Genetic Determinants of Warfarin Anticoagulation Effect

This study is currently recruiting participants.

Verified by Hadassah Medical Organization, October 2008

First Received: September 11, 2005 Last Updated: October 28, 2008 History of Changes

Sponsors and Collaborators:	Hadassah Medical Organization Israel Binational Science Foundation, United States Israel Science Foundation Ministry of Health, Israel
Information provided by:	Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT00162435

Purpose

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:

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.
Evaluation of relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin loading dose during the induction period.
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.

Condition	Intervention
Venous Thrombosis Pulmonary Embolism Atrial Fibrillation	Drug: Warfarin

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Atrial Fibrillation Blood Thinners Deep Vein Thrombosis Pulmonary Embolism

Drug Information available for: Warfarin Warfarin sodium Warfarin potassium

U.S. FDA Resources

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

Further study details as provided by Hadassah Medical Organization:

Primary Outcome 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.

Estimated Enrollment:	500
Study Start Date:	August 2002

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00162435

Contacts

Contact: Yoseph Caraco, MD

00 972 2 6778584

caraco@hadassah.org.il

Locations

Israel
Hadassah Medical Organization	Recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD 00 972 2 6776095 arik@hadassah.org.il
Contact: Hadas Lemberg, PhD 00 972 2 6777572 lhadas@hadassah.org.il
Principal Investigator: Yoseph Caraco, MD

Sponsors and Collaborators

Hadassah Medical Organization

Israel Binational Science Foundation, United States

Israel Science Foundation

Ministry of Health, Israel

Investigators

Principal Investigator:

Yoseph Caraco, MD

Hadassah Medical Organization

More Information

No publications provided by Hadassah Medical Organization

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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. Epub 2007 Sep 12.

Study ID Numbers:	yc19553-HMO-CTIL
Study First Received:	September 11, 2005
Last Updated:	October 28, 2008
ClinicalTrials.gov Identifier:	NCT00162435 History of Changes
Health Authority:	Israel: Israeli Health Ministry Pharmaceutical Administration

Study placed in the following topic categories:

Pulmonary Embolism
Heart Diseases
Anticoagulants
Vascular Diseases
Warfarin
Thrombosis
Embolism and Thrombosis

Respiratory Tract Diseases
Embolism
Lung Diseases
Venous Thrombosis
Atrial Fibrillation
Arrhythmias, Cardiac

Additional relevant MeSH terms:

Anticoagulants
Pulmonary Embolism
Heart Diseases
Hematologic Agents
Vascular Diseases
Warfarin
Pharmacologic Actions
Thrombosis
Embolism and Thrombosis

Pathologic Processes
Respiratory Tract Diseases
Embolism
Therapeutic Uses
Lung Diseases
Venous Thrombosis
Cardiovascular Diseases
Atrial Fibrillation
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on May 06, 2009