Atrial FibrillationPhase 4NCT02592980
Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients
A Phase 4 study testing Pharmacogenetic anticoagulation and Traditional anticoagulation in people with Atrial Fibrillation, run by University of Sao Paulo General Hospital at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Pharmacogenetic anticoagulation and Traditional anticoagulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2016to Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients With Low Time in Therapeutic Range - Study Design
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.
Read the 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
- Being tested
- Pharmacogenetic anticoagulation, Traditional anticoagulation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pharmacogenetic anticoagulationGenetic
Also called Warfarin
The investigators use a algorithm pharmacogenetic for adjust only the first dose in the study.
Traditional anticoagulationDrug
Also called Warfarin
The physician will adjust the dose according to current INR value based on guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Traditional anticoagulation | Experimental | For the Traditional Anticoagulation group, the physician will adjust the dose according to the current INR value based on current guidelines Receives: 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 Receives: Genetic: Pharmacogenetic anticoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
time to achieve the therapeutic target
time to achieve the therapeutic target during 12 weeks of treatment
Measured: 12 weeks
Secondary outcomes (1)
TTR (time in the therapeutic range)
TTR mean of 4 week and 12 week
Measured: 4 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2015 (estimated)
- Study startJan 2016
- Primary completionNov 2019 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- InCor Heart Institute, Farmoquimica S.A., University of Sao Paulo
- Responsible party
- Sponsor
- Investigators
- Alexandre Pereira, M.Sc, Principal investigator, Laboratório de Genética e Cardiologia Molecular - Instituto do Coração
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02592980
- Sponsor's protocol ID
- PF
- Status last verified
- Jun 2019
- First submitted
- 29 Oct 2015
- Last updated
- 5 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 26050796Marcatto 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.
PubMed 27855643
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Pharmacogenetic-based Warfarin Dosing Algorithm in Patients With Low Time in Therapeutic Range - Study Design
- ClinicalTrials.gov ID
- NCT02592980
- Acronym / sponsor ID
- PF
- Conditions
- Atrial Fibrillation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- InCor Heart Institute, Farmoquimica S.A., University of Sao Paulo
- Study start
- Jan 2016 (actual)
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 30 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Traditional anticoagulation | Experimental | Drug: Traditional anticoagulationFor the Traditional Anticoagulation group, the physician will adjust the dose according to the current INR value based on current guidelines |
| Pharmacogenetic anticoagulation | Experimental | Genetic: Pharmacogenetic anticoagulationFor 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pharmacogenetic anticoagulationAlso: WarfarinThe investigators use a algorithm pharmacogenetic for adjust only the first dose in the study. | Genetic | Pharmacogenetic anticoagulation |
| Traditional anticoagulationAlso: WarfarinThe physician will adjust the dose according to current INR value based on guidelines. | Drug | Traditional anticoagulation |
Primary outcome
time to achieve the therapeutic target
Time frame: 12 weeks
time to achieve the therapeutic target during 12 weeks of treatment
1 secondary outcome
TTR (time in the therapeutic range)
Time frame: 4 weeks and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Results publication: PubMed 26050796Santos 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.
- Derived from this study: PubMed 27855643Marcatto 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandre Pereira, M.Sc principal investigator
Laboratório de Genética e Cardiologia Molecular - Instituto do Coração
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pharmacogenetic anticoagulation and Traditional anticoagulation in people with Atrial Fibrillation, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time to achieve the therapeutic target (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02592980, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2019.