Revacept，一种用于症状性颈动脉狭窄的血小板黏附抑制剂：一项多中心随机二期临床试验。
Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Multicenter Randomized Phase II Trial.
机构信息
Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany (T.U., K.G.).
Department of Vascular Surgery, University of Western Australia, Fiona Stanley Hospital, Perth, Australia (T.R.).
出版信息
Stroke. 2022 Sep;53(9):2718-2729. doi: 10.1161/STROKEAHA.121.037006. Epub 2022 Jun 13.
BACKGROUND
Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis.
METHODS
International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up.
RESULTS
Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88-1.53)/1.05 (95% CI, 0.78-1.42; =0.629)/0.63 (95% CI, 0.43-0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21-0.99]; =0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37-1.42]; =0.343).
CONCLUSIONS
Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique Identifier: NCT01645306.
背景
有症状的颈内动脉（ICA）狭窄患者发生复发性缺血性卒中的风险较高，需要早期介入治疗和抗血小板治疗。增加出血率可能会抵消强化血小板抑制的围手术期疗效。我们旨在研究，在伴有症状性 ICA 狭窄的患者中，作为标准抗血小板治疗的辅助药物，糖蛋白 VI 竞争性拮抗剂 Revacept 是否会减少缺血性病灶的发生。
方法
这项国际性、多中心（16 个地点）、3 臂、随机（1:1:1）、双盲、平行组的研究，纳入了伴有症状性 ICA 狭窄的患者。在遵循指南的抗血小板治疗的基础上，患者接受静脉输注 20 分钟安慰剂、40mg 或 120mg Revacept，主要评估探索性疗效终点：治疗开始后扩散加权磁共振成像上新的缺血性病灶数量。主要临床终点是包括任何卒中和死亡、短暂性脑缺血发作、心肌梗死、冠状动脉介入和随访期间出血并发症的联合安全性和疗效终点。
结果
在 160 名随机患者中，158 名患者（68±10.1 岁，24%为女性）接受了研究药物治疗（51 名患者接受安慰剂，54 名患者接受 40mg Revacept，53 名患者接受 120mg Revacept），并随访了 11.2±2.3 个月。在安慰剂/40mg/120mg Revacept 组中，分别有 1.16（95%CI，0.88-1.53）/1.05（95%CI，0.78-1.42；=0.629）/0.63（95%CI，0.43-0.93）名患者检测到新的弥散加权磁共振成像病灶，无统计学差异。在接受 120mg Revacept 的患者中观察到研究期间联合安全性和疗效终点的降低（HR，0.46 [95%CI，0.21-0.99]；=0.047），但接受 40mg Revacept 的患者与安慰剂相比无此作用（HR，0.72 [95%CI，0.37-1.42]；=0.343）。
结论
Revacept 120mg 降低了伴有症状性 ICA 狭窄患者的联合安全性和疗效终点。
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