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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics Study

Intervention(s) in this Clinical Trial

• Drug: Warfarin

Primary Measures

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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hadassah Medical Organization

Overall Clinical Trial Officials and Contacts

Yoseph Caraco, MD Principal Investigator Hadassah Medical Organization  

Overall Contact: Yoseph Caraco, MD 00 972 2 6778584 caraco@hadassah.org.il

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00162435

Study ID Number: yc19553-HMO-CTIL

ClinicalTrials.gov Identifier: NCT00162435

Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration