Canagliflozin in Advanced Renal Disease With MRI Endpoints

NCT ID: NCT06182839

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2029-03-30

Brief Summary

This is a phase II, proof of concept, placebo-controlled, randomized clinical trial, assessing the effect of canagliflozin on cardiac structure and function in patients with advanced renal disease, including those on maintenance dialysis.

Our primary aim is to determine the effect of canagliflozin on cardiac structure and function in patients with advanced chronic kidney disease (CKD), compared with placebo. We hypothesize that canagliflozin will improve left ventricular (LV) hypertrophy in patients with advanced CKD. Our secondary aims are to describe the effect of canagliflozin on other cardiac magnetic resonance imaging parameters and surrogate markers of efficacy in this population.

Detailed Description

Patients with advanced renal disease, including those on maintenance dialysis, will be randomized to receive canagliflozin 300 mg orally once daily or matching placebo for one year. For patients who are not yet on renal replacement therapy, the study medication will be continued when they transition to dialysis or when they get a kidney transplant.

The prescription of all other medications, including dialysis prescription for dialysis-dependent patients, will be left to the treating physician's discretion. We will discourage changes to medications during follow-up unless deemed clinically necessary. All medications changes will be recorded at each visit.

Symptoms and adverse events will be monitored closely. Participants who experience adverse events classified as severe and probably or definitely related to the study medication will be withdrawn. Patients who develop intercurrent illnesses, are hospitalized, or have surgery (urgent or elective) will temporarily discontinue the drug.

Conditions

ESRD, CKD Stage 4, CKD Stage 5

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Canagliflozin (Invokana) 300 mg tablet

Group Type: ACTIVE_COMPARATOR

Canagliflozin 300Mg Tab

Intervention Type: DRUG

Patients will get 1 pill of Canagliflozin 300 mg daily for one year.

Placebo tablet

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will get 1 pill of placebo daily for one year.

Interventions

Canagliflozin 300Mg Tab

Patients will get 1 pill of Canagliflozin 300 mg daily for one year.

Intervention Type: DRUG

Placebo

Patients will get 1 pill of placebo daily for one year.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• advanced CKD, defined as an estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m2 not yet on dialysis OR incident hemodialysis or peritoneal dialysis patients (i.e., who were started on dialysis in the last 6 months)*

• For patients who were not previously followed in a CKD clinic and for whom it is not clear whether dialysis was initiated after an acute deterioration in renal function that is potentially reversible, at least 90 days of dialysis will be required prior to enrolment. This criterion only applies to patients for whom baseline eGFR prior to the acute event was ≥ 20 ml/min/1.73m2 or was unknown. The average creatinine values over the last 12 months will be used to calculate baseline eGFR.
• LV hypertrophy, defined as LV mass > 130 g/m2 in men and 100 g/m2 in females OR hospitalization for heart failure or atherosclerotic cardiovascular (CV) disease in the last 12 months OR type 2 diabetes OR UACR > 200 mg/g on a morning spot urine collection (this criterion is not applicable to patients who are on dialysis and have a urine output < 500 ml per day).

Exclusion Criteria

• type 1 diabetes,
• history of euglycemic ketoacidosis,
• known hypersensitivity to sodium-glucose cotransporter-2 (SGLT-2) inhibitors,
• hemodynamic instability (defined as current use of parenteral inotropic agents),
• systolic BP < 90 mmHg,
• severe liver cirrhosis (Child-Pugh class C stage),
• acute hepatitis (defined as an alanine aminotransferase > 2.0 times the upper limit of normal [ULN] or total bilirubin >1.5 times the ULN),
• recurrent severe genital or urine infections,
• patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if these agents cannot be safely discontinued (due to inhibition of the P-glycoprotein mediated efflux of digoxin by canagliflozin or induction of Uridine 5'-diphospho-glucuronosyltransferase enzymes by the other agents),
• cardiac MRI-incompatible cardiac devices (cardiac pacemaker, implanted cardiac defibrillator, internal pacing wires, Swan-Ganz catheter, aneurysm clips),
• claustrophobia,
• cochlear implants,
• metallic body in the eyes,
• pregnancy or breastfeeding,
• and any other medical condition considered to be a contra-indication by the study physician.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heart and Stroke Foundation of Canada

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Thomas Mavrakanas

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Mavrakanas, MD

Role: PRINCIPAL_INVESTIGATOR

Research Institute of the McGill University Health Center

Locations

McGill University Health Center

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Efrosyne Tsirella, Research Assistant

Role: CONTACT

efrosyne.tsirella@muhc.mcgill.ca

514-934-1934 ext. 37836

Norka Rios, Research Nurse

Role: CONTACT

norka.rios@muhc.mcgill.ca

514-934-1934 ext. 35207

Facility Contacts

Norka Rios

Role: primary

5149341934

Other Identifiers

2024-10313

Identifier Type: -

Identifier Source: org_study_id