Genotype-guided Versus Standard for Warfarin Dosing

Study Overview
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Brief Summary
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To compare the efficiency and safety between gene-oriented group and standard care group during 90 days of initial warfarin-treatment for requiring anticoagulation patients with valve replacement or atrial fibrillation with or without valvular heart disease。

Detailed Description
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Due to narrow therapeutic window, and individual differences in dosage, inappropriate use of warfarin may lead to serious complications and ineffective. Based on the results of the research on the transformation of warfarin pharmacogenomics, this study investigates the clinical application of gene-directed warfarin dose prediction model through the preset dosage regimen of warfarin during the initial treatment phase. Compared with the conventional treatment, that is to say empirical medication, this study is to verify the feasibility and value of gene-oriented warfarin dose prediction model, in order to establish a practical guidance to optimize the rational use of warfarin treatment program, to enable patients to obtain effective, safe warfarin dose, and to achieve the established anticoagulant strength faster and safer, as the same time, to reduce the times of patients was blood and the incidence of bleeding/embolism, and to save costs and ensure the safety of warfarin clinical medication.

Official Title
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Randomized Trial of Genotype-guided Versus Standard for Warfarin Dosing

Conditions
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Atrial Fibrillation, Valvular Heart Disease

Intervention / Treatment
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* Other: Gene-directed dosage of warfarin
* Other: standard dosage of warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged from 18 to 70 years old, requiring anticoagulation because of valvular or non-valvular atrial fibrillation or after valvular replacement. Patients could visit to be followed up in our hospital clinic regularly and agree to participate in the clinical trial and sign a written informed consent. Exclusion Criteria: Patients will be excluded from the trial if aged <18 years old or > 75 years old, pregnant and lactating, if treated tricuspid valve replacement, or coronary artery bypass grafting before, if diagnosed with congenital heart disease, if known their CYP2C9 or VKORC1 genotype, if taken dicoumarol drugs previously or taking them now, if not suitable for enrollment judged by researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gene-directed group<br>the first day given model prediction dose * 1.5 times（<6mg）；the second day given model prediction dose；adjusted dose based on INR from the third day | Other: Gene-directed dosage of warfarin<br>* the first day given model prediction dose * 1.5 times（<6mg）；the second day given model prediction dose；adjusted dose based on INR from the third day<br>|
| Active Comparator: Standard care group<br>the first day given 4.5mg; adjusted dose based on INR from the second day | Other: standard dosage of warfarin<br>* the first day given 4.5mg; adjusted dose based on INR from the second day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| therapeutic INR range (TTR) 90 | The percentage of time in therapeutic INR range (TTR) using the number of INRs within the therapeutic range divided by the number of INRs collected, will be assessed at Day90, and the TTR of all patients will be reported. | at Day90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| therapeutic INR range (TTR) 28 | The percentage of time in therapeutic INR range (TTR) using the number of INRs within the therapeutic range divided by the number of INRs collected, will be assessed at Day28, and the TTR of all patients will be reported. | at Day28 | 
| Time of the first time of the target INR | Time of the first time for participants to reach the target INR will be collected and reported during the study. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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warfarin, gene