A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).
研究概览
简要总结
Taken together the results from CHARISMA and PEGASUS-TIMI54, it appears that physicians may consider extending beyond 1 year or reinitiating treatment with clopidogrel 75 mg od or ticagrelor 60mg bid in patients with a prior MI and features of high ischemic and low bleeding risk. Comparative clinical or pharmacodynamic studies, however, between clopidogrel 75 mg od and ticagrelor 60 mg bid in the chronic phase of stable post MI patients have not been performed.
In a platelet substudy of PEGASUS-TIMI 54, 180 patients who had received >4 weeks of study medication had platelet reactivity assessment. Ticagrelor 60mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, with similar consistency of effect compared to 90mg bid. Platelet reactivity (PRU) was significantly reduced with ticagrelor 60mg bid compared to placebo.
In light of this, we believe that a dedicated pharmacodynamic study of ticagrelor 60 bid mg vs clopidogrel 75 mg od in a PEGASUS-like population would be informative for the practicing clinician, thus setting the rationale for conducting this specifically designed investigation.
This is a prospective, randomized, single blind, single center, crossover study. Eligible patients undergoing P2Y12 receptor antagonist therapy before screening will undergo a 14-day minimum washout period before randomization. Following screening/washout period (visit 1), patients will be randomized (visit 2, time 0) in 1:1 fashion to either clopidogrel 75 mg od or ticagrelor 60 mg bid. Following 14±2 days (visit 3) patients will receive alternate treatment for additional 14 days (visit 4). Platelet reactivity assessment will be performed with the VerifyNow P2Y12 reaction assay at time 0, prior to first study drug dose. At visit 3 platelet function will be assessed at 2-4 hours post dose and prior to crossover. At visit 4 also platelet function will be assessed at 2-4 hours post study drug post dose. All patients will receive concomitant aspirin (100 mg/d) and standard secondary prevention medication.
The primary endpoint is the platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures
- •Post-menopausal female (defined as absence of any vaginal bleeding for a year) or male aged >50 years
- •A spontaneous MI (ST or Non ST segment elevation) 1 to 3 years before enrolment. In addition, at least one of the following high-risk features: age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous MI, multivessel coronary artery disease, or non-end stage renal disease (estimated creatinine clearance of <60 ml per minute).
排除标准
- •Planned use of a P2Y12 receptor antagonist, dipyridamole, cilostazol, or anticoagulant therapy during the study period;
- •Known allergy, intolerance, hypersensitivity to ticagrelor or clopidogrel or any excipients,
- •Active pathological bleeding, severe hepatic impairment, a bleeding disorder or a history of an ischemic stroke or intracranial bleeding, a central nervous system tumor, or an intracranial vascular abnormality;
- •Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days;
- •Concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole, grapefruit juice over 1 litre daily), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine).
- •Increased risk of bradycardic events (e.g. known sick sinus syndrome or third degree AV block or previous documented syncope suspected to be due to bradycardia unless treated with a pacemaker).
- •Inability to adhere to the follow-up requirements or any other reason or condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.
研究组 & 干预措施
Clopidogrel
Clopidogrel 75 mg once daily
干预措施: Clopidogrel (Drug)
Ticagrelor
Ticagrelor 60 mg twice daily
干预措施: Ticagrelor (Drug)
Ticagrelor
Ticagrelor 60 mg twice daily
干预措施: Clopidogrel (Drug)
Clopidogrel
Clopidogrel 75 mg once daily
干预措施: Ticagrelor (Drug)
结局指标
主要结局
platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).
时间窗: 14 days
次要结局
- • VerifyNow P2Y12 assay % inhibition, using the TRAP-induced (BASE channel) response at the end of the 2 study periods(14 days)
- • High platelet reactivity rate (defined as >208 PRU) at the end of the 2 study periods(14 days)
研究者
Dimitrios Alexopoulos
Professor
University of Patras