ThromboembolismPhase 2/3Coumagen-IINCT00927862
Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin
A Phase 2/3 study testing IWPC adapted genotype-guided dosing algorithm for warfarin and Modified IWPC genetic-guided warfarin dosing algorithm in people with Thromboembolism, run by Intermountain Health Care, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to determine whether DNA analysis improves the efficiency of dosing and safety in patients who are being started on warfarin therapy.Warfarin, a blood thinner (anticoagulant) prescribed to 1-2 million patients in the United States, is a leading cause of drug-related adverse events (e.g.… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thromboembolism
- What is being tested?
- IWPC adapted genotype-guided dosing algorithm for warfarin and Modified IWPC genetic-guided warfarin dosing algorithm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,415 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Jun 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- New participants will be those >=18 years old who are appropriate candidates for and being initiated on warfarin therapy with target international normalized prothrombin time ratio (INR) range of either 2-3 or 2.5-3.5 and with intent to be treated for at least 1 month and willing to sign informed consent.
- Those with target INR 2.5-3.5 may be enrolled with dose adjustment for this higher target per Gage et-al. (i.e., 11% increase in dose).
- Dose modification also will be made for amiodarone based on prior, published experience (i.e., 22% decrease in dose).
Who cannot join
- Those not appropriate for warfarin (e.g., pregnancy) or for pharmacogenetic (PG)-guided dosing for any reason,
- Those having received rifampin within 3 weeks,
- Those with severe co-morbidities (e.g., creatinine > 2.5,hepatic insufficiency, active malignancy, advanced physiological age, noncompliance risk, expected survival <6 months), and
- Physician or patient preference.
Trial locations and contacts
1 site in 1 country.
United States1 site
Intermountain Healthcare Hospitals and Clinics
Salt Lake City, Utah, 84107
About this study
Official title: The Clinical Impact of Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin in Patients Being Initiated on Oral Anticoagulation
The purpose of this study is to determine whether DNA analysis improves the efficiency of dosing and safety in patients who are being started on warfarin therapy.Warfarin, a blood thinner (anticoagulant) prescribed to 1-2 million patients in the United States, is a leading cause of drug-related adverse events (e.g., severe bleeding), in large part due to dramatic (20-fold) differences between individuals in dose requirements. At least half of this variability now can be explained by 3 common genetic variants, age, body size, and sex; however, warfarin therapy continues to begin with the same dose in every patient with the correct individual dose determined by trial and error. This study proposes to determine genetic variations the same day from DNA simply obtained by swabbing the inside of the cheek and use this information to determine the proper dose regimen individually in each patient. The aim is to show that the investigators can achieve more rapid, efficient, and safe dosing in up to 500-1000 individuals who are initiating warfarin therapy for various clotting disorders across a large healthcare system in order to demonstrate improved dosing effectiveness, efficiency, and safety with genetic-based dosing, which could lead to a nationwide application resulting in as much as a $1 billion dollar annual benefit in healthcare outcomes.
Read the detailed description
Study Objectives:
The specific objectives of CoumaGen-II to be tested are:
- To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice at Intermountain Healthcare facilities in the Urban Central Region (i.e., Intermountain Medical Center [IMC], LDS Hospital, Alta View Hospital [AVH]), and selected physician offices that are frequent initiators of warfarin) in a major new quality improvement and clinical research initiative.
- To compare the percentage out-of-range (%OOR) international normalized prothrombin time ratios (INRs) during the first month (and secondarily, 3 months) of warfarin therapy using PG-guided dosing with parallel or historical standard (STD), empiric dosed controls.
- To compare a modified PG-guided dosing algorithm (modified-International Warfarin Pharmacogenetics Consortium [IWPC]) with a previously generated and validated, multicenter PG-guided algorithm (IWPC).
Study Design:
Qualifying patients being initiated on warfarin therapy with a target INR of 1.5-2.5, 2-3, or 2.5-3.5 will be invited to participate and sign informed consent. Enrolled patients will receive DNA sampling by buccal swab, and samples will be processed and a PG-guided initial dose calculated with a goal of <6 hours (maximum, 24 hours). Dosing and dose adjustments will be managed through the Urban Central Region (IMC/LDSH) anticoagulation management service (AMS). Dose adjustments through day 8 will use a PG-modified algorithm, after which modification will revert to the standard IHC algorithm. AMS pharmacists and study coordinators will ascertain warfarin doses, INRs, dose changes, and adverse events, and record information on case report forms.
Study Duration:
Each patient will participate for approximately 3 months (90 days ± 10 days). The anticipated enrollment period is 24 months or until 1000 patients are enrolled. The length of the enrollment period is subject to revision as it is dependent on the availability of a robust patient pool.
Further study details on dosing algorithm and genotyping methodology may be provided by Intermountain Healthcare Inc.
- Conditions
- Thromboembolism
- Being tested
- IWPC adapted genotype-guided dosing algorithm for warfarin, Modified IWPC genetic-guided warfarin dosing algorithm, Standard of care treatment
- Keywords
- warfarin metabolism, CYP2C9, genotyping, VKORC1, anticoagulation, atrial fibrillation, deep vein thrombosis, pulmonary embolism, Patients initiating warfarin for thromboembolic conditions
- Medical subject headings
- Thromboembolism, Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, Type 2, 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.
IWPC adapted genotype-guided dosing algorithm for warfarinGenetic
Also called IWPC=international warfarin pharmacogenetic collaboration
Within the first or second dose, apply an International Warfarin Pharmacogenetics Consortium (IWPC) adapted genotype-guided dosing algorithm to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, weight, height, etc.), and VKORC1 and CYP2C9 genotypes, to individualize the initial dosing of warfarin. (IWPC algorithm submitted for publication, 5-08)
Note that a second comparison will be made between the combined genotype-guided dosing groups (standard and modified IWPC warfarin dosing algorithms) and a historical comparator group.
Modified IWPC genetic-guided warfarin dosing algorithmGenetic
Also called IWPC=international warfarin pharmacogenetic collaboration
Within the first or second warfarin dose, apply a modified International Warfarin Pharmacogenetics Consortium (IWPC)-adapted genotype-guided dosing algorithm to determine the daily maintenance dose of warfarin. The active comparator algorithm (see above) will be further modified to account for the temporal pharmacodynamics of warfarin metabolism, e.g., by ignoring the CYP2C9 variants for the first 2 days.
Note that a second comparison will be made between the combined genotype-guided dosing groups (standard and modified IWPC warfarin dosing algorithms) and a historical comparator group.
Standard of care treatmentOther
The parallel, standard-dosing patient control cohort was identified by a query of the electronic medical records databases of the 3 participating hospitals for the time interval spanning enrollment of the randomized pharmacogenetic cohorts (July 2008-December 2010). Patients >=18 years of age initiating warfarin therapy with a baseline and at least 1 follow-up INR level between days 3 and 14 were selected. Initial dose selection and therapy modification was at individual Intermountain-credentialed physician/healthcare provider discretion. Standard management is non-PG-based. A standard (fixed) initial maintenance dose of 5 mg/d is generally assumed.
| Study group | Role | What they receive |
|---|---|---|
| Standard IWPC warfarin dosing algorithm | Active comparator | Standard International Warfarin Pharmacogenetics Consortium (IWPC) warfarin dosing algorithm. Receives: Genetic: IWPC adapted genotype-guided dosing algorithm for warfarin |
| Modified IWPC warfarin dosing algorithm | Experimental | Modified International Warfarin Pharmacogenetics Consortium (IWPC) warfarin dosing algorithm Receives: Genetic: Modified IWPC genetic-guided warfarin dosing algorithm |
| Historical controls | Other | The parallel, standard-dosing patient control cohort was identified by a query of the electronic medical records database of the 3 participating hospitals for the time interval spanning enrollment of the randomized pharmacogenetic (PG)-guided cohorts (July 2008 through December 2010). Patients ≥18 years old initiating warfarin therapy with a baseline and at least 1 follow-up international normalized prothrombin time ratio (INR) level between days 3-14 were selected. Initial dose selection and therapy modification was at individual Intermountain-credentialed physician/healthcare provider discretion. Standard management is non-PG based. Receives: Other: Standard of care treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percent of Out of Range (OOR) International Normalized Prothrombin Time Ratio (INRs) in the Standard and Modified Pharmacogenetic Arms.
The percent of out of range (OOR) international normalized prothrombin time ratio (INRs) in the standard and modified pharmacogentic algorithms at 1 month. To account for laboratory INR-measurement error, a 10% margin outside of the target range was allowed in determination of OOR values, ie, INRs <1.8, >3.3 for INR 2.5 target; <2.25, >3.85 for INR 3.0 target. What is reported is the percent of patients with an OOR INR at 1 month.
Measured: 1 month (from day 3 to day 30)
The Percent of Out of Range (OOR) INRs in Pharmacogenetic-guided Patients and Parallel Controls
The percent of out of range (OOR) INRs in the pharmacogenetic (PG)-dosing (standard + modified IWPC warfarin algorithms) and parallel controls. A 10% margin outside of the target INR range was allowed in determination of OOR values, ie, INRs <1.8, >3.3 for INR 2.5 target; <2.25, >3.85 for INR 3.0 target. What is reported is the percent of patients with OOR INRs at 1 month.
Measured: 1 month (from day 3 to day 30)
The Percent of Time in Therapeutic Range (TTR) for the Standard and Modified Pharmacogenetic Algorithms.
The percent of time in therapeutic INR range for the standard and modified pharmacogenetic algorithms at 1 month. To account for laboratory INR-measurement error, a 10% margin inside of the target range was allowed in determine TTR values, ie, INRs 1.8-3.3 for INR 2.5 target; 2.25-3.85 for INR 3.0 target. What is reported is the percent of TTR for each patient during 1 month.
Measured: 1 month (from baseline to day 30)
The Time in Therapeutic Range (TTR) for the Pharmacogenetic-guided Patients and Parallel Controls
The percent of time in therapeutic INR range for the pharmacogenetic (PG)-dosing (standard + modified IWPC warfarin algorithms) guided patients and parallel controls. To account for laboratory INR-measurement error, a 10% margin inside of the target range was allowed in determine TTR values, ie, INRs 1.8-3.3 for INR 2.5 target; 2.25-3.85 for INR 3.0 target. What is reported is the percent of TTR for each patient during 1 month.
Measured: 1 month (from baseline to day 30)
Secondary outcomes (5)
The Percent of INRs ≥4 or ≤1.5 for the Modified IWPC Warfarin Algorithm and the Standard IWPC Warfarin Algorithm
The percent of INRs ≥4 or ≤1.5 for the pharmacogenetic (modified IWPC warfarin algorithm and the standard IWPC warfarin) algorithms. What is reported is the percent of patients with INRs ≥4 or ≤1.5 at the end of follow-up.
Measured: 3 months (baseline to 3 months or to end of warfarin therapy, whichever occurs first)
The Percent of INRs ≥4 or ≤1.5 or SAEs Among the Modified IWPC Warfarin Algorithm and Standard IWPC Warfarin Algorithm.
What is reported is the percent of patients with INRs ≥4 or ≤1.5 or having experienced a serious adverse event (SAE) at the end of follow-up.
Measured: 3 months (from baseline to 3 months or end of warfarin therapy, whichever occurs first)
The Number of INRs Measured up to 3 Months in the Pharmacogenetic (PG) (Modified and Standard) Algorithms and Parallel Controls.
What is reported is the mean number of INRs measured/drawn among the patients in each arm.
Measured: 1-3 months (from baseline to 3 months or end of warfarin therapy, whichever occurs first)
Prediction of a Stable Maintenance Dose Among the Pharmacogenetic (PG)-Guided Dosing Algorithms and the Parallel Controls
Prediction of a stable maintenance dose (within 1 mg/day) among the pharmacogenetic (PG)-guided dosing and the parallel control group. For the parallel control group, an empiric starting dose of 5 mg/day was assumed. What is reported is the percent of patients who had their maintenance dose predicted as described above.
Measured: 3 months (from baseline to 3 months or until stable dosing is achieved, whichever occurs first)
The Percent of INRs ≥4 or ≤1.5 in the Pharmacogenetic (PG)-Guided Dosing Arms and the Parallel Control Arm
What is reported is the percent of patients with an INR ≥4 or ≤1.5 at the end of follow-up.
Measured: 3 months (baseline to 3 months or to end of warfarin therapy, whichever occurs first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study startAug 2008
- Primary completionDec 2010
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThromboembolismStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2,415 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey L Anderson, MD, Principal investigator, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00927862
- Sponsor's protocol ID
- 154-001
- Acronym
- Coumagen-II
- Status last verified
- Aug 2012
- First submitted
- 23 Jun 2009
- Last updated
- 25 Sep 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Anderson JL, Horne BD, Stevens SM, Woller SC, Samuelson KM, Mansfield JW, Robinson M, Barton S, Brunisholz K, Mower CP, Huntinghouse JA, Rollo JS, Siler D, Bair TL, Knight S, Muhlestein JB, Carlquist JF. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation. 2012 Apr 24;125(16):1997-2005. doi: 10.1161/CIRCULATIONAHA.111.070920. Epub 2012 Mar 19.
PubMed 22431865
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Impact of Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin in Patients Being Initiated on Oral Anticoagulation
- ClinicalTrials.gov ID
- NCT00927862
- Acronym / sponsor ID
- Coumagen-II / 154-001
- Conditions
- Thromboembolism
- Keywords
- warfarin metabolism, CYP2C9, genotyping, VKORC1, anticoagulation, atrial fibrillation, deep vein thrombosis, pulmonary embolism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,415 participants (actual)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Study start
- Aug 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Posted 25 Sep 2012
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 study is to determine whether DNA analysis improves the efficiency of dosing and safety in patients who are being started on warfarin therapy.Warfarin, a blood thinner (anticoagulant) prescribed to 1-2 million patients in the United States, is a leading cause of drug-related adverse events (e.g., severe bleeding), in large part due to dramatic (20-fold) differences between individuals in dose requirements. At least half of this variability now can be explained by 3 common genetic variants, age, body size, and sex; however, warfarin therapy continues to begin with the same dose in every patient with the correct individual dose determined by trial and error. This study proposes to determine genetic variations the same day from DNA simply obtained by swabbing the inside of the cheek and use this information to determine the proper dose regimen individually in each patient. The aim is to show that the investigators can achieve more rapid, efficient, and safe dosing in up to 500-1000 individuals who are initiating warfarin therapy for various clotting disorders across a large healthcare system in order to demonstrate improved dosing effectiveness, efficiency, and safety with genetic-based dosing, which could lead to a nationwide application resulting in as much as a $1 billion dollar annual benefit in healthcare outcomes.
Detailed description
Study Objectives:
The specific objectives of CoumaGen-II to be tested are:
- To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice at Intermountain Healthcare facilities in the Urban Central Region (i.e., Intermountain Medical Center [IMC], LDS Hospital, Alta View Hospital [AVH]), and selected physician offices that are frequent initiators of warfarin) in a major new quality improvement and clinical research initiative.
- To compare the percentage out-of-range (%OOR) international normalized prothrombin time ratios (INRs) during the first month (and secondarily, 3 months) of warfarin therapy using PG-guided dosing with parallel or historical standard (STD), empiric dosed controls.
- To compare a modified PG-guided dosing algorithm (modified-International Warfarin Pharmacogenetics Consortium [IWPC]) with a previously generated and validated, multicenter PG-guided algorithm (IWPC).
Study Design:
Qualifying patients being initiated on warfarin therapy with a target INR of 1.5-2.5, 2-3, or 2.5-3.5 will be invited to participate and sign informed consent. Enrolled patients will receive DNA sampling by buccal swab, and samples will be processed and a PG-guided initial dose calculated with a goal of <6 hours (maximum, 24 hours). Dosing and dose adjustments will be managed through the Urban Central Region (IMC/LDSH) anticoagulation management service (AMS). Dose adjustments through day 8 will use a PG-modified algorithm, after which modification will revert to the standard IHC algorithm. AMS pharmacists and study coordinators will ascertain warfarin doses, INRs, dose changes, and adverse events, and record information on case report forms.
Study Duration:
Each patient will participate for approximately 3 months (90 days ± 10 days). The anticipated enrollment period is 24 months or until 1000 patients are enrolled. The length of the enrollment period is subject to revision as it is dependent on the availability of a robust patient pool.
Further study details on dosing algorithm and genotyping methodology may be provided by Intermountain Healthcare Inc.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard IWPC warfarin dosing algorithm | Active comparator | Genetic: IWPC adapted genotype-guided dosing algorithm for warfarinStandard International Warfarin Pharmacogenetics Consortium (IWPC) warfarin dosing algorithm. |
| Modified IWPC warfarin dosing algorithm | Experimental | Genetic: Modified IWPC genetic-guided warfarin dosing algorithmModified International Warfarin Pharmacogenetics Consortium (IWPC) warfarin dosing algorithm |
| Historical controls | Other | Other: Standard of care treatmentThe parallel, standard-dosing patient control cohort was identified by a query of the electronic medical records database of the 3 participating hospitals for the time interval spanning enrollment of the randomized pharmacogenetic (PG)-guided cohorts (July 2008 through December 2010). Patients ≥18 years old initiating warfarin therapy with a baseline and at least 1 follow-up international normalized prothrombin time ratio (INR) level between days 3-14 were selected. Initial dose selection and therapy modification was at individual Intermountain-credentialed physician/healthcare provider discretion. Standard management is non-PG based. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- New participants will be those >=18 years old who are appropriate candidates for and being initiated on warfarin therapy with target international normalized prothrombin time ratio (INR) range of either 2-3 or 2.5-3.5 and with intent to be treated for at least 1 month and willing to sign informed consent.
- Those with target INR 2.5-3.5 may be enrolled with dose adjustment for this higher target per Gage et-al. (i.e., 11% increase in dose).
- Dose modification also will be made for amiodarone based on prior, published experience (i.e., 22% decrease in dose).
Key exclusion criteria (4 listed)
- Those not appropriate for warfarin (e.g., pregnancy) or for pharmacogenetic (PG)-guided dosing for any reason,
- Those having received rifampin within 3 weeks,
- Those with severe co-morbidities (e.g., creatinine > 2.5,hepatic insufficiency, active malignancy, advanced physiological age, noncompliance risk, expected survival <6 months), and
- Physician or patient preference.
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 |
|---|---|---|
| IWPC adapted genotype-guided dosing algorithm for warfarinAlso: IWPC=international warfarin pharmacogenetic collaborationWithin the first or second dose, apply an International Warfarin Pharmacogenetics Consortium (IWPC) adapted genotype-guided dosing algorithm to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, weight, height, etc.), and VKORC1 and CYP2C9 genotypes, to individualize the initial dosing of warfarin. (IWPC algorithm submitted for publication, 5-08) Note that a second comparison will be made between the combined genotype-guided dosing groups (standard and modified IWPC warfarin dosing algorithms) and a historical comparator group. | Genetic | Standard IWPC warfarin dosing algorithm |
| Modified IWPC genetic-guided warfarin dosing algorithmAlso: IWPC=international warfarin pharmacogenetic collaborationWithin the first or second warfarin dose, apply a modified International Warfarin Pharmacogenetics Consortium (IWPC)-adapted genotype-guided dosing algorithm to determine the daily maintenance dose of warfarin. The active comparator algorithm (see above) will be further modified to account for the temporal pharmacodynamics of warfarin metabolism, e.g., by ignoring the CYP2C9 variants for the first 2 days. Note that a second comparison will be made between the combined genotype-guided dosing groups (standard and modified IWPC warfarin dosing algorithms) and a historical comparator group. | Genetic | Modified IWPC warfarin dosing algorithm |
| Standard of care treatmentThe parallel, standard-dosing patient control cohort was identified by a query of the electronic medical records databases of the 3 participating hospitals for the time interval spanning enrollment of the randomized pharmacogenetic cohorts (July 2008-December 2010). Patients >=18 years of age initiating warfarin therapy with a baseline and at least 1 follow-up INR level between days 3 and 14 were selected. Initial dose selection and therapy modification was at individual Intermountain-credentialed physician/healthcare provider discretion. Standard management is non-PG-based. A standard (fixed) initial maintenance dose of 5 mg/d is generally assumed. | Other | Historical controls |
Primary outcome
The Percent of Out of Range (OOR) International Normalized Prothrombin Time Ratio (INRs) in the Standard and Modified Pharmacogenetic Arms.
Time frame: 1 month (from day 3 to day 30)
The percent of out of range (OOR) international normalized prothrombin time ratio (INRs) in the standard and modified pharmacogentic algorithms at 1 month. To account for laboratory INR-measurement error, a 10% margin outside of the target range was allowed in determination of OOR values, ie, INRs <1.8, >3.3 for INR 2.5 target; <2.25, >3.85 for INR 3.0 target. What is reported is the percent of patients with an OOR INR at 1 month.
The Percent of Out of Range (OOR) INRs in Pharmacogenetic-guided Patients and Parallel Controls
Time frame: 1 month (from day 3 to day 30)
The percent of out of range (OOR) INRs in the pharmacogenetic (PG)-dosing (standard + modified IWPC warfarin algorithms) and parallel controls. A 10% margin outside of the target INR range was allowed in determination of OOR values, ie, INRs <1.8, >3.3 for INR 2.5 target; <2.25, >3.85 for INR 3.0 target. What is reported is the percent of patients with OOR INRs at 1 month.
The Percent of Time in Therapeutic Range (TTR) for the Standard and Modified Pharmacogenetic Algorithms.
Time frame: 1 month (from baseline to day 30)
The percent of time in therapeutic INR range for the standard and modified pharmacogenetic algorithms at 1 month. To account for laboratory INR-measurement error, a 10% margin inside of the target range was allowed in determine TTR values, ie, INRs 1.8-3.3 for INR 2.5 target; 2.25-3.85 for INR 3.0 target. What is reported is the percent of TTR for each patient during 1 month.
The Time in Therapeutic Range (TTR) for the Pharmacogenetic-guided Patients and Parallel Controls
Time frame: 1 month (from baseline to day 30)
The percent of time in therapeutic INR range for the pharmacogenetic (PG)-dosing (standard + modified IWPC warfarin algorithms) guided patients and parallel controls. To account for laboratory INR-measurement error, a 10% margin inside of the target range was allowed in determine TTR values, ie, INRs 1.8-3.3 for INR 2.5 target; 2.25-3.85 for INR 3.0 target. What is reported is the percent of TTR for each patient during 1 month.
5 secondary outcomes
The Percent of INRs ≥4 or ≤1.5 for the Modified IWPC Warfarin Algorithm and the Standard IWPC Warfarin Algorithm
Time frame: 3 months (baseline to 3 months or to end of warfarin therapy, whichever occurs first)
The Percent of INRs ≥4 or ≤1.5 or SAEs Among the Modified IWPC Warfarin Algorithm and Standard IWPC Warfarin Algorithm.
Time frame: 3 months (from baseline to 3 months or end of warfarin therapy, whichever occurs first)
The Number of INRs Measured up to 3 Months in the Pharmacogenetic (PG) (Modified and Standard) Algorithms and Parallel Controls.
Time frame: 1-3 months (from baseline to 3 months or end of warfarin therapy, whichever occurs first)
Prediction of a Stable Maintenance Dose Among the Pharmacogenetic (PG)-Guided Dosing Algorithms and the Parallel Controls
Time frame: 3 months (from baseline to 3 months or until stable dosing is achieved, whichever occurs first)
The Percent of INRs ≥4 or ≤1.5 in the Pharmacogenetic (PG)-Guided Dosing Arms and the Parallel Control Arm
Time frame: 3 months (baseline to 3 months or to end of warfarin therapy, whichever occurs first)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22431865Anderson JL, Horne BD, Stevens SM, Woller SC, Samuelson KM, Mansfield JW, Robinson M, Barton S, Brunisholz K, Mower CP, Huntinghouse JA, Rollo JS, Siler D, Bair TL, Knight S, Muhlestein JB, Carlquist JF. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation. 2012 Apr 24;125(16):1997-2005. doi: 10.1161/CIRCULATIONAHA.111.070920. Epub 2012 Mar 19.
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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, MD 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 Phase 2/3 study testing IWPC adapted genotype-guided dosing algorithm for warfarin and Modified IWPC genetic-guided warfarin dosing algorithm in people with Thromboembolism, 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 3 inclusion and 4 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 25 Sep 2012. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Percent of Out of Range (OOR) International Normalized Prothrombin Time Ratio (INRs) in the Standard and Modified Pharmacogenetic Arms. (time frame: 1 month (from day 3 to day 30)). The study lists 4 primary outcomes in all. 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 NCT00927862, 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 25 Sep 2012.