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.
12345Is 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.
23678How 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.
2491011Eligibility 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.
+4 more
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.
+14 more
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: RivaroxabanExperimental Treatment1 Intervention
Rivaroxaban 2.5mg, twice daily.
Group II: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
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Who Is Running the Clinical Trial?
The George InstituteLead Sponsor
Central Hospital, Nancy, FranceCollaborator
George Clinical Pty LtdIndustry Sponsor
BayerIndustry Sponsor
Centre Hospitalier Régional Universitaire de NancyCollaborator
King Abdullah International Medical Research CenterCollaborator
References
Cost-Effectiveness Analysis of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in Patients with Coronary and Peripheral Artery Diseases in Italy. [2022]Rivaroxaban is a selective inhibitor of coagulation factor Xa and its combination with aspirin showed better outcomes in the prevention of recurrent cardiovascular disease than aspirin alone.
[Rivaroxaban in the prevention and treatment of thromboembolic disorders]. [2015]Rivaroxaban (Xarelto(®)) is a new anticoagulant for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits coagulation factor Xa directly, has high oral bioavailability, shows low propensity for drug-drug interactions and requires no routine coagulation monitoring. In patients undergoing elective knee or hip replacement surgery rivaroxaban (10 mg/d) is highly effective to prevent venous thromboembolism. In patients with non-valvular atrial fibrillation rivaroxaban (20 mg/d) has been approved to prevent stroke or systemic embolism. The favourable benefit-risk profile of rivaroxaban in the treatment of deep vein thrombosis (DVT) was shown in EINSTEIN-DVT and led to its clinical approval (twice daily 15 mg for 3 weeks, followed by 20 mg/d). Based on ATLAS-ACS-TIMI-51 which has shown that rivaroxaban (2.5 mg twice daily) reduced thrombotic cardiovascular events and mortality in patients with a recent acute coronary syndrome, the approval of low dose rivaroxaban has been submitted for this indication. Taken together, rivaroxaban may become an effective alternative to standard anticoagulants in the prevention and treatment of thromboembolic disorders.
[Rivaroxaban: clinical pharmacology]. [2018]Rivaroxaban (Xarelto) is a new oral, direct and selective inhibitor of the factor Xa of the coagulation cascade. The main pharmacokinetic characteristics of rivaroxaban are a bioavailability of approximately 80-100%, a maximum concentration obtained in 2 to 4 hours, a terminal half-life of elimination of 7 to 11 hours, a renal elimination for 1/3 for the active hepatic metabolism from the cytochrome P450 (3A4) for the other 2/3. The main sources of variability are the renal and the liver function and potential interactions with some strong inhibitors or inducers of the CYP450 3A4. Phase II clinical studies have shown that this compound can be orally administrated, once or twice daily, without any biological monitoring and without any need for dose adjustment. There is a contra-indication in case of severe liver insufficiency and not recommended in case of severe renal impairment. Pharmacodynamically, Rivaroxaban is a direct and selective factor Xa inhibitor without any effect on the factor IIa and without any interaction on platelets. Four phases II with 2787 patients were carried out to for venous thromboembolic (VTE) prophylaxis after major orthopaedic surgery, showing that 10 mg once daily could be the optimal dose regimen to assess in phase III. Two phases II with 1446 patients were carried out for the treatment of VTE showing that 15 mg twice daily for 3 weeks and then 20 mg once daily could be the optimal dose regimen to evaluate in the following phases 3. No strong signal for a potential liver toxicity was shown during these 6 phases II.
Rivaroxaban. A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. [2015]Rivaroxaban (Xarelto) is a novel, oral, direct Factor Xa (FXa) inhibitor in late-stage development for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits clot-associated and free FXa activity, and prothrombinase activity, and reduces thrombin generation. In animal models, rivaroxaban prevented venous and arterial thrombosis, and was effective at treating venous thrombosis. Rivaroxaban has high oral bioavailability, a rapid onset of action and predictable pharmacokinetics. In phase II studies, rivaroxaban was effective and well tolerated for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery, and for the treatment of deep vein thrombosis. In a phase III study, rivaroxaban demonstrated significantly superior efficacy to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar low bleeding. Rivaroxaban is also being assessed for the treatment and secondary prevention of VTE, prevention of stroke in patients with atrial fibrillation and secondary prevention in patients with acute coronary syndrome. Rivaroxaban is a promising alternative to current pharmacological agents for thromboembolic disorders.
Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban. [2015]Rivaroxaban is a small-molecule, direct factor Xa inhibitor that is under investigation for the prevention and treatment of venous and arterial thrombosis. To date, oral anticoagulants have been limited largely to vitamin K antagonists. Despite their remarkable benefits, vitamin K antagonists are limited by their narrow therapeutic window, the existence of multiple food and drug interactions, and the need for frequent monitoring and dose-adjustment. Rivaroxaban represents a potentially attractive alternative to warfarin, as it could enable simplified once-daily dosing, requires no therapeutic monitoring, and has a lower potential for drug interactions. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in phase-II and phase-III trials involving over 24,000 patients. Rivaroxaban is also being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes, and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The need for new oral anticoagulants, the development and pharmacology of rivaroxaban, results of completed studies of rivaroxaban, and details of ongoing phase-II and phase-III trials with rivaroxaban are the subjects of this chapter.
Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. [2021]Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.
A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm. [2022]Concerns with the safety profiles of the newer anticoagulants have been raised because of differences in treatment populations between pre-marketing studies (randomized controlled trials) and clinical practice. Little is known about the potential safety issues and the reporting in spontaneous adverse event databases associated with rivaroxaban.
Bioequivalence and Food Effect Assessment of 2 Rivaroxaban Formulations in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, and 4-Period Crossover Study. [2022]Rivaroxaban is a direct factor Xa inhibitor used for the management of thromboembolic disorders. The aim of this study was to evaluate the safety, pharmacokinetic profile, and bioequivalence of a generic and a branded rivaroxaban formulation (Xarelto) under fasted and fed conditions in healthy Chinese volunteers. An open-label, randomized, single-dose, 4-period complete, and replicate crossover study in healthy Chinese volunteers was performed. A single oral dose of 20 mg of 2 rivaroxaban formulations was administered to 72 healthy volunteers, with 36 in the fasted group and 36 consuming a high-fat diet. The evaluated pharmacokinetic parameters, including maximum rivaroxaban concentration, the area under the concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity, were assessed for BE. The plasma concentrations of rivaroxaban were measured by a validated liquid chromatography-tandem mass spectrometry method. The geometric mean ratios with 90% confidence intervals of the maximum rivaroxaban concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were all within the range of 80% to 125% under fasted and fed conditions. The within-subject variability of the test and reference products was compared, and the upper limit of the 90% confidence intervals for the test-to-reference ratio of the within-subject variability was
Rivaroxaban: a review of its use in acute coronary syndromes. [2021]Rivaroxaban (Xarelto(®)) is an orally administered highly selective direct inhibitor of factor Xa that has been approved in many countries to reduce the risk of stroke in patients with atrial fibrillation and for the treatment and prevention of venous thromboembolism. More recently, rivaroxaban at a low dosage of 2.5 mg twice daily, co-administered with aspirin alone or aspirin plus either clopidogrel or ticlopidine, was approved for use in the EU for patients with a recent acute coronary syndrome (ACS). The approval of rivaroxaban in ACS was primarily based on findings of the phase III ATLAS ACS 2-TIMI 51 trial, which showed that after a median of 13.1 months of treatment with rivaroxaban 2.5 mg twice daily (combined with aspirin or aspirin plus either clopidogrel or ticlopidine) there was a statistically significant reduction in the rate of the primary composite endpoint, which was death from cardiovascular causes, myocardial infarction or stroke, compared with placebo. Rivaroxaban 2.5 mg twice daily was also associated with a reduction in all-cause and cardiovascular mortality. There was an increase in the risk of major bleeding and intracranial haemorrhage with rivaroxaban 2.5 mg twice daily compared with placebo; however, there was no increase in the risk of fatal bleeding. Aspirin plus either ticagrelor or prasugrel was not evaluated as background dual antiplatelet therapy in ATLAS ACS 2-TIMI 51 and the safety implications of rivaroxaban used in combination with such therapy are unknown. In conclusion, results of the ATLAS ACS 2-TIMI 51 trial suggest a potentially important role for rivaroxaban 2.5 mg twice daily co-administered with aspirin alone or aspirin plus either clopidogrel or ticlopidine in patients with a recent ACS.
Prescribing of low-dose rivaroxaban in patients with atherosclerotic cardiovascular disease in the United Kingdom and the Netherlands. [2023]Low-dose rivaroxaban has been indicated for the management of atherosclerotic cardiovascular disease (ASCVD) after recent (2019-2020) updates to European guidelines. We aimed to describe prescription trends of low-dose rivaroxaban in ASCVD patients over the period 2015-2022 in two European countries, to compare the trends before and after guideline changes, and to determine the characteristics of users.
Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis. [2021]The mortality effects and risk-benefit profile of low dose rivaroxaban (2.5 mg twice daily) in patients with coronary heart disease are not completely understood. Five randomized controlled trials (26,110 patients) were selected using PubMed and Cochrane library till April 2019. The background antiplatelet therapy was aspirin in 3 trials, P2Y12 inhibitor in 1 trial, and in 1 trial 65% patients received aspirin and 35% were on dual antiplatelet therapy (DAPT). The outcomes of interest were cardiovascular mortality, all-cause mortality, myocardial infarction (MI), stroke and major bleeding events. Random effects hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Low dose rivaroxaban did not reduce the risk of cardiovascular mortality (HR 0.90, 95% CI 0.73-1.11, P = 0.34) or all-cause mortality (HR 0.91, 95% CI 0.74-1.12, P = 0.38) compared with control. However, low dose rivaroxaban was associated with reduction in MI (HR 0.85, 95% CI 0.73-0.99, P = 0.04), and stroke (HR 0.59, 95%CI 0.48-0.73, P 0.05). The use of low dose rivaroxaban in patients with coronary heart disease predominantly receiving antiplatelet monotherapy did not reduce cardiovascular or all-cause mortality. The benefits of preventing MI and stroke were balanced by increased risk of major bleeding.