Clinical trial NCT05726032: Empagliflozin in Patients With Cirrhosis and Ascites
Official title: Effects of Empagliflozin on Natriuresis and Volume Overload in Patients With Cirrhosis and Ascites
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cirrhosis
Liver Failure
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2023-02-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Proof of concept, randomized, cross over, phase II double-blind placebo-controlled study
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)
timeFrame: 14 days
measure: Change in total body water (TBW) before and after a 14-day course of study drug
timeFrame: 14 days
Secondary outcomes:
measure: Change in renal blood flow before and after administration of study drug
timeFrame: Baseline to Hour 6
measure: Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin
timeFrame: 14 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Jeffrey Testani, MD
role: PRINCIPAL_INVESTIGATOR
References: