1/2 ICECAP: Influence of Cooling duration on Efficacy in Cardiac Arrest Patients

1/2 ICECAP：冷却时间对心脏骤停患者疗效的影响

• 批准号: 10477427
• 负责人: Romergryko Geocadin
• 金额: $ 610.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477427
• 关键词: Accident and Emergency department; Adult; Adverse event; Affect; Assessment tool; Brain; Brain Injuries; Cardiac; Cardiopulmonary Resuscitation; Categories; Cerebral Ischemia; Cessation of life; Clinical; Clinical Trials; Coma; Data; Development; Devices; Dose; Emergency Situation; Enrollment; Evaluation; Goals; Guidelines; Heart; Heart Arrest; Hospitals; Infrastructure; Injury; Left; Link; Methods; Neurologic; Neurological emergencies; Neurological outcome; Neuropsychology; Outcome; Outcome Assessment; Patient Selection; Patient-Focused Outcomes; Patients; Performance; Population; Quality of life; Randomized; Recommendation; Recovery; Reporting; Resources; Safety; Selection Criteria; Survivors; Talents; Temperature; Therapeutic; United States National Institutes of Health; clinical investigation; clinical practice; disability; improved; improved outcome; innovation; natural hypothermia; neurological recovery; out-of-hospital cardiac arrest; patient population; pre-clinical; response; treatment effect

7. Project Summary/Abstract . Cardiac arrest is a common and devastating emergency of the heart and the brain. More than 380,000 patients suffer out of hospital cardiac arrest (OHCA) each year in the US. Improvements in cardiac resuscitation (the early links in the “chain of survival” for patients with OHCA) are tempered by our limited ability to resuscitate and protect the brain from global cerebral ischemia. Neurological death and disability are common outcomes in survivors of cardiac arrest. Therapeutic cooling of comatose patients resuscitated from shockable rhythms may markedly increase the rate of good neurological outcome, but poor outcomes still occur in as many as 50%, and the benefit of cooling in those resuscitated from asystole and pulseless electrical activity has not been evaluated in a randomized study. Even in patients with shockable rhythms, prior trials showing efficacy have been questioned. Therapeutic cooling is already a guideline-recommended and commonly used treatment in comatose survivors of cardiac arrest, but because of limited data, the optimal duration and patient selection criteria remain unknown and cooling devices are not FDA approved for this indication. Preclinical data and mechanistic studies strongly suggest that durations of hypothermia longer than those typically used may minimize brain injury. This study will determine if identifying an optimal duration of therapeutic hypothermia can improve outcomes, and if development of a duration response curve can substantiate efficacy in a wider patient population of cardiac arrest survivors. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having good outcome. The overarching goal of this project is to identify clinical strategies that will increase the number of patients with good neurological recovery from cardiac arrest. The results of this trial will be immediately significant, impacting both clinical practice and regulatory evaluation. The trial uses innovative adaptive dose finding methods that allow exploration of a wide range of potential durations and efficiently allocate subjects where they will be most informative. The study methods also include innovative approaches to traditional outcome assessment and innovative outcome assessment tools, including the NIH Toolbox. The study will be conducted in the NIH SIREN Emergency Clinical Trials infrastructure. SIREN leverages existing resources to achieve economies of scale, maintain talented rapidly responding teams to screen and enroll subjects in the emergency department setting, and to continue clinical investigations through the ICU stay and beyond with proven performance.

7. 项目总结/摘要。 心脏骤停是一种常见且具有破坏性的心脏和大脑紧急情况。超过38万 在美国，每年都有患者出现院外心脏骤停 (OHCA)。心脏功能改善 复苏（OHCA 患者“生存链”的早期环节）受到我们有限的影响 复苏和保护大脑免受全脑缺血的能力。神经性死亡和残疾是 心脏骤停幸存者的常见结果。昏迷患者复苏后的治疗性降温 可电击节律可能会显着提高良好神经学结果的发生率，但仍会导致不良结果 发生率高达 50%，对于那些从心搏停止和无脉复苏中复苏的患者来说，冷却的好处 尚未在随机研究中评估电活动。即使对于心律可电击的患者，事先 显示疗效的试验受到质疑。治疗性降温已成为指南推荐的方法 心脏骤停昏迷幸存者的常用治疗方法，但由于数据有限，最佳治疗方法 持续时间和患者选择标准仍然未知，且冷却设备未获得 FDA 批准用于此目的 指示。临床前数据和机制研究强烈表明，低温持续时间长于 通常使用的那些可以最大限度地减少脑损伤。这项研究将确定是否确定最佳持续时间 低温治疗可以改善结果，如果持续反应曲线的发展可以 在更广泛的心脏骤停幸存者患者群体中证实了疗效。我们假设更长的时间 冷却持续时间可能会提高获得良好神经功能恢复的患者比例，或者 可能会导致已经归类为具有良好结果的比例得到更好的恢复。这 该项目的总体目标是确定临床策略，以增加患有该病的患者数量 心脏骤停后神经系统恢复良好。这项试验的结果将立即产生重大影响， 影响临床实践和监管评估。该试验采用创新的自适应剂量发现 允许探索广泛的潜在持续时间并有效分配受试者的方法 他们将提供最丰富的信息。研究方法还包括对传统结果的创新方法 评估和创新成果评估工具，包括 NIH 工具箱。该研究将是 在 NIH SIREN 紧急临床试验基础设施中进行。 SIRN 利用现有资源 实现规模经济，维持有才华的快速反应团队来筛选和注册受试者 急诊室设置，并在 ICU 住院期间及之后继续进行临床调查 经过验证的性能。