Overcoming High On-Treatment Platelet Reactivity (HPR) During Prasugrel Therapy
试验速览
- 阶段
- 4 期
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients
研究概览
简要总结
The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable Coronary artery disease (CAD) patients who exhibit high-on prasugrel platelet reactivity defined as Vasodilator Stimulated Phosphoprotein-Phosphorylation (VASP-P) >50%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female; age ≥ 18 and < 75 years
- •Weight ≥ 60 kg
- •Currently on ASA therapy and eligible to reduce ASA dose to 81 mg daily if on higher dosing
- •On stable prasugrel maintenance dose for ≥1 month
- •Stable CAD patients defined as: subjects with documented evidence of a history of atherosclerotic coronary artery disease/surgical revascularization (defined as either a prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery). A minimum of 1 month must have elapsed between a subject's enrolment and any acute event, revascularization procedure or hospitalization for chest pain for that subject.
- •If female, may be enrolled if one of the following 3 criteria are met: 1)Had a hysterectomy or tubal ligation at least 6 months prior to signing ICF, 2)Post-menopausal for at least 1 year, 3)If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy.
- •Able and willing to provide written informed consent before entering the study
排除标准
- •Subject plans to undergo coronary revascularization at any time during the trial
- •Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)
- •History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope)
- •History or evidence of congestive heart failure (New York Heart Association Class III or above ≤ 6 months before screening
- •Severe hepatic impairment defined as ALT> 2.5 X ULN
- •Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening
- •Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on dialysis
- •Concomitant use with parenteral or oral anticoagulants
- •Platelet count <100 X103
研究组 & 干预措施
HPR Group
This arm will be split into Group A and Group B which will receive Ticagrelor/Prasugrel in a crossover manner.
干预措施: Prasugrel (Drug)
HPR Group
This arm will be split into Group A and Group B which will receive Ticagrelor/Prasugrel in a crossover manner.
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Pharmacodynamic (PD) Vasodilator Stimulated Phosphoprotein-Phosphorylation(VASP-P) in High On Prasugrel Platelet Reactivity(HPPR) stable CAD patients
时间窗: 2 hours, 4 hours, and 14 days
The primary objective is to determine the pharmacodynamic effect of ticagrelor dosing (180mg LD/ 90mg BID) at 2, 4 hours and 14 days in stable CAD patients who exhibit high-on prasugrel platelet reactivity defined as VASP-P\>50%.
次要结局
- PD VerifyNow in HPPR stable CAD patients(2 hour, 4 hour, 14 days)
- PD LTA in HPPR stable CAD patients(2 hours, 4 hours, 14 days)
- Frequency of HPR(2 hours, 4 hours, and 14 days)
- Prevalence of HPPR(2 hours, 4 hours, and 14 days)
- CYP2C19 relation to occurence of HPPR(2 hours, 4 hours, and 14 days)
- PD effect(Prasugrel) relation to CYP2C19(2 hours, 4 hours, and 14 days)