Clinical trial NCT06913647: Effect of Canagliflozin on Ultrafiltration & Fibrosis in Patients on Peritoneal Dialysis
Official title: Effect of Canagliflozin on Ultrafiltration and Fibrosis in Peritoneal Dialysis: a a Proof-of-concept Randomized Phase II Crossover Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: ESRD
CKD (Chronic Kidney Disease) Stage 5D
Keywords: SGLT-2 inhibitors
Canagliflozin
Ultrafiltration failure
Peritoneal fibrosis
Peritoneal dialysis
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2025-04-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a phase II, proof-of-concept, placebo-controlled, double-blind, cross-over randomized clinical trial.
Primary purpose: TREATMENT

Brief summary: This is a phase II, proof-of-concept, placebo-controlled, double-blind, cross-over randomized clinical trial, assessing the effect of canagliflozin on peritoneal membrane function in patients on PD.

The primary aim of this trial is to determine the short-term effects of canagliflozin, an SGLT-2 inhibitor, on glucose absorption by the peritoneal membrane and on ultrafiltration, as assessed by a standardized peritoneal equilibrium test. The secondary aims are to determine the effect of canagliflozin on solute clearance and on effluent biomarkers of inflammation, angiogenesis, and fibrosis at 26 weeks. We hypothesize that canagliflozin will prevent glucose absorption by the peritoneal membrane, as compared with placebo, and will attenuate the development of inflammation, angiogenesis, and fibrosis of the peritoneal membrane, as assessed by relevant biomarkers in the dialysate.

Detailed description: Patients with kidney failure on peritoneal dialysis who meet the study inclusion criteria will be randomized at a 2:2:1 ratio to one of the following arms:

(i) canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by matching placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label).

(ii) placebo once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 5 weeks (double-blind), followed by canagliflozin 300 mg once daily for 16 weeks (open label).

(iii) standard of care, with no active treatment, for 26 weeks (open label). Four in-person and one phone study visits have been scheduled: baseline visit, week 5, week 10, week 18 (phone visit), and week 26. A standardized peritoneal equilibration test (PET) will be performed at each of the in-person visits. There will also be two safety assessments at weeks 2 and 7, which will consist of blood tests. Patients who develop intercurrent illnesses or are hospitalized may temporarily discontinue the study drug if deemed appropriate by the treating physician.

Eligibility criteria: Inclusion Criteria:

* Adult patients with kidney failure on PD (both incident and prevalent) who are on a stable prescription of dextrose-based solutions for at least 3 months.
* Only high or high-average transporters, as classified by PET, will be included.

Exclusion Criteria:

* History of euglycemic ketoacidosis
* Known hypersensitivity to canagliflozin
* Active peritonitis or tunnel infection
* Kidney transplant scheduled in the next 6 months
* Severe liver cirrhosis (Child-Pugh class C stage)
* Recurrent severe genital or urine infections
* Patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if these agents cannot be safely discontinued
* Pregnancy or breastfeeding

Primary outcomes:
measure: Change in D4/D0
timeFrame: 5 and 10 weeks from baseline
Secondary outcomes:
measure: Change in ultrafiltration
timeFrame: 5 and10 weeks from baseline
measure: Change in sodium dip/ sieving
timeFrame: 5 and 10 weeks from baseline
measure: Change in small solute clearance
timeFrame: 5 and10 weeks from baseline
measure: Canagliflozin levels in the dialysate
timeFrame: 5 and10 weeks from baseline
measure: Change in small and middle solute clearance
timeFrame: 26 weeks from baseline
measure: Change in effluent biomarker levels
timeFrame: 26 weeks from baseline
measure: Change in residual kidney function
timeFrame: 26 weeks from baseline
measure: Change in blood pressure
timeFrame: 26 weeks from baseline
measure: 6-minute walk test
timeFrame: 26 weeks from baseline
measure: Change in dyspnea score
timeFrame: 26 weeks from baseline
measure: Change in quality of life
timeFrame: 26 weeks from baseline
measure: Major adverse cardiovascular events
timeFrame: 26 weeks from baseline
measure: Death from any cause
timeFrame: 26 weeks from baseline
measure: Safety outcomes
timeFrame: 26 weeks from baseline
Other outcomes:
measure: Feasibility outcome
timeFrame: 26 weeks from baseline
Locations:
city: Montreal
country: Canada
facility: Research Institute-McGill University Health Center
state: Quebec
Study officials:
affiliation: Research Institute-McGill University of Health Centre
name: Thomas A. Mavrakanas, MD, MSc.
role: PRINCIPAL_INVESTIGATOR
References: