Empagliflozin in Patients With Cirrhosis and Ascites (EMPA Liver)

Yale University

Status and phase: Enrolling; Phase 2

Conditions: Cirrhosis; Liver Failure

Treatments: Drug: Empagliflozin 10 MG; Drug: Matching Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05726032

2000034606

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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20 participants in 2 patient groups, including a placebo group

Empagliflozin

Active Comparator group

Description:

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

Treatment:

Drug: Empagliflozin 10 MG

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Matching Placebo