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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. (see Contacts and Locations)
Verified July 2013 by Deutsches Herzzentrum Muenchen
Sponsor:
Information provided by (Responsible Party):
Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:
NCT01352702
First received: May 11, 2011
Last updated: July 1, 2013
Last verified: July 2013

May 11, 2011
July 1, 2013
May 2011
April 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01352702 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation
Impact of Dabigatran and Phenprocoumon on Clopidogrel Mediated ADP Induced Platelet Aggregation in Patients With Atrial Fibrillation

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.

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).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Coronary Heart Disease
  • Atrial Fibrillation
  • Acute Coronary Syndrome
  • Atherosclerosis
  • Drug: Dabigatran
    Patients assigned to this group will receive Dabigatran
    Other Name: Pradaxa
  • Drug: Phenprocoumon
    Patients assigned to this group will receive Phenprocoumon
    Other Name: Marcumar
  • Experimental: Arm 1
    Dabigatran Therapy
    Intervention: Drug: Dabigatran
  • Active Comparator: Arm 2
    Phenprocoumon Therapy
    Intervention: Drug: Phenprocoumon
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
70
May 2014
April 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Julinda Mehilli, MD +49 89 1218-4582 Mehilli@dhm.mhn.de
Contact: Nikolaus Sarafoff, MD +49 89 1218-4073 n.sarafoff@googlemail.com
Germany
 
NCT01352702
GE IDE No. A01711, 2011-000504-18
No
Deutsches Herzzentrum Muenchen
Deutsches Herzzentrum Muenchen
Not Provided
Principal Investigator: Julinda Mehilli, MD Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen
Deutsches Herzzentrum Muenchen
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP