Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Pharmacodynamic Effects of Dabigatran in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel|
- TRAP-induced Platelet Aggregation [ Time Frame: 1 week ] [ Designated as safety issue: No ]TRAP-induced platelet aggregation measured by light transmittance aggregometry (LTA) was similar between groups
- Platelet Reactivity Measured by LTA [ Time Frame: 1-week ] [ Designated as safety issue: No ]Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by light transmittance aggregometry (LTA).
- Platelet Reactivity Measured by Multiple Electrode Aggregometry. [ Time Frame: 1-week ] [ Designated as safety issue: No ]Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by multiple electrode aggregometry.
- Clot Kinetic: Thrombin Activity [ Time Frame: 1-week ] [ Designated as safety issue: No ]Parameters related to thrombin activity and velocity of thrombus generation (reaction time: R; time to maximum rate of thrombus generation: TMRTG) were evaluated by thromboelastography.
- Clot Kinetic: Clot Stength [ Time Frame: 1-week ] [ Designated as safety issue: No ]Clot strength (maximal amplitude:MA) was assessed by thromboelastography.
|Study Start Date:||February 2012|
|Study Completion Date:||February 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Other Name: Pradaxa
Placebo Comparator: Placebo
Matching placebo tablets
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01852162
|United States, Florida|
|University of Florida|
|Jacksonville, Florida, United States, 32209|
|Principal Investigator:||Dominick Angiolillo, MD, PhD||University of Florida|