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.

抽象的院外心脏骤停（OHCA）是一个普遍且令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大多数复苏违规行为永远不会恢复意识。尽管复苏的进展，但超过70％的人在OHCA之后恢复流通的人出院前死亡。需要针对心脏和脑部保护的疗法来改善许多在复苏后阶段的生化/细胞变化，最终导致细胞死亡。阴离子亚硝酸盐（NO2-）在缺氧期间和低pH值期间转化为NO，与NOS活性无关，使得 NO2-一种理想的药物，可在缺血期间不增加生物利用度，而在重新灌注的早期就消耗。缺血期间或再灌注时亚硝酸盐的治疗性递送在动物中受到细胞保护心脏骤停模型。在正在进行的单中心飞行员中，硝酸钠（1-14 mg）IV的随机试验vs。从OHCA复活并运送到医院的患者中的安慰剂相同，我们发现没有亚硝酸盐对血液动力学的显着有害作用。我们认为，硝酸钠的给药是可行的，与该人群中严重的不良事件无关。这些动物和人类研究证明亚硝酸盐作为复苏期间的疗法的潜在希望，以减少神经系统损伤和改善生存。这项研究的总体目标是确定亚硝酸钠的给药是否安全，并且在院外心脏骤停的复苏过程中容易。我们提出了两个阶段临床试验。第一阶段将是一项开放标签剂量的试验试验，以确定最佳亚硝酸钠剂量在复苏时进行管理以通过医院到达达到10°m的等离子体水平。这第二阶段将是安慰剂对照，随机试验的最佳单剂量亚硝酸钠在复苏期间确定安全性和效率。对于两个阶段，所有患有OHCA的患者都西雅图的心室纤颤（VF）和非VF）在其中，护理人员尝试心脏复苏并具有已建立的IV访问将符合条件。第二阶段试验的主要安全结果将是生存到医院入院和次要效率结果将是出院的生存。

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

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