Atrial FibrillationNCT00334464
A Pharmacogenetic Study of Warfarin Dosing, "The COUMA-GEN Study"
A study of Atrial Fibrillation and Deep Vein Thrombosis, run by Intermountain Health Care, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Deep Vein Thrombosis, Pulmonary Embolism
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Nov 2007
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
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.
- Being tested
- Standard of care or genotyping dosing of warfarin dosing
- Keywords
- warfarin metabolism, CYP2C0, anticoagulation, genotyping, DVT, PE
- Medical subject headings
- Atrial Fibrillation, Venous Thrombosis, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of care or genotyping dosing of warfarin dosingDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2006 (estimated)
- Study startFeb 2006
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Deseret Foundation, LDS Hospital Cardiovascular Research
- Investigators
- Jeffrey L Anderson, Principal investigator, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00334464
- Sponsor's protocol ID
- 128-120
- Status last verified
- Aug 2008
- First submitted
- 5 Jun 2006
- Last updated
- 21 Aug 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00334464
- Acronym / sponsor ID
- 128-120
- Keywords
- warfarin metabolism, CYP2C0, anticoagulation, genotyping, DVT, PE
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Collaborators
- Deseret Foundation, LDS Hospital Cardiovascular Research
- Study start
- Feb 2006
- Study completion
- Nov 2007 (actual)
- First posted
- 7 Jun 2006 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
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 |
|---|---|---|
| Standard of care or genotyping dosing of warfarin dosing | Drug | – |
Primary outcome
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.
6 secondary outcomes
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).
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 21 Aug 2008.
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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.
Jeffrey L Anderson principal investigator
Intermountain Health Care, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Atrial Fibrillation and Deep Vein Thrombosis, run by Intermountain Health Care, 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 8 inclusion and 2 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 21 Aug 2008. 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?
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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2008.