Canagliflozin in Advanced Renal Disease With MRI Endpoints

NCT06182839 | Recruiting Phase 2

• 1 other identifier: 2024-10313
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

ESRD, CKD Stage 4, CKD Stage 5

Keywords

Canagliflozin, Advanced CKD, ESRD, Hemodialysis, Peritoneal dialysis, Cardiac MRI, SGLT-2 inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular mass to volume ratio (LVMV) from baseline to 12 months, as assessed by cardiac MRI compared with placebo

  Assessed on cardiac magnetic resonance imaging (MRI)

  12 months

Secondary Outcomes (17)

• Changes in left ventricular (LV) and atrial volumes from baseline to 12 months compared with placebo

  12 months

• LV strain parameter changes from baseline to 12 months compared with placebo

  12 months

• Changes in myocardial edema and fibrosis from baseline to 12 months compared with placebo

  12 months

• Change in myocardial oxygenation reserve from baseline to 12 months compared with placebo

  12 months

• Composite of major adverse cardiovascular events

  12 months

Study Arms (2)

Canagliflozin (Invokana) 300 mg tablet

ACTIVE COMPARATOR

Drug: Canagliflozin 300Mg Tab

Placebo tablet

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

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

Placebo tablet

Canagliflozin 300Mg Tab DRUG

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

Canagliflozin (Invokana) 300 mg tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Heart and Stroke Foundation of Canada: collaborator
• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Center

Montreal, Quebec, Canada

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Thomas Mavrakanas, MD

  Research Institute of the McGill University Health Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Efrosyne Tsirella, Research Assistant

CONTACT

514-934-1934; efrosyne.tsirella@muhc.mcgill.ca

Norka Rios, Research Nurse

CONTACT

514-934-1934; norka.rios@muhc.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be blinded to study participants and study investigators. Therefore, investigators who will interpret the cardiac magnetic resonance imaging (MRI) and who will adjudicate adverse events will be blinded to treatment group assignment. Canagliflozin 300 mg will be encapsulated to match the placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: We will conduct a single centre, prospective, randomized, parallel group (Canagliflozin VS placebo), double blind interventional study.

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: December 27, 2023
• Study Start: May 1, 2024
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

CA (1)