Using empagliflozin to treat patients with cirrhosis and fluid retention

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

This study tests whether empagliflozin, a diabetes medication, can help people with cirrhosis and fluid retention feel better by improving their body water levels and kidney function.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Yale University (Academic / other)
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05726032 on ClinicalTrials.gov

What this trial studies

This proof-of-concept trial investigates the effects of empagliflozin, a medication typically used for diabetes, on patients suffering from cirrhosis and ascites. The study is placebo-controlled and aims to assess both acute and 14-day outcomes related to natriuresis and total body water. Additionally, it will evaluate the impact of empagliflozin on neurohumoral activation and renal hemodynamics in this patient population. Participants must be on a stable dose of diuretics and meet specific renal function criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with stable cirrhosis and ascites who are on a consistent diuretic regimen.

Not a fit: Patients with recent complications of cirrhosis, severe liver dysfunction, or certain comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve fluid management and overall health outcomes for patients with cirrhosis and ascites.

How similar studies have performed: While the approach is novel in this specific context, similar studies with SGLT-2 inhibitors have shown promise in other conditions, suggesting potential for success.

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

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Testani, MD — Yale University
• Study coordinator: Veena Rao, PHD

Conditions Cirrhosis; Liver Failure