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Confronto del rischio di sanguinamento tra Rivaroxaban e Apixaban in pazienti con fibrillazione atriale (COBRRA-AF)

30 settembre 2026 aggiornato da: Ottawa Hospital Research Institute

Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Having a stroke can affect a patient's ability to speak, eat, walk, work, care for themselves, and interact with others. Not only can it ruin one's life, but it can also be fatal. A stroke occurs when blood flow to the brain is blocked by a clot, depriving brain cells of oxygen. In people with atrial fibrillation, blood flow is sluggish in the top chambers of the heart, and blood clots can form there. When a piece of a clot breaks off, it can travel to the brain and cause a stroke. That's where blood thinners come in. Blood thinners, or anticoagulants, decrease the chances of blood clots forming in the heart, reducing the risk of stroke. Studies show that blood thinners are highly effective at reducing the risk of stroke by up to 95%.

The conventional blood thinner is warfarin, taken by mouth. Warfarin requires regular blood tests to make sure a patient getting the correct dose. The patient also may have to avoid certain foods since the medication can interact with them. Newer blood thinners, known as direct-oral anticoagulants (DOACs) are available, which do not require regular blood tests and do not interact with foods. Two of the new blood thinners are called rivaroxaban and apixaban. Like warfarin, they can be taken by mouth, and studies have shown them to be as effective as warfarin.

Both rivaroxaban and apixaban have been approved for stroke prevention in AF by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF and patient values around bleeding highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.

The trial is to assess bleeding rates and superiority of using apixaban versus rivaroxaban in patients with non-valvular atrial fibrillation.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Oral anticoagulants such as Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are highly effective at reducing the risk of stroke by up to 95%. Randomized controlled trials (RCTs) have compared apixaban and rivaroxaban (both DOACs) to VKAs for stroke prevention in AF, and are approved for this use by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF, patient values around bleeding, and litigation highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.

The objective of this RCT is to compare the safety of the first 12 months of apixaban twice daily to rivaroxaban once daily in patients with non-valvular AF (NVAF). Patients will be monitored for the primary outcome of clinically relevant bleeding (CRB; a composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events during follow-up. This trial will directly inform clinical practice and the choice of first-line therapy.

Tipo di studio

Interventistico

Iscrizione (Stimato)

3018

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8Z 0B9
        • Ritirato
        • Victoria Cardiac Arrhythmia Trials
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Reclutamento
        • QEII Health Science Centre
        • Investigatore principale:
          • Ratika Parkash, MD
        • Contatto:
    • Ontario
      • Kingston, Ontario, Canada
      • Ottawa, Ontario, Canada, K1H 8L6
        • Reclutamento
        • The Ottawa Hospital - General Campus
        • Investigatore principale:
          • Lana Castellucci, MD
        • Contatto:
        • Contatto:
      • Ottawa, Ontario, Canada
        • Reclutamento
        • University Ottawa Heart Institute
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Daniel Ramirez, MD
    • Quebec

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Age ≥ 18 years old
  • Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines

Exclusion Criteria:

  • Creatinine clearance =<15 ml/min calculated using the Cockcroft-Gault formula

  • Any contraindication for anticoagulation with apixaban or rivaroxaban as determined by the treating physician such as, but not limited to:

    • active bleeding
    • history of mechanical valve
    • other indication for anticoagulation (e.g. mechanical valves, venous thrombosis)
    • dual antiplatelet agent use
    • known liver disease with coagulopathy
    • use of contraindicated medications (strong inducers/inhibitors of CYP 3A4/5, P-glycoprotein)
    • pregnancy or breastfeeding

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Separare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Apixaban group

5 mg PO, twice daily for 12 months of treatment. A dose reduction* to 2.5 mg twice daily will apply if patients meet 2 of 3 following criteria: age > 80 years; weight < 60 kg; creatinine >133 micromol/L.

*Patients with AF who are receiving DOAC should have their renal function assessed at baseline and at least annually
Droga: Apixaban

Refer to Apixaban group

Altri nomi:
  • Eliquis
Comparatore attivo: Rivaroxaban Group

20 mg PO, once daily for 12 months of treatment. A dose reduction* to 15 mg daily will apply to patients with creatinine clearance <50 ml/min.

*Patients with AF who are receiving DOAC should have their renal function assessed at baseline and at least annually
Droga: Rivaroxaban

Refer to Rivaroxaban group

Altri nomi:
  • Xarelto

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
The rate of adjudicated clinically relevant bleeding (CRB) events
Lasso di tempo: For the duration of the study: 12 months

CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events
For the duration of the study: 12 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Adjudicated Major Bleeding events
Lasso di tempo: For the duration of the study: 12 months

Major Bleeding includes clinically overt bleeding and is associated with:

  • Fatal bleeding, and/or
  • Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
  • A fall in hemoglobin of ≥20 g/L, or
  • Leading to transfusion of ≥2 units of whole blood or red cells.
For the duration of the study: 12 months
Adjudicated Clinically Relevant Non-Major Bleeding events
Lasso di tempo: For the duration of the study: 12 months

Clinically relevant non-major bleeding will be defined as:

• Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria:

  • Requiring medical intervention by a healthcare professional
  • Leading to hospitalization or increased level of care
  • Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation
For the duration of the study: 12 months
Adjudicated stroke/TIA events
Lasso di tempo: For the duration of the study: 12 months

Stroke is defined as non-traumatic focal neurologic deficit lasting ≥ 24 hours and confirmed on cerebral imaging (computed tomography or magnetic resonance imaging).

Transient ischemic attack (TIA) is defined as a temporary loss of blood flow to a part of the brain with focal neurologic deficit lasting < 24 hours without imaging evidence of acute infarction.

Strokes are to be classified as ischemic, hemorrhagic stroke, or uncertain. Hemorrhagic strokes are considered and will be reported as both bleeding events as well as stroke endpoints. The location of the bleeding can be determined from the diagnostic imaging reports.
For the duration of the study: 12 months
All-cause mortality
Lasso di tempo: For the duration of the study: 12 months

Using a binary outcome of an event or no event (Individual rates of death, all causes).
For the duration of the study: 12 months
Medication adherence
Lasso di tempo: For the duration of the study: 12 months

Reported as the number of patients self-reporting "all assigned medications were taken" "missing at least one dose of study medication", or "not able to take all of the study medications" out of the total number of medication compliance assessments done respectively
For the duration of the study: 12 months
Incremental cost-effectiveness ratio
Lasso di tempo: For the duration of the study: 12 months

We will model the prognosis of a cohort of patients receiving rivaroxaban versus apixaban. The results will be presented as incremental cost per QALY gained, incremental costs per one clinically relevant bleeding cases prevented, and incremental cost per one life year saved.
For the duration of the study: 12 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Ottawa Hospital Research Institute

Collaboratori

Canadian Institutes of Health Research (CIHR)
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Investigatori

  • Investigatore principale: Lana Castellucci, MD, FRCPC, Ottawa Hospital Research Institute

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

6 luglio 2021

Completamento primario (Stimato)

31 dicembre 2027

Completamento dello studio (Stimato)

31 dicembre 2027

Date di iscrizione allo studio

Primo inviato

19 novembre 2020

Primo inviato che soddisfa i criteri di controllo qualità

19 novembre 2020

Primo Inserito (Effettivo)

24 novembre 2020

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

1 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

30 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • COBRRA-AF

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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