Canagliflozin in Advanced Renal Disease With MRI Endpoints

• Status: Recruiting
• Trial end date: 2029-03-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborator: Heart and Stroke Foundation of Canada
• Treatments: Canagliflozin

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.