Genetic Determinants of Warfarin Anticoagulation Effect

Not Applicable

• Conditions: Atrial Fibrillation; Venous Thrombosis; Pulmonary Embolism
• Interventions: Drug: Warfarin

• Registration Number: NCT00162435
• Lead Sponsor: Hadassah Medical Organization

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-08
• Study First Submitted: 2005-09-11
• Study First Submitted QC: 2005-09-11
• Study First Posted: 2005-09-13
• Status Verified: 2018-03
• Last Update Submitted: 2018-06-11
• Last Update Posted: 2018-06-12
• Primary Completion: 2020-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patients in whom warfarin is about to be initiated
• Desired therapeutic range >2 and <3

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Exclusion Criteria

• Refusal to participate in the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Warfarin	-
Genetic	Warfarin	-

Primary Outcome Measures

Name	Time	Method
Maintenance dose of warfarin at steady state.	1-4 months
Time to reach pharmacodynamic steady state.	1-4 months
Time spent at INR <2.	1-4 months
Pharmacodynamic.	1-4 months
Time spent at INR >3.	1-4 months
Time spent at therapeutic INR <3 and >2.	1-4 months
Pharmacokinetic end points:	1-4 months
Warfarin clearance and formation clearance of 7-hydroxy-warfarin at steady state	1-4 months
The incidence of minor and major bleeding episodes.	1-4 months
Time to reach INR > 2.	1-4 months

Trial Locations

Locations (1)

Hadassah Medical Organization; 🇮🇱 Jerusalem, Israel