Title
Treatment of cardiovascular disease with low dose Rivaroxaban in Advanced Chronic Kidney Disease
Short title
The TRACK trial
Study phase
IIIb
Trial registration
ClinicalTrials.gov Identifier: NCT03969953
Clinical Trials Registry – India (CTRI) Number: CTRI/2020/06/025708
Funding
National Health and Medical Research Council (Australia)
Ministere de la Santé (France)
Study design
Investigator-initiated, multicentre, international, prospective, randomised, double blind, 1:1 placebo-controlled, parallel group, event-driven trial.
Primary objective
To determine whether low dose rivaroxaban (2.5 mg twice daily), compared to placebo, significantly reduces the risk of a composite outcome of:
- cardiovascular death,
- non-fatal myocardial infarction,
- stroke, or
- peripheral artery disease events
in patients with chronic kidney disease (CKD) stages 4 or 5 or dialysis-dependent end-stage kidney disease (ESKD), and an elevated cardiovascular risk.
Inclusion criteria
People able to provide informed consent who meet all the following inclusion criteria:
- Age ≥18 years,
- End-stage kidney disease on haemodialysis or peritoneal dialysis, OR Chronic kidney disease stage 4 or 5 (eGFR ≤29 mL/min/1.73 m2) not receiving renal replacement therapy,
- Elevated CV risk, defined by at least one of the following:
-
- History of CAD or PAD or non-haemorrhagic non-lacunar stroke, OR
- Diabetes mellitus,
- OR Age ≥65 years
Exclusion criteria
Potential participants must have NONE of the following exclusion criteria at the time of study enrollment:
- Mechanical/prosthetic heart valve,
- Indication for, or contraindication to, anticoagulant therapy,
- High bleeding risk including any coagulopathy,
- Lesion or condition considered to be a significant risk of major bleeding,
- Major bleeding episode in the 30 days prior to study enrolment, or any active and clinically significant bleeding,
- 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,
- Concurrent treatment with strong inhibitors of combined CYP3A4 and P-glycoprotein; or strong inducers of CYP3A4,
- Any stroke within 1 month prior to enrolment,
- Any previous history of a haemorrhagic or lacunar stroke,
- Severe heart failure with known ejection fraction <30% or NYHA class III or IV symptoms,
- History of hypersensitivity or known contraindication to rivaroxaban,
- Uncontrolled hypertension (systolic BP ≥180 mm Hg or diastolic BP ≥110 mm Hg),
- Haemoglobin <90 g/L, or platelet count <100 x 109/L,
- Significant liver disease or ALT >3 times upper normal limit,
- Kidney transplant recipients with a functioning allograft, or scheduled for living-donor kidney transplant surgery,
- Pregnancy or intention to become pregnant or breast-feeding,
- Inability to understand or comply with the requirements of the study.
Number of participants
2000
Treatment description
Experimental intervention
Rivaroxaban 2.5 mg orally twice daily
Control intervention
Matched placebo tablet twice daily
Primary outcome measure
Time to a composite endpoint of cardiovascular death, non-fatal myocardial infarction, stroke, or peripheral artery disease event.
Secondary efficacy outcomes
- 3-point MACE (cardiovascular death, non-fatal myocardial infarction, or stroke),
- All-cause death,
- Composite of all-cause death, non-fatal myocardial infarction, or stroke,
- Composite of all-cause death, non-fatal myocardial infarction, or stroke, or peripheral artery disease event,
- Individual components of the composite outcomes,
- Net-clinical-benefit outcome (a composite outcome of cardiovascular death, non-fatal myocardial infarction, stroke, PAD events, fatal bleeding, or symptomatic bleeding into a critical organ),
- Venous thromboembolism.
Tertiary efficacy outcomes
- thrombosis of dialysis vascular access among participants with an AV fistula/graft (including those receiving haemodialysis, peritoneal dialysis or people with CKD stage 4/5),
- self-reported EQ-5D-5L,
- health care resource utilisation and costs.
Safety outcome measures
- Modified ISTH major bleeding, defined as:
- fatal bleeding, and/or
- symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, or bleeding into the surgical site requiring reoperation, and/or
- bleeding leading to hospitalization.
- Gastrointestinal bleeding
