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Warfarin Study Protocol Summary
The objectives, design, primary and secondary endpoints, interventions, and duration of the WARFARIN Study are below.
Study Title: Warfarin Adverse Event Reduction For Adults Receiving Genetic Testing at Therapy INitiation
Objectives: This study is designed to assess if incorporating genotype testing results of CYP2C9 and VKORC1 gene variants into a warfarin dosing protocol can reduce the number of adverse events related to warfarin in older subjects (65 years or older) receiving anti-coagulation therapy.
Design: This is a multicenter, randomized, blinded, parallel-group study using information provided by the Warfarin GenoSTAT Test to modify the warfarin dosing protocol.
Interventions and Duration: All subjects will be tested using the Warfarin GenoSTAT Test to determine warfarin pharmacogenetics. A total of 2300 subjects with specific gene variants will be randomly assigned a group and given a warfarin dose recommendation using genetic and clinical variables (Arm A) or clinical variables only (Arm B). Subjects will be followed for warfarin-related adverse events for 30 days after first dose with continued follow up to 90 days after first dose. From the subjects not randomized, 1500 will be assigned to Registry for the study. Registry subjects will be given a dose recommendation and minimally followed at 30 days. All Randomized subjects will be followed at 30, 60, and 90 days to record any hemorrhage-related adverse events associated with warfarin. Each subject's sample will be stored and his/her information will be available for analysis in future studies.
Primary End Point: To determine if using warfarin-related pharmacogenetic information in calculating warfarin doses will change the rate of warfarin-related adverse events including major hemorrhage and thromboembolic events at 30 days after initial dose when compared to warfarin doses calculated without pharmacogenetic data. The target population is 65 or older.
Secondary End Points:
In the randomized portion of the study:
- comparison of the number of INR tests performed before warfarin dose stabilization (i.e. two consecutive INR tests within the target range);
- comparison of the cumulative warfarin dose necessary to reach warfarin dose stabilization (i.e. two consecutive INR tests within the target range);
- the number of major hemorrhagic adverse events at 60 and at 90 days separately after warfarin initiation;
- the number of minor hemorrhagic adverse events at 30, 60 and at 90 days separately after warfarin initiation;
- the number of major thromboembolic adverse events at 60 and at 90 days separately after warfarin initiation for;
- the percentage of the total INR tests performed in the first 30 days which are out of target range;
- the overall, Physical Composite Score (PCS) and Mental Composite Score (MCS) of the SF-12 quality of life questionnaire at 30 days and at 90 days separately after warfarin initiation;
- prescriber adherence to dosing recommendations through subject interview and comparison of dose recommendation to dose prescribed for the first four doses of warfarin;
In the registry portion of the study:
- the occurrence of a major hemorrhagic event within the first 30 days of receiving the initial dose;
- the occurrence of a major thromboembolic event within the first 30 days of receiving the initial dose;
- the number of minor hemorrhagic adverse events at 30 days after warfarin initiation;
- prescriber adherence to dosing recommendations through subject interview and comparison of dose recommend-dation to dose prescribed for the first four doses of warfarin.
Interventions and Duration: As part of the Warfarin GenoSTAT Test procedure, information about the patient and their genetic makeup is entered into the website www.warfarindosing.org. The website uses a validated algorithm to determine the recommended dose of warfarin. If the subject matches the continuation criteria they will be randomized into two groups. The subject's www.warfarindosing.org dose recommendation will be based on clinical and genetic information (study group) or based on clinical data only (standard group). The investigator will be blinded as to which group the subject is in.
All qualifying subjects will be followed at 30, 60, and 90 days to record any hemorrhage-related adverse events associated with warfarin. Only those patients with a mutation in one or both of the genes will qualify for follow-up. Wild-type subjects will not be followed.
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