Low Dose Rivaroxaban for Cardiovascular Disease

(TRACK Trial)

Recruiting in Palo Alto (17 mi)

+82 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The TRACK trial is an investigator-initiated, multicentre, prospective, randomised, quadruple-blind (participant, healthcare provider, data collector, outcomes assessor), placebo-controlled trial. TRACK is a global trial and will be conducted in renal units that provide comprehensive CKD care. Approximately 2000 participants will be recruited. The TRACK trial will assess a strategy of administering low dose rivaroxaban to reduce the risk of major adverse cardiac event (MACE) in people with Chronic Kidney Disease (CKD) stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).

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.

What data supports the effectiveness of the drug Rivaroxaban for cardiovascular disease?

Research shows that Rivaroxaban, when combined with aspirin, leads to better outcomes in preventing recurrent cardiovascular disease compared to aspirin alone. Additionally, Rivaroxaban has been effective in reducing thrombotic cardiovascular events and mortality in patients with a recent acute coronary syndrome. ^{1 2 3 4 5}

Is low dose Rivaroxaban generally safe for humans?

Rivaroxaban (also known as Xarelto) has been shown to be generally safe in various studies for conditions like preventing blood clots after surgery and treating deep vein thrombosis. However, in high-risk patients with antiphospholipid syndrome, it was associated with more adverse events compared to warfarin, indicating that safety can vary depending on the specific condition and patient group. ^{2 3 6 7 8}

How does the drug Rivaroxaban differ from other treatments for cardiovascular disease?

Rivaroxaban is unique because it is a direct inhibitor of factor Xa, which helps prevent blood clots, and it is taken orally with high bioavailability, meaning the body can use it effectively. Unlike some other anticoagulants, it does not require routine blood monitoring and has a low risk of interacting with other drugs. ^{2 4 9 10 11}

Research Team

Sunil Badve

Principal Investigator

The George Institute

Martin Gallagher

Principal Investigator

The George Institute

Eligibility Criteria

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 18 years old or older.

I am 65 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Rivaroxaban (Anticoagulant)

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.

Participant Groups

Group I: Rivaroxaban Experimental Treatment 1 Intervention

Rivaroxaban 2.5mg, twice daily.

Group II: Placebo Placebo Group 1 Intervention

Matched placebo, twice daily.

Who Is Running the Clinical Trial?

The George Institute

Lead Sponsor

Trials

84

Recruited

275,000+

Professor Anushka Patel

The George Institute

Chief Executive Officer since 2023

Medical training at the University of Queensland, postgraduate research degrees from Harvard University and University of Sydney

Dr. Patrizia Cavazzoni

The George Institute

Chief Medical Officer

MD from Harvard Medical School

Central Hospital, Nancy, France

Collaborator

Trials

782

Recruited

2,447,000+

Dr. Philippe Hénon

Central Hospital, Nancy, France

Chief Medical Officer since 2008

MD from Mulhouse Hospitals

Dr. Philippe Hénon

Central Hospital, Nancy, France

Chief Executive Officer since 2008

MD from Harvard Medical School

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. New Zealand 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. [2015]

3. France pubmed.ncbi.nlm.nih.gov

[Rivaroxaban: clinical pharmacology]. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

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

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. [2021]

7. New Zealand 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. [2022]

8. United States 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. [2022]

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

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

10. England pubmed.ncbi.nlm.nih.gov

Prescribing of low-dose rivaroxaban in patients with atherosclerotic cardiovascular disease in the United Kingdom and the Netherlands. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis. [2021]