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Empagliflozin in Patients With Cirrhosis and Ascites (EMPA Liver)

Primary Purpose

Cirrhosis, Liver Failure

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Matching Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with cirrhosis and ascites on a stable dose of diuretics (spironolactone +/- loop-diuretics based on AASLD guidelines)10 and who do not require large volume paracenteses eGFR >= 30mL/min/1.73 m2 >=18 years old Exclusion Criteria: Hospitalization due to a complication of cirrhosis in the previous 8 weeks (e.g. variceal hemorrhage, encephalopathy, acute kidney injury, spontaneous bacterial peritonitis) Direct bilirubin >=3 mg/dL Systolic blood pressure < 100 mmHg Active malignancy including hepatocellular carcinoma undergoing treatment History of bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections Use of SGLT-2 inhibitors in the last 10 days, or previous use with intolerance Type 1 diabetes History of frequent hypoglycemic episodes Use of a non-loop diuretic aside from aldosterone antagonists as they are not standard of care in patients with cirrhosis and could potentially increase the risk of hypovolemia when combined with the standard treatment for ascites along with SGLT2 inhibitor. Hepatic hydrothorax Hepatic encephalopathy grade II or greater at the time of enrollment Patients who have had TIPS placed Previous liver transplant Participation in another trial with an investigational drug within the 30 days prior to informed consent Pregnancy or breastfeeding Inability to give written informed consent or follow study protocol (e.g. clinically-significant psychiatric, addictive, or neurological disease) Change in diuretic dose in the prior 4 weeks Patients with hospitalization for alcoholic hepatitis in the past 6 months Significant worsening of creatinine (more than 50% increase) in the past 4 weeks MELD-Na <20

Sites / Locations

  • Yale UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Empagliflozin

Placebo

Arm Description

Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.

Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.

Outcomes

Primary Outcome Measures

Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)
Change in fractional excretion of sodium with administration of study drug (10 mg empagliflozin vs. identical placebo)
Change in total body water (TBW) before and after a 14-day course of study drug
Change in total body water (TBW) before and after a 14-day course of study drug (10 mg/day empagliflozin vs. identical placebo)

Secondary Outcome Measures

Change in renal blood flow before and after administration of study drug
Change in renal blood flow (RBF) as determined by PAH clearance, before and after the acute administration of study drug ((RPF assessed using ancillary protocol on page 31)
Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin
Change in plasma renin activity (PRA), total renin, aldosterone, norepinephrine and copeptin before and after a 14-day course of study drug

Full Information

First Posted
February 2, 2023
Last Updated
September 26, 2023
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT05726032
Brief Title
Empagliflozin in Patients With Cirrhosis and Ascites
Acronym
EMPA Liver
Official Title
Effects of Empagliflozin on Natriuresis and Volume Overload in Patients With Cirrhosis and Ascites
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 11, 2023 (Actual)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

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
No

5. Study Description

Brief Summary
A proof-of-concept placebo-controlled trial to explore the acute and 14-day effects of empagliflozin on natriuresis and total body water in patients with cirrhosis and ascites. We will additionally investigate its effect on neurohumoral activation, and renal hemodynamics.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Liver Failure

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Proof of concept, randomized, cross over, phase II double-blind placebo-controlled study
Masking
ParticipantCare ProviderInvestigator
Masking Description
double-blind placebo-controlled study
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Active Comparator
Arm Description
Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Intervention Description
Participants will be randomized to Empagliflozin 10 mg or placebo for 14 days. A 14 day washout period follows and then participants is crossed over to the alternate treatment for 14 days.
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Participants will be randomized to Empagliflozin 10 mg or placebo for 14 days. A 14 day washout period follows and then participants is crossed over to the alternate treatment for 14 days.
Primary Outcome Measure Information:
Title
Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)
Description
Change in fractional excretion of sodium with administration of study drug (10 mg empagliflozin vs. identical placebo)
Time Frame
14 days
Title
Change in total body water (TBW) before and after a 14-day course of study drug
Description
Change in total body water (TBW) before and after a 14-day course of study drug (10 mg/day empagliflozin vs. identical placebo)
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Change in renal blood flow before and after administration of study drug
Description
Change in renal blood flow (RBF) as determined by PAH clearance, before and after the acute administration of study drug ((RPF assessed using ancillary protocol on page 31)
Time Frame
Baseline to Hour 6
Title
Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin
Description
Change in plasma renin activity (PRA), total renin, aldosterone, norepinephrine and copeptin before and after a 14-day course of study drug
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with cirrhosis and ascites on a stable dose of diuretics (spironolactone +/- loop-diuretics based on AASLD guidelines)10 and who do not require large volume paracenteses eGFR >= 30mL/min/1.73 m2 >=18 years old Exclusion Criteria: Hospitalization due to a complication of cirrhosis in the previous 8 weeks (e.g. variceal hemorrhage, encephalopathy, acute kidney injury, spontaneous bacterial peritonitis) Direct bilirubin >=3 mg/dL Systolic blood pressure < 100 mmHg Active malignancy including hepatocellular carcinoma undergoing treatment History of bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections Use of SGLT-2 inhibitors in the last 10 days, or previous use with intolerance Type 1 diabetes History of frequent hypoglycemic episodes Use of a non-loop diuretic aside from aldosterone antagonists as they are not standard of care in patients with cirrhosis and could potentially increase the risk of hypovolemia when combined with the standard treatment for ascites along with SGLT2 inhibitor. Hepatic hydrothorax Hepatic encephalopathy grade II or greater at the time of enrollment Patients who have had TIPS placed Previous liver transplant Participation in another trial with an investigational drug within the 30 days prior to informed consent Pregnancy or breastfeeding Inability to give written informed consent or follow study protocol (e.g. clinically-significant psychiatric, addictive, or neurological disease) Change in diuretic dose in the prior 4 weeks Patients with hospitalization for alcoholic hepatitis in the past 6 months Significant worsening of creatinine (more than 50% increase) in the past 4 weeks MELD-Na <20
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine Keith
Phone
2037373571
Email
katherine.keith@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Veena Rao, PHD
Phone
2037373571
Email
veena.s.rao@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Testani, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katherine Keith

12. IPD Sharing Statement

Plan to Share IPD
No

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Empagliflozin in Patients With Cirrhosis and Ascites

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