Effect of Canagliflozin on Ultrafiltration & Fibrosis in Patients on Peritoneal Dialysis

Официальное название

Effect of Canagliflozin on Ultrafiltration and Fibrosis in Peritoneal Dialysis: a a Proof-of-concept Randomized Phase II Crossover Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Canagliflozin 300 MG
  Canagliflozin 300 mg once daily

Первичные конечные точки

• Change in D4/D0 [Срок оценки: 5 and 10 weeks from baseline]

Вторичные конечные точки (12)

• Change in ultrafiltration [Срок оценки: 5 and10 weeks from baseline]
• Change in sodium dip/ sieving [Срок оценки: 5 and 10 weeks from baseline]
• Change in small solute clearance [Срок оценки: 5 and10 weeks from baseline]
• Canagliflozin levels in the dialysate [Срок оценки: 5 and10 weeks from baseline]
• Change in small and middle solute clearance [Срок оценки: 26 weeks from baseline]
• Change in effluent biomarker levels [Срок оценки: 26 weeks from baseline]
• Change in residual kidney function [Срок оценки: 26 weeks from baseline]
• Change in blood pressure [Срок оценки: 26 weeks from baseline]
• 6-minute walk test [Срок оценки: 26 weeks from baseline]
• Change in dyspnea score [Срок оценки: 26 weeks from baseline]
• Change in quality of life [Срок оценки: 26 weeks from baseline]
• Major adverse cardiovascular events [Срок оценки: 26 weeks from baseline]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Research Institute-McGill University Health Center — Montreal

Идентификаторы

NCT: NCT06913647 · 2025-11346

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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