Protocol for Improvement of Therapy With Warfarin

NCT06789588 | Enrolling By Invitation Phase 3 DMC

• 2 other identifiers: 77321024.4.0000.5192444198/2023-7
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Atrial Fibrillation (AF)

Keywords

atrial fibrillation; oral anticoagulant; warfarin; genetic polymorphism

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Assess the incidence of adverse events

  6 month

Secondary Outcomes (2)

• incidence of adverse events (thromboembolic and hemorrhagic)

  6 month

• Time in therapeutic range

  6 month

Study Arms (2)

Group 1 Experimental

EXPERIMENTAL

Patients with AF using or indicating the need to start OAC therapy guided by a pharmacogene

Drug: pharmacogenetic algorithm

Group 2 Active Comparator

ACTIVE COMPARATOR

Patients with AF indicated for OAC therapy guided by institutional protocol.

Drug: Clinical treatment

Interventions

pharmacogenetic algorithm DRUG

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.

Group 1 Experimental

Clinical treatment DRUG

Patients with AF indicated for OAC therapy guided by institutional protocol.

Group 2 Active Comparator

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pernambuco: lead
• Universidade Federal de Pernambuco: collaborator

Study Sites (1)

University of Pernambuco

Recife, Pernambuco, 50100-010, Brazil

Location

Related Links

• Study that formed the basis for the current project.
• complementary study

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 23, 2025
• Study Start: October 21, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: January 1, 2027 - January 1, 2032

Locations

BR (1)