Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

University of Sao Paulo General Hospital

Status and phase: Unknown; Phase 4

Conditions: Atrial Fibrillation

Treatments: Drug: Traditional anticoagulation; Genetic: Pharmacogenetic anticoagulation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02592980

PF

Details and patient eligibility

About

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.

Full description

Investigators will recruit 300 patients with low TTR (<50%) from the Heart Institute- Clinical Hospital- University of São Paulo Medical School (InCor- HCFMUSP). The patients will be randomized into two groups: Traditional Anticoagulation (TA) group and Pharmacogenetic Anticoagulation (PA) group. The study protocol was approved by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School (SDC 4033/14/013). Signed informed consent will be obtained from all participants.

Only patients with atrial fibrillation, above 18 years, and with TTR <50% based on the last three values of INR will be included in this study. Patients will not be included if they have reached a stable dose of warfarin, liver dysfunction, alcoholism, use of another anticoagulant, use of chemotherapy, or if they do not meet the inclusion criteria.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Only patients with atrial fibrillation, above 18 years, and with TTR <50% based on the last three values of INR will be included in this study.

Exclusion criteria

• Patients will not be included if they have reached a stable dose of warfarin, liver dysfunction, alcoholism, use of another anticoagulant, use of chemotherapy, or if they do not meet the inclusion criteria

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 2 patient groups

Traditional anticoagulation

Experimental group

Description:

For the Traditional Anticoagulation group, the physician will adjust the dose according to the current INR value based on current guidelines

Treatment:

Drug: Traditional anticoagulation

Pharmacogenetic anticoagulation

Experimental group

Description:

For the Pharmacogenetic Anticoagulation group, the dose will be prescribed based on data from each patient applied in a pharmacogenetic algorithm. In some cases, used algorithm may provide a counter-intuitive dose, i.e., a dose that is not adequate for adjusting the current patient' INR (for example, a higher dose for a patient that already has a high INR). In these cases, the physician will adjust the dose following clinical criteria based on published guidelines

Treatment:

Genetic: Pharmacogenetic anticoagulation