Blood Thinners for Atrial Fibrillation

(COBRRA-AF Trial)

Recruiting at 8 trial locations

Overseen By Lana Castellucci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

3018 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two blood thinners, apixaban (Eliquis) and rivaroxaban (Xarelto), to determine which is safer and more effective for individuals with non-valvular atrial fibrillation, a heart condition that can lead to stroke. Both medications prevent dangerous blood clots, but the trial seeks to identify which one better reduces bleeding risks. Individuals recently diagnosed with atrial fibrillation and beginning blood thinner treatment might be suitable for this study. As a Phase 4 trial, it involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

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 is the safety track record for these treatments?

Earlier studies have shown that rivaroxaban is effective and safe for people with atrial fibrillation over the long term. However, some research found a higher risk of bleeding with rivaroxaban compared to other blood thinners like apixaban. Specifically, about 1.4% of patients taking rivaroxaban experienced major bleeding.

In contrast, studies have shown that apixaban generally carries a lower risk of major bleeding compared to older blood thinners like warfarin. Still, apixaban can also increase the risk of bleeding, especially at higher doses or in people with serious kidney problems.

Both rivaroxaban and apixaban are approved for preventing strokes in people with atrial fibrillation, supporting their safety. However, without direct comparisons between the two, this trial aims to determine which one might be safer and more effective for patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for atrial fibrillation because Apixaban and Rivaroxaban offer some unique advantages over traditional blood thinners like warfarin. Unlike warfarin, which requires frequent blood tests and dietary restrictions, Apixaban and Rivaroxaban have more predictable effects and need less monitoring. Additionally, these newer anticoagulants have a rapid onset of action, meaning they start working quickly to prevent blood clots. These features make them more convenient and potentially safer for patients, which is why they are garnering attention as promising options for managing atrial fibrillation.

What is the effectiveness track record for apixaban and rivaroxaban in treating atrial fibrillation?

Research has shown that blood thinners effectively lower the risk of stroke in people with atrial fibrillation (AF). This trial will compare two newer blood thinners: rivaroxaban and apixaban. Studies have found that these medications work as well as the older one, warfarin. Apixaban, which participants in this trial may receive, reduces the risk of major bleeding more effectively than other blood thinners and prevents strokes better than aspirin. Rivaroxaban, another treatment option in this trial, is also approved for reducing stroke risk in AF patients but may carry a higher risk of bleeding compared to apixaban. Both treatments are approved for stroke prevention in AF and do not require frequent blood tests or have food restrictions like warfarin. ^{2 4 6 7 8}

Who Is on the Research Team?

Lana Castellucci, MD, FRCPC

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Apixaban
• Rivaroxaban

Trial Overview

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.

How Is the Trial Designed?

Group I: Rivaroxaban Group Active Control 1 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 group Active Control 1 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

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Collaborator

Trials

12

Recruited

17,500+

Published Research Related to This Trial

Novel oral anticoagulants like dabigatran, apixaban, and rivaroxaban have been developed to improve stroke prevention in patients with atrial fibrillation, showing promising results in large-scale clinical trials compared to traditional vitamin K antagonists like warfarin.

These new agents target specific coagulation factors (thrombin and factor Xa) and have received FDA approval, expanding treatment options for patients with nonvalvular atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A guidance pathway for the selection of novel anticoagulants in the treatment of atrial fibrillation. Wisler, JW., Becker, RC.[2014]

Newer anticoagulants like dabigatran, rivaroxaban, and apixaban are at least as effective as warfarin for preventing strokes in patients with atrial fibrillation, without the need for regular blood monitoring.

When treating older adults with atrial fibrillation, clinicians should consider factors such as patient tolerance, cost, adherence, and the absence of a reversal agent for these newer medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ogbonna, KC., Clifford, KM.[2013]

Dabigatran, rivaroxaban, and apixaban have rapidly gained popularity in clinical practice for treating atrial fibrillation, making up 62% of new prescriptions by the end of the study period, which included 6893 patients from 2010 to 2013.

However, patients initiating these novel anticoagulants faced significantly higher costs, with an average increase of over $900 in combined spending for the first 6 months compared to those starting warfarin, highlighting the financial impact of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications. Desai, NR., Krumme, AA., Schneeweiss, S., et al.[2022]

In a study of 32,675 patients with atrial fibrillation, apixaban and dabigatran were found to significantly lower the risk of major or clinically relevant non-major bleeding compared to warfarin, indicating their safety as anticoagulants.

Rivaroxaban did not show a reduced bleeding risk compared to warfarin and was associated with a higher risk of gastrointestinal bleeding, while apixaban and dabigatran were linked to a lower risk of intracranial bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. Halvorsen, S., Ghanima, W., Fride Tvete, I., et al.[2020]

Apixaban, an oral direct factor Xa inhibitor, has been approved in the EU for preventing venous thromboembolism (VTE) after hip or knee replacement surgeries, demonstrating its efficacy in reducing the risk of blood clots in these patients.

The drug is also undergoing phase III trials for preventing strokes in patients with atrial fibrillation, indicating its potential for broader applications in thrombotic disorders, although development for acute coronary syndromes has been halted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. Watson, J., Whiteside, G., Perry, C.[2021]

Apixaban is an effective direct oral anticoagulant for treating venous thromboembolism (VTE), showing safety and efficacy in large phase III trials, making it a convenient alternative to warfarin.

However, there is limited research on its use in certain populations, such as patients over 75, those with cancer, and pediatric patients, indicating a need for further studies in these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive evaluation of apixaban in the treatment of venous thromboembolism. Koehl, JL., Hayes, BD., Al-Samkari, H., et al.[2021]

In a study of 600 patients treated for acute venous thromboembolism (VTE), both apixaban and rivaroxaban showed comparable efficacy, with low rates of VTE recurrence (2.3% for apixaban and 2% for rivaroxaban).

Apixaban was associated with a significantly lower rate of clinically relevant nonmajor bleeding (2.3%) compared to rivaroxaban (6.7%), suggesting it may be a safer option in terms of bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism. Bott-Kitslaar, DM., McBane, RD., Casanegra, AI., et al.[2020]

Apixaban is an effective oral anticoagulant for treating and preventing venous thromboembolism (VTE), showing noninferiority to the traditional enoxaparin/warfarin treatment in large phase III trials over 6 months.

It has a lower risk of major bleeding compared to enoxaparin/warfarin and is well tolerated, making it a safer alternative for patients with VTE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: A Review in Venous Thromboembolism. Greig, SL., Garnock-Jones, KP.[2020]

The review compares the effectiveness and safety of four oral anticoagulants—warfarin, dabigatran, rivaroxaban, and apixaban—in preventing thromboembolism in patients with atrial fibrillation.

New data suggests that these anticoagulants may vary in their effectiveness and safety profiles, which is crucial for guiding treatment decisions in patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anticoagulants in the prevention of complications in patients with atrial fibrillation]. Skibitskiĭ, VV., Kanorskiĭ, SG.[2017]

Healthcare professionals (HCPs) and patients demonstrated satisfactory knowledge of bleeding risks associated with apixaban, with 96.1% of HCPs recognizing symptoms that require immediate attention and 71.2% of patients identifying abnormal bleeding as a significant side effect.

The study found that a significant majority of HCPs (97.8%) who received the Prescriber Guide utilized it in patient discussions, and 90.9% of patients who received the Patient Alert Card read it at least once, indicating effective distribution and utilization of these educational materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. Mayall, S., Kahlon, R., Al-Dakkak, I., et al.[2021]

In a study of 8187 patients with venous thromboembolism (VTE), there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding between those treated with rivaroxaban and those treated with apixaban.

The 180-day risks for all-cause mortality were 5.08% for apixaban and 4.60% for rivaroxaban, while the risks for recurrent VTE were 2.16% and 2.22%, respectively, indicating similar safety and efficacy profiles for both medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study. Sindet-Pedersen, C., Staerk, L., Pallisgaard, JL., et al.[2019]

In the ARISTOTLE trial, apixaban significantly reduced the risk of stroke, systemic embolism, major bleeding, and death compared to warfarin in patients with nonvalvular atrial fibrillation, showing consistent benefits across various patient subgroups.

The AVERROES trial demonstrated that apixaban was more effective than aspirin in preventing stroke or systemic embolism in patients unsuitable for vitamin K antagonist therapy, without increasing the risk of major bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: a review of its use for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Keating, GM.[2021]

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