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/文摘