Blood Thinners for Atrial Fibrillation
(COBRRA-AF Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Overseen byLana Castellucci, MD, FRCPC
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Ottawa Hospital Research Institute
Must be taking: Anticoagulants
Must not be taking: CYP 3A4/5 inhibitors
Disqualifiers: Active bleeding, Mechanical valve, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are using medications that strongly interact with the trial drugs, you may need to stop those. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Apixaban for atrial fibrillation?
Research shows that Apixaban is effective in reducing the risk of stroke and systemic embolism (blockage of a blood vessel) in patients with atrial fibrillation, as it was found to be more effective than warfarin and aspirin in clinical trials.
12345Is it safe to use blood thinners like Apixaban and Rivaroxaban for atrial fibrillation?
Apixaban (Eliquis) and Rivaroxaban (Xarelto) are blood thinners that have been studied for safety in treating conditions like atrial fibrillation and venous thromboembolism (blood clots). They are generally considered safe, but there is a risk of bleeding, which is why additional safety measures like educational materials are provided to help manage this risk.
35678How do the drugs Apixaban and Rivaroxaban differ from other treatments for atrial fibrillation?
Apixaban and Rivaroxaban are newer oral blood thinners that target a specific part of the blood clotting process (factor Xa), offering a more convenient alternative to the older drug warfarin, as they do not require regular blood monitoring and have fewer dietary restrictions.
39101112Eligibility Criteria
This trial is for adults over 18 with a new diagnosis of atrial fibrillation confirmed by ECG who need blood thinners according to guidelines. It's not for those with severe kidney issues, active bleeding, mechanical heart valves, other anticoagulation needs, certain liver diseases, or if pregnant/breastfeeding.Inclusion Criteria
I have a new diagnosis of atrial fibrillation and need blood thinners.
I am 18 years old or older.
Exclusion Criteria
I can safely take blood thinners like apixaban or rivaroxaban without any health risks.
Your kidneys are not working well, and a certain calculation shows that your kidneys may not be able to filter waste properly.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either apixaban or rivaroxaban for 12 months to assess bleeding rates and safety
12 months
Monthly visits for monitoring and medication adherence checks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study compares the bleeding risks when using two oral blood thinners—Apixaban and Rivaroxaban—in patients with non-valvular atrial fibrillation. It aims to determine which drug has a better balance between benefits and potential harm.
2Treatment groups
Active Control
Group I: Rivaroxaban GroupActive Control1 Intervention
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
Group II: Apixaban groupActive Control1 Intervention
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
Apixaban is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Eliquis for:
- Deep vein thrombosis
- Pulmonary embolism
- Nonvalvular atrial fibrillation
🇺🇸 Approved in United States as Eliquis for:
- Deep vein thrombosis
- Pulmonary embolism
- Nonvalvular atrial fibrillation
- Stroke prevention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ciusss NimMontreal, Canada
Victoria Cardiac Arrhythmia TrialsVictoria, Canada
CISSS de l'OutaouaisGatineau, Canada
The Ottawa Hospital - General CampusOttawa, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Ottawa Hospital Research InstituteLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) NetworkCollaborator
References
Apixaban: A Review in Venous Thromboembolism. [2020]Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is available for use in the treatment and secondary prevention of venous thromboembolism (VTE). Like other direct oral anticoagulants (DOACs), apixaban has generally predictable pharmacological properties and does not require routine anticoagulation monitoring. In large phase III trials, oral apixaban was noninferior to subcutaneous enoxaparin sodium overlapped with and followed by oral warfarin (enoxaparin/warfarin) in the treatment of adults with acute VTE over 6 months with regard to the incidence of recurrent VTE or VTE-related death (AMPLIFY), and was significantly more effective than placebo in the prevention of recurrent VTE or all-cause mortality over 12 months in patients who had completed 6-12 months' anticoagulation treatment for VTE (AMPLIFY-EXT). Apixaban was generally well tolerated in these trials; the risks of major bleeding and the composite endpoint of major or clinically relevant nonmajor (CRNM) bleeding with apixaban were significantly lower than enoxaparin/warfarin in AMPLIFY and not significantly different from that of placebo in AMPLIFY-EXT. Similarly, in Japanese adults with acute VTE (AMPLIFY-J), apixaban was associated with a significantly lower risk of major or CRNM bleeding than unfractionated heparin plus warfarin, and no cases of recurrent VTE or VTE-related death over 24 weeks. Thus, apixaban is useful therapeutic alternative for the management of adults with VTE.
Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study. [2019]To investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban.
Apixaban: first global approval. [2021]Apixaban (Eliquis™), an oral direct factor Xa inhibitor, is being developed by Bristol-Myers Squibb and Pfizer as a therapy for the prevention and/or treatment of thrombotic disorders. Apixaban has been approved in the EU for the prevention of venous thromboembolism (VTE) after hip or knee replacement. A rolling submission for approval of apixaban for the prevention of stroke in patients with atrial fibrillation has also been initiated in the US. Worldwide phase III development of apixaban is underway for the prevention and treatment of VTE, and prevention of stroke in patients with atrial fibrillation. Development for acute coronary syndromes has been stopped following the discontinuation of the phase III APPRAISE-II trial. This article summarizes the milestones in the development of apixaban leading to this first approval for the prevention of VTE after hip or knee replacement.
Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. [2021]The direct factor Xa inhibitor apixaban (Eliquis(®)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring. This article reviews the efficacy and tolerability of oral apixaban to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial in patients with AF and at least one additional risk factor for stroke, apixaban recipients were significantly less likely than warfarin recipients to experience stroke or systemic embolism, major bleeding or death; the beneficial effects of treatment with apixaban versus warfarin were generally maintained across various patient subgroups. Apixaban recipients also had a significantly lower risk of intracranial haemorrhage than warfarin recipients. In the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Therapy) trial in patients with AF and at least one additional risk factor for stroke for whom vitamin K antagonist therapy was unsuitable, apixaban was associated with a significantly lower risk of stroke or systemic embolism than aspirin, without an increase in the risk of major bleeding. In conclusion, although longer-term efficacy and safety data are needed, apixaban is an important new option for use in patients with nonvalvular AF to reduce the risk of stroke or systemic embolism.
Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism. [2020]To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE).
[Anticoagulants in the prevention of complications in patients with atrial fibrillation]. [2017]This review presents new data on the comparative effectiveness and safety of treatment with oral anticoagulants warfarin, dabigatran, rivaroxaban, apixaban for prevention of thromboembolism in patients with atrial fibrillation.
Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]Label="BACKGROUND">Apixaban (ELIQUIS®) is a direct oral anticoagulant authorised for multiple indications in the European Economic Area (EEA). Additional risk minimisation measures (aRMMs) to address the risk of bleeding include educational materials comprising a Prescriber Guide and Patient Alert Card.
A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. [2020]We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin.
Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications. [2022]Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers.
A guidance pathway for the selection of novel anticoagulants in the treatment of atrial fibrillation. [2014]Oral anticoagulation with vitamin K antagonists has served as the primary treatment for the prevention of stroke and systemic embolization in patients with atrial fibrillation (AF) for decades. Over the past several years, multiple novel oral anticoagulants targeting key mediators of coagulation, including thrombin and factor Xa, have been developed. Specifically, agents targeting thrombin (dabigatran) and factor Xa (apixaban and rivaroxaban) have either reached late stages of clinical development (apixaban) or have received approval (dabigatran, rivaroxaban) by the US Food and Drug Administration for use in patients with nonvalvular AF. The promising results derived from large-scale clinical trials with these agents compared to warfarin expand the available therapeutic options for the prevention of stroke and systemic embolization in this rapidly increasing patient population. Here we present a general guidance pathway for the initiation and selection of oral anticoagulants in patients with AF.
Moving beyond warfarin-are we ready? A Review of the efficacy and safety of novel anticoagulant agents compared to warfarin for the management of atrial fibrillation in older adults. [2013]Atrial fibrillation (AF) is one of the most common cardiac arrhythmias seen in clinical practice. Stroke risk in patients diagnosed with AF increases from 1.5% in the fifth decade of life to 23.5% in patients older than 80, emphasizing the need for effective and appropriate therapies. Over the past 50 years, vitamin K antagonists-namely warfarin (Coumadin(®))-have been the mainstay for stroke prevention. The introduction of dabigatran (Pradaxa(®)), rivaroxaban (Xarelto(®)), and apixaban (Eliquis(®)) has caused both patients and providers to question whether better alternatives to warfarin therapy exist. These agents have shown to be at least as effective as warfarin in stroke risk reduction with no need for international normalized ratio monitoring. This review will examine these newer anticoagulant agents' safety and efficacy and provide clinical considerations for treating older adults with AF. Clinicians with patients unable to tolerate warfarin or with difficulty managing therapy will need to consider patient characteristics, cost, adherence, lack of a reversal agent, and long-term efficacy before prescribing these agents.
A comprehensive evaluation of apixaban in the treatment of venous thromboembolism. [2021]Introduction: The emergence of the direct oral anticoagulants (DOACs) offers patients more convenient and accessible alternatives to warfarin or parenteral agents for the treatment of venous thromboembolism (VTE). Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy.Areas covered: This article reviews results from preclinical and healthy volunteer studies, large phase III trials evaluating the safety and efficacy of apixaban, as well as key studies that led to apixaban's current licensing. This review also will provide an overview of special populations where future areas of research are needed.Expert commentary: Apixaban offers several advantages over historical therapy for the treatment and secondary prevention of VTE. However, there are some populations in which the use of apixaban has not been extensively studied such as patients >75 years old, or those with cancer, low or high body weight, or poor renal function. Likewise, there is a dearth of data on pediatric patients and patients with a history of heparin-induced thrombocytopenia or identified forms of thrombophilia. Additional comparator studies on anticoagulation reversal involving andexanet alfa are also necessary to further assess its hemostatic efficacy and prothrombotic risk.