Hypothermia for Severe TBI in Children

描述（由申请人提供）：虽然创伤性脑损伤（TB 1）仍然是儿童死亡和残疾的主要原因，但迄今为止，大多数TBI的儿科治疗方案都来自成人研究。 利用中度低温（32- 33 xC）作为模型干预，于1999年7月启动了一项初步临床试验，以“获得初步数据并进行研究，以支持随后在TBI后儿童中进行全面临床试验的基本原理”。 由于试验计划取得成功，本建议的目的是为儿童严重创伤后体温下降的第三期临床试验进行下一步“规划”。 III期试验计划的主要假设是，儿童重度TBI后诱导中度低温（32- 33 xC）并维持48小时将改善儿童6个月和12个月的功能结局。 次要假设将包括：（1）冷却的早期开始与延迟冷却相比，儿童严重TBI后48小时（6小时内）的诱导中度低温将改善长期结局（6-24小时）; 2）这种治疗将减轻控制ICP所需的治疗强度;和3）改善功能结局的评估，包括：死亡率、通过神经心理学测试和功能领域（学习、记忆、语言、行为和运动）测量的结果。 我们进一步假设，这种治疗将改善所有年龄组和性别的青春期前和青春期儿童的结局。 本临床试验计划提案的总体目标是开发并提交一项设计良好、科学有效的多中心、随机对照III期试验“低温治疗儿童重度TBI”。 具体目标包括：1）与来自先前PI联合体的成员以及邀请的专家顾问一起，开发和整理必要的科学背景、初步数据、实验方案和论证、实施、以及计划中的中度低温（32- 33 xC）的III期试验的写作在不同年龄段的儿童严重TBI后，并确定在一个计划年内对6个月和12个月结果的影响; 2）利用我们现有的专业知识和不断扩大的基于网络的软件和数据的利用。

DESCRIPTION (provided by applicant): 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 include: 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.