心房細動患者におけるリバロキサバンとアピキサバンの出血リスクの比較 (COBRRA-AF)
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Lana Castellucci, MD
- 電話番号：75481 613-737-8899
- メール：lcastellucci@toh.ca
研究連絡先のバックアップ
- 名前：Erin Thomas
- メール：erithomas@toh.ca
研究場所
-
-
British Columbia
-
Victoria、British Columbia、カナダ、V8Z 0B9
- 引きこもった
- Victoria Cardiac Arrhythmia Trials
-
-
Nova Scotia
-
Halifax、Nova Scotia、カナダ
- 募集
- QEII Health Science Centre
-
主任研究者：
- Ratika Parkash, MD
-
コンタクト：
- Katie Kawulka
- メール：katie.kawulka@nshealth.ca
-
-
Ontario
-
Kingston、Ontario、カナダ
- 募集
- Kingston General Hospital
-
主任研究者：
- Kerstin de Wit, MD
-
コンタクト：
- Huba Rana
- メール：huba.rana1@kingstonhsc.ca
-
コンタクト：
- Tanya Gilpin
- メール：tanya.gilpin@kingstonhsc.ca
-
Ottawa、Ontario、カナダ、K1H 8L6
- 募集
- The Ottawa Hospital - General Campus
-
主任研究者：
- Lana Castellucci, MD
-
コンタクト：
- Daniel Warner
- 電話番号：79590 613-737-8899
- メール：dawarner@ohri.ca
-
コンタクト：
- Erin Thomas
- メール：erithomas@toh.ca
-
Ottawa、Ontario、カナダ
- 募集
- University Ottawa Heart Institute
-
コンタクト：
- Hannah Feagan
- 電話番号：14125 613-696-7000
- メール：hfeagan@ottawaheart.ca
-
コンタクト：
- Colleen Ratelle
- メール：cratelle@ottawaheart.ca
-
主任研究者：
- Daniel Ramirez, MD
-
-
Quebec
-
Gatineau、Quebec、カナダ、J8T 4J3
- 募集
- CISSS de l'Outaouais
-
コンタクト：
- Celine Roy
- メール：celine.roy@ssss.gouv.qc.ca
-
コンタクト：
- Gladice Salem
- メール：gladice_salem@ssss.gouv.qc.ca
-
主任研究者：
- Dr. Jean-Michel Guay, MD
-
Laval、Quebec、カナダ
- まだ募集していません
- CHU de Quebec - Université Laval
-
コンタクト：
- Eric Mercier, MD
- メール：eric.mercier@fmed.ulaval.ca
-
主任研究者：
- Dr. Eric Mercier, MD
-
Montreal、Quebec、カナダ、H3L 1K5
- 募集
- Ciusss Nim
-
コンタクト：
- Dr. Alexis Cournoyer, MD
- メール：alexiscournoyermus@gmail.com
-
コンタクト：
- Chantal Lanthier
- メール：chantal.lanthier.cnmtl@ssss.gouv.qc.ca
-
主任研究者：
- Dr. Alexis Cournoyer, MD
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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 |
Refer to Apixaban group
他の名前：
|
|
アクティブコンパレータ：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 |
Refer to Rivaroxaban group
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The rate of adjudicated clinically relevant bleeding (CRB) events
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Adjudicated Major Bleeding events
時間枠：For the duration of the study: 12 months
|
Major Bleeding includes clinically overt bleeding and is associated with:
|
For the duration of the study: 12 months
|
|
Adjudicated Clinically Relevant Non-Major Bleeding events
時間枠：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:
|
For the duration of the study: 12 months
|
|
Adjudicated stroke/TIA events
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
協力者
捜査官
- 主任研究者：Lana Castellucci, MD, FRCPC、Ottawa Hospital Research Institute
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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