Atrial Fibrillation, Pulmonary Embolism, Venous Thrombosis
Conditions
Brief summary
The response to warfarin varies greatly among individuals. Some of this variability can be ascribed to genetic polymorphisms in the gene encoding for CYP2C9, the enzyme mediating the metabolism of S warfarin. In addition genetic polymorphism in other genes (i.e. VKORC1, factor VII) have been shown to account for some of the variability in the response to warfarin irrespective of CYP2C9.The present study has several segments: 1. Evaluation of the relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin maintenance dose at steady state. This study is a confirmation of previous data in our own population. 2. Evaluation of relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin loading dose during the induction period. 3. Testing the hypothesis that warfarin loading based on the individual's combined CYP2C9, VKORC1 and factor VII genotype may be more efficient and associated with reduced adverse drug effects.
Interventions
DRUGWarfarin
Sponsors
United States - Israel Binational Science Foundation
Israel Science Foundation
Ministry of Health, Israel
Hadassah Medical Organization
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients in whom warfarin is about to be initiated * Desired therapeutic range \>2 and \<3
Exclusion criteria
* Refusal to participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic end points: | 1-4 months |
| Warfarin clearance and formation clearance of 7-hydroxy-warfarin at steady state | 1-4 months |
| Pharmacodynamic. | 1-4 months |
| Maintenance dose of warfarin at steady state. | 1-4 months |
| Time to reach INR > 2. | 1-4 months |
| Time to reach pharmacodynamic steady state. | 1-4 months |
| Time spent at therapeutic INR <3 and >2. | 1-4 months |
| Time spent at INR >3. | 1-4 months |
| Time spent at INR <2. | 1-4 months |
| The incidence of minor and major bleeding episodes. | 1-4 months |
Countries
Israel
Contacts
Primary ContactYoseph Caraco, MD
Outcome results
None listed