Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome (LEOPARDS)

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ClinicalTrials.gov Identifier: NCT04113434

Recruitment Status : Recruiting

First Posted : October 2, 2019

Last Update Posted : August 8, 2023

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View this study on the modernized ClinicalTrials.gov

Sponsor:

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

Information provided by (Responsible Party):

Children's Hospital of Philadelphia

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
Acute Respiratory Distress Syndrome

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

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Study Type :	Observational
Estimated 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 :	January 7, 2020
Estimated Primary Completion Date :	June 2024
Estimated Study Completion Date :	December 2024

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Respiratory Distress Syndrome, Infant Acute Respiratory Distress Syndrome Acute Graft Versus Host Disease

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

ventilator-free days at 28 days. [ Time Frame: 28 days ]
composite endpoint of days alive and free of mechanical ventilation by day 28.

Biospecimen Retention: Samples Without DNA

Plasma

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	44 Weeks to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
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.

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04113434

Contacts

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Contact: Nadir Yehya, M.D.	215-590-1858	yehyan@chop.edu
Contact: Stephen Famularo, BA		famularois@chop.edu

Locations

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United States, Arkansas
Arkansas Children's Hospital	Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Masson Yates spriggsmk@archildrens.org
Contact: Ashlyn Madding maddingam@archildrens.org
Sub-Investigator: Ronald Sanders, MD
Sub-Investigator: Peter Mourani, MD
United States, Colorado
Children's Hospital Colorado	Recruiting
Aurora, Colorado, United States, 80045
Contact: Lexi Petruccelli lexi.petruccelli@childrenscolorado.org
Contact: Emily Palmeri Emily.Palmeri@childrenscolorado.org
Sub-Investigator: Aline Maddux, MD
United States, Florida
Variety Children's Hospital D/B/A Nicklaus Children's Hospital	Recruiting
Miami, Florida, United States, 33155
Contact: Jenny Esteeves jenny.esteves@nicklaushealth.org
Contact: Stephanie Uriguen stephanie.uriguen@nicklaushealth.org
Sub-Investigator: Keith Meyer, MD
Sub-Investigator: Prithvi Sendi, MD
United States, Georgia
Children's Healthcare of Atlanta - Emory	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Mallory Tidwell mallory.tidwell@choa.org
Sub-Investigator: Jocelyn Grunwell, MD
United States, Indiana
Riley Children's at Indiana University Health	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kirsten Ramberg kramberg@iu.edu
Sub-Investigator: Courtney Rowan, MD
United States, Missouri
Children's Mercy Hospital	Active, not recruiting
Kansas City, Missouri, United States, 64108
Washington University	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Pamela Stone stone.p@wustl.edu
Sub-Investigator: Stuart Friess, MD
United States, New Jersey
Cooperman Barnabas Medical Center	Recruiting
Livingston, New Jersey, United States, 07039
Contact: Shira Gertz, MD shira.gertz@rwjbh.org
Sub-Investigator: Shira Gertz, MD
United States, New York
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Carlos Breton cb3053@cumc.columbia.edu
Sub-Investigator: Danielle Ahn, MD
United States, Ohio
Akron Children's Hospital	Recruiting
Akron, Ohio, United States, 44308
Contact: Nicole Twinem ntwinem@akronchildrens.org
Contact: Debbie Giebner dgiebner@akronchildrens.org
Sub-Investigator: Ryan Nofziger, MD
Sub-Investigator: Christopher Page-Goertz, MD
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Nathan Gregor Nathan.Gregor@cchmc.org
Contact: Abigayle Gibson Abigayle.Gibson@cchmc.org
Sub-Investigator: Brian Varisco, MD
Nationwide Children's Hospital	Recruiting
Columbus, Ohio, United States, 43205
Contact: Lisa Steele lisa.steele@nationwidechildrens.org
Sub-Investigator: Joshua Frazier, MD
United States, Pennsylvania
Penn State Hershey Children's Hospital	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Debbie Spear dspear@pennstatehealth.psu.org
Sub-Investigator: Neal Thomas, MD
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Stephen T Famularo 215-590-2964 famularois@chop.edu
Principal Investigator: Nadir Yehya, MD
United States, Texas
Texas Children's Hospital / Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Parag Jain, M.D. pnjain@texaschildrens.org
Sub-Investigator: Parag Jain, MD
United States, Wisconsin
Children's Hospital of Wisconsin	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Sadaf Shad sshad@mcw.edu
Sub-Investigator: Jasmine Dowell, MD
Sub-Investigator: Rainer Gedeit, MD

Sponsors and Collaborators