Rivaroxaban vs Apixaban for Blood Clots

(COBRRA Trial)

No longer recruiting at 21 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

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 for treating blood clots in the legs or lungs (venous thromboembolism, or VTE). Both medications have approval but have not been directly compared. Individuals recently diagnosed with VTE who have not been on blood thinners for more than three days may qualify for this trial. The study aims to help doctors determine which medication is safer for patients with these blood clots. As a Phase 4 trial, it involves treatments that are already FDA-approved and effective, seeking 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 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 is the safety track record for apixaban and rivaroxaban?

Research shows that both apixaban and rivaroxaban are generally safe for treating blood clots, but they differ in some aspects. Studies have found that apixaban is linked to lower rates of major bleeding compared to other treatments. In one study, major bleeding occurred in 3% or fewer of patients taking apixaban. Another study showed that patients using apixaban experienced fewer bleeding events than those taking a placebo.

Rivaroxaban is also effective, but it might carry a higher risk of bleeding. Some research indicates that while rivaroxaban reduces the chance of blood clots returning, it can cause significant bleeding in some cases.

Both drugs have approval for treating blood clots, meaning they have passed safety checks. However, bleeding is a common risk with these medications. Understanding these risks can help prospective trial participants make informed decisions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Rivaroxaban and Apixaban for treating blood clots because they offer more convenient dosing options compared to some traditional anticoagulants like warfarin, which requires frequent monitoring and dose adjustments. Apixaban is taken twice daily, while Rivaroxaban starts with a twice-daily dose and transitions to once daily, which can simplify patient adherence. Both drugs are direct oral anticoagulants (DOACs) that work by directly inhibiting factor Xa, a key component in the blood clotting process, offering a more targeted approach than warfarin. This specific mechanism reduces the need for regular blood tests and dietary restrictions, making life a bit easier for patients.

What evidence suggests that this trial's treatments could be effective for VTE?

This trial will compare the effectiveness of Apixaban and Rivaroxaban in treating venous thromboembolism (VTE), a condition where blood clots form in the veins. Research has shown that Apixaban significantly lowers the risk of new clots, with only 1.3% of patients developing another clot compared to 10% of those not taking the drug. Participants in the Apixaban group will receive 10 mg orally twice a day for 1 week, then 5 mg twice a day for 3 months. Rivaroxaban also reduces the risk of new clots when taken for longer periods, without greatly increasing the risk of bleeding. Participants in the Rivaroxaban group will receive 15 mg orally twice a day for 3 weeks, then 20 mg once a day for 3 months. When directly compared, both drugs are similarly effective in reducing clot-related problems, although Rivaroxaban may have a slightly higher chance of causing bleeding. Both medications work by blocking Factor Xa, a protein important for blood clotting, which helps prevent new clots from forming. ^{1 3 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?

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 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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11915223/

Comparing the Safety and Effectiveness of Apixaban Lead- ... This study evaluates the effectiveness and safety of different apixaban lead-in durations for hospitalized adults with newly diagnosed VTE.

2. news.bms.com news.bms.com/news/details/2019/Findings-Released-from-Real-World-Data-Analysis-of-Eliquis-apixaban-for-the-Treatment-of-Venous-Thromboembolism-in-Patients-with-Active-Cancer/default.aspx

Findings Released from Real-World Data Analysis of ... By inhibiting Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis is approved for ...

3. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101714

A Comparison of Outcomes With Apixaban, Rivaroxaban ... Overall, randomized clinical trial evidence suggests that DOACs have similar efficacy and safety compared to warfarin for VTE; DOACs seem to be ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666572725000021

Reduced versus full apixaban lead-in dosing following ... This study showed that the use of a reduced apixaban lead-in for VTE management in patients who received >24 h of parenteral anticoagulation may be effective ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2509426

Apixaban for Extended Treatment of Provoked Venous ... Symptomatic recurrent VTE occurred in 4 of the 300 patients (1.3%) in the apixaban group and in 30 of the 300 patients (10.0%) in the placebo ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40888734/

Apixaban for Extended Treatment of Provoked Venous ... The primary efficacy outcome was the first symptomatic recurrent VTE. The primary safety outcome was the first episode of major bleeding ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507910/

Apixaban - StatPearls - NCBI Bookshelf As an anticoagulant, apixaban's most common adverse effect is bleeding (1% to 10%). The risk of major bleeding is 3% or less, and clinically ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1915103

Apixaban for the Treatment of Venous Thromboembolism ... The primary outcome of recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the ...