THAPCA Trials - Scientific Application

THAPCA 试验 - 科学应用

• 批准号: 8431699
• 负责人: FRANK W MOLER
• 金额: $ 202.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-09 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431699
• 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

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）： 心肺逮捕（CA）是一个悲剧性事件，通常与所有年龄段的高死亡率和较差的生活质量有关。幸存下来的儿童通常会维持神经损伤，这可能导致多年的护理各个方面的依赖。小儿CA的病理生理学和结果在院外发生（OH），通常在健康的儿童中，而发生的院内（IH）（通常是在患有复杂的基础疾病的儿童中）之间的病理生理学和结果差异很大。对于两组维持小儿大约的疗法都非常需要神经性治疗疗法。最近，患有OH心室纤颤或心动过速的成年人的里程碑标记RCT以及与出生相关的新生儿相关的缺血性缺血性脑病的新生儿表现出了在六个小时内恢复到六个小时的回报或出生或出生或出生或出生或出生后的六个小时后，具有良好的神经学结局的生存率得到了改善。但是，CA跨年龄段的病因和病理生理学存在主要不同，而新生儿和成年人的结果不能推断给儿童。在儿科（非新生）CA人群中尚未进行TH的RCT。现在迫切需要RCT来指导小儿练习。自2002年以来，我们的调查团队一直合作，并将两个联邦资助的小儿临床研究网络（Pecarn和CPCCRN）汇总在一起，在儿科心脏骤停（THAPCA）试验后进行治疗低温。 THAPCA试验的主要目标是确定在OH（Thapca-OH试验）和IH（Thapca-IH试验）环境中CA后复活的儿童中，TH是否可以提高生存率。 Vineland自适应行为量表将用作评估幸存者中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，神经行为功能从逮捕前基线变为12个月的测量，以及CA后12个月的神经心理学和神经系统异常评分。我们还将通过评估全因28天死亡率，感染的发病率，心律不齐和血液产品给药的安全性来确定TH的安全性。最后，我们将分析包括血清神经元特异性烯醇酶（NSE），磁共振成像（MRI）和脑电图（EEG）（EEG）的替代指标，并将从参加试验的受试者中收集DNA。 DNA将存储在未来研究的存储库中，以鉴定可能与缺氧缺血性损伤的可疑性和/或对治疗性低温的反应性有关的遗传多态性。 THAPCA试验将是针对儿童的重要公共卫生适用性的开创性研究。 Thapca将确定在OH或IH环境中持续CA的儿童中的良好功能结果是否会提高生存率。 Thapca与NHLBI的任务高度相关，并补充了NHLBI复苏结果联盟（ROC）。 Thapca将通过在儿童期进行与CA相关的第一个主要RCT来解决知识的关键差距。儿童心脏骤停是一个悲惨的事件，通常会导致死亡或严重的脑损伤。 Thapca试验是确定心脏骤停儿童的整个身体冷却是否会导致更好的生存和减少脑损伤的研究。