Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- ADP induced platelet aggregation
研究概览
简要总结
The aim of this study is to evaluate whether dabigatran reduces clopidogrel mediated ADP induced platelet aggregation measured by MEA as compared to phenprocoumon after a two-week treatment with either agent.
详细描述
Oral anticoagulation with vitamin K antagonists (OAC) is the standard care for reducing stroke in patients with atrial fibrillation. Just recently the direct, competitive thrombin inhibitor dabigatran has been approved by the FDA for stroke prevention in patients with atrial fibrillation. In a large multicenter trial it was shown that dabigatran was at least as effective as Vitamin K antagonists in the prevention of stroke without an increase of major hemorrhage.
Approximately 6 % of patients who undergo coronary stenting and need DAT with aspirin and clopidogrel need in addition OAC for the reduction of cardiac, cerebral and systemic thromboembolic events5. These patients will therefore need triple therapy, a therapy which is associated with increased bleeding complications. Although phenprocoumon given solely without clopidogrel has no impact on ADP induced platelet aggregation, it has been shown that phenprocoumon significantly attenuates the antiplatelet effects of clopidogrel.
ADP induced platelet aggregation measured with multiple electrode platelet aggregometry (MEA) is a marker for the efficacy of the clopidogrel therapy and (i) a low response (AUC ≥ 468) to clopidogrel has been associated with an increase of ischemic events such as stent thrombosis and (ii) patients with an enhanced response to clopidogrel (AUC ≤ 188) have higher bleeding rates.
It is therefore crucial to evaluate whether an additional antithrombotic therapy such as dabigatran alters clopidogrel mediated ADP induced platelet aggregation. While it has been shown that intravenous administration of the direct thrombin inhibitor bivalirudin further reduces ADP induced platelet aggregation in patients on clopidogrel therapy, it is unknown whether dabigatran has also an impact on ADP induced platelet aggregation.
To evaluate the impact of dabigatran on ADP induced platelet aggregation we will randomize patients with atrial fibrillation and the need for oral anticoagulation and current clopidogrel therapy for a two-week treatment with either dabigatran or phenprocoumon and we hypothesize that dabigatran is superior to phenprocoumon in the reduction of ADP induced platelet aggregation. Patients who are not concomitantly treated with clopidogrel are being studied in a different trial with a similar study design (Dabi ADP-1).
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with atrial fibrillation and an indication for oral anticoagulation (CHA2DS2-VASc score≥ 1).
- •Current clopidogrel treatment
- •Informed, written consent by the patient or her/his legally-authorized representative for participation in the study.
排除标准
- •Age ≤18 years
- •Cardiogenic shock
- •Current therapy with dabigatran
- •Patients with a recent thromboembolic event and high thromboembolic risk requiring bridging therapy with either unfractionated heparin or LMWH
- •Contraindication for oral anticoagulation
- •Active bleeding
- •Known allergy or intolerance to the study medications: dabigatran, phenprocoumon
研究组 & 干预措施
Arm 1
Dabigatran Therapy
干预措施: Dabigatran (Drug)
Arm 2
Phenprocoumon Therapy
干预措施: Phenprocoumon (Drug)
结局指标
主要结局
ADP induced platelet aggregation
时间窗: 2 weeks
To determine whether there are differences in ADP induced platelet aggregation after 2 weeks in patients receiving dabigatran or phenprocoumon.
次要结局
- Platelet function tests(2 weeks)
- Coagulation parameters(2 weeks)