Non Valvular Atrial FibrillationPhase 4APIXA-XaNCT06862726
Apixaban Versus Rivaroxaban in Non Valvular Atrial Fibrillation
A Phase 4 study testing Anti Xa dosage and Dosage of PT-INR in people with Non Valvular Atrial Fibrillation, run by Les Laboratoires des Médicaments Stériles at 1 site in Tunisia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non Valvular Atrial Fibrillation
- What is being tested?
- Anti Xa dosage and Dosage of PT-INR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteTunisia
- Study dates
- 1 Dec 2024to 31 Dec 2025
- Phase
- Phase 4
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 years of age
- Patients diagnosed with AF;
- Written informed consent obtained prior to participation in the study.
Who cannot join
- 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.
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: 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.
Read the 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.
- Conditions
- Non Valvular Atrial Fibrillation
- Being tested
- Anti Xa dosage, Dosage of PT-INR
- Keywords
- non valvular atrial fibrillation, Direct oral anticoagulant, thromboembolic events, hemorrhage, anti-FXa activity, variability
- Medical subject headings
- Thromboembolism, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti Xa dosageDrug
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
Dosage of PT-INRDrug
This arm contain 40 pateints treated by VKA,. PT-INR dosage will be performed.
| Study group | Role | What they receive |
|---|---|---|
| VKA | Active comparator | This arm contain 40 patients on anti-vitamin K. Their prothromin level and INR will be measured Receives: Drug: Dosage of PT-INR |
| Apixaban | Active comparator | This arm contain 40 patients. Anti Xa activity and Time in the range will be monitored Receives: Drug: Anti Xa dosage |
| Rivaroxaban | Active comparator | This arm contain 40 patients. Anti Xa activity and Time in the range will be monitored Receives: Drug: Anti Xa dosage |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start1 Dec 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (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 Non Valvular 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
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Les Laboratoires des Médicaments Stériles
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06862726
- Sponsor's protocol ID
- Apixa Xa
- Acronym
- APIXA-Xa
- Status last verified
- Feb 2025
- First submitted
- 25 Nov 2024
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 34230559Katritsis 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.
PubMed 26835109
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06862726
- Acronym / sponsor ID
- APIXA-Xa / Apixa Xa
- Conditions
- Non Valvular Atrial Fibrillation
- Keywords
- non valvular atrial fibrillation, Direct oral anticoagulant, thromboembolic events, hemorrhage, anti-FXa activity, variability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Les Laboratoires des Médicaments StérilesIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 6 Mar 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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VKA | Active comparator | Drug: Dosage of PT-INRThis arm contain 40 patients on anti-vitamin K. Their prothromin level and INR will be measured |
| Apixaban | Active comparator | Drug: Anti Xa dosageThis arm contain 40 patients. Anti Xa activity and Time in the range will be monitored |
| Rivaroxaban | Active comparator | Drug: Anti Xa dosageThis arm contain 40 patients. Anti Xa activity and Time in the range will be monitored |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female ≥ 18 years of age
- Patients diagnosed with AF;
- Written informed consent obtained prior to participation in the study.
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Anti Xa dosageVKA: quadriseparable tablet Apixaban: 5 mg twice daily or 2.5 twice daily Rivaroxaban: 20 mg once a day or 15 mg once a day | Drug | Apixaban, Rivaroxaban |
| Dosage of PT-INRThis arm contain 40 pateints treated by VKA,. PT-INR dosage will be performed. | Drug | VKA |
Primary outcome
To compare the variability of anti-FXa activity of apixaban versus rivaroxaban
Time frame: 6 months
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).
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 6 Mar 2025.
- Results publication: PubMed 34230559Mavri 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.
- Results publication: PubMed 26835109Katritsis 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.
- Individual participant dataSharing planned: Undecided
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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 4 study testing Anti Xa dosage and Dosage of PT-INR in people with Non Valvular Atrial Fibrillation, run by Les Laboratoires des Médicaments Stériles at 1 site in Tunisia.
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 7 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 6 Mar 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 Tunisia. 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?
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?
To compare the variability of anti-FXa activity of apixaban versus rivaroxaban (time frame: 6 months). 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 NCT06862726, 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 6 Mar 2025.