MR CLEAN-NO IV：伴或不伴静脉治疗的血管内治疗与直接血管内治疗用于治疗因近端颅内闭塞引起的急性缺血性脑卒中：一项随机临床试验的研究方案

MR CLEAN-NO IV: intravenous treatment followed by endovascular treatment versus direct endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion-study protocol for a randomized clinical trial.

机构信息

Department of Radiology & Nuclear Medicine, Amsterdam UMC, University of Amsterdam, P.O. Box 22660, Amsterdam, 1100DD, The Netherlands.

Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Trials. 2021 Feb 15;22(1):141. doi: 10.1186/s13063-021-05063-5.

BACKGROUND

Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.

METHODS

MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.

DISCUSSION

IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.

TRIAL REGISTRATION

www.isrctn.com : ISRCTN80619088 . Registered on 31 October 2017.

背景

血管内治疗 (EVT) 极大地改善了前循环近端颅内大血管闭塞 (LVO) 的急性缺血性脑卒中 (AIS) 患者的预后。目前，在 EVT 之前给予静脉注射重组组织型纤溶酶原激活剂 (IVT) 的额外获益方面存在临床平衡。本研究旨在评估在 AIS 患者中省略 EVT 前 IVT 的疗效和安全性。

方法

MR CLEAN-NO IV 是一项多中心随机开放标签临床试验，结果评估为盲法 (PROBE 设计)。年龄≥ 18 岁、有症状前 mRS < 3 分、CT 血管造影/MR 血管造影证实 LVO 适合 IVT 和 EVT 的患者，以 1:1 的比例随机接受 IVT (0.9mg/kg) 后 EVT 或直接 EVT。主要目的是评估直接 EVT 的优越性。其次，将探索直接 EVT 与 IVT 前 EVT 相比的非劣效性。主要结局是 90 天时改良 Rankin 量表评分。将使用调整预后变量的有序回归来估计治疗效果。次要结局包括 EVT 后 eTICI 分级的再灌注和 24 小时时的卒中严重程度 (国立卫生研究院卒中量表)。安全性结局包括根据海德堡标准评分的颅内出血。共纳入 540 例患者。