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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04113434
Recruitment Status : Not yet recruiting
First Posted : October 2, 2019
Last Update Posted : October 2, 2019
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
Children's Research Institute
Milton S. Hershey Medical Center
Nationwide Children's Hospital
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Indiana University Health
St. Barnabas Medical Center
Texas Children's Hospital
Columbia University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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).

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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
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : December 2024





Primary Outcome Measures :
  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 Outcome Measures :
  1. 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


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:

  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

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@email.chop.edu
Contact: Stephen Famularo, BA famularois@email.chop.edu

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 Research Institute
Milton S. Hershey Medical Center
Nationwide Children's Hospital
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Indiana University Health
St. Barnabas Medical Center
Texas Children's Hospital
Columbia University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Nadir Yehya, M.D. Children's Hospital of Philadelphia
  Study Documents (Full-Text)

Documents provided by Children's Hospital of Philadelphia:

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Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT04113434    
Other Study ID Numbers: 19-016271
R01HL148054 ( U.S. NIH Grant/Contract )
First Posted: October 2, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Gene expression data will be released to Gene Expression Omnibus simultaneously with the publication of the data. Biomarker data will be released within 2 years of publication of the main manuscript.
Access Criteria: We will follow NHLBI's guidelines for accessing BioLINCC data.

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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:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury