Clinical trial NCT01339819: Impact of Dabigatran and Phenprocoumon on ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation
Official title: Impact of Dabigatran and Phenprocoumon on ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
First posted: 2011-04-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate whether Dabigatran itself reduces 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 events. 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 ADP induced platelet aggregation in these patients. 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 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 concomitantly treated with clopidogrel are being studied in a different trial with a similar study design (Dabi ADP-2).

Eligibility criteria: Key Inclusion Criteria:

* Patients with atrial fibrillation and an indication for oral anticoagulation (CHA2DS2-VASc score≥ 1).
* Informed, written consent by the patient or her/his legally-authorized representative for participation in the study.

Key Exclusion Criteria:

* Age ≤18 years
* Cardiogenic shock
* Current therapy with dabigatran
* Current, recent (2 weeks) or expected (1 week) clopidogrel therapy
* Contraindication for oral anticoagulation
* Active bleeding
* Known allergy or intolerance to the study medications: dabigatran, phenprocoumon

Primary outcomes:
measure: ADP induced platelet aggregation
timeFrame: 2 weeks
Secondary outcomes:
measure: Platelet function tests
timeFrame: 2 weeks
measure: Coagulation parameters
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
Study officials:
affiliation: Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen
name: Julinda Mehilli, MD
role: PRINCIPAL_INVESTIGATOR
References: