Apixaban Versus Rivaroxaban in Non Valvular Atrial Fibrillation (APIXA-Xa)

Study of the Inter- and Intra-individual Variability of Anti-Xa Activity of Apixaban Versus Rivaroxaban Versus Control Arm During Non-valvular Atrial Fibrillation: Evaluation of Stability and Clinical Impact

The investigators will first measure the maximum concentration (after 2 hours of intake) and the residual concentration (just before the next intake) after at least 15 consecutive days of treatment.

In order to be able to study the stability of the anti-Xa activity of Apixaban vs Rivaroxaban, as well as their impact on the risk of thromboembolic events or hemorrhagic events, clinical follow-up and a determination of maximum and residual activity are necessary, ideally at 3 to 6 months (compared to studies carried out in the literature).

This evaluation would be made according to a multivariate analysis taking into consideration the other clinical-biological data relating to the patient, namely renal function, liver function, CHA2DS2-VASc score, HAS-BLEED score, treatment compliance, etc.

Study Overview

• Status: Enrolling by invitation
• Conditions: Non Valvular Atrial Fibrillation
• Intervention / Treatment: Drug: Dosage of PT-INR; Drug: Anti Xa dosage

Detailed Description

Atrial fibrillation (AF) is the most common heart rhythm disorder with an estimated global prevalence of between 1 and 2%. It is a serious pathology that considerably increases morbidity and mortality. Thromboembolic events are a major complication .

Thus, effective anticoagulation is one of the major pillars of the management of atrial fibrillation. This anticoagulation was for a long time based on vitamin K antagonists (VKAs) which have proven their effectiveness in significantly reducing the risk of thromboembolic complications. However, VKAs have several drawbacks, mainly related to their narrow therapeutic range, their high inter-individual variability and their multiple drug interactions. As a result, the use of VKAs is restrictive because of the need for a delicate, regular and individual adjustment of the effective dose based on the result of the INR (need for regular and close biological monitoring) .

Since 2007, a new class of oral anticoagulant encompassing direct oral anticoagulants has emerged and is increasingly beginning to take the place of VKAs in several pathologies, including AF. Indeed, DOACs are currently the first-line treatment during AF thanks to the results of randomized controlled clinical trials that have proven an efficacy at least equivalent to VKA without increasing the risk of serious bleeding. In addition, DOACs are simpler to use compared to VKAs because of their predictable pharmacodynamics and pharmacokinetics, which make it possible to use a fixed dose and dispense with biological monitoring of their plasma levels in the majority of cases.

However, it seems that there is a significant inter- and intra-individual variability related to the use of DOACs. In addition, the theory of a single dose and the non-need for monitoring is beginning to be debated. Indeed, the indications requiring an AOD assay seem to be broadening. Recently, studies have been identified in the literature that are interested in assessing the impact of the maximum and residual activity of DOAC on its efficacy and safety. Despite significant results, especially in relation to the fluctuation of residual activity, there are so far no strong conclusions of a high level of evidence that can rule on the usefulness of adjusting the dose according to the dosage of activity.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia, 1006
    • Charles Nicolle Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥ 18 years of age
• Patients diagnosed with AF;
• Written informed consent obtained prior to participation in the study.

Exclusion Criteria:

• Patients with at least one of the following criteria will not be included in the trial:
• History of hypersensitivity to study drugs or drugs with a similar chemical structure.
• Patients receiving combination therapy of P-glycoprotein inhibitors or inducers such as itraconazole, ketoconazole, voriconazole, posaconazole, ritonavir, rifampicin, phenytoin, phenobarbital, and carbamazepine, within 14 days prior to taking apixaban
• Pregnant women
• Breastfeeding
• Patients Enrolled in Other Clinical Studies
• Patients who refuse to sign consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VKA; This arm contain 40 patients on anti-vitamin K. Their prothromin level and INR will be measured	Drug: Dosage of PT-INR; This arm contain 40 pateints treated by VKA,. PT-INR dosage will be performed.
Active Comparator: Apixaban; This arm contain 40 patients. Anti Xa activity and Time in the range will be monitored	Drug: Anti Xa dosage; VKA: quadriseparable tablet Apixaban: 5 mg twice daily or 2.5 twice daily Rivaroxaban: 20 mg once a day or 15 mg once a day
Active Comparator: Rivaroxaban; This arm contain 40 patients. Anti Xa activity and Time in the range will be monitored	Drug: Anti Xa dosage; VKA: quadriseparable tablet Apixaban: 5 mg twice daily or 2.5 twice daily Rivaroxaban: 20 mg once a day or 15 mg once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the variability of anti-FXa activity of apixaban versus rivaroxaban	The patient will attend an initial appointment between 2 and 4 weeks to undergo sampling and receive their samples, followed by further appointments at 3 and 6 months. During these visits, samples will be collected to measure the anti-Xa activity of rivaroxaban and apixaban. Each sampling will occur in two steps: the first sample will be taken before the morning dose to measure anti-Xa activity at the trough (or nadir), and the second sample will be collected 2 hours later to determine the peak (or maximum value reached). The results will be expressed in nanograms per milliliter (ng/mL).	6 months

Collaborators and Investigators

• Sponsor: Les Laboratoires des Médicaments Stériles

Publications and helpful links

General Publications

• Mavri A, Vene N, Bozic-Mijovski M, Miklic M, Soderblom L, Pohanka A, Malmstrom RE, Antovic J. Apixaban concentration variability and relation to clinical outcomes in real-life patients with atrial fibrillation. Sci Rep. 2021 Jul 6;11(1):13908. doi: 10.1038/s41598-021-93372-9.
• Katritsis DG, Gersh BJ, Camm AJ. Anticoagulation in Atrial Fibrillation - Current Concepts. Arrhythm Electrophysiol Rev. 2015 Aug;4(2):100-7. doi: 10.15420/aer.2015.04.02.100.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: hemorrhage; thromboembolic events; variability; Direct oral anticoagulant; non valvular atrial fibrillation; anti-FXa activity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Dalteparin
• Other Study ID Numbers: Apixa Xa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No