End Stage Renal Disease
Conditions
Brief summary
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.
Interventions
DRUGEmpagliflozin 10 MG
Sodium glucose cotransporter 2 inhibitor (SGLT2i) dosed once-daily over 12 weeks. Administered as oral tablet.
DRUGPlacebo
Empagliflozin-matching placebo dosed once-daily over 12 weeks. Administered as oral tablet.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Boehringer Ingelheim
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥18 years on maintenance hemodialysis (HD) with residual kidney function * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Body Water from Baseline to 12 Weeks | Baseline, Week 12 | — |
| Change in Intracellular Volume from Baseline to 12 Weeks | Baseline, Week 12 | Intracellular volume is the fluid content within the body's cells. |
| Change in 24-Hour Urine Volume from Baseline to 12 Weeks | Baseline, Week 12 | Urine volume over a 24-hour period. |
| Change in Extracellular Volume from Baseline to 12 Weeks | Baseline, Week 12 | Extracellular volume is the sum of the plasma volume and interstitial fluid volume. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Intra-Dialytic Hypotension | Up to Week 12 | 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. |
| Incidence of Inter-Dialytic Hypotension | Up to Week 12 | Inter-dialytic hypotension defined symptomatic SBP \<90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting. |
| Incidence of Serious Hypotension | Up to Week 12 | Defined as hypotension requiring hospitalization, emergency room (ER) visit, or reduction of blinded study medication or other anti-hypertensive medications. |
| Incidence of Serious Hypoglycemia | Up to Week 12 | Defined as hypoglycemia requiring hospitalization, emergency room (ER) visit or the combination of glucose\<70 mg/dL and urgent glucagon or carbohydrate use. |
| Incidence of Ketoacidosis | Up to Week 12 | Defined as metabolic state associated with pathologically high serum and urine concentrations of ketone bodies. |
| Number of Adverse Events | Up to Week 12 | — |
| Number of Serious Adverse Events | Up to Week 12 | — |
| Incidence of Non-Serious Hypoglycemia | Up to Week 12 | Detected via clinical lab data. |
| Change in 24-Hour Urine Albumin Excretion from Baseline to 12 Weeks | Baseline, Week 12 | Albumin excreted in the urine over a 24-hour period. |
| Change in 24-Hour Ambulatory Blood Pressure from Baseline to 12 Weeks | Baseline, Week 12 | Blood pressure measured over a 24-hour period. |
| Change in Heart Rate Variability from Baseline to 12 Weeks | Baseline, Week 12 | Variance in time between the heart beats. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Recruitment Rate | Up to Week 12 | Defined as average number of patients recruited per month. |
| Percentage of Participants Lost to Follow-Up | Up to Week 12 | — |
| Withdrawal Rate | Up to Week 12 | Defined as percentage of participants who withdraw before completing the trial. |
Countries
United States
Contacts
Primary ContactDavid Charytan, MD, MSc
Backup ContactZoe Rimler
Outcome results
None listed