Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial

作者全名："Cheng, Xin; Hong, Lan; Churilov, Leonid; Lin, Longting; Ling, Yifeng; Zhang, Jin; Yang, Jianhong; Geng, Yu; Wu, Danhong; Liu, Xueyuan; Zhou, Xiaoyu; Zhao, Yuwu; Zhai, Qijin; Zhao, Liandong; Chen, Yangmei; Guo, Ying; Yu, Xiaofei; Gong, Fan; Sui, Yi; Li, Gang; Yang, Lumeng; Gu, Hong-Qiu; Wang, Yilong; Parsons, Mark; Dong, Qiang"

作者地址："[Cheng, Xin; Hong, Lan; Ling, Yifeng; Yang, Lumeng; Dong, Qiang] Fudan Univ, Huashan Hosp, Natl Ctr Neurol Disorders, Natl Clin Res Ctr Aging & Med,Dept Neurol, Shanghai, Peoples R China; [Churilov, Leonid] Univ Melbourne, Royal Melbourne Hosp, Melbourne Med Sch, Parkville, Vic, Australia; [Lin, Longting; Parsons, Mark] Univ New South Wales, Liverpool Hosp, Ingham Inst Appl Med Res, Dept Neurol,South Western Sydney Clin Sch, Sydney, NSW, Australia; [Zhang, Jin] Shanxi Med Univ, Hosp 1, Dept Neurol, Taiyuan, Peoples R China; [Yang, Jianhong] Ningbo First Hosp, Dept Neurol, Ningbo, Peoples R China; [Geng, Yu] Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Hangzhou Med Coll, Ctr Rehabil Med,Dept Neurol, Hangzhou, Peoples R China; [Wu, Danhong] Fudan Univ, Shanghai Peoples Hosp 5, Dept Neurol, Shanghai, Peoples R China; [Liu, Xueyuan; Zhou, Xiaoyu] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Neurol, Shanghai, Peoples R China; [Zhao, Yuwu] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Neurol, Sch Med, Shanghai, Peoples R China; [Zhai, Qijin; Zhao, Liandong] Xuzhou Med Univ, Affiliated Hosp Huaian, Dept Neurol, Huaian, Peoples R China; [Chen, Yangmei] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing, Peoples R China; [Guo, Ying] Puer Peoples Hosp, Dept Neurol, Puer, Peoples R China; [Yu, Xiaofei; Gong, Fan] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Neurol, Shanghai, Peoples R China; [Sui, Yi] Shenyang First Peoples Hosp, Shenyang Med Coll, Dept Neurol, Affiliated Brain Hosp, Shenyang, Peoples R China; [Li, Gang] Tongji Univ, Shanghai East Hosp, Dept Neurol, Shanghai, Peoples R China; [Gu, Hong-Qiu; Wang, Yilong] Beijing Tiantan Hosp, China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China; [Wang, Yilong] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China"

通信作者："Dong, Q (通讯作者)，Fudan Univ, Huashan Hosp, Natl Ctr Neurol Disorders, Natl Clin Res Ctr Aging & Med,Dept Neurol, Shanghai, Peoples R China."

来源：STROKE AND VASCULAR NEUROLOGY

ESI学科分类：　

WOS号：WOS:001153356900001

JCR分区：Q1

影响因子：5.9

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Thrombolysis; Stroke; Clinical Trial

摘要："Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window.Methods The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis.Results A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design.Discussion Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.Trial registration number ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147)."

基金机构：National Key R&D Program of China [2017YFC1308201]; Clinical Research Plan of SHDC [SHDC2020CR1041B]; Shanghai Municipal Key Clinical Specialty [shslczdzk06102]

基金资助正文："This work was supported by the National Key R & D Program of China (2017YFC1308201), Clinical Research Plan of SHDC (SHDC2020CR1041B) and Shanghai Municipal Key Clinical Specialty (shslczdzk06102). Guangzhou Recomgen Biotech Co supplied the investigational product and the insurance for this trial."