Hypothermia for Severe TBI in Children

描述(申请人提供)：虽然创伤性脑损伤(TB1)仍然是儿童死亡和残疾的主要原因，但迄今为止大多数儿童脑损伤的治疗方案都来自成人研究。利用中等低温(32-33xC)作为一种模式干预，于1999年7月在儿童脑外伤后启动了一项试点临床试验，“以获得初步数据并进行研究，以支持随后进行全面临床试验的理论基础”。在试点成功的鼓舞下，本提案的目的是为严重脑外伤后儿童体温过低的第三阶段临床试验进行下一步的“规划”。第三阶段试验计划的主要假设是，在儿童严重脑外伤后诱导中等低温(32-33xC)并维持48小时将改善儿童6个月和12个月的功能结果。次要假设将包括：1)与延迟降温(6-24小时)相比，早期开始降温(6小时内)儿童重型颅脑损伤后48小时的诱导亚低温将改善长期预后；2)这种治疗将减轻控制颅内压所需的治疗强度；以及3)改善功能结果的评估，包括：死亡率、神经心理测试结果和功能领域(学习、记忆、语言、行为和运动)。我们进一步假设，这种治疗将改善青春期前和青春期儿童中所有年龄段和不同性别的结果。这项临床试验计划提案的总体目标是开发旨在提交一项精心设计、科学有效的多中心、随机对照的“儿童重型颅脑损伤的低温治疗”的第三阶段试验。具体目标包括：1)与以前的PI联盟成员和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、实验方案和操作材料，以证明、实施和撰写计划中的不同年龄段儿童严重脑损伤后的中度低温(32-33xC)第三阶段试验，并确定在一个规划年度内对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使用。

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.