Early Identification of Warfarin Maintenance Dosage

Study Overview
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Brief Summary
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Initiation of warfarin therapy is problematic. The investigators goal was to evaluate if a new demographic/pharmacogenetic algorithm is better than a usual algorithm based on INR value at day five after four days of 5 mg/day warfarin. To this end patients with atrial fibrillation starting warfarin are randomized in two arms.

Detailed Description
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The objective of this randomized study is to evaluate the accuracy of a new demographic/pharmacogenetic as compared to usual warfarin dosing algorithm in predicting warfarin maintenance dose. In patients with atrial fibrillation starting anticoagulation, the loading dose of warfarin in the tested group is calculated on the basis of VKORC1 genotype and patient's body weight.The second day warfarin maintenance dose is calculated on the basis of surface area and CYP2C9, CYP4F2 e VKORC1 genotype. In the usual care group the maintenance dose at day 5 is calculated on the basis of a published algorithm (Pengo V, Am J Cardiol 2001). INR is checked on day 0, 5, 7, 9, 12, 15 and 19. Primary end-point of the trial is the number of INR outside the therapeutic range of 2.0 to 3.0. Secondary end-points are the number of changes in dose prescription, the difference between predicted and actual warfarin maintenance dose and thrombotic and bleeding events.

Official Title
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Early Identification of Warfarin Maintenance Dose in Patients With Atrial Fibrillation: a Randomized Trial Evaluating a New Genotype-based Versus Usual Care Initiation of Treatment

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Genetic: Calculate warfarin dose using demographic/genetic algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Indication to warfarin with INR between 2.0 and 3.0 Exclusion Criteria: Pregnancy Drug interactions Basal INR > 1.2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pharmacogenetic warfarin dose<br>Warfarin maintenance dose on the basis of demographic/pharmacogenetic data | Genetic: Calculate warfarin dose using demographic/genetic algorithm<br>* Age, body weight and genetic to calculate warfarin dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Normalized Ratio (INR) | Number of INR outside the therapeutic range (INR 2.0-3.0) | Day 0, 5, 7, 9, 12, 15, 19. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of changes in warfarin dosage |  | Day 0-19 | 
| Difference between predicted and actual warfarin maintenance dose |  | Day 19 | 
| Thromboembolic and Bleeding complications |  | Day 0-30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warfarin, Dose, Pharmacogenetic, INR