Safety and Efficacy of Empagliflozin in Hemodialysis (SEED)

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

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.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Charytan, MD, MSc; Phone Number: 617-935-1572; Email: David.Charytan@nyulangone.org
• Study Contact Backup: Name: Zoe Rimler; Phone Number: 212-263-2544; Email: Zoe.Rimler@nyulangone.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 021215
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Finnian R. Mc Causland; Phone Number: 617-732-6432; Email: fmccausland@bwh.harvard.edu
      • Principal Investigator: Finnian R. Mc Causland
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: David M Charytan, MS, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Number of Adverse Events		Up to Week 12
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 Serious Adverse Events		Up to Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	Defined as average number of patients recruited per month.	Up to Week 12
Withdrawal Rate	Defined as percentage of participants who withdraw before completing the trial.	Up to Week 12
Percentage of Participants Lost to Follow-Up		Up to Week 12

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Boehringer Ingelheim
• Investigators: Principal Investigator: David Charytan, MS, MSc, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; empagliflozin
• Other Study ID Numbers: 22-01497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: David.Charytan@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to David.Charytan@nyulangone.org . To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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