PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.
PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.
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DOI：
10.1161/atvbaha.120.315168
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
TRIP-PCI Investigators
中科院分区：
文献类型：
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作者：
Kuliopulos A;Gurbel PA;Rade JJ;Kimmelstiel CD;Turner SE;Bliden KP;Fletcher EK;Cox DH;Covic L;TRIP-PCI Investigators
文本中提供了补充数字内容。动脉血栓形成导致缺血性损伤，使许多心血管疾病患者的预后恶化。 PZ-128 是一种一流的 pepducin，通过靶向受体的细胞内表面，可逆地抑制血小板和其他血管细胞上的 PAR1（蛋白酶激活受体 1）。 TRIP-PCI（经皮冠状动脉介入治疗中凝血酶受体抑制性 Pepducin）试验的目的是评估 PZ-128 在接受心导管插入术并打算进行经皮冠状动脉介入治疗的患者中的安全性和有效性。在这项随机、双盲、安慰剂对照的 2 期试验中，100 名患者被随机分配 (2:1)，在标准口服抗血小板治疗的基础上，在心导管插入术开始前开始 2 小时输注，接受 PZ-128（0.3 或 0.5 mg/kg）或安慰剂。 PZ-128联合剂量组（1.6%，1/62）和安慰剂组（0%，0/35）之间的主要出血终点发生率没有差异。 PZ-128 组中 30 天和 90 天主要不良冠状动脉事件的次要终点没有显着差异，但数值较低（PZ-128 组分别为 0% 和 2%，安慰剂组分别为 6% 和 6%，p=0.13、p=0.29）。在基线心肌肌钙蛋白 I 升高的患者亚组中，30 天主要不良冠状动脉事件 + 心肌损伤的探索性终点显示，安慰剂组发生了 83% 的事件，而联合 PZ-128 药物组中发生了 31% 的事件，调整后相对风险为 0.14（95% CI，0.02-0.75）； P=0.02。在这次首次患者体验中，标准抗血小板治疗中添加 PZ-128 似乎是安全的、耐受性良好，并且可能减少围手术期肌坏死，从而为进一步的临床试验提供了基础。网址：https://www.clinicaltrials.gov。唯一标识符：NCT02561000。
Supplemental Digital Content is available in the text. Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention. In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02–0.75); P=0.02. In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02561000.