抗氧化剂和 NMDA 受体阻滞剂戒除韩国 OHCA 患者缺氧性脑损伤试验（AWAKE）的原理和方法。

Rationale and methods of the Antioxidant and NMDA receptor blocker Weans Anoxic brain damage of KorEa OHCA patients (AWAKE) trial.

机构信息

Samsung Medical Center, Department of Emergency Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Chonnam National University Hospital, Department of Emergency Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

出版信息

Trials. 2022 Jul 23;23(1):587. doi: 10.1186/s13063-022-06452-0.

DOI:10.1186/s13063-022-06452-0

PMID:35871083

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9308222/

Abstract

BACKGROUND

Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA).

METHODS

The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-D-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 μg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients.

DISCUSSION

The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03651557 . Registered on August 29, 2018.

摘要

背景

缺血性脑损伤是限制复苏后院外心脏骤停（OHCA）患者生存的主要障碍。

方法

本研究旨在评估高剂量或低剂量 Neu2000K（一种 N-甲基-D-天冬氨酸（NMDA）型 2B 受体选择性阻断剂，也是自由基清除剂）或安慰剂治疗成人 OHCA 患者的可行性和减轻缺血性脑损伤的潜力。这是一项 II 期、多中心、随机、双盲、前瞻性、意向治疗、安慰剂对照、三臂、安全性和疗效临床试验。这是一项由 GNT Pharma 发起的试验。将纳入成功复苏的 19 至 80 岁 OHCA 患者。主要结局是第 3 天的血神经元特异性烯醇化酶（NSE）水平。次要结局是安全性、疗效，定义为在 4 小时内研究药物给药超过 90%的参与者、每天的 NSE 直至第 5 天、血 S100beta、脑 MRI 表观扩散系数成像、脑功能分类（CPC）和第 5、14 和 90 天的改良 Rankin 量表（mRS）。假设治疗（高剂量和低剂量 Neu2000K）和对照组的 NSE 分别为 42±80 和 80±80μg/L，80%的效力，5%的Ⅰ类错误率，以及 28%的患者在终点前退出，所需的样本量为 150 例患者。