Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP)

April 4, 2024 updated by: William J Meurer, University of Michigan

Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients - A Multicenter, Randomized, Adaptive Clinical Trial to Identify the Optimal Duration of Induced Hypothermia for Neuroprotection in Comatose Survivors of Cardiac Arrest

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Cardiac arrest is a common and devastating emergency of the heart and the brain. More than 380,000 patients suffer out of hospital cardiac arrest (OHCA) each year in the US. Improvements in cardiac resuscitation (the early links in the "chain of survival" for patients with OHCA) are tempered by our limited ability to resuscitate and protect the brain from global cerebral ischemia.

Neurological death and disability are common outcomes in survivors of cardiac arrest. Therapeutic cooling of comatose patients resuscitated from shockable rhythms markedly increases the rate of good neurological outcome, but poor outcomes still occur in as many as 50%, and the benefit of cooling in those resuscitated from asystole and pulseless electrical activity has not been shown in a randomized study.

Objectives:

The overarching goal of this project is to identify clinical strategies that will increase the number of patients with good neurological recovery from cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having good outcomes.

Primary Objectives:

A. To determine, in each of two populations of adult comatose survivors of cardiac arrest (those with initial shockable rhythms and those with pulseless electrical activity (PEA)/asystole), the shortest duration of cooling that provides the maximum treatment effect as determined by a weighted 90 day modified Rankin score B. To determine, in each of two populations of adult comatose survivors of cardiac arrest (those with initial shockable rhythms and those with PEA/asystole), whether increasing durations of cooling are associated with better outcomes or recovery implying efficacy of hypothermia to no cooling.

Secondary Objectives:

To characterize the overall safety and adverse events associated with duration of cooling To characterize the effect of duration of cooling on neuropsychological outcomes To characterize the effect of duration of cooling on patient reported quality of life

Design:

This study is a randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS, across the treatment arms. The design will fit patient outcome data to a duration response model (separately for shockable and non-shockable rhythms), in which the potentially non-linear association between durations of cooling and the primary endpoint are estimated. All conclusions about the treatment arms are based on this model. The functional form of the duration-response model is flexible and able to fit many different shapes for the duration-response curve. Specifically it is parameterized to identify up to two change-points in the treatment effect across arms, allowing it to fit an increasing, decreasing, flat, plateau, or U-shape duration-response curve.

Subjects will initially be equally randomized between 12, 24, and 48 hours of cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each rhythm type, by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. Specifically, a 6-hour duration arm will be opened if the emerging duration-response curve from 12 hours is flat. Similarly, a 60-hour or 72-hour duration arm will be opened if the emerging duration response curve shows an increasing treatment benefit through 48 hours.

This trial will have frequent interim analyses to stop the trial early for futility if it is highly likely that no treatment arm offers a greater benefit then the 6-hour duration arm.

Primary Outcome Measure:

The primary outcome measure will be the modified Rankin scale at 90 days after return of spontaneous circulation. The mRS will be analyzed as a weighted score incorporating both the proportion of subjects achieving a good neurological outcome and degree of residual functional impairment among those with good neurological outcomes.

Study Population:

Comatose adult survivors of out of hospital cardiac arrest that have already been rapidly cooled using a definitive temperature control method (endovascular or surface) will be enrolled in the emergency department or intensive care unit. Hub and spoke hospitals from the SIREN network will be enriched with high potential ancillary Hubs. Approximately 50 hospitals are anticipated to each enroll an average of 9 subjects per year.

Randomization:

Central computerized randomization by web-based interface will be used. Subjects will be potentially randomized over the course of the trial to the following possible durations of cooling (in hours): 6, 12, 18, 24, 30, 36, 42, 48, 60, and 72. The first 200 patients will be randomized 1:1:1 to the 12, 24, and 48-hour durations only. After this initial "burn in" period, response adaptive randomization will be used to allocate subjects to durations inclusive of 12 to 48 hours initially, and then subsequently to the 6, 60 or 72 hour durations if specified conditions are met and the emerging duration-response curve suggests that the maximum treatment benefit might be on those durations. The response adaptive randomization probabilities for each arm will be determined separately for the two rhythm type populations. Randomization probabilities will be updated monthly, or approximately every 38 patients based on the expected accrual rate.

Consent:

Eligible patients for this trial will not have capacity to provide informed consent. Written informed consent from a legally authorized representative will be required.

Intervention:

The intervention will be random allocation to duration of cooling after cardiac arrest. Cooling in the study will be by a definitive temperature control method to a target temperature of 33 deg C. Any endovascular or surface cooling system with closed loop feedback will be allowed. Duration of cooling will be measured from the time that cooling with a definitive device is initiated in the hospital. As part of routine medical care, cooling may be initiated by emergency medical service (EMS) or in the emergency department. Eligibility will require that a temperature of <34 degrees C be obtained by 240 minutes after cardiac arrest. After the allocated duration of cooling is completed, controlled rewarming will be performed. Rewarming to a temperature of 36.5 deg C will occur over the shorter of 24 hours or a rewarming period equal to the allocated duration of cooling. Definitive cooling devices may be used for maintenance of normothermia after rewarming is complete. A clinical standardization guideline will be followed to reduce the effects of practice variability. Key physiologic and practice variables will be tracked and compliance with clinical standardization and deviation from physiologic targets reported back to study teams.

Statistical Analysis for the Primary Outcome Measure:

We will model the mean weighted mRS at 90 days across the treatment arms. The weighted mRS incorporates both the proportion of subjects achieving a good neurological outcome and degree of impairment among those with good neurological outcomes. The primary analysis is conducted separately for each rhythm type, allowing for a different treatment effect by rhythm type, and has two components. First, we identify the most likely target duration, where the target duration is the shortest duration that achieves the maximum treatment effect (Objective A). Second, we calculate whether the efficacy of any duration is superior to any shorter duration of cooling indicating a positive duration response (Objective B). Establishing a positive duration response implies confirmation that cooling is effective in improving outcome or recovery versus normothermia, when a normothermia control arm is not clinically acceptable.

A maximal sample size of 1800 subjects enrolled over 4 years (estimated accrual rate of 37.5 subjects/month) is anticipated.

Investigational Device Exemption

Study Type

Interventional

Enrollment (Estimated)

1800

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Active, not recruiting
        • University of Alabama Hospital
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • Banner University Medical Center
        • Contact:
          • Cameron Hypes
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
          • Shahed Toosi
      • Los Angeles, California, United States, 90095
        • Recruiting
        • Ronald Regan UCLA Medical Center
        • Contact:
          • Richelle Cooper
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis Medical Center
        • Contact:
          • Matthew Greer
      • San Diego, California, United States, 92103
        • Recruiting
        • UC San Diego Medical Center - Hillcrest
        • Contact:
          • Gabriel Wardi
      • San Francisco, California, United States, 94110
        • Recruiting
        • Zuckerberg San Francisco General Hospital
        • Contact:
          • Claude Hemphill
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University Medical Center
        • Contact:
          • Karen Hirsch
      • Torrance, California, United States, 90502
        • Recruiting
        • Harbor-UCLA Medical Center
        • Contact:
          • Kabir Yadav
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Active, not recruiting
        • University of Colorado Hospital
      • Denver, Colorado, United States, 80204
        • Active, not recruiting
        • Denver Health Medical Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale New Haven Hospital
        • Contact:
          • Charles Wira
    • Florida
      • Gainesville, Florida, United States, 32608
        • Recruiting
        • UF Health Shands Hospital
        • Contact:
          • Torben Becker
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Recruiting
        • Grady Memorial Hospital
        • Contact:
          • Andre Holder
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Recruiting
        • The Queen's Medical Center
        • Contact:
          • Matthew Koenig
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
          • Yanina Purim-Shem-Tov
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
          • David Beiser
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern Memorial Hospital
        • Contact:
          • Peter Pruitt
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois-Chicago Hosptial
        • Contact:
          • Marina Del Rios
      • Oak Lawn, Illinois, United States, 60453
        • Active, not recruiting
        • Advocate Christ Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • IU Health Methodist Hospital
        • Contact:
          • Benton Hunter
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky Hospital
        • Contact:
          • Vedant Gupta
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • UofL Health - Jewish Hospital
        • Contact:
          • Shahab Ghafghazi
    • Maine
      • Portland, Maine, United States, 04102
        • Recruiting
        • Maine Medical Center
        • Contact:
          • Teresa May
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center
        • Contact:
          • Neeraj Badjatia
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Hospital
        • Contact:
          • Sung-Min Cho
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Michael Silverman
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham & Women's Hospital
        • Contact:
          • Jong Lee
      • Boston, Massachusetts, United States, 02215
        • Active, not recruiting
        • Beth Israel Deaconess Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Hospital
        • Contact:
          • Cindy Hsu
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Contact:
          • Joseph Miller
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Detroit Receiving Hospital
        • Contact:
          • James Paxton
      • Detroit, Michigan, United States, 48235
        • Recruiting
        • DMC Sinai Grace Hospital
        • Contact:
          • John Wilburn
      • Grand Rapids, Michigan, United States, 49503
        • Active, not recruiting
        • Spectrum Health Butterworth Hospital
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • William Beaumont Hospital
        • Contact:
          • Robert Swor
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Recruiting
        • M Health Fairview Southdale Hospital
        • Contact:
          • Benjamin Miller
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center
        • Contact:
          • Brian Driver
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • M Health Fairview East Bank Hospital
        • Contact:
          • Benjamin Miller
      • Saint Paul, Minnesota, United States, 55101
        • Active, not recruiting
        • Regions Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
          • Aaron Barksdale
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • Cooper University Hospital
        • Contact:
          • Hope Kilgannon
    • New York
      • Brooklyn, New York, United States, 11203
        • Recruiting
        • Kings County Hospital Center
        • Contact:
          • Izad-Yar Rasheed
      • New York, New York, United States, 10032
        • Recruiting
        • NYP Columbia University Medical Center
        • Contact:
          • Sachin Agarwal
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health - Tisch Hospital
        • Contact:
          • Sam Parnia
      • Rochester, New York, United States, 14642
        • Recruiting
        • Strong Memorial Hospital
        • Contact:
          • Imad Khan
      • Stony Brook, New York, United States, 11794
        • Recruiting
        • Stony Brook University Hospital
        • Contact:
          • Ethan Brandler
      • Syracuse, New York, United States, 13210
        • Recruiting
        • SUNY Upstate Medical University
        • Contact:
          • Birendra Sah
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Hospital
        • Contact:
          • Alexander Limkakeng
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • ECU Health Medical Center
        • Contact:
          • Jason Hack
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest Baptist Medical Center
        • Contact:
          • Aarti Sarwal
    • Ohio
      • Cincinnati, Ohio, United States, 45220
        • Recruiting
        • University of Cincinnati
        • Contact:
          • Justin Benoit
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • OSU Wexner Medical Center
        • Contact:
          • Jeff Caterino
      • Columbus, Ohio, United States, 43203
        • Recruiting
        • OSU East Hospital
        • Contact:
          • Richard Gumina
      • Toledo, Ohio, United States, 43608
        • Recruiting
        • Mercy St. Vincent Medical Center
        • Contact:
          • David Ledrick
    • Oregon
      • Portland, Oregon, United States, 97216
        • Recruiting
        • Adventist Health
        • Contact:
          • Mohamud Daya
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Medical Center
        • Contact:
          • Douglas Kupas
      • Harrisburg, Pennsylvania, United States, 17101
        • Recruiting
        • UPMC Harrisburg
        • Contact:
          • Erik Kochert
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Penn Presbyterian Medical Center
        • Contact:
          • Benjamin Abella
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple University Hospital
        • Contact:
          • Nina Gentile
      • Philadelphia, Pennsylvania, United States, 19107
        • Active, not recruiting
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Hospital of the University of Pennsylvania
        • Contact:
          • Benjamin Abella
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
          • Johnathan Elmer
      • Sayre, Pennsylvania, United States, 18840
        • Recruiting
        • Guthrie Robert Packer Hospital
        • Contact:
          • Jon Rittenberger
    • Texas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Parkland Hospital
        • Contact:
          • Ava Pierce
      • Houston, Texas, United States, 77030
        • Recruiting
        • Memorial Hermann Hospital
        • Contact:
          • Elizabeth Jones
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah Hospital
        • Contact:
          • Joseph Tonna
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Medical Center
        • Contact:
          • Robert O'Connor
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • VCU Medical Center
        • Contact:
          • Mary Ann Peberdy
    • Washington
      • Everett, Washington, United States, 98201
        • Recruiting
        • Providence Regional Medical Center Everett
        • Contact:
          • Rafael Wabl
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Harborview Medical Center
        • Contact:
          • Nick Johnson
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital
        • Contact:
          • Tom Aufderheide

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 6 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 12 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 18 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 24 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 30 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 36 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 42 Hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 48 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 60 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 72 hours - shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 6 hours - non shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 12 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 18 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 24 hour - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 30 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 36 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 42 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 48 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 60 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Experimental: 72 hours - non-shockable
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
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weighted Modified Rankin Scale (mRS)
Time Frame: 90 days after return of spontaneous circulation
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
All Cause Mortality
Time Frame: 90 days after return of spontaneous circulation
All patients who are dead at follow up.
90 days after return of spontaneous circulation
NIH Toolbox Crystallized Cognition Composite Score
Time Frame: 90 days after return of spontaneous circulation
Composite T-scores from a subset of study neuropsychological tests evaluating.
90 days after return of spontaneous circulation
NIH Toolbox Fluid Cognition Composite Score
Time Frame: 90 days after return of spontaneous circulation
Composite T-scores from a subset of study neuropsychological tests evaluating cognitive functioning in awake survivors collected on the NIH Toolbox platform. The fluid cognition composite score is more reflective of capacity for new learning and information. processing in novel situations
90 days after return of spontaneous circulation
Pneumonia
Time Frame: 90 days after return of spontaneous circulation
Determined by simplified Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) definitions of Ventilator-Associated Event (VAE) or Pneumonia.
90 days after return of spontaneous circulation
Other infection
Time Frame: 90 days after return of spontaneous circulation
Determined by simplified CDC NHSN (Center for Disease Control National Healthcare Safety Network) definitions of Urinary Tract Infection or Blood Stream Infection.
90 days after return of spontaneous circulation
Malignant cardiac arrhythmia
Time Frame: 90 days after return of spontaneous circulation
Defined as any arrhythmia that requires termination with chest compressions, pacing, defibrillation, or electrical cardioversion. Arrhythmias (including atrial fibrillation) managed only with medication are excluded.
90 days after return of spontaneous circulation
Seizures
Time Frame: 90 days after return of spontaneous circulation
Defined as unambiguous convulsive or electroencephalographic seizure activity triggering urgent initial or additional anticonvulsant therapy. This definition does not include those given further anticonvulsants as secondary prophylaxis or as treatment for vague or uncertain exam findings or nondiagnostic electroencephalography. It does not include myoclonus.
90 days after return of spontaneous circulation
Neurological worsening
Time Frame: 90 days after return of spontaneous circulation
Determined by a decrease in Full Outline of Unresponsiveness (FOUR) score of ≥4 points that persists on two consecutive days or is associated with a neurological death. It excludes transient fluctuations in neurological examination or changes attributed to pharmacological sedation or paralysis.
90 days after return of spontaneous circulation
Electrolyte abnormalities
Time Frame: 90 days after return of spontaneous circulation
Defined as a measured serum Na, K, Mg, or Ca that is either higher or lower than study defined boundaries on at least two sequential measurements and resulting in a change in IV therapy. It excludes deliberate hypernatremia or hypermagnesemia induced to treat intracranial hypertension or shivering.
90 days after return of spontaneous circulation
Coagulopathies
Time Frame: 90 days after return of spontaneous circulation
Defined as requiring all 3 of the following parameters: (1) some form of major bleeding associated with (2) laboratory confirmation of an abnormal clotting axis and (3) treatment with blood product transfusion or reversal agent. Laboratory testing may include International Normalized Ratio (INR), partial thromboplastin time (PTT), clotting time, or thromboelastography.
90 days after return of spontaneous circulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

Medical University of South Carolina
Johns Hopkins University
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: William Meurer, University of Michigan
  • Principal Investigator: Robert Silbergleit, University of Michigan
  • Principal Investigator: Romer Geocadin, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2020

Primary Completion (Estimated)

July 15, 2025

Study Completion (Estimated)

August 31, 2025

Study Registration Dates

First Submitted

December 30, 2019

First Submitted That Met QC Criteria

December 30, 2019

First Posted (Actual)

January 3, 2020

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • G160072
  • U01NS073476 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

1 year after publication on main outcome results paper

IPD Sharing Access Criteria

Data use agreement with the appropriate NHLBI repository

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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