Department Neurology, Lariboisière Hospital, APHP and University Denis Didierot, Paris 7, Paris, France.
FHU Neuro Vasc, Paris, France.
Trials. 2020 Feb 3;21(1):136. doi: 10.1186/s13063-020-4072-2.
The GABA-α5 receptor antagonist S44819 is a promising candidate to enhance functional recovery after acute ischemic stroke (IS). S44819 is currently evaluated in this indication; RESTORE brain study started in Dec 2016 and was completed in March 2019.
METHODS/DESIGN: The study is a 3-month international, randomized, double-blind, parallel group, placebo-controlled phase II multicentre study. Patients in 14 countries who suffered an IS leading to a moderate or severe deficit defined by NIHSS score ranging from 7 to 20 and are aged between 18 to 85 years are included between 3 and 8 days after the stroke onset. Approximately 580 patients are to be included. The primary objective of the study is to demonstrate the superiority of at least one of the two doses of S44819 (150 or 300 mg bid) compared to placebo on top of usual care on functional recovery measured with the modified Rankin scale at 3 months. Comparisons between two doses of S44819 and placebo are assessed with ordinal logistic regression evaluating the odds of shifting from one category to the next in the direction of a better outcome at day 90. Secondary objectives include the evaluation of S44819 effects on neurological examination using the National Institute of Health Stroke Scale total score, activities of daily living using the Barthel Index total score, and cognitive performance using the Montreal Cognitive Assessment scale total score and Trail Making Test times. Safety and tolerability of the two doses of S44819 will also be analyzed.
The RESTORE BRAIN study might represent the first proof of concept study of an innovative therapeutic approach that is primarily based on enhancing functional recovery after IS.
Randomized Efficacy and Safety Trial with Oral S 44819 after Recent ischemic cerebral Event, an international, multi-centre, randomized, double-blind placebo-controlled phase II study. ClinicalTrials.gov, NCT02877615; Eudract 2016-001005-16. Registered 24 August 2016.
GABA-α5 受体拮抗剂 S44819 是一种有前途的候选药物，可增强急性缺血性中风（IS）后的功能恢复。S44819 目前正在该适应症中进行评估；RESTORE 大脑研究于 2016 年 12 月开始，并于 2019 年 3 月完成。
方法/设计：该研究是一项为期 3 个月的国际、随机、双盲、平行分组、安慰剂对照的 II 期多中心研究。在中风发作后 3 至 8 天内，来自 14 个国家的患有中度或重度缺陷的 IS 患者（NIHSS 评分范围为 7 至 20），年龄在 18 至 85 岁之间，符合纳入标准。预计将纳入约 580 名患者。该研究的主要目的是证明至少一种剂量的 S44819（150 或 300mg bid）优于安慰剂，在 3 个月时用改良 Rankin 量表测量的功能恢复方面具有优势。通过评估 ordinal logistic 回归，评估 90 天时向更好结局方向转变的可能性，比较 S44819 两种剂量与安慰剂之间的差异。次要目标包括使用 NIHSS 总评分评估 S44819 对神经检查的影响、使用巴氏量表总评分评估日常生活活动、使用蒙特利尔认知评估量表总评分和 Trail Making 测试时间评估认知表现。还将分析两种剂量的 S44819 的安全性和耐受性。
RESTORE BRAIN 研究可能代表了首例创新治疗方法的概念验证研究，该方法主要基于增强 IS 后的功能恢复。
近期缺血性脑血管事件后口服 S44819 的疗效和安全性随机试验，一项国际、多中心、随机、双盲、安慰剂对照的 II 期研究。ClinicalTrials.gov，NCT02877615；Eudract 2016-001005-16。于 2016 年 8 月 24 日注册。
