多中心随机临床试验，针对急性缺血性脑卒中的血管内治疗。围手术期药物的影响：乙酰水杨酸、未分级肝素、两者均用或两者均不用（MR CLEAN-MED）。原理和研究设计。

Multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke. The effect of periprocedural medication: acetylsalicylic acid, unfractionated heparin, both, or neither (MR CLEAN-MED). Rationale and study design.

机构信息

Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

Trials. 2020 Jul 14;21(1):644. doi: 10.1186/s13063-020-04514-9.

BACKGROUND

Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT.

METHODS

MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 × 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS ≥ 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5-7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality.

DISCUSSION

Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA.

TRIAL REGISTRATION

ISRCT, ISRCTN76741621 . Dec 6, 2017.

背景

尽管血管内治疗（EVT）对前循环大血管闭塞引起的缺血性卒中具有相当大的有益效果，但许多患者即使完全再通后也无法恢复。在某种程度上，这可能归因于不完全的微血管再灌注，而抗血小板药物和肝素可能会改善这种情况。目前尚不清楚接受 EVT 治疗的患者围手术期抗血栓药物治疗是否能改善功能预后。本研究旨在评估在前循环颅内大血管闭塞性缺血性卒中患者接受 EVT 治疗期间，单独或联合使用乙酰水杨酸（ASA）和未分级肝素（UFH）对患者的影响。

方法

MR CLEAN-MED 是一项多中心 III 期试验，采用前瞻性、2×3 析因随机、开放标签、终点设盲（PROBE）设计，旨在纳入 1500 例患者。该试验旨在评估静脉内 ASA（300mg）、UFH（低或中剂量）、两者联合或均不联合作为 EVT 辅助治疗的效果。我们招募的是符合以下条件的成年患者：临床诊断为卒中（NIHSS≥2），且 CTA 或 MRA 证实存在前循环颅内大血管闭塞，且在症状发作后 6 小时内有 EVT 指征且可行。主要结局是 90 天时改良 Rankin 量表（mRS）评分。采用有序逻辑回归分析估计治疗对 mRS 的影响，并对主要预后变量进行调整。次要结局包括 24 小时和 5-7 天时的 NIHSS 评分、随访梗死体积、症状性颅内出血（sICH）和死亡率。

讨论

是否应在前循环大血管闭塞患者接受 EVT 期间给予抗血栓药物治疗，目前存在临床争议，因为 ASA 和/或 UFH 可能改善功能预后，但也可能增加 sICH 的风险。当一项或两项研究治疗对结局有预期效果时，我们将能够使接受 EVT 治疗的患者的结局提高 5%。这相当于荷兰每年可多治疗 50 多名患者，欧洲每年可多治疗 1800 多名患者，美国每年可多治疗 1300 多名患者。