days). Pursuant to the NIH policy, all data obtained from this proposal will be made available for research by qualified individuals within the scientific community after publication of the proposed studies. Gene expression data from Aims 2 and 3 will be made available simultaneous with publication of the results of these aims by uploading to the Gene Expression Omnibus. For dissemination of plasma biomarker results and the associated clinical dataset, we will use BioLINCC program at NHLBI, with release of a de-identified dataset with untraceable identifiers within 2 years of publication of the main manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nadir Yehya, M.D. principal investigator
Children's Hospital of Philadelphia
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome, run by Children's Hospital of Philadelphia at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28 Day Mortality in Pediatric ARDS. (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04113434, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.