Clinical trial NCT00830570: The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings
Official title: in Typical Community Practice Settings
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Embolism and Thrombosis
Embolism
Vascular Diseases
Warfarin
Venous Thromboembolism
Thrombosis
Thromboembolism
Keywords: CYP2C9
VKORC1
polymorphism
warfarin
Coumadin
Lead sponsor: Medco Health Solutions, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mayo Clinic
name: Washington University School of Medicine
First posted: 2009-01-28
Enrollment: 1635
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The active study population consists of male and female covered lives with Medco for clients have agreed to enroll their members for ages 40-75 for new warfarin starts who match the inclusion criteria.

Brief summary: The purpose of this quasi-experiment study, which could also be classified as a prospective observational intervention study, is to assess the impact of cytochrome P450 2C9 (CYP 2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1) testing within a primary patient care setting.

Detailed description: Anticoagulation therapy with warfarin is the most common mode of treatment and prophylaxis for venous and arterial thromboembolic conditions. Warfarin is metabolized in the liver by the cytochrome P450 system, the cytochrome P450 2C9 (CYP 2C9) isoenzyme specifically, and polymorphisms in the CYP 2C9 gene have been associated with changes in metabolic function of the translated isoenzyme . These polymorphisms result in reduced metabolism of warfarin as compared to subjects having the wild type gene, consequently leading to systemic accumulation of warfarin; it is theorized that this leads to higher risk of adverse events. Other allelic variations have also been linked to changes in vitamin K conservation through their effects on vitamin K epoxide reductase complex, subunit 1 (VKORC1) . The combined impact of CYP 2C9 and VKORC1 polymorphisms on warfarin's pharmacology have recently been reported.

It is hypothesized that evaluation of genomic allelic type guided warfarin dosing will reduce thromboembolic and bleeding risks associated with warfarin therapy, and that adoption of a genetic testing strategy in a primary patient care setting would improve warfarin effectiveness and patient safety, and reduce costs to health care payers.

Eligibility criteria: Inclusion Criteria:

* Female and male age range of 40-75
* Patients who are in the induction phase of warfarin
* Patients receiving warfarin to prevent or treat thromboembolic conditions (e.g., post orthopedic surgery prophylaxis, deep venous thrombosis, atrial fibrillation, pulmonary embolism, heart failure)
* Patient willing to provide informed consent prior to the specimen collection procedure
* Patient whose physician is willing to order the genetic test

Exclusion Criteria:

* Age \< 40 or \> 75
* Previous use of warfarin within 180 days of initiating new warfarin therapy
* Hospitalized for seven or more days before first claim for warfarin
* Previous history of genetic testing for warfarin therapy
* Known hypersensitivity to warfarin
* Patient or physician refusal to participate in the study
* Patients using warfarin residing in Olmsted County, MN

Primary outcomes:
measure: The primary objective of the study is to determine whether the addition of genotyping to usual care will reduce the hospitalization rates for hemorrhage or thromboembolism related to warfarin use during the first 6 months of treatment.
timeFrame: 6 months
Secondary outcomes:
measure: The secondary objective is to determine physician and patient acceptance of the technology.
timeFrame: 6 months
Other outcomes:
Locations:
city: Franklin Lakes
country: United States
facility: Medco Health Solutions, Inc.
state: New Jersey
Study officials:
affiliation: Medco Health Solutions, Inc.
name: Robert Epstein, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Epstein RS, Moyer TP, Aubert RE, O Kane DJ, Xia F, Verbrugge RR, Gage BF, Teagarden JR. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol. 2010 Jun 22;55(25):2804-12. doi: 10.1016/j.jacc.2010.03.009. Epub 2010 Apr 8.