Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  Purpose

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.


Condition Intervention
Coronary Artery Disease
Drug: Dabigatran

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Platelet reactivity [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Thrombin generation profiles [ Time Frame: 1-week ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: February 2012
Study Completion Date: February 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran
Dabigatran 150mg
Drug: Dabigatran
Dabigatran 150mg
Other Name: Pradaxa
Placebo Comparator: Placebo
Placebo
Drug: Dabigatran
Dabigatran 150mg
Other Name: Pradaxa

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852162

Locations
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01852162     History of Changes
Other Study ID Numbers: UFJ 2011-112
Study First Received: May 8, 2013
Last Updated: March 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Coronary artery disease
antiplatelet therapy
anticoagulant therapy

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases
Dabigatran
Anticoagulants
Antithrombins
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014