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

2/2 ICECAP：冷却时间对心脏骤停患者疗效的影响

• 批准号: 10265473
• 负责人: Viswanathan Ramakrishnan
• 金额: $ 50.4万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 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/10265473
• 关键词: Accident and Emergency department; Address; Affect; Applications Grants; Assessment tool; Brain; Brain Injuries; Cardiac; Cardiopulmonary Resuscitation; Case Report Form; Cerebral Ischemia; Cessation of life; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Collection; Coma; Common Data Element; Companions; Data; Data Coordinating Center; Data Set; Databases; Development; Devices; Dose; Eligibility Determination; Emergency Situation; Enrollment; Evaluation; Goals; Guidelines; Health Sciences; Heart; Heart Arrest; Hospitals; Infrastructure; Injury; Left; Link; Manuscripts; Medical; Methods; Michigan; Monitor; Multi-site clinical study; Multicenter Trials; National Heart, Lung, and Blood Institute; Neurologic; Neurological emergencies; Neurological outcome; Online Systems; Outcome; Outcome Assessment; Patient Selection; Patients; Performance; Periodicity; Procedures; Protocols documentation; Public Health; Randomized; Recovery; Reporting; Research Design; Resources; Resuscitation; Risk; Role; Safety; Selection Criteria; Shock; South Carolina; Specific qualifier value; Survivors; System; Talents; Temperature; Therapeutic; United States National Institutes of Health; Universities; Work; base; clinical investigation; clinical practice; clinical research site; data management; data quality; design; disability; electronic data; experience; implementation facilitation; improved; improved outcome; innovation; method development; natural hypothermia; neurological recovery; novel; organizational structure; out-of-hospital cardiac arrest; patient population; pre-clinical; response; treatment effect; trial design

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.项目概要/摘要。 心脏骤停是心脏和大脑的常见和毁灭性的紧急情况。38万多 在美国，每年都有患者遭受院外心脏骤停（OHCA）。改善心脏 复苏（OHCA患者“生存链”的早期环节）受到我们有限的 复苏和保护大脑免受全脑缺血的能力。神经死亡和残疾是 心脏骤停幸存者的常见结局。昏迷病人的治疗性降温 可电击节律可显著增加神经学结局良好的比率，但结局不良的比率仍然存在。 发生在多达50%，和冷却的好处，在那些从心搏停止和无脉复苏 电活动尚未在随机研究中进行评估。即使是有电击节律的病人， 先前显示疗效的试验受到质疑。治疗性冷却已经是指南推荐的 和心脏骤停昏迷幸存者的常用治疗，但由于数据有限， 持续时间和患者选择标准仍然未知，并且FDA未批准冷却装置用于此目的 适应症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使脑损伤最小化。这项研究将确定是否确定一个最佳的持续时间， 治疗性低温可以改善结果，如果持续时间反应曲线的发展可以 证实了在更广泛的心脏骤停幸存者患者人群中的疗效。我们假设 冷却的持续时间可以提高获得良好神经恢复的患者的比例， 在已经被归类为具有良好结果的比例中，可能导致更好的恢复。的 该项目的总体目标是确定临床策略，以增加患者数量， 心脏骤停后神经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。该试验使用创新的适应性剂量发现 允许探索广泛的潜在持续时间并有效分配主题的方法， 它们将提供最丰富的信息。研究方法也包括传统结果的创新方法 评估和创新的结果评估工具，包括NIH的评估工具。本研究将 在NIH SIREN紧急临床试验基础设施中进行。SIREN利用现有资源， 实现规模经济，保持快速反应的人才团队，以筛选和招募受试者， 急诊科设置，并继续通过ICU住院及以后的临床研究， 经过验证的性能