EMPA Liver: Empagliflozin in Patients With Cirrhosis and Ascites

• Sponsor: Yale University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05726032
• Collaborator: (none)
• Enrollment: 20
• Arms: 2
• Anticipated Duration (Months): 18

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis; Liver Failure	Drug: Empagliflozin 10 MG; Drug: Matching Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Proof of concept, randomized, cross over, phase II double-blind placebo-controlled studyProof of concept, randomized, cross over, phase II double-blind placebo-controlled study
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: double-blind placebo-controlled study
• Primary Purpose: Other
• Official Title: Effects of Empagliflozin on Natriuresis and Volume Overload in Patients With Cirrhosis and Ascites
• Anticipated Study Start Date: Apr 1, 2023
• Anticipated Primary Completion Date: Apr 1, 2024
• Anticipated Study Completion Date: Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Empagliflozin Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.	Drug: Empagliflozin 10 MG; 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.
Placebo Comparator: Placebo Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.	Drug: Matching Placebo; 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.

Outcome Measures

Primary Outcome Measures

1. Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo) [14 days]

   Change in fractional excretion of sodium with administration of study drug (10 mg empagliflozin vs. identical placebo)

2. Change in total body water (TBW) before and after a 14-day course of study drug [14 days]

   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

1. Change in renal blood flow before and after administration of study drug [Baseline to Hour 6]

   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)

2. Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin [14 days]

   Change in plasma renin activity (PRA), total renin, aldosterone, norepinephrine and copeptin before and after a 14-day course of study drug

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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

2. eGFR >= 30mL/min/1.73 m2

3. =18 years old

Exclusion Criteria:

1. Hospitalization due to a complication of cirrhosis in the previous 8 weeks (e.g. variceal hemorrhage, encephalopathy, acute kidney injury, spontaneous bacterial peritonitis)

2. Direct bilirubin >=3 mg/dL

3. Systolic blood pressure < 100 mmHg

4. Active malignancy including hepatocellular carcinoma undergoing treatment

5. History of bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections

6. Use of SGLT-2 inhibitors in the last 10 days, or previous use with intolerance

7. Type 1 diabetes

8. History of frequent hypoglycemic episodes

9. 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.

10. Hepatic hydrothorax

11. Hepatic encephalopathy grade II or greater at the time of enrollment

12. Patients who have had TIPS placed

13. Previous liver transplant

14. Participation in another trial with an investigational drug within the 30 days prior to informed consent

15. Pregnancy or breastfeeding

16. Inability to give written informed consent or follow study protocol (e.g. clinically-significant psychiatric, addictive, or neurological disease)

17. Change in diuretic dose in the prior 4 weeks

18. Patients with hospitalization for alcoholic hepatitis in the past 6 months

19. Significant worsening of creatinine (more than 50% increase) in the past 4 weeks

20. MELD-Na <20

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Jeffrey Testani, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT05726032
• Other Study ID Numbers: 2000034606
• First Posted: Feb 13, 2023
• Last Update Posted: Feb 13, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Liver Cirrhosis; Liver Failure; Fibrosis; Ascites; Empagliflozin

Study Results

No Results Posted as of Feb 13, 2023