Empagliflozin in Patients With Cirrhosis and Ascites

Cirrhosis Clinical Trial

— EMPA Liver  

Official title:

Effects of Empagliflozin on Natriuresis and Volume Overload in Patients With Cirrhosis and Ascites

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05726032
• Other study ID #: 2000034606
• Status: Recruiting
• Phase: Phase 2
• Start date: September 11, 2023
• Est. completion date: September 1, 2025

Study information

• Verified date: April 2024
• Source: Yale University
• Contact: Veena Rao, PHD
• Phone: 2037373571
• Email: veena.s.rao[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Cirrhosis
• Fibrosis
• Liver Cirrhosis
• Liver Failure

Intervention

Drug:
• Empagliflozin 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.
• Matching 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.

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FENa with administration of study drug (10 mg empagliflozin vs. identical placebo)	Change in fractional excretion of sodium with administration of study drug (10 mg empagliflozin vs. identical placebo)	14 days
Primary	Change in total body water (TBW) before and after a 14-day course of study drug	Change in total body water (TBW) before and after a 14-day course of study drug (10 mg/day empagliflozin vs. identical placebo)	14 days
Secondary	Change in renal blood flow before and after administration of study drug	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)	Baseline to Hour 6
Secondary	Change in plasma renin activity,total renin, aldosterone, norepinephrine and copeptin	Change in plasma renin activity (PRA), total renin, aldosterone, norepinephrine and copeptin before and after a 14-day course of study drug	14 days