Embolism and ThrombosisMHSMayoWarf1NCT00830570
The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings
An observational study of Embolism and Thrombosis and Embolism, run by Medco Health Solutions, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Embolism and Thrombosis, Embolism, Vascular Diseases
- What is being tested?
- CYP 2C9 and VKORC1 Testing for Warfarin
- How many people
- 1,635 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Jan 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Medco Health Solutions, Inc.
Franklin Lakes, New Jersey, 07003
About this study
Official title: in Typical Community Practice Settings
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.
Read the 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.
- Conditions
- Embolism and Thrombosis, Embolism, Vascular Diseases, Warfarin, Venous Thromboembolism, Thrombosis
- Being tested
- CYP 2C9 and VKORC1 Testing for Warfarin
- Keywords
- CYP2C9, VKORC1, polymorphism, warfarin, Coumadin
- Medical subject headings
- Embolism and Thrombosis, Embolism, Vascular Diseases, Venous Thromboembolism, Thrombosis, Thromboembolism, Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYP 2C9 and VKORC1 Testing for WarfarinOther
Also called Genetic testing for drug sensitivity
Test patients for their warfarin sensitivity and provide this information to their physician authorizing the test.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: CYP 2C9 and VKORC1 Testing for Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
The secondary objective is to determine physician and patient acceptance of the technology.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2009 (estimated)
- Study startJul 2007
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Embolism and ThrombosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,635 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medco Health Solutions, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, Washington University School of Medicine
- Investigators
- Robert Epstein, MD, MS, Principal investigator, Medco Health Solutions, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00830570
- Sponsor's protocol ID
- MedcoWarfarin1
- Acronym
- MHSMayoWarf1
- Status last verified
- Nov 2010
- First submitted
- 26 Jan 2009
- Last updated
- 16 Nov 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20381283
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- in Typical Community Practice Settings
- ClinicalTrials.gov ID
- NCT00830570
- Acronym / sponsor ID
- MHSMayoWarf1 / MedcoWarfarin1
- Conditions
- Embolism and Thrombosis, Embolism, Vascular Diseases, Warfarin, Venous Thromboembolism, Thrombosis
- Keywords
- CYP2C9, VKORC1, polymorphism, warfarin, Coumadin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,635 participants (actual)
- Lead sponsor
- Medco Health Solutions, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, Washington University School of Medicine
- Study start
- Jul 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 28 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Other: CYP 2C9 and VKORC1 Testing for WarfarinActive 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. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYP 2C9 and VKORC1 Testing for WarfarinAlso: Genetic testing for drug sensitivityTest patients for their warfarin sensitivity and provide this information to their physician authorizing the test. | Other | 3 |
Primary outcome
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
1 secondary outcome
The secondary objective is to determine physician and patient acceptance of the technology.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2010.
- Results publication: PubMed 20381283Epstein 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Epstein, MD, MS principal investigator
Medco Health Solutions, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Embolism and Thrombosis and Embolism, run by Medco Health Solutions, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00830570, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2010.