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

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: NCT04217551
Recruitment Status : Recruiting
First Posted : January 3, 2020
Last Update Posted : September 18, 2020
Sponsor:
Collaborators:
Johns Hopkins University
Medical University of South Carolina
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
William J Meurer, University of Michigan

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.

Condition or disease Intervention/treatment Phase
Cardiac Arrest, Out-Of-Hospital Hypothermia, Induced Hypoxia-Ischemia, Brain Device: Therapeutic Hypothermia Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Bayesian Adaptive Design
Masking: Single (Outcomes Assessor)
Masking Description: The outcomes assessors will be blinded to the treatment assignment of the participant.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 18, 2020
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. All Cause Mortality [ Time Frame: 90 days after return of spontaneous circulation ]
    All patients who are dead at follow up.

  2. 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.

  3. 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

  4. Pneumonia [ Time Frame: 90 days after return of spontaneous circulation ]
    Determined by simplified CDC NHSN (Center for Disease Control National Healthcare Safety Network) definitions of Ventilator-Associated Event (VAE) or Pneumonia.

  5. 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.

  6. 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.

  7. 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.

  8. Neurological worsening [ Time Frame: 90 days after return of spontaneous circulation ]
    Determined by a decrease in 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.

  9. 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.

  10. 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 INR, PTT, clotting time, or thromboelastography.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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

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): NCT04217551


Contacts
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Contact: William Meurer 734-232-2142 wmeurer@med.umich.edu
Contact: Mickie Speers 734-232-2142 lraes@med.umich.edu

Locations
Show Show 21 study locations
Sponsors and Collaborators
University of Michigan
Johns Hopkins University
Medical University of South Carolina
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: William Meurer University of Michigan
Principal Investigator: Robert Silbergleit University of Michigan
Principal Investigator: Romer Geocadin Johns Hopkins University
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Responsible Party: William J Meurer, Associate Professor of Emergency Medicine and Neurology, University of Michigan
ClinicalTrials.gov Identifier: NCT04217551    
Other Study ID Numbers: G160072
U01NS073476 ( U.S. NIH Grant/Contract )
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: September 18, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data will be stored in the NHLBI data repository after trial completion.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: 1 year after publication on main outcome results paper
Access Criteria: Data use agreement with the appropriate NHLBI repository

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by William J Meurer, University of Michigan:
Bayesian Adaptive Clinical Trial
Hypothermia, therapeutic
Coma
Additional relevant MeSH terms:
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Brain Ischemia
Hypoxia-Ischemia, Brain
Heart Arrest
Out-of-Hospital Cardiac Arrest
Ischemia
Hypoxia
Hypothermia
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Signs and Symptoms, Respiratory
Body Temperature Changes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Hypoxia, Brain