Low Dose Rivaroxaban for Cardiovascular Disease

(TRACK Trial)

Not currently recruiting at 106 trial locations

Overseen By Jenny Landrigan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The George Institute

Must not be taking: P2Y12 inhibitors, Phosphodiesterase inhibitors

Disqualifiers: Mechanical heart valve, High bleeding risk, Recent major bleeding, Severe heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years or until trial closure

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low dose of rivaroxaban can reduce the risk of major heart problems in people with advanced Chronic Kidney Disease (CKD) or those on dialysis. Rivaroxaban prevents blood clots, which can cause heart attacks or strokes. The study includes two groups: one receives rivaroxaban, and the other receives a placebo (a pill with no active drug) for comparison. Suitable candidates for this trial include those with severe kidney issues and a history of heart disease, diabetes, or who are 65 years or older. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot participate if you are taking certain medications like P2Y12 inhibitors or phosphodiesterase inhibitors and do not wish to stop them. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that low dose rivaroxaban is likely to be safe for humans?

Research has shown that rivaroxaban is generally safe for treating heart and blood vessel conditions. Studies have found that rivaroxaban, used alone or with aspirin, can lower the risk of strokes and heart attacks in people with coronary artery disease (CAD) and peripheral artery disease (PAD). However, some studies indicate that rivaroxaban might increase the risk of serious bleeding compared to using aspirin alone.

Research on low doses of rivaroxaban suggests it may not reduce death rates from heart-related or other causes in patients who recently had acute conditions. Despite this, it remains a generally safe option for treating conditions related to blood clots.

Rivaroxaban has already received FDA approval for other heart-related treatments, indicating it has passed many safety checks for those uses. While there is some risk, evidence suggests that many people tolerate rivaroxaban well, with bleeding being the most common concern. Discussing these findings with a healthcare provider is important to understand their personal implications. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for cardiovascular disease, which often involves higher doses of anticoagulants like rivaroxaban or warfarin, this treatment uses a low dose of rivaroxaban, specifically 2.5 mg twice daily. This lower dosage aims to minimize the risk of bleeding, a common side effect with standard doses, while still providing effective protection against blood clots. Researchers are excited about this approach because it could offer a safer alternative for patients who need anticoagulation therapy without compromising on efficacy.

What evidence suggests that low dose rivaroxaban might be an effective treatment for cardiovascular disease in CKD patients?

Research has shown that rivaroxaban might lower the risk of death from any cause and from heart-related issues in people with coronary heart disease. In a study with nearly 38,000 patients, this benefit appeared over about 18 months. However, other research found that a low dose of rivaroxaban did not reduce heart-related deaths or overall deaths in patients who recently had a heart problem. Notably, rivaroxaban alone did not improve heart outcomes compared to aspirin and caused more bleeding. This mixed evidence suggests that rivaroxaban may help in certain heart conditions, but results can vary. Participants in this trial will receive either low-dose rivaroxaban or a placebo to further investigate these outcomes. ^{1 2 6 7 8}

Who Is on the Research Team?

Sunil Badve

Principal Investigator

The George Institute

Martin Gallagher

Principal Investigator

The George Institute

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older with advanced chronic kidney disease (stages 4 or 5) or on dialysis, and who also have a high risk of heart problems due to conditions like diabetes, previous strokes, or being over the age of 65. Participants must not have uncontrolled high blood pressure, recent major bleeding, certain heart valve issues, severe liver disease, very low blood counts, be pregnant/breastfeeding in some regions, among other exclusions.

Inclusion Criteria

People able to provide informed consent who meet all of the following inclusion criteria:

I am 65 years old or older.

I am at high risk for heart problems.

Exclusion Criteria

You have a mechanical or prosthetic heart valve that requires medication to prevent blood clots.

I need or cannot take blood thinners.

I have received a kidney transplant and it is working, or I am scheduled for one.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose rivaroxaban or placebo to assess the reduction in risk of major adverse cardiac events

5 years or until trial closure

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rivaroxaban

Trial Overview

The TRACK trial is testing whether a low dose of Rivaroxaban can lower the chance of serious heart events in patients with late-stage chronic kidney disease at elevated cardiovascular risk. It's a large global study comparing Rivaroxaban against a placebo pill without any active medicine in it.

How Is the Trial Designed?

Group I: Rivaroxaban Experimental Treatment 1 Intervention

Rivaroxaban 2.5mg, twice daily.

Group II: Placebo Placebo Group 1 Intervention

Matched placebo, twice daily.

Rivaroxaban is already approved in United States, European Union for the following indications:

Approved in United States as Xarelto for:

• Deep vein thrombosis (DVT)
• Venous thromboembolism (VTE)
• Stroke prevention in non-valvular atrial fibrillation
• Prevention of VTE in patients undergoing knee or hip replacement surgery

Approved in European Union as Xarelto for:

• Deep vein thrombosis (DVT)
• Venous thromboembolism (VTE)
• Stroke prevention in non-valvular atrial fibrillation
• Prevention of VTE in patients undergoing knee or hip replacement surgery
• Prevention of atherothrombotic events in patients with acute coronary syndrome

Who Is Running the Clinical Trial?

The George Institute

Lead Sponsor

Trials

84

Recruited

275,000+

Emerald Clinical Inc.

Industry Sponsor

Central Hospital, Nancy, France

Collaborator

Trials

782

Recruited

2,447,000+

George Clinical Pty Ltd

Industry Sponsor

Trials

15

Recruited

21,300+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Centre Hospitalier Régional Universitaire de Nancy

Collaborator

Trials

3

Recruited

8,800+

King Abdullah International Medical Research Center

Collaborator

Trials

49

Recruited

121,000+

Published Research Related to This Trial

Rivaroxaban 2.5 mg twice daily, when combined with aspirin or aspirin plus clopidogrel/ticlopidine, significantly reduced the risk of death from cardiovascular causes, myocardial infarction, or stroke in patients with recent acute coronary syndrome, based on the ATLAS ACS 2-TIMI 51 trial involving a median treatment duration of 13.1 months.

While rivaroxaban showed efficacy in reducing cardiovascular events, it also increased the risk of major bleeding and intracranial hemorrhage compared to placebo, although there was no increase in fatal bleeding, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban: a review of its use in acute coronary syndromes. Plosker, GL.[2021]

Rivaroxaban is an effective oral medication that inhibits Factor Xa, showing significant efficacy in preventing and treating thromboembolic disorders, including venous thromboembolism after major orthopedic surgery.

In phase III studies, rivaroxaban was found to be more effective than enoxaparin for preventing blood clots after knee surgery, with a similar low risk of bleeding, making it a promising alternative to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban. A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. Perzborn, E., Kubitza, D., Misselwitz, F.[2015]

A study involving 72 healthy Chinese volunteers demonstrated that a generic formulation of rivaroxaban is bioequivalent to the branded version (Xarelto), with pharmacokinetic parameters falling within the acceptable range of 80% to 125% under both fasted and fed conditions.

The study found no serious adverse events, indicating that both formulations are safe for use in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence and Food Effect Assessment of 2 Rivaroxaban Formulations in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, and 4-Period Crossover Study. Tao, Y., Jiang, X., Shi, P., et al.[2022]

Rivaroxaban is a direct factor Xa inhibitor that is effective in preventing venous thromboembolism in patients undergoing elective knee or hip replacement surgery, with a recommended dose of 10 mg per day.

In patients with non-valvular atrial fibrillation, rivaroxaban (20 mg per day) is approved for stroke prevention, and its low dose (2.5 mg twice daily) has shown promise in reducing cardiovascular events in those with recent acute coronary syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. Helbing, T., Bode, C., Moser, M.[2015]

In a review of five randomized controlled trials involving 26,110 patients, low dose rivaroxaban (2.5 mg twice daily) did not significantly reduce cardiovascular or all-cause mortality in patients with coronary heart disease.

However, it was effective in reducing the risk of myocardial infarction (MI) and stroke, but this benefit came with an increased risk of major bleeding events, highlighting a critical risk-benefit trade-off.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis. Khan, SU., Khan, MZ., Asad, ZUA., et al.[2021]

Rivaroxaban combined with aspirin is more effective in preventing recurrent cardiovascular events than aspirin alone, with an incremental cost-effectiveness ratio (ICER) of €16,522 per quality-adjusted life-year (QALY) gained, based on a lifetime analysis of patients with coronary artery disease (CAD) or peripheral artery disease (PAD).

The cost-effectiveness of the combination therapy was consistent across subgroups, showing ICERs of €8003 for PAD and €18,599 for CAD, indicating that this treatment strategy is economically viable for improving cardiovascular outcomes in these patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in Patients with Coronary and Peripheral Artery Diseases in Italy. Ferrara, P., Cortesi, PA., Di Laura, D., et al.[2022]

Following the 2020 European guideline updates, the use of low-dose rivaroxaban for managing atherosclerotic cardiovascular disease (ASCVD) significantly increased in both the UK and the Netherlands, with incidence rates rising from 12.4 to 124.0 per 100,000 person-years in the UK and from 2.4 to 16.3 in the Netherlands.

Users of low-dose rivaroxaban were generally younger and more likely to be male compared to nonusers, indicating a specific demographic trend in the prescription of this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing of low-dose rivaroxaban in patients with atherosclerotic cardiovascular disease in the United Kingdom and the Netherlands. Hunt, NB., Pajouheshnia, R., Salih, A., et al.[2023]

Rivaroxaban is a direct factor Xa inhibitor that offers a simplified alternative to traditional vitamin K antagonists like warfarin, allowing for once-daily dosing without the need for frequent monitoring or dose adjustments.

In phase-II and phase-III trials involving over 24,000 patients, rivaroxaban has demonstrated safety and efficacy for preventing and treating venous thromboembolism, and is also being studied for other conditions like pulmonary embolism and stroke prevention in atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban. Mousa, SA.[2015]

Rivaroxaban (Xarelto) is a direct and selective factor Xa inhibitor with high bioavailability (80-100%) and can be taken orally without the need for regular monitoring or dose adjustments, making it convenient for patients.

In clinical trials involving 4,233 patients, rivaroxaban demonstrated effective dosing regimens for preventing and treating venous thromboembolism (VTE) after major orthopedic surgery, with no significant liver toxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivaroxaban: clinical pharmacology]. Mismetti, P., Laporte, S.[2018]

In a study involving 120 high-risk patients with thrombotic antiphospholipid syndrome, rivaroxaban was found to be associated with a higher rate of thromboembolic events compared to warfarin, with 12% of patients on rivaroxaban experiencing events like ischemic strokes and myocardial infarctions.

The trial, which had a mean follow-up of 569 days, was terminated early due to the increased risk associated with rivaroxaban, indicating that it does not provide a safety or efficacy advantage over warfarin in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Pengo, V., Denas, G., Zoppellaro, G., et al.[2021]

A total of 2,418 spontaneous adverse event reports associated with rivaroxaban were analyzed from Australia, Canada, and the USA, revealing that haemorrhage was a common adverse event, particularly gastrointestinal bleeding.

The analysis indicated that a significant number of adverse events were linked to the use of other medications that could increase bleeding risk, highlighting the importance of monitoring patients' comorbidities and medication use when prescribing rivaroxaban.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm. McDonald, CJ., Kalisch Ellett, LM., Barratt, JD., et al.[2022]

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