Pediatric Traumatic Brain Injury Consortium: Hypothermia

儿科创伤性脑损伤联盟：体温过低

基本信息

批准号：
7198415
负责人：
P. David ADELSON
金额：
$ 202.41万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-15 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7198415
关键词：
Acute Adolescent Adult Age Appendix Area Behavior Cause of Death Cerebral perfusion pressure Child Childhood Childhood Injury Clinical Clinical Data Clinical Research Clinical Treatment Clinical Trials Controlled Clinical Trials Critical Care Critiques Data Development Duct (organ) structure Funding Futility Future Glasgow Outcome Scale Goals Grant Guidelines Head Hospitals Hour Hypoxia Injury Intervention Intracranial Hypertension Investigation Ischemic Brain Injury Laboratory Study Learning Managed Care Manuals Measures Medical Memory Modeling NCI Consortium or Network Neurocognitive Numbers Outcome Outcome Assessment Outcome Measure Outcomes Research Patients Pediatrics Performance Personal Communication Phase Planet Mars Population Principal Investigator Progress Reports Publishing Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Range Recovery Regulation Research Research Infrastructure Research Personnel Safety Temperature Testing Therapeutic Training Traumatic Brain Injury Treatment Efficacy Treatment Protocols United States National Institutes of Health Update Vision age related base disability immature animal improved infant brain injury man mortality natural hypothermia novel pre-clinical programs response success trend young adult

项目摘要

DESCRIPTION (provided by applicant): Despite preventative measures, traumatic brain injury (TBI) remains the leading cause of death and disability in children. While most pediatric treatment regimens for TBI to date are derived from adult studies, no therapeutic regimen has been particularly successful in improving outcome in children. There have been numerous laboratory studies utilizing moderate hypothermia (HYPO) (32-33¿C) in mature and immature animals, successful Phase II and III clinical studies in adult patients for 24 to 48 h after TBI, and a number of trials in children of HYPO following hypoxia-ischemic (HIE) brain injuries that have supported the efficacy of this intervention. The most recently published trial of treatment with HYPO for HIE within 6 hours showed significant improvement in outcome, particularly in mortality, as compared to severe disability. While the multi-center Phase III randomized controlled clinical trial (RCT) of moderate HYPO in adults was stopped early due to futility but not lack of efficacy, the secondary analysis did highlight that younger adult patients (< 40 y) tended toward improved outcome compared to older subjects. This finding along with a trend toward improved outcomes with early cooling (< 6 h) has resulted in a funded HYPO RCT specifically inclusive of patients ages 16- 45 y and early pre-hospital cooling that has recently begun. Based on the results from our Pilot Clinical Trial (PCT) utilizing moderate HYPO following severe TBI in children, the following application is for a multicenter Phase III RCT to determine whether induced early cooling (within 6 h) (32-33¿C) after severe TBI in children and maintained for 48 h will improve mortality at 3 mos post injury as compared to normothermia (37- 38¿C). The Secondary Hypotheses, again based on the analysis of the PCT, are that early HYPO after severe TBI in children and maintained for 48 h: 1) will improve global function as measured by the GOS/ GOS- Extended Pediatrics (GOS- E Peds) and neurocognitive status across the domains of intellectual development, learning and memory, and behavior at 6 and 12 mos after injury; 2) will be more effective in younger children < 6 y compared to older children, > 6y, and 3) will lessen intracranial hypertension and the intensity of therapy necessary for control of ICP.

描述（由适用提供）：尽管进行了预防测量，但创伤性脑损伤（TBI）仍然是儿童死亡和残疾的主要原因。尽管迄今为止，大多数TBI的小儿治疗方案来自成人研究，但没有治疗方案在改善儿童的预后特别成功。在成熟和不成熟的动物中使用中度低温（HYPO）（HYPO）（HYPO）（32-33？c）进行了许多实验室研究，在TBI后为成年患者进行了成功的II和III期临床研究，在TBI后24至48小时，在缺血性脑损伤后进行了多项试验，这些试验支持了这种练习的效率。与严重的残疾相比，最近发表的最新发表的HIE治疗试验在6小时内显示了预后，尤其是死亡率的显着改善。尽管成人中度低调的多中心III期随机对照临床试验（RCT）由于能量而早期停止，但并非缺乏效率，但次级分析确实强调，与老年受试者相比，年轻的成年患者（<40 Y）倾向于改善结果。这一发现以及通过早期冷却（<6 h）改善结局的趋势，导致了资助的降低RCT，特别包括16-45岁的患者和最近开始的疗医院前冷却。根据我们的试验临床试验（PCT）的结果，使用中度降低了儿童的严重TBI，以下应用是多中心III期RCT来确定儿童严重TBI后诱导的早期冷却（6 h）（32-33¿C）是否在儿童身后进行了48小时，并保持48 h的死亡率和在3个MOS后的死亡率相比，与NORM horm hormothermia相比会提高死亡的死亡率（37-38-38-38-38-38-38-38。次要假设再次基于对PCT的分析，是在儿童严重TBI之后的早期低调，并维持48 h：1）将改善全球功能，这将通过GOS/ GOS/ GOS扩展的儿科（GOS-E PED）（GOS-E PED）（GOS-E PED）和神经认知状态在6和12受伤的智力发展，记忆和行为的范围内，在6和12的范围内进行了神经认知状态； 2）与年龄较大的儿童相比，在<6 y的年幼儿童中，> 6岁和3）将更有效，而颅内高血压和控制ICP所需的治疗强度将更少。