Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation (Dabi-ADP-2)
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.
Coronary Heart Disease
Acute Coronary Syndrome
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation|
- ADP induced platelet aggregation [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]To determine whether there are differences in ADP induced platelet aggregation after 2 weeks in patients receiving dabigatran or phenprocoumon.
- Platelet function tests [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]ADPtest HS (MEA) , TRAP, Collagen
- Coagulation parameters [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]aPTT, INR, Thrombin coagulation time
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Patients assigned to this group will receive Dabigatran
Other Name: Pradaxa
Active Comparator: Arm 2
Patients assigned to this group will receive Phenprocoumon
Other Name: Marcumar
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).
|Contact: Julinda Mehilli, MD||+49 89 1218-4582||Mehilli@dhm.mhn.de|
|Contact: Nikolaus Sarafoff, MD||+49 89 email@example.com|
|Deutsches Herzzentrum Muenchen||Recruiting|
|Munich, Germany, 80636|
|Contact: Julinda Mehilli, MD +49 89 1218-4582 Mehilli@dhm.mhn.de|
|Contact: Nikolaus Sarafoff, MD +49 89 1218-4073 firstname.lastname@example.org|
|Principal Investigator:||Julinda Mehilli, MD||Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen|