Department of Neurology, Maastricht University Medical Center+, Maastricht, Netherlands; School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands.
Department of Neurology, Maastricht University Medical Center+, Maastricht, Netherlands; School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands.
Lancet. 2023 Apr 22;401(10385):1371-1380. doi: 10.1016/S0140-6736(23)00575-5. Epub 2023 Mar 29.
Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).
MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.
Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).
In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.
Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.
血管内治疗对前循环缺血性中风在 6 小时窗口期内是有效且安全的。MR CLEAN-LATE 旨在评估在基于 CT 血管造影（CTA）上的侧支循环存在的情况下选择在晚窗口期（症状发作后 6-24 小时或最后一次看到良好）进行的血管内治疗对患者的疗效和安全性。
MR CLEAN-LATE 是一项多中心、开放标签、盲终点、随机、对照、3 期试验，在荷兰的 18 个卒中干预中心进行。纳入年龄在 18 岁及以上、具有缺血性中风、前循环大血管闭塞且 CTA 上有侧支循环，以及国立卫生研究院中风量表（NIHSS）上的神经功能缺损评分至少为 2 的患者。符合晚窗血管内治疗条件的患者根据国家指南（基于 DAWN 和 DEFUSE-3 试验的临床和灌注成像标准得出）进行治疗，不纳入 MR CLEAN-LATE 登记。患者被随机分配（1:1）接受血管内治疗或不接受血管内治疗（对照组），此外还接受最佳药物治疗。随机分配是基于网络的，块大小范围为 8 到 20，按中心分层。主要结局是随机分组后 90 天的改良 Rankin 量表（mRS）评分。安全性结局包括随机分组后 90 天的全因死亡率和症状性颅内出血。所有提供延迟同意或在获得同意前死亡的随机分配患者均构成改良意向治疗人群，其中评估了主要和安全性结局。分析调整了预先设定的混杂因素。治疗效果用有序逻辑回归估计，并以调整后的常见比值比（OR）和 95%置信区间（CI）表示。这项试验在 ISRCTN、ISRCTN19922220 注册。
在 2018 年 2 月 2 日至 2022 年 1 月 27 日期间，共随机分配了 535 名患者，其中 502 名（94%）患者提供了延迟同意或在获得同意前死亡（血管内治疗组 255 名，对照组 247 名；女性 261 名[52%]）。血管内治疗组 90 天的 mRS 评分中位数低于对照组（3 [IQR 2-5] vs 4 [2-6]），我们观察到血管内治疗组的 mRS 结果向更好的方向转变（调整后的常见 OR 1.67 [95% CI 1.20-2.32]）。两组的全因死亡率无显著差异（血管内治疗组 255 名患者中有 62 名[24%]，对照组 247 名患者中有 74 名[30%]；调整后的 OR 0.72 [95% CI 0.44-1.18]）。血管内治疗组的症状性颅内出血发生率高于对照组（17 名[7%] vs 4 名[2%]；调整后的 OR 4.59 [95% CI 1.49-14.10]）。
在这项研究中，对于前循环大血管闭塞引起的缺血性中风患者，如果在发病后 6-24 小时或最后一次看到良好时进行血管内治疗，并且根据 CTA 上的侧支循环存在情况选择患者，血管内治疗是有效且安全的。在晚窗选择血管内治疗的患者可能主要基于侧支循环的存在。
急性卒中治疗新疗法合作组织、荷兰心脏基金会、史赛克、美敦力、Cerenovus、生命科学与健康高级产业集群、荷兰脑基金会。
