Treatment of heart and blood vessel disease (cardiovascular disease) with low dose blood thinner (low dose rivaroxaban) in people with advanced kidney disease or receiving dialysis (advanced chronic kidney disease).

Phase 1

• Conditions: Improvement of cardiovascular outcomes in patients with advancedchronic kidney disease. In easily understood language, this is Heart and blood vessel disease and Kidney disease.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: CTIS2024-512483-59-00
• Lead Sponsor: The George Institute For Global Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-15
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

1. People able to provide informed consent who meet all of the following inclusion criteria, 2. Age =18 years, 3. Kidney failure on haemodialysis or peritoneal dialysis, OR CKD stage 4 or 5 (eGFR =29 mL/min/1.73 m2) not receiving renal replacement therapy, 4. Elevated CV risk, defined by at least one of the following: a. History of CAD or PAD or non-haemorrhagic non-lacunar stroke, OR b. Diabetes mellitus, OR c. Age =65 years.

Exclusion Criteria

1. Mechanical/prosthetic heart valve (does not include bioprosthetic valves that do not require therapeutic anticoagulation), 2. Indication for, or contraindication to, anticoagulant therapy, 3. High bleeding risk including any coagulopathy, 4. Lesion or condition considered to be a significant risk of major bleeding, 5. Major bleeding episode in the 30 days prior to study enrolment, or any active and clinically significant bleeding, 6. Current treatment with P2Y12 inhibitors/adenosine diphosphate (ADP) receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) or phosphodiesterase inhibitors (dipyridamole), where the treating physician or patient does not wish to stop these medications, 7. Concurrent treatment with strong inhibitors of combined CYP3A4 and P-glycoprotein; or strong inducers of CYP3A4, 8. Any stroke within 1 month prior to enrolment, 9. Any previous history of a haemorrhagic or lacunar stroke, 10. Severe heart failure with known ejection fraction <30% or NYHA class III or IV symptoms, 11. History of hypersensitivity or known contraindication to rivaroxaban, 12. Uncontrolled hypertension (systolic BP =180 mm Hg or diastolic BP =110 mm Hg) at the time of screening, 13. Haemoglobin <90 g/L, or platelet count <100 x 109/L, 14. Significant liver disease (defined as Child-Pugh Class B or C) or ALT >3 times upper normal limit, 15. Kidney transplant recipients with a functioning allograft, or scheduled for living-donor kidney transplant surgery, 16. All countries except Europe: Pregnancy or intention to become pregnant or breast-feeding; Europe only: Women who are not in a postmenopausal state, where postmenopausal is defined as no menses for 12 months without alternative medical causes, 17. Inability to understand or comply with the requirements of the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether low dose rivaroxaban (2.5mg twice daily),<br>compared to placebo, significantly reduces the risk of a composite<br>outcome of Cardio vascular (CV) death, non-fatal myocardial infarction,<br>stroke or peripheral arterial disease events, in patients with chronic<br>kidney disease stages 4 or 5 or dialysis-dependent kidney failure, and an<br>elevated CV risk.;Secondary Objective: To determine whether, in people with CKD stages 4 or 5 kidney failure or dialysis and an elevated CV risk, low dose rivaroxaban compared to placebo reduces the risk of CV death, all cause death risk, risk of individual components of composite outcomes, and risk of venous thromboembolism.;Primary end point(s): •CV death, • non-fatal myocardial infarction, • stroke, or • PAD events

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):1.3-point MACE , 2.All-cause death, 3.Composite of all-cause death,non-fatal myocardial infarction,or stroke, 4.Composite of all-cause death, non-fatal myocardial infarction, or stroke, or peripheral artery disease event, 5.Individual components of the composite outcomes, 6.Net-clinical-benefit outcome 7. Venous thromboembolism.