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

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

Official Title
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Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)

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

Intervention / Treatment
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* Device: Therapeutic Hypothermia


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 2 days to < 18 years with corrected gestational age of at least 38 weeks Chest compressions for at least 2 minutes Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA) Requires continuous mechanical ventilation through endotracheal tube or tracheostomy Definitive temperature control device initiated Randomization within 6 hours of Return of Spontaneous Circulation (ROSC) Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria: Glasgow Coma Motor Score (GCMS) = 6 LAR does not speak English or Spanish Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO) Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy Pre-existing terminal illness, unlikely to survive to one year Cardiac arrest associated with brain, thoracic, or abdominal trauma Active and refractory severe bleeding prior to randomization Extensive burns or skin lesions incompatible with surface cooling Planned early withdrawal of life support before 120 hours Sickle cell anemia Pre-existing cryoglobulinemia Non-fatal drowning in ice covered water Central nervous system tumor with ongoing chemotherapy Previous enrollment in P-ICECAP trial Prisoner Chronic hypothermia New post-cardiac arrest diabetes insipidus Pregnancy

Ages Eligible for Study
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Minimum Age: 2 Days
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Bayesian Adaptive Design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cooling 0 hours<br>Participants will be kept at a normal temperature for the whole 5 days. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 12 hours<br>The participant will be cooled to 33°Celsius (C) for 12 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 18 hours<br>The participant will be cooled to 33°C for 18 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 24 hours<br>The participant will be cooled to 33°C for 24 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 36 hours<br>The participant will be cooled to 33°C for 36 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 48 hours<br>The participant will be cooled to 33°C for 48 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 60 hours<br>The participant will be cooled to 33°C for 60 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 72 hours<br>The participant will be cooled to 33°C for 72 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 84 hours<br>The participant will be cooled to 33°C for 84 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|
| Experimental: Cooling 96 hours<br>The participant will be cooled to 33°C for 96 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day. | Device: Therapeutic Hypothermia<br>* Participants will receive therapeutic hypothermia for the assigned number of hours with controlled rewarming, A zero hour cooling duration (normothermia) treatment arm will be opened for enrollment if there is not an increase in the treatment effect across the durations. Alternatively, longer durations (84 or 96 hours) will be opened for enrollment if the treatment effects are increasing (rather than plateauing or decreasing) through 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scales - Third Edition (VABS-3) Mortality Composite Score at 12 months after return of spontaneous circulation | The VABS-3 score, designed to be administered to surviving children with any level of function including comatose status to age-appropriate neurobehavioral functioning, ranges from 20 to 140 with age-corrected standardized mean and standard deviation of 100 and 15, respectively. Deaths will be scored as 0 in this trial. | 12 months after out-of-hospital cardiac arrest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pediatric Cerebral Performance Category (PCPC) at 12 months from baseline | The Pediatric Cerebral Performance Category is a global scale based on observer impressions. It's a six point graded scale of increasing disability from 1 normal function, to 6 death. Scores include 1 for good, 2 for mild disability, 3 for moderate disability, 4 for severe disability, and 5 for vegetative state or coma. Higher scores indicating worse performance or functional morbidity. | Baseline and 12 months after cardiac arrest | 
| Pediatric Resuscitation after Cardiac Arrest (PRCA) at 12 months | The PRCA adapted from the Pediatric Stroke Outcome measure, ranges from 0-21 where lower scores indicate less impairment. Deaths will be assigned the worst score of 21 for PRCA. | 12 months after cardiac arrest | 
| Survival at 12 months |  | 12 months after cardiac arrest | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric