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).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The George Institute For Global Health

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

9 Jun 2023 → ongoing

Decision date (initial)

2024-06-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

France - Ministère de la Santé (Ministry of Health) · Australia - National Health and Medical Research Council

External identifiers

EU CT number

2024-512483-59-00

EudraCT number

2020-000334-17

ClinicalTrials.gov

NCT03969953

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine whether low dose rivaroxaban (2.5mg twice daily),
compared to placebo, significantly reduces the risk of a composite
outcome of Cardio vascular (CV) death, non-fatal myocardial infarction,
stroke or peripheral arterial disease events, in patients with chronic
kidney disease stages 4 or 5 or dialysis-dependent kidney failure, and an
elevated CV risk.

Secondary objectives 1

1. 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.

Conditions and MedDRA coding

Improvement of cardiovascular outcomes in patients with advanced chronic kidney disease. In easily understood language, this is Heart and blood vessel disease and Kidney disease.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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

1. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. •CV death, • non-fatal myocardial infarction, • stroke, or • PAD events

Secondary endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The George Institute For Global Health

Sponsor organisation

The George Institute For Global Health

Address

International Tower 3, Level 18 300 Barangaroo Avenue Level 18 300 Barangaroo Avenue

City

Barangaroo

Postcode

2000

Country

Australia

Scientific contact point

Organisation

The George Institute For Global Health

Contact name

Sunil Badve

Public contact point

Organisation

The George Institute For Global Health

Contact name

Namrata Nath Kumar

Locations

3 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications