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 据估计，每年院外和院内心脏骤停的发生率分别为250-350,000人和250-750,000人 在美国，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)血流停止时的缺血和b)二次再灌流和炎性损伤 自主循环恢复(ROSC)后。只有3%-7%的CA幸存者恢复到CA前的水平 神经状况，开发干预措施减轻再灌注损伤是改善患者病情的关键 存活率和神经结局。一系列动物和人体研究表明，使用 针对兴奋性、氧化损伤和炎症途径的药物干预可能 减少缺血/再灌注损伤，改善CA术后存活率和神经预后。一个小规模的 随机对照试验(RCT)已经提供了初步证据来支持镁 CA术后应用(Mg)作为神经保护剂可能会改善存活者的神经预后。 然而，需要更多的数据来支持将其用作CA后时期的标准护理。因此，我们 建议收集必要和充分的数据，以设计CA后镁神经保护的多点随机对照试验。 我们假设，在CA术后期间给予镁是可行和安全的，它可能会减弱 兴奋性毒性，从而改善与发病率和再灌注损伤相关的下游级联损伤。 死亡率。目前的申请提出了三个目标：对于目标1，单站点试点RCT将评估可行性 CA术后给予镁和采集血清标本的安全性。镁对糖尿病患者血清标志物的影响 脑损伤、炎症和氧化应激，以及ROSC、存活率和独立神经功能 功能也将被评估。对于目标2，研究人员将为多个站点建立单一IRB(S-IRB)批准 使用知情同意例外(EFIC)的CA后MG的试点随机对照试验。符合条件的网站将被邀请参加 参与一项先导研究。对于目标3，目标2中确定的站点将展示招聘和数据的能力 最多4名患者接受镁治疗，4名CA后患者接受安慰剂治疗。所获得的数据 通过执行AIMS 1-3，将用于通知设计和实施一项大规模试验，以 评估镁(使用标准的CA后护理)与安慰剂(使用标准的CA后护理)对生存的影响 CA术后自主神经功能恢复。