Empagliflozin in Patients With Cirrhosis and Ascites

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.

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 paracenteseseGFR >= 30mL/min/1.73 m2>=18 years oldExclusion 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/dLSystolic blood pressure < 100 mmHgActive malignancy including hepatocellular carcinoma undergoing treatmentHistory of bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infectionsUse of SGLT-2 inhibitors in the last 10 days, or previous use with intoleranceType 1 diabetesHistory of frequent hypoglycemic episodesUse 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 hydrothoraxHepatic encephalopathy grade II or greater at the time of enrollmentPatients who have had TIPS placedPrevious liver transplantParticipation in another trial with an investigational drug within the 30 days prior to informed consentPregnancy or breastfeedingInability 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 weeksPatients with hospitalization for alcoholic hepatitis in the past 6 monthsSignificant worsening of creatinine (more than 50% increase) in the past 4 weeksMELD-Na <20