Empagliflozin in Patients With Cirrhosis and Ascites

NCT05726032 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2000034606
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhosis; Liver Failure

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• 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

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.

Drug: Empagliflozin 10 MG

Placebo

PLACEBO COMPARATOR

Empagliflozin vs placebo for 14 days, followed by 14 day washout period, before crossing over to the alternate drug.

Drug: Matching Placebo

Interventions

Empagliflozin 10 MG DRUG

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.

Empagliflozin

Matching Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Hepatic encephalopathy grade II or greater at the time of enrollment
• Patients who have had TIPS placed
• Previous liver transplant
• Participation in another trial with an investigational drug within the 30 days prior to informed consent
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Boehringer Ingelheim: collaborator
• Yale University: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Fibrosis; Liver Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Jeffrey Testani, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veena Rao, PHD

CONTACT

2037373571; veena.s.rao@yale.edu

Kara Otis

CONTACT

2037373571; kara.otis@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blind placebo-controlled study
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Proof of concept, randomized, cross over, phase II double-blind placebo-controlled study

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 13, 2023
• Study Start: September 11, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)