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: 10019591
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019591
• 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; 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.项目摘要/摘要。 心脏骤停是心脏和大脑的一种常见和毁灭性的紧急情况。超过38万 在美国，每年都有患者在医院外遭受心脏骤停(UchA)。心脏方面的改善 我们有限的心肺复苏术(早期环节的存活链)受到了我们的限制 复苏和保护大脑免受全球脑缺血的能力。神经性死亡和残疾是 心脏骤停幸存者的常见结局。昏迷患者复苏后的治疗性降温 电击节律可以显著增加神经预后良好的比率，但预后仍然很差。 发生的几率高达50%，在那些从停搏和无脉搏中复苏的人中，降温的好处 电活动尚未在随机研究中进行评估。即使在有电击节律的患者中， 之前显示有效的试验受到了质疑。治疗性降温已经是一项指南-推荐 和常用的治疗心脏骤停昏迷幸存者的方法，但由于数据有限，最佳 持续时间和患者选择标准仍然未知，冷却设备没有得到FDA的批准 指示。临床前数据和机制研究强烈表明，低温持续时间长于 通常使用的那些可能会将脑损伤降至最低。这项研究将确定是否确定最佳持续时间 治疗性低温可以改善预后，如果持续时间反应曲线的发展可以 证实在更广泛的心脏骤停幸存者患者群体中的有效性。我们假设更长的时间 降温的持续时间可能会改善患者达到良好神经恢复的比例，或者 在已经归类为结果良好的比例中，可能会产生更好的恢复。这个 该项目的总体目标是确定临床策略，以增加 心脏骤停后神经功能恢复良好。这场试验的结果将立即产生重大影响， 对临床实践和监管评估都有影响。这项试验使用了创新的适应性剂量发现 允许探索广泛的潜在持续时间的方法，并在以下情况下有效地分配对象 它们将是信息量最大的。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，包括国家卫生研究院工具箱。这项研究将是 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，保持有才华的快速反应团队来筛选和登记受试者 急诊科设置，并通过ICU停留和以后继续临床调查 久经考验的性能。