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Randomized clinical trial of sodium nitrite for out of hospital cardiac arrest

亚硝酸钠治疗院外心脏骤停的随机临床试验

基本信息

批准号：
9922344
负责人：
Francis Kim
金额：
$ 66.88万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9922344
关键词：
Accident and Emergency department Advanced Cardiac Life Support Animal Model Animals Anions Applications Grants Biochemical Biochemical Process Biological Availability Blood Circulation Brain Brain Injuries Cardiopulmonary Resuscitation Caring Cell Death Clinical Trials Complex Conscious Control Groups Data Dose Electric Countershock Emergency medical service Enzymes Futility Genetic Goals Heart Heart Arrest Hospital Records Hospitalization Hospitals Human Hypoxia Inflammation Intravenous Ischemia Lead Measures Mitochondria Morbidity - disease rate Nervous System Trauma Neurons Nitric Oxide Nitric Oxide Donors Nitric Oxide Synthase Nitrites Organ Outcome Paramedical Personnel Patients Pharmaceutical Preparations Pharmacology Phase Placebo Control Placebos Plasma Population Production Protein Isoforms Public Health Randomized Randomized Clinical Trials Reactive Oxygen Species Reperfusion Therapy Reporting Resuscitation Rodent Model Rogaine Running Safety Serious Adverse Event Side Signal Transduction Sodium Nitrite Testing Therapeutic Thrombosis Time Tissues United States Vasoconstrictor Agents Ventricular Fibrillation base cell injury effective therapy experience first responder hemodynamics hospital admission rate improved improved outcome mortality open label out-of-hospital cardiac arrest pharmacokinetic model phase II trial preclinical study randomized trial safety outcomes service providers sudden cardiac death

项目摘要

Abstract Out-of-hospital cardiac arrest (OHCA) is a common and debilitating public health problem. Neurologic injury is the major cause of morbidity and mortality in these patients with most resuscitated victims never regaining consciousness. Despite advances in resuscitation, over 70% of those who have circulation restored after OHCA die before hospital discharge. Therapies directed at heart and brain protection are needed to ameliorate many of the biochemical/cellular changes during the post resuscitation phase, which ultimately lead to cell death. The anion nitrite (NO2-) is converted to NO during hypoxia and during low pH, independent of NOS activity, making NO2- an ideal drug to increase NO bioavailability during ischemia and early in reperfusion when there is critical depletion. Therapeutic delivery of nitrite during ischemia or at time of reperfusion is cytoprotective in animal models of cardiac arrest. In an ongoing single-center pilot randomized trial of sodium nitrite (1-14 mg) IV vs. identically-appearing placebo in patients resuscitated from OHCA and transported to hospital, we found no significant deleterious effect of nitrite on hemodynamics. We believe that administration of sodium nitrite is feasible and not associated with serious adverse events in this population. These animal and human studies demonstrate the potential promise of nitrite as a therapy during resuscitation to reduce neurologic injury and improve survival. The overall goal of this study is to determine whether the administration of sodium nitrite is safe and efficacious during on going resuscitation for out-of-hospital cardiac arrest. We propose a two-stage clinical trial. The first phase will be an open-label dose finding trial to determine the optimal sodium nitrite dose to be administered at the time of resuscitation to achieve a plasma level of 10 M by hospital arrival. The second phase will be a placebo-control, randomized trial of the optimal single dose of sodium nitrite delivered during resuscitation to determine safety and efficacy. For both phases, all patients who have OHCA (both ventricular fibrillation (VF) and non-VF) in Seattle in which paramedics attempt cardiac resuscitation and have established IV access will be eligible. The primary safety outcome for the phase 2 trial will be survival to hospital admission and the secondary efficacy outcome will be survival to discharge.

摘要院外心脏骤停（OHCA）是一种常见且使人衰弱的公共卫生问题。神经损伤是这些患者的发病率和死亡率的主要原因是大多数复苏的受害者从未恢复意识尽管复苏取得了进展，但在OHCA后恢复循环的患者中，在出院前死亡需要针对心脏和大脑保护的治疗来改善许多复苏后阶段的生化/细胞变化，最终导致细胞死亡。的在缺氧和低pH期间，阴离子亚硝酸盐（NO2-）转化为NO，与NOS活性无关， NO2-一种理想的药物，以增加NO的生物利用度在缺血和早期再灌注时，有关键耗尽亚硝酸盐在动物缺血或再灌注时的治疗性递送具有细胞保护作用心脏骤停的模型在一项正在进行的亚硝酸钠（1-14 mg）IV与在从OHCA复苏并送往医院的患者中，我们发现没有亚硝酸盐对血液动力学的显著有害作用。我们认为亚硝酸钠的使用在该人群中可行且与严重不良事件无关。这些动物和人类的研究证明了亚硝酸盐作为复苏期间减少神经损伤的治疗方法的潜在前景，提高生存率。本研究的总体目标是确定亚硝酸钠的给药是否安全，在院外心脏骤停的持续复苏期间有效。我们提出了一个两阶段临床试验第一阶段将是一个开放标签的剂量探索试验，以确定最佳的亚硝酸钠剂量在复苏时给药，以在到达医院时达到10 μ M的血浆水平。的第二阶段将是一个安慰剂对照，随机试验的最佳单剂量亚硝酸钠交付以确定安全性和有效性。对于这两个阶段，所有患有OHCA的患者（均室颤（VF）和非VF），其中护理人员尝试心脏复苏，已建立的IV访问将符合条件。II期试验的主要安全性结局是生存至住院和次要疗效结局将是生存至出院。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Usefulness of Intravenous Sodium Nitrite During Resuscitation for the Treatment of Out-of-Hospital Cardiac Arrest.

DOI：
10.1016/j.amjcard.2018.04.060
发表时间：
2018-08-15
期刊：
The American journal of cardiology
影响因子：
0
作者：
Kim F;Dezfulian C;Empey PE;Morrell M;Olsufka M;Scruggs S;Kudenchuk P;May S;Maynard C;Sayre MR;Nichol G
通讯作者：
Nichol G

The quest continues to identify coronary occlusion in OHCA without ST elevation.

继续探索在不伴有 ST 段抬高的 OHCA 中识别冠状动脉闭塞。