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

Sponsor

University of Michigan (Other)

Overall Status

Recruiting

CT.gov ID

NCT05376267

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), Kennedy Krieger Institute, Baltimore, MD (Other)

900

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest, Out-Of-Hospital Hypothermia, Induced Hypoxia-Ischemia, Brain	Device: Therapeutic Hypothermia	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

900 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Bayesian Adaptive DesignBayesian 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:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2029

Anticipated Study Completion Date :

Jul 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cooling 0 hours Participants will be kept at a normal temperature for the whole 5 days.	Device: Therapeutic Hypothermia 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.
Experimental: Cooling 12 hours 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 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.
Experimental: Cooling 18 hours 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 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.
Experimental: Cooling 24 hours 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 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.
Experimental: Cooling 36 hours 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 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.
Experimental: Cooling 48 hours 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 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.
Experimental: Cooling 60 hours 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 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.
Experimental: Cooling 72 hours 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 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.
Experimental: Cooling 84 hours 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 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.
Experimental: Cooling 96 hours 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 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.

Outcome Measures

Primary Outcome Measures

Vineland Adaptive Behavior Scales - Third Edition (VABS-3) Mortality Composite Score at 12 months after return of spontaneous circulation [12 months after out-of-hospital cardiac arrest]
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.

Secondary Outcome Measures

Change in Pediatric Cerebral Performance Category (PCPC) at 12 months from baseline [Baseline and 12 months after cardiac arrest]
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.
Pediatric Resuscitation after Cardiac Arrest (PRCA) at 12 months [12 months after cardiac arrest]
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.
Survival at 12 months [12 months after cardiac arrest]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Days to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham / Children's of Alabama	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Loma Linda University Children's Hospital	Loma Linda	California	United States	92354
4	Memorial Health - Miller Children's and Women's Hospital of Long Beach	Long Beach	California	United States	90806-1701
5	University of California Los Angeles (UCLA) Mattel Children's Hospital	Los Angeles	California	United States	90095
6	University of California - Oakland / UCSF Benoiff Children's Hospital Oakland	Oakland	California	United States	94609
7	Children's Hospital of Orange County	Orange	California	United States	92868-4203
8	University of California, Davis	Sacramento	California	United States	95817
9	University of California - San Francisco (UCSF) Benioff Children's Hospital San Francisco	San Francisco	California	United States	94158
10	Stanford	Santa Clara	California	United States	95050
11	University of Florida (UF) Health Shands Children's Hospital	Gainesville	Florida	United States	32610-0296
12	University of Miami	Miami	Florida	United States	33124
13	Ann & Robert Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
14	Children's Hospital of Illinois	Peoria	Illinois	United States	61637
15	Riley Children's Health	Indianapolis	Indiana	United States	46202
16	University of Iowa, Carver College of Medicine	Iowa City	Iowa	United States	52242
17	University of Maryland Children's Hospital	Baltimore	Maryland	United States	21201
18	Johns Hopkins Medicine Children's Center	Baltimore	Maryland	United States	21287
19	MassGeneral Hospital for Children	Boston	Massachusetts	United States	02114
20	University of Michigan CS Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
21	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
22	University of Minnesota Fairview Masonic Children's Hospital	Minneapolis	Minnesota	United States	55454
23	Washington University / St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
24	University of Buffalo / Oishei Children's Hospital	Buffalo	New York	United States	14203
25	Cohen Children's Medical Center of NY / Northwell Health	New Hyde Park	New York	United States	11040
26	Mount Sinai Icahn / Kravis Children's Hospital	New York	New York	United States	10029
27	University of Rochester Medical Center	Rochester	New York	United States	14642-8667
28	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7220
29	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
30	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
31	Ohio State University / Nationwide Children's Hospital	Columbus	Ohio	United States	43205
32	Oregon Health & Science University Doernbecher Children's Hospital	Portland	Oregon	United States	97239
33	Penn State University / Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
34	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
35	Children's Hospital of Pittsburgh (UPMC)	Pittsburgh	Pennsylvania	United States	15224
36	University of Tennesses Health Center / Le Bonheur Children's	Memphis	Tennessee	United States	38104
37	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
38	Texas Children's Hospital, Baylor	Houston	Texas	United States	77030
39	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
40	Primary Children's Hospital, University of Utah School of Medicine	Salt Lake City	Utah	United States	84108
41	Children's Wisconsin	Milwaukee	Wisconsin	United States	53226
42	University of Alberta / Stollery Children's Hospital	Edmonton	Alberta	Canada
43	The Hospital for Sick Children	Toronto	Ontario	Canada
44	McGill University Hospital	Montréal	Quebec	Canada
45	Birmingham Children's Hospital, United Kingdom	Birmingham		United Kingdom