Neuroprotection following cardiac arrest: A Randomized Control Trial of Magnesium

心脏骤停后的神经保护：镁的随机对照试验

• 批准号: 10742460
• 负责人: Sam Parnia
• 金额: $ 25.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10742460
• 关键词: Adverse event; American Heart Association; Animals; Anoxia; Anoxic Encephalopathy; Apoptosis; Attenuated; Biological Assay; Biological Markers; Blood; Blood Pressure; Blood flow; Brain; Brain Injuries; Cardiopulmonary Resuscitation; Caring; Cell Death; Cessation of life; Circulation; Collection; Critical Care; Data; Data Collection; Dedications; Eligibility Determination; Enzymes; Event; Goals; Grant; Heart Arrest; Hospitals; Hour; Human; Incidence; Inflammation; Inflammatory; Informed Consent; Infrastructure; Injury; Institutional Review Boards; International; Intervention; Ischemia; Link; MK801; Magnesium; Meta-Analysis; Methods; Mg supplementation; Minocycline; Mitochondria; Morbidity - disease rate; Multi-Institutional Clinical Trial; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Nervous System Physiology; Neurological outcome; Neurological status; Neuroprotective Agents; Normal saline; Odds Ratio; Outcome; Oxidative Stress; Pathway interactions; Patients; Pilot Projects; Placebos; Process; Process Assessment; Process Measure; Randomized; Randomized, Controlled Trials; Reperfusion Injury; Reperfusion Therapy; Research; Research Design; Research Personnel; Resuscitation; Retrospective Studies; Sampling; Series; Serum; Serum Markers; Site; Standardization; Stroke; Survival Rate; Survivors; Temperature; Testing; Time; Traumatic Brain Injury; Ventilator; Work; design; excitotoxicity; feasibility testing; improved; mortality; neuroprotection; novel; oxidative damage; pharmacologic; pilot test; prevent; recruit; safety and feasibility; sample collection; secondary endpoint; severe injury; standard of care; survival outcome; timeline

Project Summary/Abstract Cardiac arrest has an estimated annual incidence of 250-350,000 out-of-hospital and 250-750,000 in-hospital events in the U.S., with survival rates as low as 5% and 20% respectively. These outcomes reflect a two-step injury process: a) ischemia during cessation of blood flow and b) secondary reperfusion and inflammatory injury following return of spontaneous circulation (ROSC). With only 3-7% of CA survivors recovering to their pre-CA neurological status, developing interventions to attenuate reperfusion injury are critical to improve patients’ survival and neurological outcomes. A series of animal and human studies have shown that the use of pharmacological interventions targeted against excitoxicity, oxidative injury and inflammatory pathways may reduce ischemia/reperfusion injury and improve post-CA survival and neurological outcomes. A small-scale randomized control trial (RCT) has provided preliminary evidence to support the hypothesis that magnesium (Mg) in the post-CA period as a neuroprotective agent may improve neurological outcomes among survivors. However, additional data is needed to support its use as standard of care in the post-CA period. We therefore propose to collect necessary and sufficient data to design a multisite RCT of Mg neuroprotection following CA. We hypothesize that administering Mg in the post-CA period is feasible and safe, and that it may attenuate excitotoxity, thereby ameliorating the downstream cascade of reperfusion injuries associated with morbidity and mortality. The current application proposes three aims: For Aim 1, a single site pilot RCT will assess the feasibility and safety of administrating Mg and collecting serum samples post-CA. The effects of Mg on serum markers of brain injury, inflammation, and oxidative stress, as well as, rates of ROSC, survival and independent neurological function will also be assessed. For Aim 2, researchers will establish single-IRB (S-IRB) approval for a multi-site pilot RCT of Mg post-CA using Exception From Informed Consent (EFIC). Eligible sites will then be invited to participate in a pilot study. For Aim 3, sites identified in Aim 2 will demonstrate capacity for recruitment and data collection by administering the Mg therapy in up to 4 and placebo in up to 4 post-CA patients. The data obtained through the execution of Aims 1-3 will be used to inform the design and implementation of a large-scale trial to assess the impact of Mg (with standard post-CA care) versus placebo (with standard post-CA care) on survival and independent neurological function after CA.

项目总结/摘要 心脏骤停的估计年发病率为250- 350，000例院外和250- 750，000例院内 在美国发生的事件，存活率分别低至5%和20%。这些结果反映了两个步骤 损伤过程：a）血流停止期间的局部缺血和B）继发性再灌注和炎性损伤 恢复自主循环（ROSC）。只有3-7%的CA幸存者恢复到CA前 神经系统状态，开发干预措施以减轻再灌注损伤对于改善患者的神经功能状态至关重要。 存活率和神经学结果。一系列动物和人类研究表明， 针对兴奋毒性、氧化损伤和炎症途径的药物干预可 减少缺血/再灌注损伤并改善CA后存活率和神经学结果。小规模 一项随机对照试验（RCT）提供了初步证据支持镁 (Mg)在CA后时期作为神经保护剂可能会改善幸存者的神经功能结局。 然而，需要额外的数据来支持其作为CA后阶段的标准治疗。因此我们 建议收集必要和充分的数据，以设计CA后镁神经保护的多中心RCT。 我们假设在CA后阶段给予镁是可行和安全的， 兴奋性毒性，从而改善与发病率相关的再灌注损伤的下游级联， mortality.目前的申请提出了三个目标：对于目标1，一个单一的网站试点随机对照试验将评估可行性 以及CA后镁给药和血清标本采集的安全性。镁对慢性乙型肝炎血清标志物的影响 脑损伤、炎症和氧化应激，以及ROSC率、生存率和独立神经功能 功能也将得到评估。对于目标2，研究人员将为多中心研究建立单一IRB（S-IRB）批准 使用知情同意例外（EFIC）进行CA后镁的试点RCT。然后，将邀请符合条件的研究中心 参与试点研究。对于目标3，目标2中确定的研究中心将证明招募和数据的能力 通过在多达4名CA后患者中施用Mg疗法和在多达4名CA后患者中施用安慰剂来收集。获得的数据 通过执行目标1-3，将用于为大规模试验的设计和实施提供信息， 评估Mg（标准CA后护理）与安慰剂（标准CA后护理）对生存率的影响 和独立的神经功能。