Pharmacodynamic Assessment of Ticagrelor vs High Dose Clopidogrel in Patients With ST Elevation Myocardial Infarction Exhibiting High Platelet Reactivity Post Fibrinolysis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Platelet reactivity at 2 hours post randomization between the 2 treatment arms
研究概览
简要总结
This is a two-center, prospective, randomized, single-blind, investigator initiated, pharmacodynamic study of parallel design, carried out in 2 PCI-capable cardiology centers (Patras University Hospital and Konstantopoulio General Hospital of Athens).
Patients with ST elevation myocardial infarction, having undergone fibrinolysis in the previous 3 to 48 hours, who present high residual PR (defined as PRU ≥208 ) on admission, pre coronary angiography, will be randomized after written informed consent, in a 1:1 ratio to either:
Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD, until discharge.
Or
Clopidogrel 600mg loading dose (LD), followed by a 150mg once daily maintenance dose (MD) starting 12±6 hours post LD, until discharge.
Platelet reactivity assessment will be performed at randomization (Hour 0) and at 2, 24 hours after randomization, as well as pre-discharge, using the VerifyNow assay, in platelet reactivity units (PRU).
Documentation of major adverse cardiac events (death, myocardial infarction, stroke, ischemia driven revascularization procedure with PCI or CABG) and bleeding (according to BARC criteria) will be performed until patient's discharge.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-85 years old
- •Patients with STEMI, having undergone fibrinolytic therapy in the previous 3 to 48 hours
- •Presenting HPR (≥208 PRU) post 300mg clopidogrel loading dose ( assessment immediately before coronary angiography)
- •Informed consent obtained in writing
排除标准
- •Pregnancy
- •Breastfeeding
- •Inability to give informed consent
- •Cardiogenic shock
- •Major periprocedural complications (death, stent thrombosis, vessel perforation, arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, vascular injury (arteriovenous shunt, retroperitoneal bleeding), major bleeding (need for bood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding)
- •Known hypersensitivity to ticagrelor or clopidogrel
- •History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
- •Other bleeding diathesis, or considered by investigator to be at high risk for bleeding
- •Any previous history of stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
- •Thombocytopenia (<100.000 / μL) at randomization
- •Anaemia (Hct <30%) at randomization
- •Polycytaemia (Hct > 52%) at randomization
- •Periprocedural IIb/IIIa inhibitors administration
- •Per os anticoagulants
- •Recent (< 6 weeks) major surgery or trauma, including GABG.
- •Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
- •Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin /rifampicin, phenytoin, carbamazepine).
- •Increased risk of bradycardiac events.
- •Dialysis required.
- •Severe uncontrolled chronic obstructive pulmonary disease
- •Known severe hepatic impairement
研究组 & 干预措施
Ticagrelor
Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD, until discharge.
干预措施: Ticagrelor 180mg loading dose and 90mg bid maintenance dose (Drug)
Clopidogrel
Clopidogrel 600mg loading dose (LD), followed by a 150mg once daily maintenance dose (MD) starting 12±6 hours post LD, until discharge.
干预措施: Clopidogrel 600mg loading dose and 150mg maintenance dose (Drug)
结局指标
主要结局
Platelet reactivity at 2 hours post randomization between the 2 treatment arms
时间窗: 2 hours
Platelet reactivity at 2 hours post randomization between the 2 treatment arms
次要结局
- Platelet reactivity at 24 hours post randomization between the 2 treatment arms.(24 hours)
- Platelet reactivity pre-discharge between the 2 treatment arms(5 days)
- High on treatment platelet reactivity (HPR) rate (≥208 PRU) at 2 hours post randomization(2 hours)
- High on treatment platelet reactivity (HPR) rate (≥208 PRU) at 24 hours post randomization(24 hours)
- High on treatment platelet reactivity (HPR) rates (≥208 PRU) pre discharge(5 days)
研究者
Dimitrios Alexopoulos
Professor
University of Patras