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

Atrial Fibrillation Clinical Trial

— Dabi-ADP-2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01352702
• Other study ID #: GE IDE No. A01711
• Secondary ID: 2011-000504-18
• Status: Terminated
• Phase: Phase 4
• First received: May 11, 2011
• Last updated: February 4, 2015
• Start date: May 2011
• Est. completion date: May 2014

Study information

• Verified date: February 2015
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key 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.

Key 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atherosclerosis
• Atrial Fibrillation
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Myocardial Ischemia

Intervention

Drug:
• Dabigatran
Patients assigned to this group will receive Dabigatran
• Phenprocoumon
Patients assigned to this group will receive Phenprocoumon

Locations

Country	Name	City	State
Germany	Deutsches Herzzentrum Muenchen	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ADP induced platelet aggregation	To determine whether there are differences in ADP induced platelet aggregation after 2 weeks in patients receiving dabigatran or phenprocoumon.	2 weeks	No
Secondary	Platelet function tests	ADPtest HS (MEA) , TRAP, Collagen	2 weeks	No
Secondary	Coagulation parameters	aPTT, INR, Thrombin coagulation time	2 weeks	No