评估HT047治疗急性缺血性中风患者疗效和安全性的原理与设计：一项多中心、随机、双盲、安慰剂对照、平行组II期试验。

Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial.

作者信息

Heo Sung Hyuk, Song Jungbin, Kim Bum Joon, Kim Hocheol, Chang Dae-Il

机构信息

Department of Neurology, Kyung Hee University Hospital.

Department of Herbal Pharmacology, Kyung Hee University College of Korean Medicine, Seoul, Republic of Korea.

出版信息

Medicine (Baltimore). 2019 Oct;98(43):e17655. doi: 10.1097/MD.0000000000017655.

DOI:10.1097/MD.0000000000017655

PMID:31651889

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6824685/

Abstract

BACKGROUND

Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047.

METHODS

A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1-2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2.

DISCUSSION

This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.

摘要

背景

尽管已有多种神经保护剂被评估为急性缺血性中风的潜在治疗方法，但尚无一种显示出确切的治疗效果，确切疗效仍然难以捉摸。HT047是黄芩和葛根的草药提取物，在传统韩医学中，这两种草药都被广泛用于治疗缺血性中风。本试验的目的是研究HT047是否能改善急性缺血性中风患者的神经状态，尤其是运动功能，并确定HT047的安全性。

方法

将对在过去14天内发生急性缺血性中风的患者进行一项多中心、双盲、随机、安慰剂对照、三臂平行组II期试验。参与试验的患者必须Fugl-Meyer评估（FMA）运动评分≤55，存在手臂或腿部无力，且韩国版美国国立卫生研究院卒中量表（K-NIHSS）评分≥4且≤15。78名参与者将按1:1:1的比例随机分组，接受高剂量HT047（750毫克，每日3次）、低剂量HT047（500毫克，每日3次）或安慰剂治疗12周。主要终点是基线至第12周时FMA运动评分的变化。次要终点如下：第4周和第8周时FMA运动评分相对于基线的变化；根据治疗开始时间（1周内或1 - 2周）或根据预后危险因素（高血压、糖尿病、血脂异常等）的存在情况，第4周、第8周和第12周时FMA运动评分相对于基线的变化；第4周和第12周时K-NIHSS、韩国版改良Rankin量表（K-mRS）和改良Barthel指数相对于基线的变化；以及第12周时K-NIHSS评分为0至2或K-mRS评分为0、≤1和≤2的受试者比例。