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

Primary Purpose

Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Therapeutic Hypothermia
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest, Out-Of-Hospital focused on measuring Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama HospitalRecruiting
  • Banner University Medical CenterRecruiting
  • Cedars-Sinai Medical CenterRecruiting
  • Ronald Regan UCLA Medical CenterRecruiting
  • UC Davis Medical CenterRecruiting
  • UC San Diego Medical Center - HillcrestRecruiting
  • Zuckerberg San Francisco General HospitalRecruiting
  • Stanford University Medical CenterRecruiting
  • Harbor-UCLA Medical CenterRecruiting
  • University of Colorado HospitalRecruiting
  • Denver Health Medical CenterRecruiting
  • Yale New Haven HospitalRecruiting
  • UF Health Shands HospitalRecruiting
  • Grady Memorial HospitalRecruiting
  • The Queen's Medical CenterRecruiting
  • Northwestern Memorial HospitalRecruiting
  • Rush University Medical CenterRecruiting
  • University of Illinois-Chicago HosptialRecruiting
  • University of Chicago Medical CenterRecruiting
  • Advocate Christ Medical CenterRecruiting
  • IU Health Methodist HospitalRecruiting
  • University of Kentucky HospitalRecruiting
  • Maine Medical CenterRecruiting
  • University of Maryland Medical CenterRecruiting
  • Johns Hopkins HospitalRecruiting
  • Massachusetts General HospitalRecruiting
  • Brigham & Women's HospitalRecruiting
  • Beth Israel Deaconess Medical CenterRecruiting
  • University of Michigan HospitalRecruiting
  • Detroit Receiving HospitalRecruiting
  • Henry Ford HospitalRecruiting
  • DMC Sinai Grace HospitalRecruiting
  • Spectrum Health Butterworth HospitalRecruiting
  • William Beaumont HospitalRecruiting
  • M Health Fairview Southdale HospitalRecruiting
  • Hennepin County Medical CenterRecruiting
  • M Health Fairview East Bank HospitalRecruiting
  • Regions HospitalRecruiting
  • University of Nebraska Medical CenterRecruiting
  • Cooper University HospitalRecruiting
  • Kings County Hospital CenterRecruiting
  • NYP Columbia University Medical CenterRecruiting
  • Strong Memorial HospitalRecruiting
  • Stony Brook University HospitalRecruiting
  • SUNY Upstate Medical UniversityRecruiting
  • Duke University HospitalRecruiting
  • Wake Forest Baptist Medical CenterRecruiting
  • University of CincinnatiRecruiting
  • OSU East HospitalRecruiting
  • OSU Wexner Medical CenterRecruiting
  • Mercy St. Vincent Medical CenterRecruiting
  • Adventist HealthRecruiting
  • Geisinger Medical CenterRecruiting
  • UPMC HarrisburgRecruiting
  • Hospital of the University of PennsylvaniaRecruiting
  • Penn Presbyterian Medical CenterRecruiting
  • Thomas Jefferson University HospitalRecruiting
  • Temple University HospitalRecruiting
  • University of Pittsburgh Medical CenterRecruiting
  • Guthrie Robert Packer HospitalRecruiting
  • Parkland HospitalRecruiting
  • Memorial Hermann HospitalRecruiting
  • University of Utah HospitalRecruiting
  • University of Virginia Medical CenterRecruiting
  • VCU Medical CenterRecruiting
  • Harborview Medical CenterRecruiting
  • Froedtert HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

6 hours - shockable

12 hours - shockable

18 hours - shockable

24 hours - shockable

30 hours - shockable

36 hours - shockable

42 Hours - shockable

48 hours - shockable

60 hours - shockable

72 hours - shockable

6 hours - non shockable

12 hours - non-shockable

18 hours - non-shockable

24 hour - non-shockable

30 hours - non-shockable

36 hours - non-shockable

42 hours - non-shockable

48 hours - non-shockable

60 hours - non-shockable

72 hours - non-shockable

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

All Cause Mortality
All patients who are dead at follow up.
NIH Toolbox Crystallized Cognition Composite Score
Composite T-scores from a subset of study neuropsychological tests evaluating.
NIH Toolbox Fluid Cognition Composite Score
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
Pneumonia
Determined by simplified Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) definitions of Ventilator-Associated Event (VAE) or Pneumonia.
Other infection
Determined by simplified CDC NHSN (Center for Disease Control National Healthcare Safety Network) definitions of Urinary Tract Infection or Blood Stream Infection.
Malignant cardiac arrhythmia
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.
Seizures
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.
Neurological worsening
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.
Electrolyte abnormalities
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.
Coagulopathies
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.

Full Information

First Posted
December 30, 2019
Last Updated
May 8, 2023
Sponsor
University of Michigan
Collaborators
Johns Hopkins University, Medical University of South Carolina, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT04217551
Brief Title
Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients
Acronym
ICECAP
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 18, 2020 (Actual)
Primary Completion Date
July 15, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Johns Hopkins University, Medical University of South Carolina, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Keywords
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Bayesian Adaptive Design
Masking
Outcomes Assessor
Masking Description
The outcomes assessors will be blinded to the treatment assignment of the participant.
Allocation
Randomized
Enrollment
1800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
6 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
12 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
18 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
24 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
30 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
36 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
42 Hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
48 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
60 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
72 hours - shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
6 hours - non shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
12 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
18 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
24 hour - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
30 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
36 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
42 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
48 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
60 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Arm Title
72 hours - non-shockable
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Therapeutic Hypothermia
Intervention Description
Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, using a closed-loop temperature control device.
Primary Outcome Measure Information:
Title
Weighted Modified Rankin Scale (mRS)
Description
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.
Time Frame
90 days after return of spontaneous circulation
Secondary Outcome Measure Information:
Title
All Cause Mortality
Description
All patients who are dead at follow up.
Time Frame
90 days after return of spontaneous circulation
Title
NIH Toolbox Crystallized Cognition Composite Score
Description
Composite T-scores from a subset of study neuropsychological tests evaluating.
Time Frame
90 days after return of spontaneous circulation
Title
NIH Toolbox Fluid Cognition Composite Score
Description
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
Time Frame
90 days after return of spontaneous circulation
Title
Pneumonia
Description
Determined by simplified Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) definitions of Ventilator-Associated Event (VAE) or Pneumonia.
Time Frame
90 days after return of spontaneous circulation
Title
Other infection
Description
Determined by simplified CDC NHSN (Center for Disease Control National Healthcare Safety Network) definitions of Urinary Tract Infection or Blood Stream Infection.
Time Frame
90 days after return of spontaneous circulation
Title
Malignant cardiac arrhythmia
Description
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.
Time Frame
90 days after return of spontaneous circulation
Title
Seizures
Description
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.
Time Frame
90 days after return of spontaneous circulation
Title
Neurological worsening
Description
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.
Time Frame
90 days after return of spontaneous circulation
Title
Electrolyte abnormalities
Description
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.
Time Frame
90 days after return of spontaneous circulation
Title
Coagulopathies
Description
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.
Time Frame
90 days after return of spontaneous circulation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William Meurer
Phone
734-232-2142
Email
wmeurer@med.umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Mickie Speers
Phone
734-232-2142
Email
lraes@med.umich.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Meurer
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Silbergleit
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Romer Geocadin
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Kurz
Facility Name
Banner University Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cameron Hypes
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shahed Toosi
Facility Name
Ronald Regan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richelle Cooper
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Greer
Facility Name
UC San Diego Medical Center - Hillcrest
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriel Wardi
Facility Name
Zuckerberg San Francisco General Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claude Hemphill
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Hirsch
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kabir Yadav
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Perman
Facility Name
Denver Health Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Haukoos
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charles Wira
Facility Name
UF Health Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torben Becker
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andre Holder
Facility Name
The Queen's Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Koenig
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Pruitt
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanina Purim-Shem-Tov
Facility Name
University of Illinois-Chicago Hosptial
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marina Del Rios
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Beiser
Facility Name
Advocate Christ Medical Center
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60453
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Dodd
Facility Name
IU Health Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benton Hunter
Facility Name
University of Kentucky Hospital
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vedant Gupta
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teresa May
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neeraj Badjatia
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung-Min Cho
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Silverman
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jong Lee
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Donnino
Facility Name
University of Michigan Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cindy Hsu
Facility Name
Detroit Receiving Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Paxton
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Miller
Facility Name
DMC Sinai Grace Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Wilburn
Facility Name
Spectrum Health Butterworth Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Reynolds
Facility Name
William Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Swor
Facility Name
M Health Fairview Southdale Hospital
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Miller
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian Driver
Facility Name
M Health Fairview East Bank Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Miller
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kealy Ham
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aaron Barksdale
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hope Kilgannon
Facility Name
Kings County Hospital Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Izad-Yar Rasheed
Facility Name
NYP Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sachin Agarwal
Facility Name
Strong Memorial Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Imad Khan
Facility Name
Stony Brook University Hospital
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ethan Brandler
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birendra Sah
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Limkakeng
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aarti Sarwal
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Justin Benoit
Facility Name
OSU East Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Gumina
Facility Name
OSU Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeff Caterino
Facility Name
Mercy St. Vincent Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Ledrick
Facility Name
Adventist Health
City
Portland
State/Province
Oregon
ZIP/Postal Code
97216
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamud Daya
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Douglas Kupas
Facility Name
UPMC Harrisburg
City
Harrisburg
State/Province
Pennsylvania
ZIP/Postal Code
17101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik Kochert
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Abella
Facility Name
Penn Presbyterian Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Abella
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Gaieski
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Gentile
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johnathan Elmer
Facility Name
Guthrie Robert Packer Hospital
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon Rittenberger
Facility Name
Parkland Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ava Pierce
Facility Name
Memorial Hermann Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Jones
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Tonna
Facility Name
University of Virginia Medical Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert O'Connor
Facility Name
VCU Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary Ann Peberdy
Facility Name
Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Johnson
Facility Name
Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tom Aufderheide

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
34495880
Citation
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.
Results Reference
derived

Learn more about this trial

Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients

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