Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Platelet Reactivity by VerifyNow P2Y12
研究概览
简要总结
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients. However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects.
详细描述
Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for prevention of thrombotic events in patients with acute coronary syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events, including cardiovascular mortality. Ticagrelor was recently approved for clinical use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose. Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS patients, including those presenting with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, there are discordant data on the onset of its antiplatelet effects in this particular setting. In particular, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of ticagrelor has therefore been advocated. However, if the administration of a higher ticagrelor loading dose may overcome this limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with ST-elevation myocardial infarction undergoing primary PCI.
- •Age between 18 and 80 years old.
排除标准
- •History of prior intracranial bleeding.
- •On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.
- •Known allergies to aspirin or ticagrelor.
- •On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
- •Treatment with IIb/IIIa glycoprotein inhibitors.
- •Fibrinolytics within 24 hours
- •Known blood dyscrasia or bleeding diathesis.
- •Known platelet count <80x106/mL.
- •Known hemoglobin <10 g/dL.
- •Active bleeding.
- •Hemodynamic instability.
- •Known creatinine clearance <30 mL/minute.
- •Known severe hepatic dysfunction.
- •Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
- •Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- •Pregnant females*.
- •Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
研究组 & 干预措施
Ticagrelor 180
Standard ticagrelor 180mg loading dose
干预措施: Ticagrelor 180mg (Drug)
Ticagrelor 270mg
High ticagrelor 270mg loading dose
干预措施: Ticagrelor 270mg (Drug)
Ticagrelor 360mg
High ticagrelor 360mg loading dose
干预措施: Ticagrelor 360mg (Drug)
结局指标
主要结局
Platelet Reactivity by VerifyNow P2Y12
时间窗: 1 hour
The primary end-point of the study was the comparison of the P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1 hour after administration
次要结局
- Pharmacokinetic Profiles of Ticagrelor (AUC0-t)(24 hours)
- Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) at All Time Points(30 min and 1, 2, 4, 8, 24 hours)
- Pharmacokinetic Profiles of Ticagrelor (Cmax)(24 hours)
- Platelet Reactivity by VerifyNow P2Y12 at Other Time Points(30 min and 2, 4, 8, 24 hours)
- Pharmacokinetic Profiles of Ticagrelor (Tmax)(24 hours)