Hypothermia in Children After Trauma

Study Overview
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Brief Summary
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The primary hypothesis for this application for a multicenter phase III randomized clinical trial (RCT) is that induced moderate hypothermia (HYPO) (32-33 °C) after severe traumatic brain injury (TBI) in children and maintained for 48 hours will improve mortality at 3 months and 12 month functional outcome as assessed by the Glasgow Outcome Scale (GOS).

Detailed Description
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The primary specific aim of this RCT is to determine the effect of induced moderate HYPO (32-33 °C) after severe TBI in children on mortality at 3 months post injury. The primary outcome measure will be the GOS; the primary time point for evaluation is 3 months. Further secondary functional outcome measures will include the GOS - Extended Pediatrics (GOS - E Peds), and Vineland Adaptive Behavior Scale (VABS) and will be assessed in conjunction with the GOS at 6 and 12 months post injury. The secondary hypotheses are based on the results and analysis of the Pilot Clinical Trial (completed and recently published [Adelson et al. NEUROSURGERY. 56 (4): 740-754, 2005]). These secondary hypotheses include that induced moderate hypothermia (HYPO) (32-33 °C) after severe TBI in children and maintained for 48 h: will improve other outcome assessments including neurocognitive status on performance-based neuropsychological testing across the domains of intellectual development, learning and memory, language, motor and psychomotor skills, visuo-spatial abilities, attention and executive function, and behavior at only 6 and 12 months after injury; HYPO will improve long term outcome of all age ranges and across genders in infants, young, preadolescent, and adolescent children; AND HYPO will lessen intracranial hypertension and lessen the intensity of therapy necessary for control of ICP. Based on these hypotheses, further secondary specific aims are proposed: Specific Aim 2: To determine the effect of early induced moderate HYPO (32-33°C) after severe TBI in children on global function and neurocognitive outcomes in the areas of intellectual ability/ development, memory and learning, and behavior at 6 and 12 months post injury. Specific Aim 3: To determine the effect of early induced moderate HYPO after severe TBI in children of different age ranges (< 6 y and 6- < 16 y) on mortality and 6 and 12 months functional and neurocognitive outcomes. Specific Aim 4: To determine the effect of early moderate HYPO after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).

Official Title
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Pediatric Traumatic Brain Injury Consortium: Hypothermia

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Procedure: induced moderate hypothermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a GCS </= 8 Glasgow Motor Score < 6 Closed head injury Age 0 < 18 y Exclusion Criteria Unavailable to initiate cooling within 6 hours of injury Glasgow Coma Scale (GCS) score = 3 and abnormal brainstem function Normal initial CT scan (No blood, fracture, swelling, and/or shift) Penetrating brain injury No known mechanism of injury Unknown time of injury Uncorrectable coagulopathy (PT/PTT > 16/40 sec, INR > 1.7) Hypotensive episode (Systolic Blood Pressure <5th percentile for age>10 min) Documented Hypoxic episode (O2 saturation < 94% for > 30 min) Pregnancy

Ages Eligible for Study
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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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Induced moderate hypothermia (32-33 C) | Procedure: induced moderate hypothermia<br>* Subjects assigned to the treatment arm will be cooled to 32-33 °C for 48 hours and then slowly warmed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary specific aim of this RCT is to determine the effect of induced moderate HYPO (32-33 °C) after severe TBI in children on mortality. |  | 3 month post injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of HYPO after severe TBI in children on global function and neurocognitive outcomes in the areas of intellectual ability/development, memory and learning, and behavior. |  | at 6 and 12 months post injury | 
| To determine the effect of HYPO after severe TBI in children of different age ranges (< 6y; 6-<16y; and 16-<18y) on mortality and 6 and 12 months functional and neurocognitive outcomes. |  | 3, 6 and 12 months post injury | 
| To determine the effect of HYPO after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP). |  | 7 days post injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypothermia, pediatric TBI