Empagliflozin in Patients With Cirrhosis and Ascites

Phase 2

Recruiting

• Conditions: Cirrhosis; Liver Failure
• Interventions: Drug: Matching Placebo; Drug: Empagliflozin 10 MG

• Registration Number: NCT05726032
• Lead Sponsor: Yale University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-02
• Study First Submitted QC: 2023-02-02
• Study First Posted: 2023-02-13
• Study Start: 2023-09-11
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2025-09-01
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 or amiloride 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 requiring thoracentesis in the prior 8 weeks
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 2 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 > or equal to 20
21. Hemoglobin <8

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Matching Placebo	Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.
Empagliflozin	Empagliflozin 10 MG	Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.

Primary Outcome Measures

Name	Time	Method
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)
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

Name	Time	Method
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)
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

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States