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

NCT00334464 | Completed

• 1 other identifier: 128-120
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Atrial Fibrillation; Deep Vein Thrombosis; Pulmonary Embolism

Keywords

warfarin metabolism; CYP2C0; anticoagulation; genotyping; DVT; PE

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (6)

• 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)

Interventions

Standard of care or genotyping dosing of warfarin dosing DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Intermountain Health Care, Inc.: lead
• Deseret Foundation: collaborator
• LDS Hospital Cardiovascular Research: collaborator

Study Sites (1)

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thrombosis; Pulmonary Embolism

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jeffrey L Anderson

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 5, 2006
• First Posted: June 7, 2006
• Study Start: February 1, 2006
• Study Completion: November 1, 2007
• Last Updated: August 21, 2008

Record last verified: 2008-08

Locations

US (1)