Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study
Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study
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DOI：
10.1016/s0140-6736(09)60230-0
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发表时间：
2009-03-14
期刊：
影响因子：
168.9
通讯作者：
Harrington, Robert A.
中科院分区：
文献类型：
--
作者：
Becker, Richard C.;Moliterno, David J.;Harrington, Robert A.
背景：需要一种抗血栓药物来安全地减少接受经皮冠状动脉介入治疗(PCI)患者的心血管事件。因此，我们评估了口服血小板蛋白酶激活受体-1拮抗剂SCH 530348的耐受性和安全性。方法在一项多中心国际研究中，我们将45岁或以上接受非紧急经皮冠状动脉介入治疗或冠状动脉造影术的患者随机分配到口服负荷剂量SCH 530348(10 mg、20 mg或40 mg)或匹配的安慰剂，比例为3：1。在SCH 530348组中，随后接受经皮冠状动脉介入治疗(主要经皮冠状动脉介入治疗)的患者继续服用口服维持量(每天0.5mg1.0或2.5mg)，而安慰剂组的患者继续服用安慰剂60天。主要终点是根据心肌梗死溶栓(TIMI)分级，临床上有意义的大出血或轻微出血的发生率。研究人员和患者都不知道治疗分配。分析采用意向治疗。这项研究在ClinicalTrials.gov上注册，编号NCT00132912。结果257名患者被分配给安慰剂，773名患者被分配到SCH 530348。在SCH 530348 10毫克组、20毫克组和40毫克组的129名患者中分别有2名(2%)、120名患者中的3名(3%)和173名患者中的7名(4%)出现了主要终点，而安慰剂组中有5名患者(3%)出现了主要终点(p=0.5786)。口服SCH 530348每天1次，每次0.5 mg、1 mg和2.5 mg，3例(2%)、5例(4%)和4例(3%)发生TIMI大出血和轻度出血(p=0.7561)。有必要在第三阶段试验中进一步测试，以准确确定SCH 530348的安全性和有效性。
Background An antithrombotic drug is needed that safely reduces cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We therefore assessed the tolerability and safety of SCH 530348-an oral platelet protease-activated receptor-1 antagonist.Methods We randomly assigned patients aged 45 years or older and undergoing non-urgent PCI or Coronary angiography with planned PCI to an oral loading dose of SCH 530348 (10 mg, 20 mg, or 40 mg) or matching placebo in a 3:1 ratio in a multicentre international study. Those in the SCH 530348 group who subsequently underwent PCI (primary PCI cohort) continued taking an oral maintenance dose (0.5 mg, 1.0 mg, or 2.5 mg per day), and patients in the placebo group continued placebo for 60 days. The primary endpoint was the incidence of clinically significant major or minor bleeding according to the thrombolysis in myocardial infarction (TIMI) scale. Both investigators and patients were unaware of treatment allocation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00132912.Findings 257 patients were assigned to placebo and 773 to SCH 530348. The primary endpoint occurred in 2 (2%) of 129, 3 (3%) of 120, and 7 (4%) of 173 patients, respectively, in the SCH 530348 10 mg, 20 mg, and 40 mg groups compared with 5 (3%) of 151 patients in the placebo group (p=0.5786). TIMI major plus minor bleeding occurred in 3 (2%) of 136, 5 (4%) of 139, and 4 (3%) of 138 patients given SCH 530348 0.5 mg, 1.0 mg, and 2.5 mg once per day, respectively (p=0.7561).Interpretation Oral SCH 530348 was generally well tolerated and did not cause increased TIMI bleeding, even when administered concomitantly with aspirin and clopidogrel. Further testing in phase III trials to accurately define the safety and efficacy of SCH 530348 is warranted.