A Pharmacogenetic Study of Warfarin Dosing, "The COUMA-GEN Study"

• Status: Completed
• Trial end date: 2007-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Anticoagulation with warfarin is a common and potentially hazardous therapeutic intervention. It is a leading cause of iatrogenic bleeding events and, hence, of malpractice claims. There are no good alternatives presently for warfarin anticoagulation, and even when alternatives become available (i.e., ximelagatran), cost, labeling, and experience (outcomes-related) issues will continue to favor an extensive and ongoing use of warfarin. If the present study is able to confirm an advantage for a genotype-driven algorithm, in terms of improved efficiency, therapeutic efficacy, and, especially, safety, then a pharmacogenetics approach to warfarin dosing can be recommended as the basis for an Intermountain Health Care (IHC)-wide quality improvement initiative that should improve patient outcomes, reduce resource use (costs of achieving safe and therapeutic anticoagulation), and reduce adverse clinical events. COUMA-GEN is a prospective, randomized study of patients who are to begin chronic warfarin therapy for specific, qualifying clinical reasons (i.e., atrial fibrillation (AF), deep vein thrombosis (DVT), or post-orthopedic surgery prophylaxis). Qualifying patients will be consented and randomized to an individualized, genotype-based warfarin-dosing regimen or to standard care (without knowledge of genotype). In each study arm, a predicted maintenance dose will be determined. All patients will receive a baseline International Normalized Ratio (INR). For patients in all 3 entry strata, a starting dose of warfarin that is twice the assigned daily maintenance dose (according to the specific treatment arm) will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Intermountain Health Care, Inc.
• Collaborators: Deseret Foundation; LDS Hospital Cardiovascular Research
• Treatments: Warfarin

Criteria

Inclusion Criteria:

• The patient (male or non-pregnant/non lactating female1) must be > 18 years of age.

• The patient or legally authorized representative must sign a written informed consent, prior to the procedure.

• The potentially eligible patient is at high (post-orthopedic surgery) risk of DVT and the treatment plan will include anticoagulation using warfarin with standard of care follow up including INR assessment.

• The potentially eligible patient is diagnosed with DVT or at high (post-orthopedic surgery) risk of DVT and the treatment plan will include anticoagulation using warfarin with standard of care follow up including INR assessment.

• Patient is diagnosed with atrial fibrillation (AF) and the treatment plan will include anticoagulation using warfarin with standard of care follow up including INR assessment.

• Heart failure patients (EF<25% or apical akinesis or left ventricular aneurysm or extensive wall motion abnormality) in sinus rhythm being started on warfarin to reduce the risk of thromboembolism.

• Women of childbearing potential must be using adequate measures of contraception (as determined by the Investigator) to avoid pregnancy and should be highly unlikely to conceive during the study period.

• Women of childbearing potential must have a negative pregnancy test at screen.

Exclusion Criteria:

• Pregnant and/or lactating women and women of child bearing potential not using acceptable means of contraception.

• Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study.