Table 1_Design of the “EAST” strategy in patients with symptomatic intracranial atherosclerotic stenosis.docx

IntroductionThere is a high risk of stroke occurrence and recurrence in patients with intracranial atherosclerotic stenosis (ICAS) despite aggressive medical therapy. Evolocumab is a monoclonal antibody which can inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) and effectively reduce the level of low-density lipoprotein cholesterol. We hypothesize that evolocumab added to statin therapy (EAST) can stabilize intracranial plaques in patients with symptomatic ICAS.
Methods and analysisThis is a prospective, randomized, open-label, blinded end-point study, which will assess the efficacy and safety of evolocumab in patients with symptomatic ICAS. Eighty patients who suffer a stroke/transient ischemic attack (TIA) caused by ICAS recently will be randomly allocated in a 1:1 ratio to the evolocumab plus statin treatment group or the statin treatment group. High resolution vessel wall magnetic resonance imaging (HR-vwMRI) will be performed at recruitment and after 6 months and 12 months. The primary outcome is changes in plaque characteristics assessed by HR-vwMRI at 6th month and 12th month after treatment. Cognitive and neurological function will also be evaluated at recruitment and follow-up. This trial is being conducted at the first affiliated hospital of Nanjing medical university, China.
Ethics and disseminationAll participants will sign written informed consents. Peer-reviewed articles will be published to disseminate study outcomes.
Clinical trial registrationClinicalTrials.gov, identifier: NCT05741086.

## 引言
尽管接受了强化药物治疗，颅内动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis, ICAS）患者仍存在较高的卒中发生及复发风险。依洛尤单抗（evolocumab）是一种单克隆抗体，可抑制前蛋白转化酶枯草溶菌素9型（proprotein convertase subtilisin-kexin type 9, PCSK9），有效降低低密度脂蛋白胆固醇水平。本研究假设，在他汀类药物治疗基础上加用依洛尤单抗（EAST）可稳定症状性颅内动脉粥样硬化性狭窄患者的颅内斑块。

## 方法与分析
本研究为一项前瞻性、随机、开放标签、盲法终点试验，旨在评估依洛尤单抗用于症状性颅内动脉粥样硬化性狭窄患者的疗效与安全性。80例近期因颅内动脉粥样硬化性狭窄发生卒中或短暂性脑缺血发作（transient ischemic attack, TIA）的患者，将以1:1的比例随机分配至依洛尤单抗联合他汀治疗组与单纯他汀治疗组。研究将在受试者入组时、治疗后6个月及12个月时行高分辨血管壁磁共振成像（high resolution vessel wall magnetic resonance imaging, HR-vwMRI）检查。主要结局指标为治疗后6个月及12个月时，通过HR-vwMRI评估的斑块特征变化。同时将在入组及随访阶段评估受试者的认知与神经功能。本试验在中国南京医科大学第一附属医院开展。

## 伦理与传播
所有受试者均将签署书面知情同意书。本研究结果将以同行评议学术论文的形式发表，以传播试验成果。

## 临床试验注册
临床试验注册平台：ClinicalTrials.gov，注册号：NCT05741086。