De-Escalation of Antiplatelet Therapy to Evaluate Platelet Reactivity and Clinical Outcomes After Coronary Stenting in Patients at High Bleeding Risk and Recent Acute Coronary Syndrome: DESC-HBR Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Proportion of Patients Achieving Optimal Platelet Reactivity (OPR) at peak level following Drug Maintenance Dose (MD) Using the VerifyNow System
研究概览
简要总结
High bleeding risk (HBR) patients, comprising up to 50% of those presenting with acute coronary syndrome (ACS), are a high-risk group that is increasing in size due to an aging population. The optimal selection of the potency and duration of antiplatelet therapy to reduce the risk of recurrent ischemic and bleeding events in HBR patients is still a matter of debate. Multiple strategies to reduce bleeding during secondary prevention, such as reducing the duration of dual antiplatelet therapy, using single antiplatelet therapy with a P2Y12 inhibitor, or de-escalating to a lower potency or lower-dose P2Y12 inhibitor, have been proposed. De-escalation to a lower potency or lower-dose P2Y12 inhibitor is particularly attractive because it maintains efficient pharmacological inhibition of multiple platelet pathways while potentially reducing bleeding through less aggressive activity. Yet, there has been no study comparing the effects of different de-escalation strategies with the standard potent P2Y12 inhibitors in HBR patients. The aim of the DESC-HBR study is to assess the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid in HBR patients, in comparison with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR). Secondary objectives involve exploring the effect of de-escalation on clinical events and patients' quality of life.
详细描述
The aim of the DESC-HBR trial is to compare the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid, with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR). The secondary objective is to explore the effect of de-escalating P2Y12 inhibitor therapy on clinical events and patients' quality of life. The primary outcome is the proportion of patients in the OPR range measured through the VerifyNow system at peak level after drug maintenance dose (MD) at 14±2 days. OPR is defined as a platelet reactive unit (PRU) between 85 and 208 reactivity units based on international consensus. A key secondary outcome will be major, minor and nuisance bleeding according to the bleeding academic research consortium (BARC) definition up to 5 months. Secondary pharmacodynamic outcomes include platelet reactivity with the VerifyNow and T-TAS system at different timepoints (baseline, 2h after first dose, through levels before MD and peak levels after MD at 14±2 days). Further pharmacodynamic assessment at 1 and 2 weeks after P2Y12 inhibitor discontinuation will be performed in the subset of patients discontinuing P2Y12 inhibitor at study conclusion or in case of P2Y12 discontinuation at anytime during the study.Other secondary endpoints will be explored including all-cause death, major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR) and stroke, net adverse clinical events (NACE), a composite of MACCE and BARC 2-5 bleeding, and each individual endpoint singularly appraised. Quality of life will be evaluated with health mobility and performance scales (i.e. EQ-5D-5L, SF-12), perceived stress scale (i.e. PPS).Cost-effectives analysis will be also carried out by inputting direct and indirect costs in relation to outcomes. Study visits are scheduled at baseline,14±2 days, 3 and 5 months after randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
CLOPIDOGREL 75 mg qd
50 patients treated with clopidogrel 75mg
干预措施: P2Y12 inhibitor de-escalation (Drug)
PRASUGREL 5mg qd
50 patients treated with prasugrel 5mg
干预措施: P2Y12 inhibitor de-escalation (Drug)
TICAGRELOR 60mg bid
50 patients treated with ticagrelor 60mg bid
干预措施: P2Y12 inhibitor de-escalation (Drug)
Continue Potent P2Y12i Full-Dose
50 patients in the full-dose potent P2Y12 inhibitor (prasugrel 10 mg or ticagrelor 90 mg bid according to prior prescription)
干预措施: P2Y12 inhibitor de-escalation (Drug)
结局指标
主要结局
Proportion of Patients Achieving Optimal Platelet Reactivity (OPR) at peak level following Drug Maintenance Dose (MD) Using the VerifyNow System
时间窗: 2 hours after drug MD at 14±2 days from study inclusion
The incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system. OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus.
次要结局
- Cost-effectiveness(5 Months after enrollment)
- Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS)(baseline, 2 hours after the first treatment administration, before and after MD at 14±2 days from study inclusion.)
- Adverse clinical event(14±2 days, 3 and 5 months from study inclusion)
- Incidence of Bleeding Events According to Multiple Bleeding Definitions(5 Months after enrollment)
- Proportion of high platelet reactivity (HPR) and the proportion of low platelet reactivity (LPR) measured through the VerifyNow system(baseline, 2 hours after the first treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days)
- Platelet reactive units (PRU) at VerifyNow system(baseline, 2 hours after the first treatment administration and before MD at 14±2 days from study inclusion)