Genetic Determinants of Warfarin Anticoagulation Effect

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00162435
• Other study ID #: yc19553-HMO-CTIL
• Status: Recruiting
• Phase: N/A
• Start date: August 2002
• Est. completion date: December 2020

Study information

• Verified date: March 2018
• Source: Hadassah Medical Organization
• Contact: Yoseph Caraco, MD
• Phone: 00 972 2 6778584
• Email: caraco[@]hadassah.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Embolism
• Pulmonary Embolism
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Warfarin

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (4)

Lead Sponsor	Collaborator
Hadassah Medical Organization	Israel Science Foundation, Ministry of Health, Israel, United States - Israel Binational Science Foundation

Country where clinical trial is conducted

Israel, 

Outcome

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