NCT04217551

Brief Summary

A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest.

Trial Health

55
Monitor

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
1,158

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started May 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

76 active sites

Status
active not 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

First Submitted

Initial submission to the registry

December 30, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 3, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

May 18, 2020

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 5, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 5, 2025

Completed
Last Updated

June 25, 2025

Status Verified

June 1, 2025

Enrollment Period

5.3 years

First QC Date

December 30, 2019

Last Update Submit

June 18, 2025

Conditions

Keywords

Bayesian Adaptive Clinical TrialHypothermia, therapeuticComa

Outcome Measures

Primary Outcomes (1)

  • Weighted Modified Rankin Scale (mRS)

    The mRS is a 7 level ordinal scale of disability that ranges from 0 (no symptoms at all) to 6 (death). ICECAP uses weighting of mRS states to capture changes in functional status.

    90 days after return of spontaneous circulation

Secondary Outcomes (10)

  • All Cause Mortality

    90 days after return of spontaneous circulation

  • NIH Toolbox Crystallized Cognition Composite Score

    90 days after return of spontaneous circulation

  • NIH Toolbox Fluid Cognition Composite Score

    90 days after return of spontaneous circulation

  • Pneumonia

    90 days after return of spontaneous circulation

  • Other infection

    90 days after return of spontaneous circulation

  • +5 more secondary outcomes

Study Arms (20)

6 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 6 hours of hypothermia with a target of 33 degrees followed by 6 hours of controlled rewarming.

Device: Therapeutic Hypothermia

12 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 12 hours of hypothermia with a target of 33 degrees followed by 12 hours of controlled rewarming.

Device: Therapeutic Hypothermia

18 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 18 hours of hypothermia with a target of 33 degrees followed by 18 hours of controlled rewarming.

Device: Therapeutic Hypothermia

24 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 24 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

30 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 30 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

36 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 36 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

42 Hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 42 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

48 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 48 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

60 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 60 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

72 hours - shockable

EXPERIMENTAL

Participants with shockable initial rhythm will be assigned to receive 72 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

6 hours - non shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 6 hours of hypothermia with a target of 33 degrees followed by 6 hours of controlled rewarming.

Device: Therapeutic Hypothermia

12 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 12 hours of hypothermia with a target of 33 degrees followed by 12 hours of controlled rewarming.

Device: Therapeutic Hypothermia

18 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 18 hours of hypothermia with a target of 33 degrees followed by 18 hours of controlled rewarming.

Device: Therapeutic Hypothermia

24 hour - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 24 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

30 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 30 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

36 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 36 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

42 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 42 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

48 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 48 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

60 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 60 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

72 hours - non-shockable

EXPERIMENTAL

Participants with non-shockable initial rhythm will be assigned to receive 72 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Device: Therapeutic Hypothermia

Interventions

Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.

12 hours - non-shockable12 hours - shockable18 hours - non-shockable18 hours - shockable24 hour - non-shockable24 hours - shockable30 hours - non-shockable30 hours - shockable36 hours - non-shockable36 hours - shockable42 Hours - shockable42 hours - non-shockable48 hours - non-shockable48 hours - shockable6 hours - non shockable6 hours - shockable60 hours - non-shockable60 hours - shockable72 hours - non-shockable72 hours - shockable

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Coma after resuscitation from out of hospital cardiac arrest
  • Cooled to \<34 deg C with 240 minutes of cardiac arrest
  • Definitive temperature control applied
  • Age ≥ 18 years
  • Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours
  • Enrollment within 6 hours of initiation of cooling

You may not qualify if:

  • Hemodynamic instability
  • Pre-existing neurological disability or condition that confounds outcome determination
  • Pre-existing terminal illness, unlikely to survive to outcome determination
  • Planned early withdrawal of life support
  • Presumed sepsis as etiology of arrest
  • Prisoner

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (76)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

Location

Banner University Medical Center

Tucson, Arizona, 85719, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Ronald Regan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

George Washington University Hospital

Washington D.C., District of Columbia, 20037, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois-Chicago Hosptial

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Macomb Hospital

Clinton Township, Michigan, 48038, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

DMC Sinai Grace Hospital

Detroit, Michigan, 48235, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

M Health Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

South Shore University Hospital

Bay Shore, New York, 11706, United States

Location

NYU Langone Health - Tisch Hospital

New York, New York, 10016, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

NYP Columbia University Medical Center

New York, New York, 10032, United States

Location

Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

ECU Health Medical Center

Greenville, North Carolina, 27834, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45220, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

OSU East Hospital

Columbus, Ohio, 43203, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Mercy St. Vincent Medical Center

Toledo, Ohio, 43608, United States

Location

Adventist Health

Portland, Oregon, 97216, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

UPMC Harrisburg

Harrisburg, Pennsylvania, 17101, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Guthrie Robert Packer Hospital

Sayre, Pennsylvania, 18840, United States

Location

Parkland Hospital

Dallas, Texas, 75235, United States

Location

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

Providence Regional Medical Center Everett

Everett, Washington, 98201, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

  • Meurer WJ, Schmitzberger FF, Yeatts S, Ramakrishnan V, Abella B, Aufderheide T, Barsan W, Benoit J, Berry S, Black J, Bozeman N, Broglio K, Brown J, Brown K, Carlozzi N, Caveney A, Cho SM, Chung-Esaki H, Clevenger R, Conwit R, Cooper R, Crudo V, Daya M, Harney D, Hsu C, Johnson NJ, Khan I, Khosla S, Kline P, Kratz A, Kudenchuk P, Lewis RJ, Madiyal C, Meyer S, Mosier J, Mouammar M, Neth M, O'Neil B, Paxton J, Perez S, Perman S, Sozener C, Speers M, Spiteri A, Stevenson V, Sunthankar K, Tonna J, Youngquist S, Geocadin R, Silbergleit R; ICECAP trial investigators. Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest. Trials. 2024 Jul 23;25(1):502. doi: 10.1186/s13063-024-08280-w.

    PMID: 39044295BACKGROUND
  • Meurer W, Schmitzberger F, Yeatts S, Ramakrishnan V, Abella B, Aufderheide T, Barsan W, Benoit J, Berry S, Black J, Bozeman N, Broglio K, Brown J, Brown K, Carlozzi N, Caveney A, Cho SM, Chung-Esaki H, Clevenger R, Conwit R, Cooper R, Crudo V, Daya M, Harney D, Hsu C, Johnson NJ, Khan I, Khosla S, Kline P, Kratz A, Kudenchuk P, Lewis RJ, Madiyal C, Meyer S, Mosier J, Mouammar M, Neth M, O'Neil B, Paxton J, Perez S, Perman S, Sozener C, Speers M, Spiteri A, Stevenson V, Sunthankar K, Tonna J, Youngquist S, Geocadin R, Silbergleit R. Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest. Res Sq [Preprint]. 2024 Jun 21:rs.3.rs-4033108. doi: 10.21203/rs.3.rs-4033108/v1.

  • Chen CT, Lin JW, Wu CH, Kuo RN, Shih CH, Hou PC, Yen DH, How CK. A Simple Risk Score for Predicting Neurologic Outcome in Out-of-Hospital Cardiac Arrest Patients After Targeted Temperature Management. Crit Care Med. 2022 Mar 1;50(3):428-439. doi: 10.1097/CCM.0000000000005266.

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

  • William Meurer

    University of Michigan

    PRINCIPAL INVESTIGATOR
  • Robert Silbergleit

    University of Michigan

    PRINCIPAL INVESTIGATOR
  • Romer Geocadin

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

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
Associate Professor of Emergency Medicine and Neurology

Study Record Dates

First Submitted

December 30, 2019

First Posted

January 3, 2020

Study Start

May 18, 2020

Primary Completion

September 5, 2025

Study Completion

September 5, 2025

Last Updated

June 25, 2025

Record last verified: 2025-06

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