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meChANisms and sAfety of SGLT2 Inhibition in peRitoneal dialYsis (CANARY)

Primary Purpose

Peritoneal Dialysis Complication, End Stage Kidney Disease, Sodium-glucose Co-transporter-2 Inhibitors

Status
Not yet recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Empagliflozin 25 MG
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peritoneal Dialysis Complication

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.).

Sites / Locations

  • Toronto General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Empagliflozin

Arm Description

Outcomes

Primary Outcome Measures

Change in measured GFR
GFR will be determined from the average of creatinine and urea clearance from a 24-hour urine collection.

Secondary Outcome Measures

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.
Change in ultrafiltration volume
Change in fraction of glucose remaining in the dialysate
Change in dialysate/plasma creatinine
Change in dialysate/plasma urea
Change in sodium dialysate concentration
Change in glycated hemoglobin (HbA1c)
Change in systolic and diastolic blood pressure
Change in body weight
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.
Change in fractional urine excretion of sodium
Urinary analysis will be performed to quantify the amount of sodium excretion.
Change in fractional urine excretion of glucose
Urinary analysis will be performed to quantify the amount of glucose excretion.
Change in eGFRβ2-microglobulin
Blood sample analysis to assess middle molecule clearance.
Change in degree of albuminuria
Urinary analysis will be performed to determine if there has been any change in the severity of albuminuria
Change in BNP (NT-proB-type Natriuretic Peptide)
Change in markers of neurohumoral activation, erythropoiesis, and inflammation.
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.

Full Information

First Posted
January 18, 2023
Last Updated
April 13, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT05715814
Brief Title
meChANisms and sAfety of SGLT2 Inhibition in peRitoneal dialYsis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
April 1, 2025 (Anticipated)
Study Completion Date
April 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Dialysis Complication, End Stage Kidney Disease, Sodium-glucose Co-transporter-2 Inhibitors, Kidney Dysfunction, Residual Kidney Function

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 25 MG
Other Intervention Name(s)
JARDIANCE
Intervention Description
PO once daily
Primary Outcome Measure Information:
Title
Change in measured GFR
Description
GFR will be determined from the average of creatinine and urea clearance from a 24-hour urine collection.
Time Frame
Before and 2 weeks after initiation of empagliflozin.
Secondary Outcome Measure Information:
Title
Rebound in GFR after Cessation of Therapy
Description
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.
Time Frame
2 weeks
Title
Change in ultrafiltration volume
Time Frame
2 weeks
Title
Change in fraction of glucose remaining in the dialysate
Time Frame
2 weeks
Title
Change in dialysate/plasma creatinine
Time Frame
2 weeks
Title
Change in dialysate/plasma urea
Time Frame
2 weeks
Title
Change in sodium dialysate concentration
Time Frame
2 weeks
Title
Change in glycated hemoglobin (HbA1c)
Time Frame
2 weeks
Title
Change in systolic and diastolic blood pressure
Time Frame
2 weeks
Title
Change in body weight
Time Frame
2 weeks
Title
Change in body composition (percent body mass, body fat, and muscle mass)
Description
Bioimpedence measurements will be taken to study the effects of intervention on body composition.
Time Frame
2 weeks
Title
Change in fractional urine excretion of sodium
Description
Urinary analysis will be performed to quantify the amount of sodium excretion.
Time Frame
2 weeks
Title
Change in fractional urine excretion of glucose
Description
Urinary analysis will be performed to quantify the amount of glucose excretion.
Time Frame
2 weeks
Title
Change in eGFRβ2-microglobulin
Description
Blood sample analysis to assess middle molecule clearance.
Time Frame
2 weeks
Title
Change in degree of albuminuria
Description
Urinary analysis will be performed to determine if there has been any change in the severity of albuminuria
Time Frame
2 weeks
Title
Change in BNP (NT-proB-type Natriuretic Peptide)
Time Frame
2 weeks
Title
Change in markers of neurohumoral activation, erythropoiesis, and inflammation.
Time Frame
2 weeks
Title
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.
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vesta Lai
Phone
416-340-4800
Ext
8508
Email
vesta.lai@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sunita KS Singh, MD MSc FRCPC
Organizational Affiliation
University Health Network, Toronto General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2N2
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vesta Lai
Phone
416-340-4800
Ext
8508
Email
vesta.lai@uhn.ca

12. IPD Sharing Statement

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meChANisms and sAfety of SGLT2 Inhibition in peRitoneal dialYsis

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