Genetic Response to Warfarin in Healthy Subjects
|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.
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|