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.

项目摘要/摘要 心脏骤停的年发病率估计为250-350,000院外，住院250-750,000 在美国的事件，生存率分别低至5％和20％。这些结果反映了两个步骤 损伤过程：a）在停止血流和b）次级再灌注和炎症性损伤期间缺血 发起人自发循环（ROSC）返回之后。只有3-7％的CA表面表面恢复到其前CA 神经系统状况，发展减轻再灌注损伤的干预措施对于改善患者的重要性至关重要 生存和神经系统结局。一系列动物和人类研究表明，使用 针对兴奋性，氧化损伤和炎症途径的药理干预措施可能 减少缺血/再灌注损伤并改善CA后的生存和神经系统效果。小型 随机对照试验（RCT）提供了初步证据，以支持镁的假设 （MG）在CA后作为神经保护剂时，可以改善生存之间的神经学结局。 但是，需要其他数据来支持其在CA后期的护理标准。因此，我们 提议收集必要和足够的数据，以设计大约之后的MG神经保护的多站点RCT。 我们假设在CA后期管理MG是可行且安全的，并且可能会减弱 兴奋性，从而改善了与发病率和发病率相关的再灌注损伤的下游级联 死亡。当前的申请提案三个目标：对于AIM 1，单个站点飞行员RCT将评估可行性 和管理MG的安全性并在CA后收集血清样品。 MG对血清标记的影响 脑损伤，感染和氧化应激，以及ROSC的速率，生存和独立神经系统 功能也将被评估。对于AIM 2，研究人员将建立单个IRB（S-IRB）批准多站点 使用知情同意书（EFIC）的例外情况下，MG后CA的驾驶员RCT。然后，符合条件的网站将被邀请到 参加试点研究。对于AIM 3，AIM 2中确定的站点将证明招聘和数据的能力 通过在多达4例CA后患者中施用多达4种的MG疗法和安慰剂来收集。获得的数据 通过执行AIMS 1-3，将用于告知大型试验的设计和实施 评估MG（标准CA后护理）与安慰剂（具有标准CA后护理）对生存的影响 大约之后的独立神经功能。