A Pharmacogenetic Study of Warfarin Dosing, "The COUMA-GEN Study"
Deep Vein Thrombosis
Drug: Standard of care or genotyping dosing of warfarin dosing
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Controlled Clinical Pharmacogenetic Study of a CYP2C9 Plus VKORC1 Polymorphism-Based Individualized Dosing Algorithm for Warfarin to Increase Efficiency of Achieving Therapeutic Dosing|
- A comparison of the per-patient percentage of out-of-range INRs (<2, >3) over the observation period of up to 3 months as compared with standard (empiric) dosing of warfarin.
- The percentage of out-of-range INRs among patients with at least 1 variant allele
- The time within the therapeutic INR range of 2-3 (TTR) over the length of study follow-up
- The proportion of patients reaching therapeutic INR on days 5 and 8
- The time to first therapeutic INR value
- The total number of INR measurements made (for safety, efficiency or dose determination reasons)
- The number of adverse clinical events in each group, defined as an INR>3.9, clinical bleeding events more than minor (e.g., bruising), major bleeding events, thromboembolic events, stroke (all-cause), MI, and death (all-cause).
|Study Start Date:||February 2006|
|Study Completion Date:||November 2007|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334464
|United States, Utah|
|Salt Lake City, Utah, United States, 84143|
|Principal Investigator:||Jeffrey L Anderson||Intermountain Health Care, Inc.|