Institutional Ethics Committee Osmania Medical College
Approved
Institutional Ethics Committee, Post Graduate Institute of Medical Education and Research
Approved
Muljibhai Patel Society for Research in Nephro-Urology Ethics Committee
Approved
The George Institute Ethics Committee
Approved
The George Institute Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: Z992||Dependence on renal dialysis,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Dose: 2.5mg , dose Frequency: Twice daily Route Of administration: Oral Duration Of therapy: Depends on the time of randomization of participant (24 to 60 months)
Intervention
rivaroxaban
Dose: 2.5mg ,
dose Frequency: Twice daily Route Of administration: Oral Duration Of therapy: Depends on the time of randomization of participant (24 to 60 months)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Age ≥18 years
2. ESKD on haemodialysis or peritoneal dialysis, OR CKD stage 4 or 5 (eGFR ≤29 mL/min/1.73 m2) not receiving renal replacement therapy
3. Elevated CV risk, defined by at least one of the following: a. History of Coronary artery disease(CAD) or Peripheral artery disease(PAD) or non-haemorrhagic non-lacunar stroke, OR b. Diabetes mellitus, OR c. Age ≥65 years
ExclusionCriteria
Details
Potential participants must have NONE of the following exclusion criteria at the time of study
enrolment
1.Mechanical/prosthetic heart valve,
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
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 or ALT >3 times upper normal limit
15.Kidney transplant recipients with a functioning allograft, or scheduled for living-donor kidney transplant surgery
16.Pregnancy or intention to become pregnant or breast-feeding
17.Inability to understand or comply with the requirements of the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
The primary a composite of cardiovascular death, non-fatal myocardial infarction, stroke, and peripheral artery disease event.
From baseline till end of the study
Secondary Outcome
Outcome
TimePoints
Individual components of the composite outcomes, all-cause death.
Safety: Major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH), fatal bleeding, non-fatal symptomatic intracranial haemorrhage (ICH), nonfatal, non-ICH, symptomatic bleeding into critical organ, site of major bleeding.
From baseline till end of the study
Target Sample Size
Total Sample Size="2000" Sample Size from India="600" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
People with advanced kidney disease have high rates of heart
and vascular disease. There are few treatments that are proven to improve the
health of these patients. The purpose of this research study is to find out
whether a low dose of blood thinning medication (rivaroxaban 2.5 mg twice
daily) can reduce heart and vascular disease (such as heart attack and stroke),
which are very common in people with advanced kidney disease. This dose of
rivaroxaban is half the dose required to achieve the full blood-thinning effect
at this level of kidney function.
Blood thinning medicines such as the study medication, have
been proven and are frequently used to help people who are at high risk of
heart and vascular disease. Because blood thinning medications prevent blood
clots, these medications also increase the risk of bleeding. In the general
population the benefit of blood thinning medication is greater than the harms
of these medications (such as increased bleeding).
With this research we hope to learn whether the blood
thinning medicine, low-dose rivaroxaban, has more benefits than harms in
preventing heart and vascular disease in people with advanced kidney disease.
As part of this study, participants will receive either
low-dose rivaroxaban tablets (the blood thinning medicine) or a placebo.
Participants will be randomly assigned to receive either the rivaroxaban or the
placebo. This study is a ‘double blind trial’, so neither participant nor
the treating doctor (or the other staff
in the hospital) will know which tablet (rivaroxaban or placebo) the
participant is being given.
The study medication at low dose (rivaroxaban 2.5mg) is
approved by medicine regulatory bodies in the USA, Europe, Canada and
Australia, for the prevention of heart and vascular disease in people with
normal kidney function or mild to moderate kidney disease, but it is not
specifically approved in people with advanced kidney disease. This trial is
designed to see if the medication is beneficial to patients with advanced
kidney disease.
The study will run across many sites in
Australia and overseas, and will include about 2,000 participants. The study
will last about 5 years but many participants will be in the study for between
2 to 3 years, depending on when they join the study in the 5-year period.