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Safety, Tolerability, and Feasibility of Empagliflozin Therapy in Dialysis-dependent ESKD

Primary Purpose

End-stage Kidney Disease, Kidney Disease, Chronic, Dialysis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Empagliflozin
Placebo
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-stage Kidney Disease

Eligibility Criteria

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

Inclusion Criteria: include diabetic and non-diabetic adults dialysis treatment history of ≥3 months Exclusion Criteria: type 1 diabetes ongoing intravenous antibiotic therapy for infectious disease active treatment for malignancy unhealed lower extremity skin ulceration history of Fournier's gangrene diabetic ketoacidosis severe hypoglycemia (requiring external assistance within the past one year) allergy to empagliflozin pregnancy

Sites / Locations

  • University of UtahRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Empagliflozin 10mg

Empagliflozin 25mg

Placebo

Arm Description

Empagliflozin10mg oral: Those randomized to 10 mg daily dose will be treated with 10 mg QD throughout the dose escalation and the treatment phase for a total of 12 weeks.

Empagliflozin 25 mg oral: Those randomized to 25 mg daily dose will be treated with 10 mg QD for the first 2 weeks before escalating the dose to 25 mg QD in week 3, based on tolerability. At the end of the dose-escalation phase (weeks 3-4), participants will continue the randomized assignment for additional 8 weeks (weeks 5-12, treatment phase), for a total of 12 weeks.

Encapsulated placebo with an identical appearance to empagliflozin: Those randomized to placebo will be treated with an oral placebo QD throughout the dose escalation and the treatment phase for a total of 12 weeks.

Outcomes

Primary Outcome Measures

The proportion of participants in each intervention group who remain in follow-up and adhere to the full randomized dose of empagliflozin at the end of the 12-week intervention period.

Secondary Outcome Measures

Proportions of participants in each group who reduce and/or discontinue treatment for safety
Safety outcomes (to be assessed in each treatment group): Proportions of participants with any of the following prespecified adverse events of interest: (i) Severe hypoglycemia1; (ii) Ketoacidosis; (iii) Hypotension; (iv) Genital infection; (v) Hepatic injury Composite of the individual components of the prespecified adverse events of interest (i) through (v) Occurrence of any hospitalization and/or visit to Emergency Department
Proportions of participants in each group who reduce and/or discontinue treatment because of intolerance (i.e., allergy, nausea) or other reasons unrelated to safety (i.e., pill burden, study withdrawal due to transplant)
Proportions of participants in each group who have ≥ 80% pill count compliance.
Dialytic clearance of empagliflozin
Long-term accumulation of empagliflozin

Full Information

First Posted
October 26, 2022
Last Updated
May 11, 2023
Sponsor
University of Utah
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT05614115
Brief Title
Safety, Tolerability, and Feasibility of Empagliflozin Therapy in Dialysis-dependent ESKD
Official Title
Safety, Tolerability, and Feasibility of Empagliflozin Therapy in Dialysis-dependent ESKD
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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

5. Study Description

Brief Summary
The purpose of this study is to find out if empagliflozin, a new diabetic medication that has been shown to be very effective in lowering the risk of heart failure, is safe and tolerated in dialysis patients. In the recent years, empagliflozin has become a major tool to prevent heart failure hospitalization and to reduce the risk for cardiovascular death in diabetic and non-diabetic patients. Although patients with severe chronic kidney disease and ESKD have very high risk of heart failure and cardiovascular death, they have been excluded from all of the previous studies. If this medication is found to be well tolerated and safe in dialysis patients through this study, future clinical studies can evaluate if this medication can also reduce the risk of heart failure and cardiovascular death in dialysis patients.
Detailed Description
Patients on dialysis have a very high risk of heart failure and heart-related death compared to people who do not require dialysis. While treatment options for heart failure have improved over the years for those without kidney disease, there has been very limited discoveries to improve survival for dialysis patients. Empagliflozin, a new diabetic medication that works by making the kidney put out more sugar in the urine, has recently shown to have significant efficacy to protect the kidney and to reduce heart failure hospitalization and cardiovascular death in both diabetic and non-diabetic patients. Studies suggest that this medication may have benefits on the heart, fat cells, blood vessels, and possibly other organ systems. The benefit remains consistent whether you have diabetes or not. Empagliflozin is now approved by the U.S. Food and Drug Administration (FDA) to treat not only diabetes but also chronic kidney disease and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults regardless of the diabetes status. The clinical studies, however, have excluded those with severe kidney disease and those requiring dialysis. The safety of empagliflozin in the dialysis patients has not been established, and thus it is not available for people with end-stage kidney disease. If empagliflozin is safe in dialysis patients, it may potentially become a very powerful tool to lower the risk of heart-related complications and prolong survival. Although empagliflozin is approved by the FDA to treat patients with chronic kidney disease, heart failure, and/or diabetes, our study will evaluate empagliflozin as an investigational drug to assess if it is safe in patients receiving chronic dialysis. If we can establish safety, the next step would be to conduct a larger clinical study to evaluate its ability to lower heart failure and death risk in dialysis patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-stage Kidney Disease, Kidney Disease, Chronic, Dialysis, Diabetic, Non-diabetic, Kidney Dysfunction, Kidney Failure, Hemodialysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
The study will be conducted in two phases, a dose-escalation phase (week 0-4) and a treatment phase (week 5-12).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind, placebo-controlled
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin 10mg
Arm Type
Experimental
Arm Description
Empagliflozin10mg oral: Those randomized to 10 mg daily dose will be treated with 10 mg QD throughout the dose escalation and the treatment phase for a total of 12 weeks.
Arm Title
Empagliflozin 25mg
Arm Type
Experimental
Arm Description
Empagliflozin 25 mg oral: Those randomized to 25 mg daily dose will be treated with 10 mg QD for the first 2 weeks before escalating the dose to 25 mg QD in week 3, based on tolerability. At the end of the dose-escalation phase (weeks 3-4), participants will continue the randomized assignment for additional 8 weeks (weeks 5-12, treatment phase), for a total of 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Encapsulated placebo with an identical appearance to empagliflozin: Those randomized to placebo will be treated with an oral placebo QD throughout the dose escalation and the treatment phase for a total of 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Other Intervention Name(s)
Jardiance®, CL-JAR-100113 02.28.2022
Intervention Description
is a sodium-glucose co-transporter 2 (SGLT2) inhibitor.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator
Primary Outcome Measure Information:
Title
The proportion of participants in each intervention group who remain in follow-up and adhere to the full randomized dose of empagliflozin at the end of the 12-week intervention period.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportions of participants in each group who reduce and/or discontinue treatment for safety
Description
Safety outcomes (to be assessed in each treatment group): Proportions of participants with any of the following prespecified adverse events of interest: (i) Severe hypoglycemia1; (ii) Ketoacidosis; (iii) Hypotension; (iv) Genital infection; (v) Hepatic injury Composite of the individual components of the prespecified adverse events of interest (i) through (v) Occurrence of any hospitalization and/or visit to Emergency Department
Time Frame
12-weeks
Title
Proportions of participants in each group who reduce and/or discontinue treatment because of intolerance (i.e., allergy, nausea) or other reasons unrelated to safety (i.e., pill burden, study withdrawal due to transplant)
Time Frame
12-weeks
Title
Proportions of participants in each group who have ≥ 80% pill count compliance.
Time Frame
12-weeks
Title
Dialytic clearance of empagliflozin
Time Frame
4 hours post-dose during hemodialysis
Title
Long-term accumulation of empagliflozin
Time Frame
10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: include diabetic and non-diabetic adults dialysis treatment history of ≥3 months Exclusion Criteria: type 1 diabetes ongoing intravenous antibiotic therapy for infectious disease active treatment for malignancy unhealed lower extremity skin ulceration history of Fournier's gangrene diabetic ketoacidosis severe hypoglycemia (requiring external assistance within the past one year) allergy to empagliflozin pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Monique E Cho, MD
Phone
801-581-8090
Email
monique.cho@hsc.utah.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jonathan Gutierrez
Phone
801-587-1911
Email
jonathan.gutierrez@utah.edu
Facility Information:
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Gutierrez
Phone
801-587-1911
Email
jonathan.gutierrez@utah.edu
First Name & Middle Initial & Last Name & Degree
Mary Jane Tinnes
Phone
801-585-2254
Email
maryjane.tinnes@hsc.utah.edu

12. IPD Sharing Statement

Learn more about this trial

Safety, Tolerability, and Feasibility of Empagliflozin Therapy in Dialysis-dependent ESKD

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