Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Conditions
Keywords
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric
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.
Interventions
DEVICETherapeutic 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.
Sponsors
University of Michigan
National Heart, Lung, and Blood Institute (NHLBI)
Kennedy Krieger Institute, Baltimore, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcomes assessors will be blinded to the treatment assignment of the participant.
Intervention model description
Bayesian Adaptive Design
Eligibility
Sex/Gender
ALL
Age
2 Days to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Australia, Canada, New Zealand, United Kingdom, United States
Contacts
CONTACTFrank Moler, MD
CONTACTMoni Weber
PRINCIPAL_INVESTIGATORFrank Moler, MD
University of Michigan
PRINCIPAL_INVESTIGATORAlex Topjian, MD
Children's Hospital of Philadelphia
PRINCIPAL_INVESTIGATORWilliam Meurer, MD
University of Michigan
Outcome results
None listed