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

The objectives of this study are to determine

• whether the pharmacogenetic guided arm can maintain patients a greater time in therapeutic range (TTR - percentage of values in the targeted therapeutic range once a therapeutic INR has been established) without clinical adverse events (i.e., bleeding complications or thromboembolic events),
• whether the pharmacogenetic guided arm can achieve a higher percentage of therapeutic warfarin levels by days 5 and 8 of therapy (without intervening non-study dose adjustment), and
• whether the pharmacogenetic guided arm can reduce the need for unplanned dose adjustments and additional INR measurements because of excessive (or insufficient) INR level and clinical adverse events, i.e., bleeding complications or thromboembolic events.

The goal is to achieve >75% TTR in the PG-algorithm arm. Compare proportion of patients reaching therapeutic INR on days 5 and 8 and the subsequent and overall proportion ("time") of INR measurements in therapeutic range (TTR) over 3 months between standard and PG-based arms.

This study will enroll 200 qualifying, consenting patients of either gender, 18 years and above, any ethnicity, with life expectancies > 1 year, beginning on chronic outpatient warfarin therapy for AF, or emergency department/outpatient therapy for spontaneous DVT, or inpatient therapy (and continued for 1 mo) after orthopedic surgery for DVT prevention, or heart failure patients (EF<25% or apical akinesis or left ventricular aneurysm or extensive wall motion abnormality) being started on therapy to reduce the risk of thromboembolism.

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.