Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

NCT ID: NCT02592980

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2020-12-31

Brief 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.

Detailed 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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Traditional anticoagulation

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

Group Type: EXPERIMENTAL

Traditional anticoagulation

Intervention Type: DRUG

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

Pharmacogenetic anticoagulation

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

Group Type: EXPERIMENTAL

Pharmacogenetic anticoagulation

Intervention Type: GENETIC

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

Interventions

Pharmacogenetic anticoagulation

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

Intervention Type: GENETIC

Traditional anticoagulation

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

Intervention Type: DRUG

Other Intervention Names

Warfarin; Warfarin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InCor Heart Institute

OTHER

Sponsor Role: collaborator

Farmoquimica S.A.

INDUSTRY

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre Pereira, M.Sc

Role: PRINCIPAL_INVESTIGATOR

Laboratório de Genética e Cardiologia Molecular - Instituto do Coração

Locations

Heart Institute

São Paulo, , Brazil

Countries

Brazil

References

Santos PC, Marcatto LR, Duarte NE, Gadi Soares RA, Cassaro Strunz CM, Scanavacca M, Krieger JE, Pereira AC. Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration. Pharmacogenomics. 2015 Jul;16(8):865-76. doi: 10.2217/pgs.15.48. Epub 2015 Jun 8.

Reference Type: RESULT

PMID: 26050796 (View on PubMed)

Marcatto LR, Sacilotto L, Bueno CT, Facin M, Strunz CM, Darrieux FC, Scanavacca MI, Krieger JE, Pereira AC, Santos PC. Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial. BMC Cardiovasc Disord. 2016 Nov 17;16(1):224. doi: 10.1186/s12872-016-0405-1.

Reference Type: DERIVED

PMID: 27855643 (View on PubMed)

Other Identifiers

PF

Identifier Type: -

Identifier Source: org_study_id