The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings (MHSMayoWarf1)

This study has been completed.
Sponsor:
Collaborators:
Mayo Clinic
Washington University School of Medicine
Information provided by:
Medco Health Solutions, Inc.
ClinicalTrials.gov Identifier:
NCT00830570
First received: January 26, 2009
Last updated: November 15, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention
Embolism and Thrombosis
Embolism
Vascular Diseases
Warfarin
Venous Thromboembolism
Thrombosis
Thromboembolism
Other: CYP 2C9 and VKORC1 Testing for Warfarin

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: in Typical Community Practice Settings

Resource links provided by NLM:


Further study details as provided by Medco Health Solutions, Inc.:

Primary Outcome Measures:
  • 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. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The secondary objective is to determine physician and patient acceptance of the technology. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood draw and buccal swab


Enrollment: 1635
Study Start Date: July 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Historical control group. Patients in this group are drawn from the same plan populations as the intervention group, but they are identified during the 1-year period prior to the start of patient enrollment in the intervention group. The historical control group is closely matched with the intervention group on demographic characteristics, practice patterns, and benefit plan features that may affect resource utilization.
2
Concurrent control group. Patients in this group are drawn from different set of plan populations, but they initiate warfarin treatment during the same time period as patients in the intervention group. Outcomes data for the concurrent control group will be used to evaluate whether any differences between the intervention group and the historical control group can be attributed to changes in clinical practice over time. Baseline data for the concurrent control group will help validate the incidence assumptions used in the calculation of statistical power. This use of baseline population norms is an effective means of limiting bias in quasi-experimental studies.
3
Active study group. For plans participating in the active arm of the study, enrollment is offered to every patient who initiates warfarin therapy during the enrollment period (beginning in July 2007) and who meets the eligibility criteria. Patients are identified for the active study group if they have a warfarin pharmacy claim and no prior warfarin claims during the preceding 180 days. Only patients who remain eligible for the pharmacy benefit throughout the study period are included in the final sample.
Other: CYP 2C9 and VKORC1 Testing for Warfarin
Test patients for their warfarin sensitivity and provide this information to their physician authorizing the test.
Other Name: Genetic testing for drug sensitivity

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

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830570

Locations
United States, New Jersey
Medco Health Solutions, Inc.
Franklin Lakes, New Jersey, United States, 07003
Sponsors and Collaborators
Medco Health Solutions, Inc.
Mayo Clinic
Washington University School of Medicine
Investigators
Principal Investigator: Robert Epstein, MD, MS Medco Health Solutions, Inc.
  More Information

Publications:
Responsible Party: Robert Epstein, MD, MS, Medco Health Solutions, Inc.
ClinicalTrials.gov Identifier: NCT00830570     History of Changes
Other Study ID Numbers: MedcoWarfarin1
Study First Received: January 26, 2009
Last Updated: November 15, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Medco Health Solutions, Inc.:
CYP2C9
VKORC1
polymorphism
warfarin
Coumadin

Additional relevant MeSH terms:
Embolism
Vascular Diseases
Venous Thromboembolism
Venous Thrombosis
Thromboembolism
Thrombosis
Embolism and Thrombosis
Cardiovascular Diseases
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014