Safety and Efficacy of Empagliflozin in Hemodialysis

Study Overview
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Brief Summary
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A 12-week, phase II, randomized, double-blind, placebo-controlled, multi-center study to assess the safety, tolerability, and preliminary efficacy of empagliflozin versus placebo among patients initiating hemodialysis (n=60) for the treatment of end-stage kidney disease.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Safety, Tolerability, and Preliminary Efficacy of Empagliflozin Among Patients Initiating Hemodialysis for the Treatment of End-Stage Kidney Disease

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Empagliflozin 10 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 years initiating hemodialysis (HD) (within 180 days of first HD session) Thrice-weekly HD Willingness and capacity to provide informed consent For women of childbearing potential, a negative pregnancy test is required at screening Exclusion Criteria: Does not have capacity to consent Anuria (daily urine volume < 200 mL/day) Planned kidney transplant within 3 months Recurrent urinary tract infections (>2 episodes/year or antibiotic prophylaxis) New York Heart Association (NYHA) Class IV heart failure (HF) Myocardial infarction, unstable angina, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 12 weeks History of diabetic ketoacidosis Type 1 Diabetes Mellitus Hereditary glucose-galactose malabsorption or primary renal glucosuria Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis); Alanine aminotransferase (ALT) levels >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN, unless consistent with Gilbert's disease Active malignancy (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ) defined as malignancy under active treatment with chemotherapy, radiation or immunotherapy, or being treated as palliative. Major surgery within 12 weeks Atraumatic amputation within past 12 months of screening, or an active skin ulcer, osteomyelitis, gangrene, or critical ischemia of the lower extremity within 6 months of screening Combination use of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) Current use of an SGLT2 inhibitor (within 6 weeks prior to randomization) Known allergies, hypersensitivity, or intolerance to SGLT2i or its excipients Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline Pregnant or breast-feeding or planning to become pregnant or breast-feed during the study Women of childbearing potential not willing to use a highly-effective method(s) of birth control, or who are unwilling or unable to be tested for pregnancy. Any condition that in the opinion of the investigator would make participation not in the best interest of the subject

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin<br>Participants with end-stage kidney disease (ESRD) initiating hemodialysis will receive Empagliflozin 10 mg daily for 12 weeks. | Drug: Empagliflozin 10 MG<br>* Sodium glucose cotransporter 2 inhibitor (SGLT2i) dosed once-daily over 12 weeks. Administered as oral tablet.<br>* Other names: Jardiance;|
| Placebo Comparator: Placebo<br>Participants with ESRD initiating hemodialysis will receive Empagliflozin-matching placebo daily for 12 weeks. | Drug: Placebo<br>* Empagliflozin-matching placebo dosed once-daily over 12 weeks. Administered as oral tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Extracellular Volume from Baseline to 12 Weeks | Extracellular volume is the sum of the plasma volume and interstitial fluid volume. | Baseline, Week 12 | 
| Change in Intracellular Volume from Baseline to 12 Weeks | Intracellular volume is the fluid content within the body's cells. | Baseline, Week 12 | 
| Change in Total Body Water from Baseline to 12 Weeks |  | Baseline, Week 12 | 
| Change in 24-Hour Urine Volume from Baseline to 12 Weeks | Urine volume over a 24-hour period. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-Hour Urine Albumin Excretion from Baseline to 12 Weeks | Albumin excreted in the urine over a 24-hour period. | Baseline, Week 12 | 
| Change in 24-Hour Ambulatory Blood Pressure from Baseline to 12 Weeks | Blood pressure measured over a 24-hour period. | Baseline, Week 12 | 
| Change in Heart Rate Variability from Baseline to 12 Weeks | Variance in time between the heart beats. | Baseline, Week 12 | 
| Incidence of Intra-Dialytic Hypotension | Intra-dialytic hypotension defined as nadir systolic blood pressure (SBP) <90 mmHg if pre-HD SBP≤160 mmHg, or nadir SBP <100 mmHg if pre-HD SBP >160 mmHg. | Up to Week 12 | 
| Incidence of Inter-Dialytic Hypotension | Inter-dialytic hypotension defined symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting. | Up to Week 12 | 
| Incidence of Serious Hypotension | Defined as hypotension requiring hospitalization, emergency room (ER) visit, or reduction of blinded study medication or other anti-hypertensive medications. | Up to Week 12 | 
| Incidence of Non-Serious Hypoglycemia | Detected via clinical lab data. | Up to Week 12 | 
| Incidence of Serious Hypoglycemia | Defined as hypoglycemia requiring hospitalization, emergency room (ER) visit or the combination of glucose<70 mg/dL and urgent glucagon or carbohydrate use. | Up to Week 12 | 
| Incidence of Ketoacidosis | Defined as metabolic state associated with pathologically high serum and urine concentrations of ketone bodies. | Up to Week 12 | 
| Number of Adverse Events |  | Up to Week 12 | 
| Number of Serious Adverse Events |  | Up to Week 12 |