NCT05376267

Brief Summary

This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
900

participants targeted

Target at P75+ for not_applicable

Timeline
22mo left

Started Aug 2022

Longer than P75 for not_applicable

Geographic Reach
5 countries

61 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress68%
Aug 2022Mar 2028

First Submitted

Initial submission to the registry

May 11, 2022

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 17, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

August 5, 2022

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2028

Last Updated

June 5, 2026

Status Verified

June 1, 2026

Enrollment Period

5.7 years

First QC Date

May 11, 2022

Last Update Submit

June 3, 2026

Conditions

Keywords

Bayesian Adaptive Clinical TrialHypothermia, therapeuticComaPediatric

Outcome Measures

Primary Outcomes (1)

  • Vineland Adaptive Behavior Scales - Third Edition (VABS-3) Mortality Composite Score at 12 months after return of spontaneous circulation

    The VABS-3 score, designed to be administered to surviving children with any level of function including comatose status to age-appropriate neurobehavioral functioning, ranges from 20 to 140 with age-corrected standardized mean and standard deviation of 100 and 15, respectively. Deaths will be scored as 0 in this trial.

    12 months after out-of-hospital cardiac arrest

Secondary Outcomes (3)

  • Change in Pediatric Cerebral Performance Category (PCPC) at 12 months from baseline

    Baseline and 12 months after cardiac arrest

  • Pediatric Resuscitation after Cardiac Arrest (PRCA) at 12 months

    12 months after cardiac arrest

  • Survival at 12 months

    12 months after cardiac arrest

Study Arms (10)

Cooling 0 hours

EXPERIMENTAL

Participants will be kept at a normal temperature for the whole 5 days.

Device: Therapeutic Hypothermia

Cooling 12 hours

EXPERIMENTAL

The participant will be cooled to 33°Celsius (C) for 12 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 18 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 18 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 24 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 24 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 36 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 36 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 48 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 48 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 60 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 60 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 72 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 72 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 84 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 84 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Cooling 96 hours

EXPERIMENTAL

The participant will be cooled to 33°C for 96 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Device: Therapeutic Hypothermia

Interventions

Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.

Cooling 0 hoursCooling 12 hoursCooling 18 hoursCooling 24 hoursCooling 36 hoursCooling 48 hoursCooling 60 hoursCooling 72 hoursCooling 84 hoursCooling 96 hours

Eligibility Criteria

Age2 Days - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age 2 days to \< 18 years with corrected gestational age of at least 38 weeks
  • Chest compressions for at least 2 minutes
  • Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
  • Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
  • Definitive temperature control device initiated
  • Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
  • Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours

You may not qualify if:

  • Glasgow Coma Motor Score (GCMS) = 6
  • LAR does not speak English or Spanish
  • Duration of Cardiopulmonary Resuscitation (CPR) \> 60 minutes
  • Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
  • Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
  • Pre-existing terminal illness, unlikely to survive to one year
  • Cardiac arrest associated with brain, thoracic, or abdominal trauma
  • Active and refractory severe bleeding prior to randomization
  • Extensive burns or skin lesions incompatible with surface cooling
  • Planned early withdrawal of life support before 120 hours
  • Sickle cell anemia
  • Pre-existing cryoglobulinemia
  • Non-fatal drowning in ice covered water
  • Central nervous system tumor with ongoing chemotherapy
  • Previous enrollment in P-ICECAP trial
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (61)

University of Alabama at Birmingham / Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

ACTIVE NOT RECRUITING

Memorial Health - Miller Children's and Women's Hospital of Long Beach

Long Beach, California, 90806-1701, United States

RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

University of California Los Angeles (UCLA) Mattel Children's Hospital

Los Angeles, California, 90095, United States

RECRUITING

University of California - Oakland / UCSF Benoiff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868-4203, United States

RECRUITING

University of California, Davis

Sacramento, California, 95817, United States

RECRUITING

University of California - San Francisco (UCSF) Benioff Children's Hospital San Francisco

San Francisco, California, 94158, United States

RECRUITING

Stanford

Santa Clara, California, 95050, United States

RECRUITING

University of Florida (UF) Health Shands Children's Hospital

Gainesville, Florida, 32610-0296, United States

RECRUITING

University of Miami

Miami, Florida, 33124, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Comer Children's Hospital, University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Children's Hospital of Illinois

Peoria, Illinois, 61637, United States

RECRUITING

Riley Children's Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa, Carver College of Medicine

Iowa City, Iowa, 52242, United States

RECRUITING

University of Maryland Children's Hospital

Baltimore, Maryland, 21201, United States

RECRUITING

Johns Hopkins Medicine Children's Center

Baltimore, Maryland, 21287, United States

RECRUITING

MassGeneral Hospital for Children

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan CS Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

RECRUITING

University of Minnesota Fairview Masonic Children's Hospital

Minneapolis, Minnesota, 55454, United States

WITHDRAWN

Washington University / St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68114, United States

RECRUITING

Albany Medical Center

Albany, New York, 12208, United States

RECRUITING

University of Buffalo / Oishei Children's Hospital

Buffalo, New York, 14203, United States

RECRUITING

Cohen Children's Medical Center of NY / Northwell Health

New Hyde Park, New York, 11040, United States

RECRUITING

Mount Sinai Icahn / Kravis Children's Hospital

New York, New York, 10029, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642-8667, United States

RECRUITING

Montefiore Einstein Hospital Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7220, United States

RECRUITING

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Ohio State University / Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

RECRUITING

Oregon Health & Science University Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

RECRUITING

Penn State University / Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh (UPMC)

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Tennesses Health Center / Le Bonheur Children's

Memphis, Tennessee, 38104, United States

RECRUITING

Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

RECRUITING

Children's Memorial Hermann Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital, Baylor

Houston, Texas, 77030, United States

RECRUITING

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Primary Children's Hospital, University of Utah School of Medicine

Salt Lake City, Utah, 84108, United States

WITHDRAWN

American Family Children's Hospital

Madison, Wisconsin, 53705, United States

RECRUITING

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

RECRUITING

Townsville University Hospital

Douglas, Queensland, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, Australia

RECRUITING

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

RECRUITING

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Perth Children's Hospital

Nedlands, Western Australia, Australia

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

RECRUITING

Starship Children's Hospital

Grafton, Auckland, 1142, New Zealand

RECRUITING

Birmingham Children's Hospital, United Kingdom

Birmingham, United Kingdom

RECRUITING

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Out-of-Hospital Cardiac ArrestHypothermiaHypoxia-Ischemia, BrainComa

Interventions

Hypothermia, Induced

Condition Hierarchy (Ancestors)

Heart ArrestHeart DiseasesCardiovascular DiseasesBody Temperature ChangesSigns and SymptomsPathological Conditions, Signs and SymptomsBrain IschemiaCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHypoxia, BrainVascular DiseasesHypoxiaSigns and Symptoms, RespiratoryUnconsciousnessConsciousness DisordersNeurobehavioral ManifestationsNeurologic Manifestations

Intervention Hierarchy (Ancestors)

CryotherapyTherapeutics

Study Officials

  • Frank Moler, MD

    University of Michigan

    PRINCIPAL INVESTIGATOR
  • Alex Topjian, MD

    Children's Hospital of Philadelphia

    PRINCIPAL INVESTIGATOR
  • William Meurer, MD

    University of Michigan

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank Moler, MD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The outcomes assessors will be blinded to the treatment assignment of the participant.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Bayesian Adaptive Design
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pediatrics

Study Record Dates

First Submitted

May 11, 2022

First Posted

May 17, 2022

Study Start

August 5, 2022

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

March 31, 2028

Last Updated

June 5, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will share

The data will be stored in the NHLBI data repository after trial completion.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
1 year after publication on main outcome results paper
Access Criteria
Data use agreement with the appropriate NHLBI repository

Locations