COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Apixaban
  Refer to Apixaban group
• Препарат Rivaroxaban
  Refer to Rivaroxaban group

Первичные конечные точки

• The rate of adjudicated clinically relevant bleeding (CRB) events [Срок оценки: For the duration of the study: 12 months]

Вторичные конечные точки (6)

• Adjudicated Major Bleeding events [Срок оценки: For the duration of the study: 12 months]
• Adjudicated Clinically Relevant Non-Major Bleeding events [Срок оценки: For the duration of the study: 12 months]
• Adjudicated stroke/TIA events [Срок оценки: For the duration of the study: 12 months]
• All-cause mortality [Срок оценки: For the duration of the study: 12 months]
• Medication adherence [Срок оценки: For the duration of the study: 12 months]
• Incremental cost-effectiveness ratio [Срок оценки: For the duration of the study: 12 months]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 8 центров

• Victoria Cardiac Arrhythmia Trials — Victoria
• QEII Health Science Centre — Halifax
• Kingston General Hospital — Kingston
• The Ottawa Hospital - General Campus — Ottawa
• University Ottawa Heart Institute — Ottawa
• CISSS de l'Outaouais — Gatineau
• CHU de Quebec - Université Laval — Laval
• Ciusss Nim — Montreal

Идентификаторы

NCT: NCT04642430 · COBRRA-AF

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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