Atrial Fibrillation (AF)Phase 3WARFALGORITNCT06789588
Protocol for Improvement of Therapy With Warfarin
A Phase 3 study testing pharmacogenetic algorithm and Clinical treatment in people with Atrial Fibrillation (AF), run by University of Pernambuco at 1 site in Brazil.
Trial summary
Atrial Fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. The presence of AF, as an independent factor, increases mortality by up to two times. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation (AF)
- What is being tested?
- pharmacogenetic algorithm and Clinical treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 1 siteBrazil
- Study dates
- 21 Oct 2024to Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Be greater than or equal to 18 years old
- Patients using warfarin or indicated to start therapy
- Patients with AF in its various etiologies and in paroxysmal, persistent or permanent clinical presentations, with a diagnosis established through clinical examination confirmed by conventional electrocardiographic recording or by 24-hour ambulatory electrocardiographic recording (Holter)
Who cannot join
- Patients who are not able to understand the explanations about the exams, as well as clarifications inherent to their participation in the research
- Patients who stop following the instructions provided by researchers or whose questionnaires are incomplete;
- Patients with liver disease or cancer of any etiology.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Pharmacogenetic Algorithm for Warfarin Dose Predictor: Protocol for Improvement and Effectiveness of Therapy Anticoagulant
Atrial Fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. The presence of AF, as an independent factor, increases mortality by up to two times. One in every six cerebrovascular accidents (CVA) occurs in patients with AF, generating an annual risk of around 7% per year, which represents an increase of up to seven times in relation to the risk in the general population, leading to the need for start anticoagulant therapy. Warfarin is still the Oral Anticoagulant (OC) of choice, being the most used in several clinical situations. The variability of response to anticoagulants is related to pharmacokinetic and pharmacodynamic factors, adherence to treatment, age, diet, body mass index (BMI), liver function, body deposition of vitamin K, individual drug metabolism, drug interactions, comorbidities, in addition to of genetic factors. It is estimated that the annual risks associated with the use of OCs are between 2% and 8% for bleeding. The clinical benefit and risk of OAC therapy are associated with the time in which the values of therapeutic - TTR (time in therapeutic range). Measuring the quality of anticoagulation assesses whether therapy is being maintained within this range. Increased TTR is associated with a decrease in thromboembolic and/or hemorrhagic events. In the context of OCs, pharmacogenetics is the science that predicts the response to drugs, based on individual genetic markers. By understanding the relationship between the genotype and the response to a drug, pharmacogenomics has the potential to help healthcare professionals to predict the therapeutic dose of warfarin by genotyping patients for several Single Nucleotide Polymorphisms (SNPs) that affect metabolism or sensitivity to warfarin. Therefore, the main objectives of genotype-guided therapy are to improve the safety and efficacy of anticoagulant therapy. In Brazil, more specifically in the Brazilian Northeast, the use of a dose predictor algorithm is not common, which leads to high rates of complications and consequently increases the length of hospital stay. As a result, there is an increasing need to implement therapeutic technologies applied to precision health, explore studies on genetic polymorphisms and therapies guided by pharmacogenomics, aiming to understand the individual genetic effect on the metabolism of drugs such as warfarin.
Read the detailed description
Atrial Fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Patients with AF have a 5 times greater risk of causing stroke, especially ischemic stroke, than any other cardiovascular disease. This arrhythmia causes stasis and changes in the thrombosis-antithrombosis balance, which can form thrombi and embolize systemically, reaching the brain and causing stroke, leading to the need to start anticoagulant therapy. Warfarin is still the Oral Anticoagulant (OAC) of choice, being the most used in various clinical situations. With sensitivity to the drug varying in each person, treatment needs to be monitored regularly using the International Normalized Ratio (INR). The known genetic variants that have the greatest impact on the response to warfarin are the variants in the warfarin target, VKORC1, carriers of this variant require a lower dose of warfarin, and the enzyme encoded by CYP2C9, which is the most important when it comes to of involvement with the pharmacokinetics of warfarin. Polymorphisms in the CYP2C9 and VKORC1 genes are responsible for approximately 12 and 24%, respectively, of the variation in warfarin dose among. patients of European descent. Therefore, in the presence of one or more polymorphisms in one of these genes, it is necessary to adjust the warfarin doses. Previous studies have indicated that pharmacogenetic algorithms generally predict warfarin dose more accurately than other dosing methods. In Brazil, more specifically in the Brazilian Northeast, the use of a dose predictor algorithm is not common, which leads to high rates of complications and consequently increases the length of hospital stay. As an objective, the present study plans to implement a pharmacogenetic algorithm protocol for predicting warfarin dose, guided by genotype, versus a clinical protocol based only on drug dosage, in the population with atrial fibrillation, and to evaluate the superiority of the treatment.
- Conditions
- Atrial Fibrillation (AF)
- Being tested
- pharmacogenetic algorithm, Clinical treatment
- Keywords
- atrial fibrillation, oral anticoagulant, warfarin, genetic polymorphism
- 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 algorithmDrug
The dose predictor algorithm proposed in this work aims to maintain and quality treatment in an individualized and effective manner. In the routine use protocol, warfarin is prescribed based only on the INR collected within 5 days. The proposed intervention protocol is based on the patient's clinical and genetic factors, such as genetic polymorphisms, age, weight, height, race, use of amiodarone, statins, antifungals or antibiotics, tobacco use, clinical indication and what the RNI target.
Clinical treatmentDrug
Patients with AF indicated for OAC therapy guided by institutional protocol.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 Experimental | Experimental | Patients with AF using or indicating the need to start OAC therapy guided by a pharmacogene Receives: Drug: pharmacogenetic algorithm |
| Group 2 Active Comparator | Active comparator | Patients with AF indicated for OAC therapy guided by institutional protocol. Receives: Drug: Clinical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Assess the incidence of adverse events
Measured: 6 month
Secondary outcomes (2)
incidence of adverse events (thromboembolic and hemorrhagic)
clinical evaluation of the decrease of adverse events
Measured: 6 month
Time in therapeutic range
Assess the INR and its time within the therapeutic range
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2025
- Study start21 Oct 2024
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial Fibrillation (AF)Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group 1 (Intervention): Patients with AF using or indicating the need to start OAC therapy guided by a pharmacogenetic algorithm that predicts the dose of warfarin. Group 2 (control): Patients with AF indicated for OAC therapy guided by institutional protocol.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pernambuco
- Sponsor type
- University, hospital or other
- Collaborators
- Universidade Federal de Pernambuco
- Responsible party
- Principal investigator, Maria Mariana Barros Melo Da Silveira, University of Pernambuco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06789588
- Sponsor's protocol ID
- 77321024.4.0000.5192
- Other IDs
- 444198/2023-7
- Acronym
- WARFALGORIT
- Status last verified
- May 2025
- First submitted
- 17 Jan 2025
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Respecting the general data protection law of the country of origin (Law No. 13,709/2018), obliterating the data that would identify the participants, we will grant, if necessary, the disclosure of genetic and clinical results, for research purposes.
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Algorithm for Warfarin Dose Predictor: Protocol for Improvement and Effectiveness of Therapy Anticoagulant
- ClinicalTrials.gov ID
- NCT06789588
- Acronym / sponsor ID
- WARFALGORIT / 77321024.4.0000.5192
- Conditions
- Atrial Fibrillation (AF)
- Keywords
- atrial fibrillation, oral anticoagulant, warfarin, genetic polymorphism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- University of PernambucoUniversity, hospital or other
- Collaborators
- Universidade Federal de Pernambuco
- Study start
- 21 Oct 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 23 Jan 2025 (actual)
- 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.
Atrial Fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. The presence of AF, as an independent factor, increases mortality by up to two times. One in every six cerebrovascular accidents (CVA) occurs in patients with AF, generating an annual risk of around 7% per year, which represents an increase of up to seven times in relation to the risk in the general population, leading to the need for start anticoagulant therapy. Warfarin is still the Oral Anticoagulant (OC) of choice, being the most used in several clinical situations. The variability of response to anticoagulants is related to pharmacokinetic and pharmacodynamic factors, adherence to treatment, age, diet, body mass index (BMI), liver function, body deposition of vitamin K, individual drug metabolism, drug interactions, comorbidities, in addition to of genetic factors. It is estimated that the annual risks associated with the use of OCs are between 2% and 8% for bleeding. The clinical benefit and risk of OAC therapy are associated with the time in which the values of therapeutic - TTR (time in therapeutic range). Measuring the quality of anticoagulation assesses whether therapy is being maintained within this range. Increased TTR is associated with a decrease in thromboembolic and/or hemorrhagic events. In the context of OCs, pharmacogenetics is the science that predicts the response to drugs, based on individual genetic markers. By understanding the relationship between the genotype and the response to a drug, pharmacogenomics has the potential to help healthcare professionals to predict the therapeutic dose of warfarin by genotyping patients for several Single Nucleotide Polymorphisms (SNPs) that affect metabolism or sensitivity to warfarin. Therefore, the main objectives of genotype-guided therapy are to improve the safety and efficacy of anticoagulant therapy. In Brazil, more specifically in the Brazilian Northeast, the use of a dose predictor algorithm is not common, which leads to high rates of complications and consequently increases the length of hospital stay. As a result, there is an increasing need to implement therapeutic technologies applied to precision health, explore studies on genetic polymorphisms and therapies guided by pharmacogenomics, aiming to understand the individual genetic effect on the metabolism of drugs such as warfarin.
Detailed description
Atrial Fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Patients with AF have a 5 times greater risk of causing stroke, especially ischemic stroke, than any other cardiovascular disease. This arrhythmia causes stasis and changes in the thrombosis-antithrombosis balance, which can form thrombi and embolize systemically, reaching the brain and causing stroke, leading to the need to start anticoagulant therapy. Warfarin is still the Oral Anticoagulant (OAC) of choice, being the most used in various clinical situations. With sensitivity to the drug varying in each person, treatment needs to be monitored regularly using the International Normalized Ratio (INR). The known genetic variants that have the greatest impact on the response to warfarin are the variants in the warfarin target, VKORC1, carriers of this variant require a lower dose of warfarin, and the enzyme encoded by CYP2C9, which is the most important when it comes to of involvement with the pharmacokinetics of warfarin. Polymorphisms in the CYP2C9 and VKORC1 genes are responsible for approximately 12 and 24%, respectively, of the variation in warfarin dose among. patients of European descent. Therefore, in the presence of one or more polymorphisms in one of these genes, it is necessary to adjust the warfarin doses. Previous studies have indicated that pharmacogenetic algorithms generally predict warfarin dose more accurately than other dosing methods. In Brazil, more specifically in the Brazilian Northeast, the use of a dose predictor algorithm is not common, which leads to high rates of complications and consequently increases the length of hospital stay. As an objective, the present study plans to implement a pharmacogenetic algorithm protocol for predicting warfarin dose, guided by genotype, versus a clinical protocol based only on drug dosage, in the population with atrial fibrillation, and to evaluate the superiority of the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Group 1 (Intervention): Patients with AF using or indicating the need to start OAC therapy guided by a pharmacogenetic algorithm that predicts the dose of warfarin. Group 2 (control): Patients with AF indicated for OAC therapy guided by institutional protocol.
| Arm | Type | Receives |
|---|---|---|
| Group 1 Experimental | Experimental | Drug: pharmacogenetic algorithmPatients with AF using or indicating the need to start OAC therapy guided by a pharmacogene |
| Group 2 Active Comparator | Active comparator | Drug: Clinical treatmentPatients with AF indicated for OAC therapy guided by institutional protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Be greater than or equal to 18 years old
- Patients using warfarin or indicated to start therapy
- Patients with AF in its various etiologies and in paroxysmal, persistent or permanent clinical presentations, with a diagnosis established through clinical examination confirmed by conventional electrocardiographic recording or by 24-hour ambulatory electrocardiographic recording (Holter)
Key exclusion criteria (3 listed)
- Patients who are not able to understand the explanations about the exams, as well as clarifications inherent to their participation in the research
- Patients who stop following the instructions provided by researchers or whose questionnaires are incomplete;
- Patients with liver disease or cancer of any etiology.
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 algorithmThe dose predictor algorithm proposed in this work aims to maintain and quality treatment in an individualized and effective manner. In the routine use protocol, warfarin is prescribed based only on the INR collected within 5 days. The proposed intervention protocol is based on the patient's clinical and genetic factors, such as genetic polymorphisms, age, weight, height, race, use of amiodarone, statins, antifungals or antibiotics, tobacco use, clinical indication and what the RNI target. | Drug | Group 1 Experimental |
| Clinical treatmentPatients with AF indicated for OAC therapy guided by institutional protocol. | Drug | Group 2 Active Comparator |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 6 month
Assess the incidence of adverse events
2 secondary outcomes
incidence of adverse events (thromboembolic and hemorrhagic)
Time frame: 6 month
Time in therapeutic range
Time frame: 6 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Study that formed the basis for the current project.Link provided by the sponsor.
- complementary studyLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Respecting the general data protection law of the country of origin (Law No. 13,709/2018), obliterating the data that would identify the participants, we will grant, if necessary, the disclosure of genetic and clinical results, for research purposes.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pharmacogenetic algorithm and Clinical treatment in people with Atrial Fibrillation (AF), run by University of Pernambuco 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 3 inclusion and 3 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: enrolling by invitation, as of the sponsor's last update on 4 Jun 2025. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of Treatment-Emergent Adverse Events (time frame: 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2025.