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Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation (Dabi-ADP-2)

This study is currently recruiting participants.
Verified April 2012 by Deutsches Herzzentrum Muenchen
Sponsor:
Information provided by (Responsible Party):
Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:
NCT01352702
First received: May 11, 2011
Last updated: April 24, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Coronary Heart Disease
Atrial Fibrillation
Acute Coronary Syndrome
Atherosclerosis
 Drug: Dabigatran
Drug: Phenprocoumon
 Phase 4

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 70
Study Start Date: May 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Dabigatran Therapy
 Drug: Dabigatran
Patients assigned to this group will receive Dabigatran
Other Name: Pradaxa
Active Comparator: Arm 2
Phenprocoumon Therapy
 Drug: Phenprocoumon
Patients assigned to this group will receive Phenprocoumon
Other Name: Marcumar

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01352702

Contacts
Contact: Julinda Mehilli, MD +49 89 1218-4582 Mehilli@dhm.mhn.de
Contact: Nikolaus Sarafoff, MD +49 89 1218-4073 n.sarafoff@googlemail.com

Locations
Germany
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     n.sarafoff@googlemail.com    
Sponsors and Collaborators
Deutsches Herzzentrum Muenchen
Investigators
Principal Investigator: Julinda Mehilli, MD Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen
  More Information

No publications provided

Responsible Party: Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier: NCT01352702     History of Changes
Other Study ID Numbers: GE IDE No. A01711, 2011-000504-18
Study First Received: May 11, 2011
Last Updated: April 24, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Atherosclerosis
Atrial Fibrillation
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Acute Coronary Syndrome
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Pathologic Processes
Angina Pectoris
Chest Pain
 Pain
Signs and Symptoms
Phenprocoumon
Clopidogrel
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013