Canagliflozin for heart health in patients with advanced kidney disease

Canagliflozin in Advanced Renal Disease With MRI Endpoints

This study is testing if a diabetes medication called canagliflozin can improve heart health in people with advanced kidney disease and those on dialysis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Academic / other)
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT06182839 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effects of canagliflozin, a medication typically used for diabetes, on cardiac structure and function in patients with advanced chronic kidney disease (CKD) and those on dialysis. Participants will be randomly assigned to receive either canagliflozin or a placebo for one year, with the primary goal of assessing improvements in left ventricular hypertrophy through cardiac MRI. The study also aims to monitor other cardiac parameters and surrogate markers of efficacy, while ensuring that all other medications are managed by the treating physician.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced CKD (eGFR < 20 ml/min/1.73m2) who are not yet on dialysis or those who have recently started dialysis.

Not a fit: Patients with stable kidney function or those not meeting the specific criteria for advanced CKD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved heart health outcomes for patients with advanced kidney disease.

How similar studies have performed: While the use of SGLT-2 inhibitors like canagliflozin in CKD is gaining interest, this specific application in advanced renal disease with cardiac endpoints is relatively novel.

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.

Where this trial is running

Montreal, Quebec

• McGill University Health Center — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Thomas Mavrakanas, MD — Research Institute of the McGill University Health Center
• Study coordinator: Efrosyne Tsirella, Research Assistant

Conditions ESRD, CKD Stage 4, CKD Stage 5; Canagliflozin, Advanced CKD, ESRD, Hemodialysis, Peritoneal dialysis, Cardiac MRI, SGLT-2 inhibitors