Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

Atrial Fibrillation Clinical Trial

Official title:

Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients With Low Time in Therapeutic Range - Study Design

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02592980
• Other study ID #: PF
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: December 2020

Study information

• Verified date: June 2019
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: December 2020
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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.

Locations

Country	Name	City	State
Brazil	Heart Institute	Sao Paulo

Sponsors (4)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Farmoquimica S.A., InCor Heart Institute, University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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 populati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	time to achieve the therapeutic target	time to achieve the therapeutic target during 12 weeks of treatment	12 weeks
Secondary	TTR (time in the therapeutic range)	TTR mean of 4 week and 12 week	4 weeks and 12 weeks