Safety and Efficacy of Empagliflozin in Hemodialysis

End Stage Renal Disease Clinical Trial

— SEED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05786443
• Other study ID #: 22-01497
• Status: Recruiting
• Phase: Phase 2
• Start date: January 31, 2024
• Est. completion date: December 30, 2025

Study information

• Verified date: March 2024
• Source: NYU Langone Health
• Contact: David Charytan, MD, MSc
• Phone: 617-935-1572
• Email: David.Charytan[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

Drug:
• Empagliflozin 10 MG
Sodium glucose cotransporter 2 inhibitor (SGLT2i) dosed once-daily over 12 weeks. Administered as oral tablet.
• Placebo
Empagliflozin-matching placebo dosed once-daily over 12 weeks. Administered as oral tablet.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	NYU Langone Health	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
NYU Langone Health	Boehringer Ingelheim, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recruitment Rate	Defined as average number of patients recruited per month.	Up to Week 12
Other	Withdrawal Rate	Defined as percentage of participants who withdraw before completing the trial.	Up to Week 12
Other	Percentage of Participants Lost to Follow-Up		Up to Week 12
Primary	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
Primary	Change in Intracellular Volume from Baseline to 12 Weeks	Intracellular volume is the fluid content within the body's cells.	Baseline, Week 12
Primary	Change in Total Body Water from Baseline to 12 Weeks		Baseline, Week 12
Primary	Change in 24-Hour Urine Volume from Baseline to 12 Weeks	Urine volume over a 24-hour period.	Baseline, Week 12
Secondary	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
Secondary	Change in 24-Hour Ambulatory Blood Pressure from Baseline to 12 Weeks	Blood pressure measured over a 24-hour period.	Baseline, Week 12
Secondary	Change in Heart Rate Variability from Baseline to 12 Weeks	Variance in time between the heart beats.	Baseline, Week 12
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of Non-Serious Hypoglycemia	Detected via clinical lab data.	Up to Week 12
Secondary	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
Secondary	Incidence of Ketoacidosis	Defined as metabolic state associated with pathologically high serum and urine concentrations of ketone bodies.	Up to Week 12
Secondary	Number of Adverse Events		Up to Week 12
Secondary	Number of Serious Adverse Events		Up to Week 12