Rivaroxaban + Aspirin for Peripheral Artery Disease

Overseen By Paige V Yates, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must be taking: Aspirin

Must not be taking: Non-aspirin antiplatelets, Anticoagulants, CYP 3A4 inhibitors, CYP 3A4 inducers

Disqualifiers: High bleeding risk, Recent stroke, Severe heart failure, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a drug that prevents blood clots in patients with poor blood flow in their arteries. The drug works by blocking a protein that helps blood to clot, which may improve their symptoms. When combined with aspirin, it has shown significant benefits in reducing deaths and heart-related problems in these patients.

Do I need to stop my current medications for the trial?

The trial requires participants to be on aspirin therapy before enrolling. You cannot take dual-antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy. If you are on medications that are strong inhibitors or inducers of CYP 3A4, you may need to stop those. The protocol does not specify a washout period.

What safety data exists for the combination of rivaroxaban and aspirin in treating peripheral artery disease?

The combination of low-dose rivaroxaban and aspirin has been evaluated in the COMPASS and VOYAGER trials for patients with peripheral artery disease (PAD). These studies found that the combination therapy reduced major adverse cardiovascular events and mortality compared to aspirin alone, but it also increased bleeding risk. The COMPASS trial specifically showed a 28% reduction in a composite outcome of major adverse cardiovascular events, major adverse limb events, and fatal or critical organ bleeding, indicating a net clinical benefit. Overall, the combination therapy provides comprehensive protection for PAD patients, though with an increased risk of bleeding. ^{1 2 3 4 5}

Is the drug Rivaroxaban 2.5 mg oral tablet a promising treatment for Peripheral Artery Disease?

Yes, the drug Rivaroxaban 2.5 mg oral tablet, when combined with aspirin, is promising for treating Peripheral Artery Disease. It significantly reduces the risk of major heart and limb events, including heart attacks, strokes, and amputations, compared to using aspirin alone. This combination can help improve survival and reduce complications in patients with this condition. ^{1 2 3 4 6}

What data supports the idea that Rivaroxaban + Aspirin for Peripheral Artery Disease is an effective drug?

The available research shows that using Rivaroxaban with Aspirin for Peripheral Artery Disease (PAD) is effective. One study found that this combination reduced the risk of major heart-related events and death by 24% compared to using Aspirin alone. It also lowered the chance of serious limb problems, like amputation, in PAD patients. Another study confirmed these benefits, suggesting that this drug combination could improve treatment for many PAD patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Aaron W Aday, MD

Principal Investigator

VUMC Cardiovascular Medicine

Are You a Good Fit for This Trial?

This trial is for adults with peripheral artery disease (PAD), evidenced by specific symptoms or past surgeries related to PAD. They must be taking aspirin and able to consent. Excluded are those in other drug studies, with recent or upcoming surgeries, severe heart failure, high bleeding risk, certain drug treatments (like strong CYP3A4 inhibitors/inducers), active infections, poor kidney function, serious non-cardiovascular diseases, known allergies to study drugs, liver issues affecting blood clotting, or women who could become pregnant without effective birth control.

Inclusion Criteria

I am currently taking aspirin.

I have had a limb or foot amputated due to poor blood flow.

I have a significant narrowing in my arteries.

Exclusion Criteria

I have not had a stroke or a bleeding in the brain in the last month.

I am not pregnant, breastfeeding, and if capable of becoming pregnant, I am using effective birth control.

My heart is very weak (EF<30%) or I have severe symptoms limiting my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 81mg of aspirin + rivaroxaban 2.5mg twice daily or placebo for 30 days

4 weeks

1 visit (in-person) at baseline, 1 visit (in-person) at end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin 81Mg Ec Tab
• Placebo
• Rivaroxaban 2.5 Mg Oral Tablet

Trial Overview The study tests if rivaroxaban can improve PAD symptoms compared to a placebo. Participants will also take low-dose aspirin. The goal is to see how rivaroxaban affects blood clots formation and the health of blood vessels and platelets.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 2 Interventions

Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days.

Group II: Control Placebo Group 2 Interventions

Participants will receive 81mg daily of aspirin + placebo for 30 days.

Rivaroxaban 2.5 Mg Oral Tablet is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xarelto for:

• Prevention of venous thromboembolic events (VTE) in patients who have undergone total hip replacements and total knee replacement surgery
• Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Reduction of risk of recurrent DVT and/or PE

Approved in United States as Xarelto for:

• Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Reduction of risk of recurrent DVT and/or PE
• Reduction of risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease

Approved in Canada as Xarelto for:

• Prevention of venous thromboembolic events (VTE) in patients who have undergone total hip replacements and total knee replacement surgery
• Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Reduction of risk of recurrent DVT and/or PE

Approved in Japan as Xarelto for:

• Prevention of venous thromboembolic events (VTE) in patients who have undergone total hip replacements and total knee replacement surgery
• Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Reduction of risk of recurrent DVT and/or PE

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 27,395 patients with coronary or peripheral artery disease, the combination of rivaroxaban and aspirin significantly increased the risk of major and minor bleeding compared to aspirin alone, particularly within the first year of treatment.

The gastrointestinal tract was the most common site for major bleeding, with about 75% of these events being of mild or moderate intensity, and most bleeding was manageable with standard supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major Bleeding in Patients With Coronary or Peripheral Artery Disease Treated With Rivaroxaban Plus Aspirin. Eikelboom, JW., Bosch, JJ., Connolly, SJ., et al.[2020]

In a trial involving 27,395 patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban and aspirin reduced the risk of cardiovascular death, stroke, or heart attack by 24% and decreased overall mortality by 18%.

Rivaroxaban alone did not provide additional benefits compared to aspirin, but the combination therapy also significantly lowered the risk of major limb events, such as amputations, in patients with peripheral artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rivaroxaban plus aspirin for the prevention of cardiovascular events: an evaluation of COMPASS. Bhagirath, VC., Eikelboom, JW., Anand, SS.[2019]

In the COMPASS trial involving 27,395 patients, the combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily significantly reduced overall mortality compared to aspirin alone, with a hazard ratio of 0.82 over a median follow-up of 23 months.

The combination therapy also led to a significant reduction in cardiovascular (CV) deaths (1.7% vs 2.2% for aspirin alone), particularly benefiting patients with higher baseline risk factors, indicating a tailored approach to treatment could enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease. Eikelboom, JW., Bhatt, DL., Fox, KAA., et al.[2021]

In a meta-analysis of 11,560 patients with peripheral artery disease (PAD), low-dose rivaroxaban combined with aspirin significantly reduced the risk of major cardiovascular events and limb complications compared to aspirin alone, with a hazard ratio of 0.79.

While the combination treatment increased the risk of major bleeding (hazard ratio of 1.51), it did not lead to a significant rise in severe bleeding events, indicating a favorable safety profile for this treatment strategy in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials. Anand, SS., Hiatt, W., Dyal, L., et al.[2022]

A secondary analysis of the COMPASS trial indicates that the combination of rivaroxaban (2.5 mg twice daily) and aspirin (100 mg daily) may provide significant benefits for patients with peripheral arterial disease.

This treatment regimen has the potential to change standard management practices for peripheral arterial disease, which currently has limited therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does rivaroxaban have a role in treating patients with PAD? Thomas, R.[2020]

In the COMPASS trial, patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) who received rivaroxaban plus aspirin experienced a significant reduction in major adverse cardiovascular events (MACE) and major adverse limb events (MALE) compared to those taking aspirin alone.

The economic analysis showed that the combination treatment resulted in a minimal incremental cost of $0.16 per member per month, indicating a net health benefit, especially for patients with two or more risk factors for MACE or MALE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Implications of Preventing Major Cardiovascular and Limb Events with Rivaroxaban plus Aspirin in Patients with Coronary or Peripheral Artery Disease in the United States. Hernandez, L., Shah, A., Zhao, Q., et al.[2022]

The COMPASS trial demonstrated that combining rivaroxaban with aspirin significantly reduces the risk of major cardiovascular and limb events in patients with peripheral artery disease (PAD), achieving a 28% reduction in net clinical benefit outcomes.

This combination therapy addresses both platelet activation and the coagulation cascade, providing a more comprehensive approach to managing the high vascular risk associated with PAD compared to traditional antiplatelet therapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing residual thrombotic risk in patients with peripheral artery disease: impact of the COMPASS trial. Hernández, JL., Lozano, FS., Riambau, V., et al.[2020]

Citations

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

Major Bleeding in Patients With Coronary or Peripheral Artery Disease Treated With Rivaroxaban Plus Aspirin. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Low-dose rivaroxaban plus aspirin for the prevention of cardiovascular events: an evaluation of COMPASS. [2019]

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

Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease. [2021]

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

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials. [2022]

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

Does rivaroxaban have a role in treating patients with PAD? [2020]

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

Economic Implications of Preventing Major Cardiovascular and Limb Events with Rivaroxaban plus Aspirin in Patients with Coronary or Peripheral Artery Disease in the United States. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Reducing residual thrombotic risk in patients with peripheral artery disease: impact of the COMPASS trial. [2020]