Genetic Determinants of Warfarin Anticoagulation Effect

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Venous Thrombosis; Pulmonary Embolism; Atrial Fibrillation	Drug: Warfarin	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	500 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single
Primary Purpose:	Treatment
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 Start Date :	August 2002
Estimated Primary Completion Date :	December 2020
Estimated Study Completion Date :	December 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Genetic	Drug: Warfarin
Experimental: Control	Drug: Warfarin

Outcome Measures

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Primary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

United States - Israel Binational Science Foundation

Israel Science Foundation

Ministry of Health, Israel

Investigators

Principal Investigator:	Yoseph Caraco, MD	Hadassah Medical Organization

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Yosef Caraco, Head, Clinical Pharmacology Unit, Division of Medicine, Hadassah Medical Organization
ClinicalTrials.gov Identifier:	NCT00162435 History of Changes
Other Study ID Numbers:	yc19553-HMO-CTIL
First Posted:	September 13, 2005
Last Update Posted:	March 6, 2017
Last Verified:	March 2017

Additional relevant MeSH terms:

Atrial Fibrillation; Thrombosis; Embolism; Pulmonary Embolism; Venous Thrombosis; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases	Pathologic Processes; Embolism and Thrombosis; Vascular Diseases; Lung Diseases; Respiratory Tract Diseases; Warfarin; Anticoagulants