加拿大卡尔加里大学Shelagh B Coutts团队研究了轻微缺血性中风和颅内闭塞患者接受替萘普酶静脉溶栓的疗效与安全性。相关论文发表在2024年5月17日出版的《柳叶刀》杂志上。

患有轻微缺血性中风和颅内闭塞的个体预后不良的风险增加。替萘普酶静脉溶栓可能改善该人群的疗效。该研究旨在测试静脉注射替萘普酶在轻度缺血性中风和颅内闭塞或局灶性灌注异常患者非溶栓标准治疗中的优越性。

研究组进行了一项多中心、前瞻性、平行组、开放标签、盲法结果评估、随机对照试验，澳大利亚、奥地利、巴西、加拿大、芬兰、爱尔兰、新西兰、新加坡、西班牙和英国48家医院的成年患者（年龄≥18岁）被纳入研究。符合条件的轻度急性缺血性卒中（美国国立卫生研究院卒中量表评分0-5）和颅内闭塞或局灶性灌注异常患者在卒中发作后12小时内入选。参与者被随机分配（1:1），使用最小充分平衡算法静脉注射替萘普酶（0.25 mg/kg）或非溶栓治疗标准（对照）。主要结局是在第90天评估的意向治疗（ITT）人群（所有随机分配到治疗组且未撤回参与同意的患者）恢复到发病前改良Rankin量表评分的基线功能。ITT人群报告了安全性结局，包括症状性颅内出血和死亡。

试验因无效而提前停止。2015年4月27日至2024年1月19日期间，共有886名患者入选；女性369例（42%），男性517例（58%）。454例（51%）分配给对照组，432例（49%）分配给静脉注射替萘普酶组。主要结局发生在对照组452名患者中的338名（75%）和替萘普酶组432名患者中的309名（72%）（风险比[RR]0.96，95%CI 0.88-1.04，p=0.29）。替萘普酶组的患者死亡人数（20人死亡[5%]）多于对照组（5人死亡[1%]；校正后的危险比为3.8；95%可信区间为1.4–10.2，p=0.0085）。替萘普酶组有8例（2%）症状性颅内出血，而对照组有2例（<1%）（RR 4.2；95%CI 0.9-19.7，p=0.059）。

研究结果表明，静脉注射替萘普酶治疗没有益处，也可能有害处。轻度脑卒中和颅内闭塞的患者不应常规接受静脉溶栓治疗。

附：英文原文

Title: Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author: Shelagh B Coutts, Sandeep Ankolekar, Ramana Appireddy, Juan F Arenillas, Zarina Assis, Peter Bailey, Philip A Barber, Rodrigo Bazan, Brian H Buck, Ken S Butcher, Marie-Christine Camden, Bruce Campbell, Leanne K Casaubon, Luciana Catanese, Kausik Chatterjee, Philip M C Choi, Brian Clarke, Dar Dowlatshahi, Julia Ferrari, Thalia S Field, Aravind Ganesh, Darshan Ghia, Mayank Goyal, Stefan Greisenegger, Omid Halse, Mackenzie Horn, Gary Hunter, Oje Imoukhuede, Peter J Kelly, James Kennedy, Carol Kenney, Timothy J Kleinig, Kailash Krishnan, Fabrico Lima, Jennifer L Mandzia, Martha Marko, Sheila O Martins, George Medvedev, Bijoy K Menon, Sachin M Mishra, Carlos Molina, Aimen Moussaddy, Keith W Muir, Mark W Parsons, Andrew M W Penn, Arthur Pille, Octávio M Pontes-Neto, Christine Roffe, Joaquin Serena, Robert Simister, Nishita Singh, Neil Spratt, Daniel Strbian, Carol H Tham, M Ivan Wiggam, David J Williams, Mark R Willmot, Teddy Wu, Amy Y X Yu, George Zachariah, Atif Zafar, Charlotte Zerna, Michael D Hill

Issue&Volume: 2024-05-17

Abstract:

Background

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

Methods

In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0–5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual.

Findings

The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059).

Interpretation

There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis.

DOI: 10.1016/S0140-6736(24)00921-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00921-8/abstract