Though traumatic brain injury (TB1) remains the leading cause of death and disability in children, most all pediatric treatment regimens for TBI to date are derived from adult studies. Utilizing moderate hypothermia (32-33xC) as a model intervention, a Pilot Clinical Trial was initiated in July 1999 """"""""to obtain preliminary data and conduct studies to support the rationale for a subsequent full-scale clinical trial"""""""" in children after TBI. Encouraged by the success of the Pilot, the purpose of the present proposal is to take the next step in """"""""planning"""""""" for the Phase III clinical trial of Hypothermia for Children following Severe TBI. The Primary Hypothesis planned for the Phase III trial is that induced moderate hypothermia (32-33xC) after severe TBI in children and maintained for 48 hours will improve 6- and 12-month functional outcome in children. Secondary Hypotheses will include: 1) that early initiation of cooling (within 6 hours) of 48 hours of induced moderate hypothermia after severe TBI in children will improve long term outcome as compared to delayed cooling (6-24 hours); 2) that this treatment will lessen the intensity of therapy necessary for control of ICP; and 3) improve assessments of functional outcome including: mortality, outcome as measured by neuropsychological testing and domains of function (learning, memory, language, behavior and motor). We further postulate that this treatment will improve outcome across all age groups and across genders in preadolescent and adolescent children. The Overall Aim of this Clinical Trials Planning Proposal is to develop with the intention to submit a well-designed, scientifically valid multi-center, randomized controlled Phase III trial of """"""""Hypothermia for Severe TBI in Children"""""""".
The specific aims i nclude: 1) With members from the previous consortium of PI's and the addition of invited expert consultants, to develop and collate the requisite scientific background, preliminary data, experimental protocols, and operational materials necessary for the justification, implementation, and the writing of the planned Phase III trial of moderate hypothermia (32-33xC) after severe TBI in children of different age ranges and determine the effect on 6 and 12 month outcome during the one planning year; 2) Utilizing our present expertise and the ever expanding utilization of web based software and data. ? ?
