Cirrhosis, Liver Failure
Conditions
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.
Interventions
DRUGEmpagliflozin 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.
DRUGMatching 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.
Sponsors
Yale University
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
double-blind placebo-controlled study
Intervention model description
Proof of concept, randomized, cross over, phase II double-blind placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 total renin, aldosterone, norepinephrine | 14 days | Change in total renin, aldosterone, norepinephrine before and after a 14-day course of study drug |
Countries
United States
Contacts
CONTACTVeena Rao, PHD
CONTACTKara Otis
PRINCIPAL_INVESTIGATORJeffrey Testani, MD
Yale University
Outcome results
None listed