Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Comparaison du risque hémorragique entre le rivaroxaban et l'apixaban chez les patients atteints de fibrillation auriculaire (COBRRA-AF)

30 septembre 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

3018

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

  • Nom: Lana Castellucci, MD
  • Numéro de téléphone: 75481 613-737-8899
  • E-mail: lcastellucci@toh.ca

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8Z 0B9
        • Retiré
        • Victoria Cardiac Arrhythmia Trials
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Recrutement
        • QEII Health Science Centre
        • Chercheur principal:
          • Ratika Parkash, MD
        • Contact:
    • Ontario
      • Kingston, Ontario, Canada
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recrutement
        • The Ottawa Hospital - General Campus
        • Chercheur principal:
          • Lana Castellucci, MD
        • Contact:
          • Daniel Warner
          • Numéro de téléphone: 79590 613-737-8899
          • E-mail: dawarner@ohri.ca
        • Contact:
      • Ottawa, Ontario, Canada
        • Recrutement
        • University Ottawa Heart Institute
        • Contact:
        • Contact:
        • Chercheur principal:
          • Daniel Ramirez, MD
    • Quebec

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Seul

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 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
Médicament: Apixaban

Refer to Apixaban group

Autres noms:
  • Équis
Comparateur actif: 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
Médicament: Rivaroxaban

Refer to Rivaroxaban group

Autres noms:
  • Xarelto

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
The rate of adjudicated clinically relevant bleeding (CRB) events
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Adjudicated Major Bleeding events
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Ottawa Hospital Research Institute

Collaborateurs

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

Les enquêteurs

  • Chercheur principal: Lana Castellucci, MD, FRCPC, Ottawa Hospital Research Institute

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

6 juillet 2021

Achèvement primaire (Estimé)

31 décembre 2027

Achèvement de l'étude (Estimé)

31 décembre 2027

Dates d'inscription aux études

Première soumission

19 novembre 2020

Première soumission répondant aux critères de contrôle qualité

19 novembre 2020

Première publication (Réel)

24 novembre 2020

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

30 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • COBRRA-AF

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner