Intravenous tenecteplase for acute ischemic stroke between 4.5 and 6 h of onset (EXIT-BT2): Rationale and Design.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY

European Stroke Journal Pub Date : 2024-06-10 DOI:10.1177/23969873241258058

Yi-Han Wang, Zhen-Ni Guo, Ming-Rui Chen, Zhi-Guo Yao, Thanh N Nguyen, Jeffrey L Saver, Yi Yang, Hui-Sheng Chen

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引用次数: 0

Abstract

Rationale: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal.

Aim: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment.

Sample size estimates: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment.

Design: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5-10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines.

Outcome: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0-1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (-6/+12) h after randomization.

Conclusions: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.

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静脉注射替奈普酶治疗发病 4.5 至 6 小时的急性缺血性脑卒中（EXIT-BT2）：原理与设计。

理由：迄今为止，静脉溶栓治疗急性缺血性卒中（AIS）患者的获益时间仅限于发病后 4.5 小时内，且未进行晚期神经影像学选择。我们的 EXIT-BT（将丁酰苯胺溶栓的时间窗延长至发病后 6 小时）II 期试验表明，静脉注射替奈普酶 (TNK) 对发病后 4.5 到 6 小时之间的 AIS 具有安全性、可行性和潜在益处。EXIT-BT2试验是一项关键性研究，旨在证实或反驳这一信号。目的：研究TNK治疗发病4.5至6小时之间的AIS的有效性和安全性，无论是否进行血管内治疗：样本量估计：根据年龄、性别、糖尿病史、血管闭塞位置、美国国立卫生研究院卒中量表基线评分、卒中病因和血管内治疗计划进行分层，最多需要1440名患者，以80%的力量检验优越性假设：EXIT-BT2是一项前瞻性、随机、开放标签、终点盲法评估（PROBE）的多中心研究。符合条件的发病时间在4.5到6小时之间的AIS患者将按1:1的比例随机分配到TNK组或对照组。TNK 组将接受 TNK 治疗（0.25 毫克/千克，5-10 秒内单次注射，最多 25 毫克）。对照组将接受符合国家急性缺血性中风指南的标准医疗护理。从随机分组到中风发作后 90 天内，两组都将接受符合国家指南的标准中风治疗：主要疗效终点是极佳的功能预后，定义为随机分组后 90 天的改良 Rankin 量表评分为 0-1；主要安全性终点是无症状性脑出血，定义为随机分组后 24 (-6/+12) h 内因颅内出血导致的美国国立卫生研究院卒中量表评分上升⩾4：EXIT-BT2的结果可确定静脉注射TNK对发病4.5至6小时之间的AIS是否具有有利的风险/收益特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Stroke Journal Multiple-

CiteScore

7.50

自引率

6.60%

发文量

102

期刊介绍： Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.