Rivaroxaban vs Apixaban for Blood Clots

(COBRRA Trial)

Recruiting at 18 trial locations

Overseen By Lana Castellucci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Contraindicated medications

Disqualifiers: Active malignancy, Liver disease, 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: 3 months

2760 Participants Needed

Trial Summary

What is the purpose of this trial?

Apixaban and rivaroxaban have been compared to standard therapy for treatment of acute symptomatic venous thromboembolism (VTE) in randomized controlled trials (RCTs), and are both approved by Health Canada. No safety or efficacy data is available from direct head-to-head comparison of these two anticoagulants. Lawsuits in the United States over bleeding events, patient perceptions, and concerns with medication adherence are additional factors highlighting the importance of a comparison trial. This multi-center, pragmatic, prospective, randomized, open-label, blinded end-point (PROBE) trial aims to compare the safety of apixaban and rivaroxaban for the treatment of VTE.

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 are contraindicated (not recommended) with apixaban or rivaroxaban, 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 treating blood clots?

Research shows that Apixaban is effective in treating and preventing blood clots, as it was found to be as effective as other treatments like enoxaparin and warfarin, with a lower risk of bleeding. It is also approved for preventing blood clots after hip or knee replacement surgery. ^{1 2 3 4 5}

Is it safe to use Apixaban (Eliquis) and Rivaroxaban (Xarelto) for blood clots?

Both Apixaban and Rivaroxaban are generally considered safe for treating blood clots, with Apixaban showing a lower risk of major and minor bleeding compared to Rivaroxaban. ^{2 3 4 6 7}

How do the drugs apixaban and rivaroxaban differ in treating blood clots?

Apixaban and rivaroxaban are both oral drugs used to prevent blood clots, but apixaban is associated with a lower risk of major bleeding and gastrointestinal bleeding compared to rivaroxaban, while maintaining similar effectiveness in preventing clots. ^{2 3 8 9 10}

Research Team

Lana Castellucci, MD, FRCPC

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

Adults over 18 with a new diagnosis of acute venous thromboembolism (VTE), including deep vein thrombosis or pulmonary embolism, can join this trial. They must not have had more than 72 hours of anticoagulation treatment and should have adequate kidney function. People with active bleeding, certain liver diseases, heavy body weight, or those on conflicting medications cannot participate.

Inclusion Criteria

I am 18 years old or older.

I have a new diagnosis of a serious blood clot in my leg or lungs.

Informed consent obtained

Exclusion Criteria

I cannot take certain blood thinners due to conditions like bleeding, cancer, being over 120kg, liver disease, other medications, another need for blood thinners, or being pregnant/breastfeeding.

I have been on blood thinners for more than 72 hours.

Your kidneys are not working well enough, as measured by a specific calculation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either apixaban or rivaroxaban for the treatment of acute venous thromboembolism

3 months

Regular visits for monitoring and medication adherence checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Apixaban
• Rivaroxaban

Trial Overview This study compares the safety of two blood thinners—Rivaroxaban and Apixaban—in treating VTE. It's a head-to-head test to see which causes fewer bleeding problems in patients. The trial is multi-center and designed so that neither the participants nor the outcome assessors know who receives which drug.

Participant Groups

Group I: Apixaban group Active Control 1 Intervention

10 mg orally (PO), twice a day (BID) for 1 week, then 5 mg PO BID for 3 months of treatment

Group II: Rivaroxaban group Active Control 1 Intervention

15 mg orally (PO), twice a day (BID) for 3 weeks, then 20 mg PO once a day (OD) for 3 months of treatment

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+

Findings from Research

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]

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]

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, 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]

In a study involving 6,959 patients with venous thromboembolism (VTE), edoxaban, rivaroxaban, and apixaban showed no significant differences in preventing recurrent VTE, indicating similar effectiveness among these anticoagulants.

The safety profiles of the three drugs were also comparable, with no significant differences in the risk of serious bleeding events such as intracranial hemorrhage or gastrointestinal bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study. Fukasawa, T., Seki, T., Nakashima, M., et al.[2023]

In a meta-analysis of 12 clinical trials involving 12,195 patients, apixaban was found to significantly reduce the risk of major bleeding events (RR 0.56) and total bleeding events (RR 0.81) compared to enoxaparin in patients undergoing knee arthroplasty.

No significant differences in bleeding events were observed between rivaroxaban and enoxaparin for knee arthroplasty, and both drugs showed similar safety profiles in hip arthroplasty, indicating that apixaban may be a safer option for knee surgery patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis. Alves, C., Batel-Marques, F., Macedo, AF.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Apixaban: A Review in Venous Thromboembolism. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis. [2015]

10. New Zealand pubmed.ncbi.nlm.nih.gov

A randomized direct comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban. [2022]