Effect of Canagliflozin on Ultrafiltration and Fibrosis in Peritoneal Dialysis: a a Proof-of-concept Randomized Phase II Crossover Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in D4/D0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The cross-over part of the study for the assessment of the primary outcome will be blinded (first 10 weeks for arms 1 & 2). Canagliflozin pills will be encapsulated. For placebo, cellulose will be used to fill identical capsules.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Active treatment followed by placebo
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)
干预措施: Canagliflozin 300 MG (Drug)
Placebo followed by active treatment
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)
干预措施: Canagliflozin 300 MG (Drug)
Standard of care
Standard of care, with no active treatment, for 26 weeks (open label)
结局指标
主要结局
Change in D4/D0
时间窗: 5 and 10 weeks from baseline
Change in the ratio of intraperitoneal glucose at 0 and 4h post infusion (D4/D0 ratio) in a standardized PET with canagliflozin, compared with placebo.
次要结局
- Major adverse cardiovascular events(26 weeks from baseline)
- Death from any cause(26 weeks from baseline)
- Safety outcomes(26 weeks from baseline)
- Change in ultrafiltration(5 and10 weeks from baseline)
- Change in sodium dip/ sieving(5 and 10 weeks from baseline)
- Change in small solute clearance(5 and10 weeks from baseline)
- Canagliflozin levels in the dialysate(5 and10 weeks from baseline)
- Change in small and middle solute clearance(26 weeks from baseline)
- Change in quality of life(26 weeks from baseline)
- Change in effluent biomarker levels(26 weeks from baseline)
- Change in residual kidney function(26 weeks from baseline)
- Change in blood pressure(26 weeks from baseline)
- 6-minute walk test(26 weeks from baseline)
- Change in dyspnea score(26 weeks from baseline)
研究者
Thomas Mavrakanas
Associate Professor
McGill University Health Centre/Research Institute of the McGill University Health Centre