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 TBI in children and maintained for 48 h will improve mortality, and 12 month functional outcome as assessed by the Glasgow Outcome Scale (GOS).

Condition	Intervention	Phase
Traumatic Brain Injury	Procedure: induced moderate hypothermia	Phase III

Further Study Details: 

Primary Outcomes: The Primary Specific Aim (Specific Aim 1) of this RCT is to determine the effect of induced moderate HYPO (32-33°C) after severe TBI in children on mortality and functional outcome (GOS) at 12 months post injury. The primary outcome measure will be the G
Secondary Outcomes: 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]).
Expected Total Enrollment:  410

The Primary Specific Aim (Specific Aim 1) of this RCT is to determine the effect of induced moderate HYPO (32-33°C) after severe TBI in children on mortality and functional outcome (GOS) at 12 months post injury. The primary outcome measure will be the GOS; the primary time point for evaluation is 12 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 3, 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: 1) 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; 2) HYPO will improve long term outcome of all age ranges and across genders in infants, young, preadolescent, and adolescent children; and 3) 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 induced moderate HYPO (32-33°C) after severe TBI in children on neurocognitive outcomes at 6 and 12 months post injury and treatment;

Specific Aim 3 To determine the effect of induced moderate HYPO (32-33°C) after severe TBI in children of different age ranges on mortality and 3, 6 and 12 months functional and neurocognitive outcomes;

Specific Aim 4 To determine the effect of induced moderate HYPO (32-33°C) after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).

Ages Eligible for Study:  up to  17 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Patients with a GCS < 8, either prior to or after admission
2. Glasgow Motor Score < 6
3. Close head injury
4. Age 0 – < 17 y (204 mos)
5. Available to initiate cooling including informed consent within 8 h of injury

Exclusion Criteria:(No exclusions will be based on gender or ethnicity.)

1. Normal CT scan
2. Penetrating Brain Injury
3. Brain Dead on Admission to ED
4. Failure to Obtain Informed Consent > 8 h from injury
5. Uncorrectable Coagulopathy (PT/PTT >16/40 sec, INR >1.7)
6. Hypotensive episode defined as Systolic Blood Pressure < 5th percentile for age > 10 min
7. Hypoxia episode defined as O2 saturation < 94% for > 30 min. post resuscitation
8. Follow up unlikely (e.g., distance from treating center, illegal alien, etc.)
9. Pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00222742

P. David Adelson, MD      412-692-6347    david.adelson@chp.edu
S. Danielle Brown, RN, MS      412-692-8794 

Pennsylvania
      University of Pittsburgh/Children''''s Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States

Study chairs or principal investigators

P. David Adelson, MD,  Principal Investigator,  University of Pittsburgh   

Study ID Numbers:  1R01-NS052478-01; 1R01NS052478-01
Last Updated:  September 21, 2005
Record first received:  September 16, 2005
ClinicalTrials.gov Identifier:  NCT00222742
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-27