Department of Neurology, Chang Gung Memorial Hospital Chiayi Branch, Chiayi County, Taiwan
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
BMJ Open. 2022 Apr 29;12(4):e060068. doi: 10.1136/bmjopen-2021-060068.
Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis.
In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan.
This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles.
ClinicalTrials.gov, Identifier: NCT05001984; Pre-results.
双联抗血小板治疗和高强度他汀类药物是急性症状性颅内动脉粥样硬化狭窄（ICAS）患者的主要治疗方法。阿利西尤单抗是一种单克隆抗体，可抑制脯氨酰肽链内切酶/丝氨酸羧肽酶 9，与他汀类药物相比，能更有效地降低低密度脂蛋白胆固醇水平，且副作用较少。我们假设，在他汀类药物治疗的基础上加用阿利西尤单抗治疗可以稳定颅内斑块并降低动脉狭窄程度。
在这项前瞻性、随机、开放标签、盲终点研究中，我们将使用高分辨率血管壁 MRI 来评估阿利西尤单抗在 ICAS 导致急性缺血性脑卒中患者中的疗效和安全性。我们将招募 66 名发病 7 天内发生急性缺血性脑卒中且大脑中动脉、基底动脉或颅内颈内动脉存在症状性颅内动脉狭窄（>30%）的患者。其中，22 名患者将被随机分配到干预组，接受皮下注射 75 mg 阿利西尤单抗，每 2 周 1 次，共 26 周，而对照组则不接受治疗。两组患者均接受抗血小板药物和高强度他汀类药物治疗，包括 20 mg 瑞舒伐他汀或 40-80 mg 阿托伐他汀或最大耐受剂量。所有患者在入组时和 26 周后均进行 MRI 检查。主要结局是治疗 6 个月后 MRI 上颅内动脉粥样硬化斑块的变化。该试验正在台湾嘉义长庚纪念医院进行。
该试验已获得长庚纪念医院机构审查委员会的批准（批准号 202002482A3）。将从所有研究参与者处获得书面知情同意。研究结果将发表为同行评议文章。
ClinicalTrials.gov，标识符：NCT05001984；预结果。
