Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

NCT02592980 | Unknown Phase 4 DMC

• 1 other identifier: PF
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• time to achieve the therapeutic target

  time to achieve the therapeutic target during 12 weeks of treatment

  12 weeks

Secondary Outcomes (1)

• TTR (time in the therapeutic range)

  4 weeks and 12 weeks

Study Arms (2)

Traditional anticoagulation

EXPERIMENTAL

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

Drug: Traditional anticoagulation

Pharmacogenetic anticoagulation

EXPERIMENTAL

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

Genetic: Pharmacogenetic anticoagulation

Interventions

Pharmacogenetic anticoagulation GENETIC

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

Also known as: Warfarin

Pharmacogenetic anticoagulation

Traditional anticoagulation DRUG

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

Also known as: Warfarin

Traditional anticoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• InCor Heart Institute: collaborator
• Farmoquimica S.A.: collaborator
• University of Sao Paulo: collaborator

Study Sites (1)

Heart Institute

São Paulo, 05403900, Brazil

Location

Related Publications (2)

• 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.

  PMID: 26050796 RESULT

• 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.

  PMID: 27855643 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Alexandre Pereira, M.Sc

  Laboratório de Genética e Cardiologia Molecular - Instituto do Coração

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: October 30, 2015
• Study Start: January 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2020
• Last Updated: July 5, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)