Impact of Dabigatran and Phenprocoumon on ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation (Dabi-ADP-1)

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Dabigatran; Drug: Phenprocoumon

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).

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 80636
    • Deutsches Herzzentrum Muenchen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Dabigatran Therapy	Drug: Dabigatran; Patients assigned to this group will receive Dabigatran; Other Names: Pradaxa
Active Comparator: Arm 2; Phenprocoumon Therapy	Drug: Phenprocoumon; Patients assigned to this group will receive Phenprocoumon; Other Names: Marcumar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet function tests	ADPtest HS (MEA) , TRAP, Collagen	2 weeks
Coagulation parameters	aPTT, INR, Thrombin coagulation time	2 weeks

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 20, 2011
• First Posted (Estimate): April 21, 2011

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran; Phenprocoumon
• Other Study ID Numbers: GE IDE No. A01611; 2011-000503-40 (EudraCT Number)