meChANisms and sAfety of SGLT2 Inhibition in peRitoneal dialYsis

End Stage Kidney Disease Clinical Trial

— CANARY  

Official title:

A Single Arm, Open Label, Pilot Study to Evaluate the Safety and Efficacy of Once Daily 25mg Empagliflozin in Patients on Peritoneal Dialysis With Residual Kidney Function

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05715814
• Other study ID #: 21-6198
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2024
• Est. completion date: June 1, 2025

Study information

• Verified date: May 2024
• Source: University Health Network, Toronto
• Contact: Vesta Lai
• Phone: 416-340-4800
• Email: vesta.lai[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary aim of this study is to determine the safety and mechanisms of SGLT2 inhibition in individuals on peritoneal dialysis (PD) with residual kidney function (RKF).

Description:

The importance of RKF on the survival of patients on PD has been demonstrated in several observational studies. Despite this, there are limited pharmacological interventions available to slow the loss of RKF in these patients. There is an unmet need for novel cardiovascular and kidney protective strategies for patients on renal replacement therapies, including PD.

SGLT2 inhibitors have been shown to have both cardiovascular and kidney protective effects in individuals with kidney disease, with and without diabetes. These benefits have been attributed to diverse mechanisms and kidney benefits have been largely attributed to reductions in intraglomerular pressure at the single nephron level, reversibly lowering GFR in the short-term with long-term benefits. However, the beneficial effects of SGLT2 inhibitors have never been studied in patients on dialysis.

The CANARY study will provide insight into the safety and mechanisms of SGLT2 inhibitors in individuals on dialysis with RKF, with and without type 2 diabetes, over a period of 2 weeks. Demonstrating that protective mechanisms associated with SGLT2 inhibitors are intact in patients on PD with RKF would provide a strong rationale for a larger clinical trial to explore the use of these novel drugs in this unique clinical application. Additionally, our proposed study would provide timely mechanistic data to inform clinical decisions in the context of other large clinical trials such as EMPA-KIDNEY. These findings would help physicians make decisions on leaving patients on SGLT2 inhibitors even beyond end-stage kidney disease.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed and dated written informed consent.

• Patients aged =18 years on PD with RKF defined as at least 250 cc of urine output per day (assessed via 24-hour urine collection) and a minimum measured GFR of 2 ml/min/1.73m2, as measured at least once in the last 3 months.

• Stable PD prescription, as determined by investigators.

• Stable dose of RAAS blockade if on a medication within this class for the last 30 days.

Exclusion Criteria:

• Type 1 diabetes.

• Recent (in the 30 days prior to screening) acute coronary syndrome or cerebrovascular event.

• PD peritonitis within 30 days of screening.

• History of organ transplant, including pancreas, pancreatic islet cells or kidney transplant.

• Planned surgery/procedures or radiologic investigations requiring contrast during the trial.

• Pregnant, planning to become pregnant, or nursing an infant during the study period

• History of any DKA event

• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, hemolytic anemia) at screening.

• Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial.

• Alcohol or drug abuse within the 3 months prior to screening that would interfere with trial participation based on Investigator's judgement.

• Use of SGLT2 inhibitor within 30 days prior to screening.

• Intake of an investigational drug in another trial within 30 days prior to screening.

• Patient not able to understand and comply with study requirements, based on Investigator's judgment.

• Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome, severe hepatic impairments etc.).

Related Conditions & MeSH terms

• End Stage Kidney Disease
• Kidney Diseases
• Kidney Dysfunction
• Kidney Failure, Chronic
• Peritoneal Dialysis Complication

Intervention

Drug:
• Empagliflozin 25 MG
PO once daily

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in measured GFR	GFR will be determined from the average of creatinine and urea clearance from a 24-hour urine collection.	Before and 2 weeks after initiation of empagliflozin.
Secondary	Rebound in GFR after Cessation of Therapy	A GFR measurement will be performed 2 weeks after cessation of empagliflozin, with the aim of capturing the reversible "rebound" in GFR after cessation of therapy.	2 weeks
Secondary	Change in ultrafiltration volume		2 weeks
Secondary	Change in fraction of glucose remaining in the dialysate		2 weeks
Secondary	Change in dialysate/plasma creatinine		2 weeks
Secondary	Change in dialysate/plasma urea		2 weeks
Secondary	Change in sodium dialysate concentration		2 weeks
Secondary	Change in glycated hemoglobin (HbA1c)		2 weeks
Secondary	Change in systolic and diastolic blood pressure		2 weeks
Secondary	Change in body weight		2 weeks
Secondary	Change in body composition (percent body mass, body fat, and muscle mass)	Bioimpedence measurements will be taken to study the effects of intervention on body composition.	2 weeks
Secondary	Change in fractional urine excretion of sodium	Urinary analysis will be performed to quantify the amount of sodium excretion.	2 weeks
Secondary	Change in fractional urine excretion of glucose	Urinary analysis will be performed to quantify the amount of glucose excretion.	2 weeks
Secondary	Change in eGFRß2-microglobulin	Blood sample analysis to assess middle molecule clearance.	2 weeks
Secondary	Change in degree of albuminuria	Urinary analysis will be performed to determine if there has been any change in the severity of albuminuria	2 weeks
Secondary	Change in BNP (NT-proB-type Natriuretic Peptide)		2 weeks
Secondary	Change in markers of neurohumoral activation, erythropoiesis, and inflammation.		2 weeks
Secondary	The safety of empaglifllozin use in PD patients with RKF with regard to anuria (<100cc/day), volume depletion, diabetic ketoacidosis, genito-urinary infections, PD peritonitis and death will be evaluated.		2 weeks