Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy

NCT ID: NCT01852162

Last Updated: 2015-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-02-28

Brief Summary

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.

Detailed Description

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dabigatran

Dabigatran 150mg

Group Type: EXPERIMENTAL

Dabigatran

Intervention Type: DRUG

Dabigatran 150mg

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets

Interventions

Dabigatran

Dabigatran 150mg

Intervention Type: DRUG

Placebo

Matching placebo tablets

Intervention Type: DRUG

Other Intervention Names

Pradaxa

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick Angiolillo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

UFJ 2011-112

Identifier Type: -

Identifier Source: org_study_id