Back to resultsSafety and Efficacy of Empagliflozin in Hemodialysis (SEED)
Primary Purpose
End Stage Renal Disease
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for End Stage Renal Disease
Eligibility Criteria
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
Sites / Locations
- Brigham and Women's Hospital
- NYU Langone Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Empagliflozin
Placebo
Arm Description
Participants with end-stage kidney disease (ESRD) initiating hemodialysis will receive Empagliflozin 10 mg daily for 12 weeks.
Participants with ESRD initiating hemodialysis will receive Empagliflozin-matching placebo daily for 12 weeks.
Outcomes
Primary Outcome Measures
Change in Extracellular Volume from Baseline to 12 Weeks
Extracellular volume is the sum of the plasma volume and interstitial fluid volume.
Change in Intracellular Volume from Baseline to 12 Weeks
Intracellular volume is the fluid content within the body's cells.
Change in Total Body Water from Baseline to 12 Weeks
Change in 24-Hour Urine Volume from Baseline to 12 Weeks
Urine volume over a 24-hour period.
Secondary Outcome Measures
Change in 24-Hour Urine Albumin Excretion from Baseline to 12 Weeks
Albumin excreted in the urine over a 24-hour period.
Change in 24-Hour Ambulatory Blood Pressure from Baseline to 12 Weeks
Blood pressure measured over a 24-hour period.
Change in Heart Rate Variability from Baseline to 12 Weeks
Variance in time between the heart beats.
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.
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.
Incidence of Serious Hypotension
Defined as hypotension requiring hospitalization, emergency room (ER) visit, or reduction of blinded study medication or other anti-hypertensive medications.
Incidence of Non-Serious Hypoglycemia
Detected via clinical lab data.
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.
Incidence of Ketoacidosis
Defined as metabolic state associated with pathologically high serum and urine concentrations of ketone bodies.
Number of Adverse Events
Number of Serious Adverse Events
Full Information
NCT ID
NCT05786443
First Posted
March 15, 2023
Last Updated
July 12, 2023
Sponsor
NYU Langone Health
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT05786443
Brief Title
Safety and Efficacy of Empagliflozin in Hemodialysis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 15, 2023 (Anticipated)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Boehringer Ingelheim
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Empagliflozin
Arm Type
Experimental
Arm Description
Participants with end-stage kidney disease (ESRD) initiating hemodialysis will receive Empagliflozin 10 mg daily for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants with ESRD initiating hemodialysis will receive Empagliflozin-matching placebo daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Other Intervention Name(s)
Jardiance
Intervention Description
Sodium glucose cotransporter 2 inhibitor (SGLT2i) dosed once-daily over 12 weeks. Administered as oral tablet.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Empagliflozin-matching placebo dosed once-daily over 12 weeks. Administered as oral tablet.
Primary Outcome Measure Information:
Title
Change in Extracellular Volume from Baseline to 12 Weeks
Description
Extracellular volume is the sum of the plasma volume and interstitial fluid volume.
Time Frame
Baseline, Week 12
Title
Change in Intracellular Volume from Baseline to 12 Weeks
Description
Intracellular volume is the fluid content within the body's cells.
Time Frame
Baseline, Week 12
Title
Change in Total Body Water from Baseline to 12 Weeks
Time Frame
Baseline, Week 12
Title
Change in 24-Hour Urine Volume from Baseline to 12 Weeks
Description
Urine volume over a 24-hour period.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change in 24-Hour Urine Albumin Excretion from Baseline to 12 Weeks
Description
Albumin excreted in the urine over a 24-hour period.
Time Frame
Baseline, Week 12
Title
Change in 24-Hour Ambulatory Blood Pressure from Baseline to 12 Weeks
Description
Blood pressure measured over a 24-hour period.
Time Frame
Baseline, Week 12
Title
Change in Heart Rate Variability from Baseline to 12 Weeks
Description
Variance in time between the heart beats.
Time Frame
Baseline, Week 12
Title
Incidence of Intra-Dialytic Hypotension
Description
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.
Time Frame
Up to Week 12
Title
Incidence of Inter-Dialytic Hypotension
Description
Inter-dialytic hypotension defined symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting.
Time Frame
Up to Week 12
Title
Incidence of Serious Hypotension
Description
Defined as hypotension requiring hospitalization, emergency room (ER) visit, or reduction of blinded study medication or other anti-hypertensive medications.
Time Frame
Up to Week 12
Title
Incidence of Non-Serious Hypoglycemia
Description
Detected via clinical lab data.
Time Frame
Up to Week 12
Title
Incidence of Serious Hypoglycemia
Description
Defined as hypoglycemia requiring hospitalization, emergency room (ER) visit or the combination of glucose<70 mg/dL and urgent glucagon or carbohydrate use.
Time Frame
Up to Week 12
Title
Incidence of Ketoacidosis
Description
Defined as metabolic state associated with pathologically high serum and urine concentrations of ketone bodies.
Time Frame
Up to Week 12
Title
Number of Adverse Events
Time Frame
Up to Week 12
Title
Number of Serious Adverse Events
Time Frame
Up to Week 12
Other Pre-specified Outcome Measures:
Title
Recruitment Rate
Description
Defined as average number of patients recruited per month.
Time Frame
Up to Week 12
Title
Withdrawal Rate
Description
Defined as percentage of participants who withdraw before completing the trial.
Time Frame
Up to Week 12
Title
Percentage of Participants Lost to Follow-Up
Time Frame
Up to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Charytan, MD, MSc
Phone
617-935-1572
Email
David.Charytan@nyulangone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Zoe Rimler
Phone
212-263-2544
Email
Zoe.Rimler@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Charytan, MS, MSc
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
021215
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Safety and Efficacy of Empagliflozin in Hemodialysis
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