The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6–24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation. MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6–24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220. Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2–6) in the endovascular treatment group and 6 (2–6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00–1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60–1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group. Our results show that the effectiveness of late-window (after 6–24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making. The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

中文翻译：

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基于并行选择的急性缺血性卒中晚期血管内治疗 (MR CLEAN-LATE)：荷兰一项 3 期、多中心、开放标签、随机对照试验的 2 年随访


MR CLEAN-LATE 试验为根据 CT 血管造影上是否存在侧支血流而预先选择的患者在晚期窗口（6-24 小时后）内对急性缺血性卒中进行血管内治疗的安全性和有效性提供了证据。我们的目的是评估随机分组后两年的临床结果。 MR CLEAN-LATE 是一项在荷兰 18 个卒中干预中心进行的 3 期、多中心、开放标签、盲终点、随机对照试验。如果可以在症状出现或最后一次就诊后 6-24 小时内开始血管内治疗，则因前循环大血管闭塞且至少有部分侧支血流而导致急性缺血性卒中的患者（年龄 18 岁或以上） CT血管造影上受影响的大脑中动脉区域被随机分配（1:1）接受最佳药物治疗的血管内治疗（血管内治疗组）或单独最佳药物治疗（对照组）。使用排列块（块大小 8 至 20）进行基于网络的随机化，按中心分层。收集临床结果并分析结果的研究人员不知道治疗分配情况；主治医生、当地研究人员和患者均了解所接受的治疗。 MR CLEAN-LATE 的主要结果是随机化后 90 天的改良 Rankin 量表 (mRS) 评分。对于这项为期 2 年的预设分析，主要结果是 2 年时的 mRS 评分（负 3 个月至正 6 个月）。主要分析和安全性分析是根据修改后的意向治疗原则进行的，包括提供（延迟）同意或在获得同意之前死亡的患者。缺失数据通过链式方程进行多重插补处理。 试验已完成并在 ISRCTN 注册，ISRCTN19922220。 2018 年 2 月 2 日至 2022 年 1 月 27 日期间，535 名患者被随机分配参加 MR CLEAN-LATE 试验，其中 502 名患者 (94%) 给予延期同意，并构成修改后的意向治疗人群（255 名患者接受血管内治疗）治疗组 247 例，对照组 247 例）。 261 名患者（52%）为女性，241 名患者（48%）为男性。血管内治疗组 226 名患者 (89%) 和对照组 202 名患者 (82%) 可获得 2 年 mRS 评分数据。血管内治疗组 2 年时的中位 mRS 评分为 4（IQR 2-6），对照组为 6（2-6）。血管内治疗组的 mRS 表现出向更好功能结果的转变（调整后的共同比值比 1·41 [95% CI 1·00–1·99]；p=0·049）。血管内治疗组 2 年全因死亡率为 34%（255 人中的 87 人），对照组为 41%（247 人中的 101 人）（调整后风险比 0·81 [95% CI 0·60–1·08 ]；p=0·15)。血管内治疗组有 23 名患者和对照组有 13 名患者在 90 天至 2 年内报告了主要血管事件（即短暂性脑缺血发作、缺血性中风、出血性中风和心脏事件）。我们的结果表明，在根据 CT 血管造影是否存在侧支血流预先选择的人群中，晚窗口（6-24 小时后）血管内治疗在改善临床结果方面的有效性可持续长达 2 年。这一发现对于促进成本效益、医疗保健政策制定和临床决策的进一步评估可能很重要。 荷兰健康研究和健康创新组织 (ZonMW)、急性中风新疗法联盟、荷兰心脏基金会、史赛克、美敦力、Cerenovus、Health Holland Top Sector 生命科学与健康以及荷兰脑基金会。