Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients
Status:
Unknown status
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
Background: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy
and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding
events. Recently, the investigators developed a pharmacogenetic-based warfarin dosing
algorithm specifically calibrated for a Brazilian patient sample. The newly developed
algorithm was shown to be more accurate for individuals from the Brazilian population than
algorithms developed from international samples. The aims of this study are: to evaluate the
impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to
achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of
genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a
tertiary cardiovascular hospital. Methods/Design: The investigators will recruit 300 patients
with TTR<50% based on the last three INR values. At the first consultation, patients will be
randomized into two groups: TA (Traditional Anticoagulation) group and PA (Pharmacogenetic
Anticoagulation) group. For the first group, the physician will adjust the dose according to
current INR value and, for the second group, a pharmacogenetic algorithm will be used. At the
second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be
measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards,
patients who are INR stable will begin measuring their INR in 30 day intervals; if the
patient´s INR is not stable, the patient will return in 7 days for a new measurement of the
INR. The main outcomes will be the time to achieve the therapeutic target and the percentage
of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis
will be carried out. Discussion: With a sample size of 150 patients for each arm separately,
the study will have a power of 93% to observe a difference of 10% between TTR means of the TA
and PA groups. This randomized study will include patients with low TTR and it will evaluate
whether a population-specific genetic algorithm might be more effective than traditional
anticoagulation for a selected group of poorly anticoagulated patients.
Phase:
Phase 4
Details
Lead Sponsor:
University of Sao Paulo General Hospital
Collaborators:
Farmoquimica S.A. InCor Heart Institute University of Sao Paulo