Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01852162
First received: May 8, 2013
Last updated: March 3, 2014
Last verified: March 2014

May 8, 2013
March 3, 2014
February 2012
January 2014   (final data collection date for primary outcome measure)
Platelet reactivity [ Time Frame: 1 week ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01852162 on ClinicalTrials.gov Archive Site
Thrombin generation profiles [ Time Frame: 1-week ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy
Pharmacodynamic Effects of Dabigatran in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of treatment for prevention of atherothrombotic events in patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI). Many patients on dual antiplatelet therapy in this setting may be affected by other thromboembolic conditions, in particular atrial fibrillation, therefore having an indication to also receive oral anticoagulation for stroke prevention. Thus, a considerable percentage of patients are under "triple therapy" which consists of aspirin plus clopidogrel plus an oral anticoagulant. The ever raising population with CAD warranting triple therapy and the growing number of patients being treated with dabigatran underscores the importance of understanding the pharmacodynamic effects of this treatment regimen.

Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of treatment for prevention of atherothrombotic events in patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI). Many patients on dual antiplatelet therapy in this setting may be affected by other thromboembolic conditions, in particular atrial fibrillation, therefore having an indication to also receive oral anticoagulation for stroke prevention. Thus, a considerable percentage of patients are under "triple therapy" which consists of aspirin plus clopidogrel plus an oral anticoagulant. Although this combination therapy allows a reduction of atherothrombotic and thromboembolic events, patients on triple therapy are at an increased risk of bleeding complications.

Dabigatran, a synthetic, reversible direct thrombin inhibitor, has been studied as an alternative to warfarin in patients with atrial fibrillation and has been shown to be at least as efficacious with a favorable safety profile. In particular, dabigatran at a dose of 110 mg is associated with rates of stroke and systemic embolism similar to warfarin, with lower rates of major hemorrhage, while a dose of 150 mg is associated with lower thrombotic events with similar rates of bleeding events. These findings have led the Food and Drug Administration (FDA) to approve dabigatran for use in atrial fibrillation patients in December 2011 and this has also been implemented in practice guidelines to be a superior strategy to warfarin. However, the FDA only approved the 150mg formulation.

Dabigatran has high affinity and specificity for its target serine protease thrombin, and one small study shows that dabigatran produced potent inhibition of thrombin-induced platelet aggregation in vitro. However, there are no studies assessing the ex vivo pharmacodynamic effects of dabigatran in patients on dual antiplatelet therapy. The ever raising population with CAD warranting triple therapy and the growing number of patients being treated with dabigatran underscores the importance of understanding the pharmacodynamic effects of this treatment regimen.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Coronary Artery Disease
Drug: Dabigatran
Dabigatran 150mg
Other Name: Pradaxa
  • Experimental: Dabigatran
    Dabigatran 150mg
    Intervention: Drug: Dabigatran
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Dabigatran
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
February 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with known CAD
  • On maintenance treatment with aspirin (81 to 325mg per day) and clopidogrel (75 mg per day) for at least for at least 4-weeks as per standard of care.
  • Age between 18 and 80 years old.

Exclusion Criteria:

  • Transient ischemic attack or ischemic stroke in the past 6 months.
  • Prior hemorrhagic stroke (irrespective of timing).
  • Known allergies to dabigatran.
  • On treatment with Coumadin derivate or have an indication to be on Coumadin treatment (atrial fibrillation, prosthetic valve, DVT/pulmonary embolism).
  • Platelet count <80x106/mL
  • Active bleeding or hemodynamic instability.
  • Creatinine clearance <30 mL/minute.
  • Baseline ALT >2.5 times the upper limit of normal.
  • Hemoglobin < 10 gm/dL
  • Pregnant females*. *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01852162
UFJ 2011-112
Yes
University of Florida
University of Florida
Not Provided
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
University of Florida
March 2014

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