Phase 3
N=2,415
Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin
Thromboembolism
Bottom Line
View on ClinicalTrials.gov: NCT00927862 ↗Enrolled (actual)
2,415
Serious AEs
8.3%
Results posted
Sep 2012
Primary outcome: Primary: The Percent of Out of Range (OOR) International Normalized Prothrombin Time Ratio (INRs) in the Standard and Modified Pharmacogenetic Arms. — 30.6; 31.8 percent — p=<0.05
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- IWPC adapted genotype-guided dosing algorithm for warfarin (Genetic); Modified IWPC genetic-guided warfarin dosing algorithm (Genetic); Standard of care treatment (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Intermountain Health Care, Inc.
- Primary completion
- Dec 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Percent of Out of Range (OOR) International Normalized Prothrombin Time Ratio (INRs) in the Standard and Modified Pharmacogenetic Arms. |
30.6; 31.8 | <0.05 sig |
| PRIMARY The Percent of Out of Range (OOR) INRs in Pharmacogenetic-guided Patients and Parallel Controls |
31.2; 41.5 | — |
| PRIMARY The Percent of Time in Therapeutic Range (TTR) for the Standard and Modified Pharmacogenetic Algorithms. |
70.2; 67.5 | — |
| PRIMARY The Time in Therapeutic Range (TTR) for the Pharmacogenetic-guided Patients and Parallel Controls |
68.9; 58.4 | — |
| SECONDARY The Percent of INRs ≥4 or ≤1.5 for the Modified IWPC Warfarin Algorithm and the Standard IWPC Warfarin Algorithm |
15.2; 15.4 | — |
| SECONDARY The Percent of INRs ≥4 or ≤1.5 or SAEs Among the Modified IWPC Warfarin Algorithm and Standard IWPC Warfarin Algorithm. |
53.6; 59.2 | — |
| SECONDARY The Number of INRs Measured up to 3 Months in the Pharmacogenetic (PG) (Modified and Standard) Algorithms and Parallel Controls. |
7.70; 7.47 | — |
| SECONDARY Prediction of a Stable Maintenance Dose Among the Pharmacogenetic (PG)-Guided Dosing Algorithms and the Parallel Controls |
63.2; 37.6 | — |
| SECONDARY The Percent of INRs ≥4 or ≤1.5 in the Pharmacogenetic (PG)-Guided Dosing Arms and the Parallel Control Arm |
15.3; 27.4 | — |
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., 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.
Eligibility Criteria
Inclusion Criteria
- 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).
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT00927862). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.