Clinical trial NCT00162435: Genetic Determinants of Warfarin Anticoagulation Effect
Official title: Warfarin Induction Regimen Based Upon CYP2C9, VKORC1 Factor VII Genotyping, PMR and INR Monitoring, as Compared to the Conventional Regimen: a Prospective Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Venous Thrombosis
Pulmonary Embolism
Atrial Fibrillation
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
Collaborators: name: United States - Israel Binational Science Foundation
name: Israel Science Foundation
name: Ministry of Health, Israel
First posted: 2005-09-13
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic end points:
timeFrame: 1-4 months
measure: Warfarin clearance and formation clearance of 7-hydroxy-warfarin at steady state
timeFrame: 1-4 months
measure: Pharmacodynamic.
timeFrame: 1-4 months
measure: Maintenance dose of warfarin at steady state.
timeFrame: 1-4 months
measure: Time to reach INR > 2.
timeFrame: 1-4 months
measure: Time to reach pharmacodynamic steady state.
timeFrame: 1-4 months
measure: Time spent at therapeutic INR <3 and >2.
timeFrame: 1-4 months
measure: Time spent at INR >3.
timeFrame: 1-4 months
measure: Time spent at INR <2.
timeFrame: 1-4 months
measure: The incidence of minor and major bleeding episodes.
timeFrame: 1-4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
Study officials:
affiliation: Hadassah Medical Organization
name: Yoseph Caraco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Caraco Y, Blotnick S, Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther. 2008 Mar;83(3):460-70. doi: 10.1038/sj.clpt.6100316. Epub 2007 Sep 12.