Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 33 of 1105 for:    pharmacogenomics OR pharmacogenetics

Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02592980
Recruitment Status : Active, not recruiting
First Posted : October 30, 2015
Last Update Posted : July 4, 2019
Sponsor:
Collaborators:
InCor Heart Institute
Farmoquimica S.A.
University of Sao Paulo
Information provided by (Responsible Party):
University of Sao Paulo General Hospital

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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Genetic: Pharmacogenetic anticoagulation Drug: Traditional anticoagulation Phase 4

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients With Low Time in Therapeutic Range - Study Design
Actual Study Start Date : January 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Traditional anticoagulation
For the Traditional Anticoagulation group, the physician will adjust the dose according to the current INR value based on current guidelines
Drug: Traditional anticoagulation
The physician will adjust the dose according to current INR value based on guidelines.
Other Name: Warfarin

Experimental: 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
Genetic: Pharmacogenetic anticoagulation
The investigators use a algorithm pharmacogenetic for adjust only the first dose in the study.
Other Name: Warfarin




Primary Outcome Measures :
  1. time to achieve the therapeutic target [ Time Frame: 12 weeks ]
    time to achieve the therapeutic target during 12 weeks of treatment


Secondary Outcome Measures :
  1. TTR (time in the therapeutic range) [ Time Frame: 4 weeks and 12 weeks ]
    TTR mean of 4 week and 12 week



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02592980


Locations
Layout table for location information
Brazil
Heart Institute
Sao Paulo, Brazil, 05403900
Sponsors and Collaborators
University of Sao Paulo General Hospital
InCor Heart Institute
Farmoquimica S.A.
University of Sao Paulo
Investigators
Layout table for investigator information
Principal Investigator: Alexandre Pereira, M.Sc Laboratório de Genética e Cardiologia Molecular - Instituto do Coração

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT02592980     History of Changes
Other Study ID Numbers: PF
First Posted: October 30, 2015    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Warfarin
Anticoagulants