Genetic Response to Warfarin in Healthy Subjects
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|ClinicalTrials.gov Identifier: NCT01520402|
Recruitment Status : Completed
First Posted : January 30, 2012
Results First Posted : February 7, 2013
Last Update Posted : February 12, 2013
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Warfarin||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Quantitative Pharmacogenomics of the Anticoagulant Response to Warfarin in Healthy Subjects|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||May 2011|
|Actual Study Completion Date :||May 2011|
Healthy subjects age 18-74 with no medical indication for warfarin therapy, who are free of medications and co-morbid medical conditions with the potential to interfere with warfarin metabolism, and who are willing to follow a fixed vitamin K diet (men 120 micrograms/day, women 90 micrograms/day) are included.
Enrolled subjects on a fixed vitamin K diet followed a standard warfarin dosing algorithm with daily point-of-care INR checks to goal INR ≥ 2 for two consecutive days, then to baseline INR≤1.2 off warfarin. Genotyping for common and rare polymorphisms in CYP2C9, VKORC1, and CYP4F2 performed at study entry and unblinded at completion. Plasma Vitamin K and S-warfarin levels are obtained at goal INR ≥ 2 and study exit (INR ≤1.2 off warfarin).
- Median Cumulative Therapeutic Warfarin Dose (Milligrams)Requirements by Genotype [ Time Frame: average of 2 - 13 days ]To assess the effect of genotype variants (CYP2C9 and VKORC1 -1639 G>A) on the anticoagulant response to warfarin, the primary outcome was the cumulative dose required to achieve an INR value in the usual clinical therapeutic range (>2.0) for two consecutive days.
- Median Cumulative Warfarin Dose Requirement by Genotype Category (CYP2C9 and VKORC1 -1639 G>A Combination) [ Time Frame: 2-30 days ]Subjects were also grouped into four categories based on CYP2C9 and VKORC1 genotype profile: Group 1 (CYP2C9 wild-type and VKORC1 wild-type), Group 2 (CYP2C9 wild-type and VKORC1 variant), Group 3 (CYP2C9 variant and VKORC1 wild-type), and Group 4 (CYP2C9 variant and VKORC1 variant). Median cumulative warfarin dose requirement was determined for each genotype category.
- Median Cumulative Warfarin Dose Requirements by CYP4F2 Genotype Status [ Time Frame: average of 2 - 30 days ]To assess the effect of CYP4F2 genotype variants on the anticoagulant response to warfarin.
- Explained Variation in Combined Therapeutic Warfarin Dose Models [ Time Frame: average of 2 - 30 days ]The proportion of variance (R^2) explained by each predictor was calculated using multivariate regression analysis and adjusted for age, gender and reported race, with outcome values logarithmically transformed. The study was powered to detect R^2 > 20%, and significance was accepted at p<0.05.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01520402
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|Principal Investigator:||Jonathan L Halperin, MD||Icahn School of Medicine at Mount Sinai|