Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial
Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial
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DOI：
10.1016/s0140-6736(15)00515-2
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发表时间：
2016-01-23
期刊：
影响因子：
168.9
通讯作者：
Alexander, John H.
中科院分区：
文献类型：
--
作者：
Lincoff, A. Michael;Mehran, Roxana;Alexander, John H.
背景 REG1 是一种新型抗凝系统，由凝血因子 IXa 的 RNA 适体抑制剂 pegnivacogin 和互补序列反转寡核苷酸 anivamersen 组成。我们测试了这样的假设：在经皮冠状动脉介入治疗期间，使用pegnivacogin几乎完全抑制因子IXa，然后用anivamersen部分逆转，与比伐卢定相比，可以减少缺血事件，而不增加出血。方法我们在北美和欧洲的225家医院进行了一项随机、开放标签、主动对照、多中心、优效性试验，以比较REG1与比伐卢定。我们计划将 13 200 名接受经皮冠状动脉介入治疗的患者以 1:1 的比例随机分配至 REG1（pegnivacogin 1 mg/kg 推注[>99% 因子 IXa 抑制]，然后经皮冠状动脉介入治疗后用阿尼瓦默森 80% 逆转）或比伐卢定。排除标准包括48小时内ST段抬高型心肌梗死。主要疗效终点是随机分组后第 3 天的全因死亡、心肌梗塞、中风和计划外目标病变血运重建的复合终点。主要安全终点是大出血。分析是按意向治疗进行的。该试验已在 ClinicalTrials.gov 注册，标识符 NCT01848106。由于严重过敏反应，该试验在入组 3232 名患者后提前终止。结果，1616 名患者被分配 REG1，1616 名患者被分配比伐卢定，其中分别有 1605 名和 1601 名患者接受了指定治疗。 1605 名接受 REG1 治疗的患者中有 10 名 (1%) 报告出现严重过敏反应，而接受 REG1 治疗的患者中有 1 名（
Background REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding.Methods We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13 200 patients undergoing percutaneous coronary intervention in a 1: 1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions.Findings 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (