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

Utah System of Higher Education (USHE)

Status and phase: Completed; Phase 1

Conditions: Non-diabetic; Kidney Failure; Diabetic; Hemodialysis; Dialysis; End-stage Kidney Disease; Kidney Dysfunction; Kidney Disease, Chronic

Treatments: Other: Placebo; Drug: Empagliflozin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05614115

1R01DK131265 (U.S. NIH Grant/Contract)

IRB_00155825

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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62 participants in 3 patient groups, including a placebo group

Empagliflozin 10mg

Experimental group

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.

Treatment:

Drug: Empagliflozin

Empagliflozin 25mg

Experimental group

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.

Treatment:

Drug: Empagliflozin

Placebo

Placebo Comparator group

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.

Treatment:

Other: Placebo