Effects of Empagliflozin on Natriuresis and Volume Overload in Patients With Cirrhosis and Ascites
Overview
- Phase
- Phase 2
- Intervention
- Empagliflozin 10 MG
- Conditions
- Cirrhosis
- Sponsor
- Yale University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
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 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.
- •Hepatic hydrothorax requiring thoracentesis in the prior 8 weeks
Arms & Interventions
Empagliflozin
Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.
Intervention: Empagliflozin 10 MG
Placebo
Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.
Intervention: Matching Placebo
Outcomes
Primary Outcomes
Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)
Time Frame: 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
Time Frame: 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 Outcomes
- Change in renal blood flow before and after administration of study drug(Baseline to Hour 6)
- Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin(14 days)