Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

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.

Conditions

• Atrial Fibrillation

Interventions

GENETIC

Pharmacogenetic anticoagulation

The investigators use a algorithm pharmacogenetic for adjust only the first dose in the study.

DRUG

Traditional anticoagulation

The physician will adjust the dose according to current INR value based on guidelines.

Sponsors & Collaborators

• InCor Heart Institute

  collaborator OTHER

• Farmoquimica S.A.

  collaborator INDUSTRY

• University of Sao Paulo

  collaborator OTHER

• University of Sao Paulo General Hospital

  lead OTHER

Principal Investigators

• Alexandre Pereira, M.Sc · Laboratório de Genética e Cardiologia Molecular - Instituto do Coração

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-01-31

Primary Completion

2019-11-30

Completion

2020-12-31

Countries

• Brazil

Study Locations