Randomized, Crossover Study of the Antithrombotic Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin When Administered With Bivalirudin
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
研究概览
简要总结
The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).
详细描述
The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.
It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female volunteers between 18 and 65 years old.
- •Body mass index (BMI) 18 - 30 kg/m2 inclusive.
- •Healthy as assessed by a detailed medical history and physical examination.
- •Laboratory est results within the normal range.
- •Ability to provide signed informed consent.
排除标准
- •History of clinically relevant disease, bleeding, acute infectious disease or signs of acute illness.
- •Allergy or hypersensitivity to aspirin or thienopyridines, or atopy diagnosed by a physician.
- •Use of medication within one month prior to study drug administration.
- •History of drug abuse or alcohol consumption >20 g/day.
- •Inability to abstain from intensive muscular effort or sport competition.
- •Loss of >400 mL blood or blood donation within 3 months.
- •Positive serology for hepatitis B (HBs Ag) or hepatitis C.
- •Conditions associated with hemorrhagic risk.
- •Positive pregnancy test.
研究组 & 干预措施
Ticagrelor + ASA + Bivalirudin
Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
干预措施: Ticagrelor + ASA + Bivalirudin (Drug)
Clopidogrel + ASA + Bivalirudin
Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
干预措施: Clopidogrel + ASA + Bivalirudin (Drug)
结局指标
主要结局
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
时间窗: Pre-treatment baseline and 24 hrs post treatment
Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
次要结局
- Platelet Reactivity(24-hours post-treatment)
- Blood Thrombogenicity(24-hours post-treatment)
研究者
Juan J Badimon
Director, AtheroThrombosis Research Unit
Icahn School of Medicine at Mount Sinai