THAPCA Trials - Scientific Application

THAPCA 试验 - 科学应用

基本信息

批准号：
8137950
负责人：
FRANK W MOLER
金额：
$ 312.8万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-09 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8137950
关键词：
Accident and Emergency department Adaptive Behaviors Address Adult Adverse event Apnea Arrhythmia Birth Blood Circulation Brain Injuries Brain imaging Cardiopulmonary Arrest Caring Cessation of life Child Childhood Clinical Research Clinical Trials Complement Complex DNA Dependency Disease Electroencephalogram Enrollment Etiology Event Functional disorder Funding Future Genetic Polymorphism Grant Heart Arrest Hospitals Hour Hypoxia Incidence Infection Injury Intensive Care Knowledge Magnetic Resonance Imaging Measurement Measures Mission National Heart, Lung, and Blood Institute Nervous System Trauma Neurologic Neurological outcome Neuron-Specific Enolase Newborn Infant Outcome Palpable Pattern Physiologic pulse Population Predictive Value Predisposition Public Health Quality of life Rehabilitation therapy Research Personnel Resuscitation Safety Seminal Serum Site Surveys Survivors Testing Therapeutic United States National Institutes of Health Ventricular Fibrillation Ventricular Tachycardia Work age group blood product functional outcomes improved mortality natural hypothermia neonatal hypoxic-ischemic brain injury neonate neurobehavioral neuropsychological repository

项目摘要

DESCRIPTION (provided by applicant): Cardiopulmonary arrest (CA) is a tragic event that is often associated with high mortality and poor quality of life outcome in all age groups. Children who survive CA commonly sustain neurological injury that potentially results in many years of dependency for all aspects of care. The pathophysiology and outcome of pediatric CA differs greatly between those that occur out-of-hospital (OH), commonly in healthy children, and those that occur in-hospital (IH), typically in children with complex underlying disorders. There is a great need for neuroprotec- tive therapies for both groups sustaining pediatric CA. Recently, landmark RCTs in adults with OH ventricular fibrillation or tachycardia associated CA and in newborns with birth associated hypoxic ischemic encephalopathy have demonstrated improved survival with good neurological outcome after therapeutic hypothermia (TH) when initiated within six hours of return of return of spontaneous circulation or birth. There are, however, major differ- ences in the etiology and pathophysiology of CA across age groups, and results in neonates and adults cannot be extrapolated to children. No RCT of TH has been performed in the pediatric (non-newborn) CA population. RCTs are now urgently needed to guide pediatric practice. Our investigative team has worked together since 2002 and has brought together two federally funded pediatric clinical research networks (PECARN and CPCCRN) to conduct the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Trials. The primary objective of the THAPCA Trials will be to determine if TH improves survival with good neurobehavioral outcome in children who have been resuscitated after CA in the OH (THAPCA-OH Trial) and IH (THAPCA-IH Trial) settings. The Vineland Adaptive Behavior Scales will be used as the primary measure to assess neurobehavioral outcome in survivors. Secondary endpoints include survival at 12 months post CA, change in neurobehavioral function from pre-arrest baseline to the 12-month measurement, and neuropsychological and neurological abnormality scores at 12 months post CA. We will also determine the safety of TH by assessing all-cause 28-day mortality, incidence of infections, arrhythmias, and blood product administration within 7 days of CA. Finally, we will analyze surrogate indicators of brain injury including serum neuron specific enolase (NSE), magnetic resonance imaging (MRI), and electroencephalograms (EEG), and will collect DNA from subjects enrolled in the trials. DNA will be stored in a repository for future studies to identify genetic polymorphisms that may be associated with altered suscep- tibility to hypoxic-ischemic injury and/or responsiveness to therapeutic hypothermia. The THAPCA Trials will be seminal studies with important public health applicability in children. THAPCA will establish whether TH results in improved survival with good functional outcome in children who have sustained CA in the OH or IH setting. THAPCA is highly relevant to the mission of the NHLBI, and complements the NHLBI Resuscitation Outcomes Consortium (ROC). THAPCA will address critical gaps in knowledge by conducting the first major RCT related to CA in childhood. Cardiac arrest in children is a tragic event that often results in death or severe brain injury. The THAPCA Trials are studies that will determine whether whole body cooling of children who have had cardiac arrest will result in better survival and less brain injury.

描述（由申请人提供）：心肺骤停（CA）是一种悲剧事件，通常与所有年龄段的高死亡率和低生活质量相关。存活下来的 CA 儿童通常会遭受神经损伤，这可能会导致多年来对各方面护理的依赖。儿科 CA 的病理生理学和结果在院外 (OH)（通常发生在健康儿童中）和院内 (IH)（通常发生在患有复杂基础疾病的儿童中）之间存在很大差异。对于维持儿科 CA 的两组患者来说，都非常需要神经保护疗法。最近，针对患有 OH 心室颤动或心动过速相关 CA 的成人以及患有出生相关缺氧缺血性脑病的新生儿的里程碑式随机对照试验表明，在恢复自主循环或恢复后 6 小时内开始治疗性低温 (TH) 后，可提高生存率并具有良好的神经学结果。诞生。然而，不同年龄组的CA的病因和病理生理学存在重大差异，新生儿和成人的结果不能推断到儿童。尚未在儿科（非新生儿）CA 人群中进行 TH 的随机对照试验。现在迫切需要随机对照试验来指导儿科实践。我们的调查团队自 2002 年以来一直合作，汇集了两个联邦资助的儿科临床研究网络（PECARN 和 CPCCRN），开展小儿心脏骤停后低温治疗 (THAPCA) 试验。 THAPCA 试验的主要目标是确定 TH 是否可以提高在 OH（THAPCA-OH 试验）和 IH（THAPCA-IH 试验）环境中 CA 后复苏的儿童的生存率并获得良好的神经行为结果。瓦恩兰适应性行为量表将用作评估幸存者神经行为结果的主要措施。次要终点包括 CA 后 12 个月的生存率、神经行为功能从逮捕前基线到 12 个月测量值的变化，以及 CA 后 12 个月的神经心理和神经异常评分。我们还将通过评估全因 28 天死亡率、感染发生率、心律失常以及 CA 7 天内的血液制品使用情况来确定 TH 的安全性。最后，我们将分析脑损伤的替代指标，包括血清神经元特异性烯醇化酶 (NSE)、磁共振成像 (MRI) 和脑电图 (EEG)，并收集参加试验的受试者的 DNA。 DNA将被存储在一个存储库中，以供未来研究识别可能与缺氧缺血性损伤易感性改变和/或对低温治疗反应性改变相关的遗传多态性。 THAPCA 试验将是具有重要公共卫生适用性的开创性研究。 THAPCA 将确定 TH 是否会提高 OH 或 IH 环境下患有 CA 的儿童的生存率并获得良好的功能结果。 THAPCA 与 NHLBI 的使命高度相关，并且是对 NHLBI 复苏结果联盟 (ROC) 的补充。 THAPCA 将通过开展第一个与儿童 CA 相关的大型随机对照试验来解决关键的知识差距。儿童心脏骤停是一种悲惨事件，通常会导致死亡或严重脑损伤。 THAPCA 试验将确定对心脏骤停儿童进行全身冷却是否会带来更好的生存率和更少的脑损伤。