Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation

NCT ID: NCT01352702

Last Updated: 2015-02-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-05-31

Brief Summary

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.

Detailed Description

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).

Conditions

Coronary Heart Disease; Atrial Fibrillation; Acute Coronary Syndrome; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Dabigatran Therapy

Group Type: EXPERIMENTAL

Dabigatran

Intervention Type: DRUG

Patients assigned to this group will receive Dabigatran

Arm 2

Phenprocoumon Therapy

Group Type: ACTIVE_COMPARATOR

Phenprocoumon

Intervention Type: DRUG

Patients assigned to this group will receive Phenprocoumon

Interventions

Dabigatran

Patients assigned to this group will receive Dabigatran

Intervention Type: DRUG

Phenprocoumon

Patients assigned to this group will receive Phenprocoumon

Intervention Type: DRUG

Other Intervention Names

Pradaxa; Marcumar

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julinda Mehilli, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen

Locations

Deutsches Herzzentrum Muenchen

Munich, , Germany

Countries

Germany

Other Identifiers

2011-000504-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GE IDE No. A01711

Identifier Type: -

Identifier Source: org_study_id