Bumetanide vs. Furosemide in Cirrhosis (BUFF)

Bumetanide vs. Furosemide for Adults Hospitalized With Cirrhosis: the BUFF Trial

Patients with cirrhosis are frequently hospitalized due to an acute decompensation of their liver disease including bleeding, jaundice, encephalopathy, and volume overload. Volume overload is associated with increased mortality from acute hypoxic respiratory failure, hemorrhage from esophageal varices, and spontaneous bacterial peritonitis.

Clinical practice guidelines describe sodium restriction and diuretics as first-line treatment, combined with regular body weight monitoring to assess response. In patients with suboptimal response to furosemide, alternative loop diuretics like torsemide or bumetanide may improve natriuresis. Bumetanide has a theoretic advantage over furosemide due to its more rapid and complete intestinal absorption, combined with a prolonged half-life in patients with hepatic dysfunction. In this pragmatic study, the aim is to compare the efficacy of diuresis with bumetanide versus furosemide among hospitalized patients with cirrhosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis
• Intervention / Treatment: Drug: Bumetanide; Drug: Furosemide

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Andrea T White, PhD; Phone Number: 8015817818; Email: andrea.white@hsc.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
      • Contact: Andrea T White, PhD; Phone Number: 801-581-7818; Email: andrea.white@hsc.utah.edu
      • Principal Investigator: Stacy A Johnson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of liver cirrhosis
• Clinician placed an order for bumetanide or furosemide in electronic health record within 24 hours of presentation to the hospital

Exclusion Criteria:

• Allergy to bumetanide or furosemide
• Contraindication to diuretic administration (e.g. active bleeding, clinical suspicion of hepatorenal syndrome, hypotension)
• Incarcerated or in custody of law enforcement
• Diuretic ordered for purpose other than volume overload (e.g. hyperkalemia, continuation of home medication without clinical signs of volume overload)
• Inpatient admission not anticipated
• Not admitted to an inpatient hospital bed following initial evaluation in the emergency department

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bumetanide	Drug: Bumetanide; Standard of care treatment with bumetanide (intravenous or oral administration) per treating clinician's orders
Experimental: Furosemide	Drug: Furosemide; Standard of care treatment with furosemide (intravenous or oral administration) per treating clinician's orders

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in weight	Percent change in weight measured in kilograms from date of emergency department presentation (Day 0) to Day 7 of hospitalization, or date of discharge, whichever is earlier	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of acute kidney injury	Stage 2 or higher acute kidney injury developing within 14 days of presentation to emergency department in accordance with KDIGO criteria	14 days
Need for replacement therapy	New initiation of intermittent or continuous hemodialysis within 14 days of presentation to the emergency department	14 days
Severe electrolyte derangement	New decrease in serum potassium to less than 2.5 mEq/L within 14 days of presentation to the emergency department	14 days
Hospital length of stay	Time from initial presentation to the emergency department to the time of discharge from the hospital or time of death, if a subject dies within the hospital	30 days
Unplanned hospital readmission	Readmission to the hospital for an unexpected reason within 30 days of a prior hospital admission	30 days
30-day mortality	Death occurring within the 30 days following presentation to the emergency department and subsequent hospital admission	30 days

Collaborators and Investigators

• Sponsor: Stacy Johnson
• Investigators: Principal Investigator: Stacy A Johnson, MD, University of Utah

Study record dates

Study Major Dates

• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: furosemide; cirrhosis; diuresis; bumetanide; volume overload
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fibrosis; Edema; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Aniline Compounds; Amines; Benzene Derivatives; Acids, Carbocyclic; Sulfonamides; Sulfanilamides; Sulfones; Aminobenzoates; Benzoates; meta-Aminobenzoates; Furosemide; Bumetanide
• Other Study ID Numbers: IRB_00186841

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Findings from the study will be presented at one or more scientific conferences. Results will be submitted for publication to a peer-reviewed journal. Data will be made available to other researchers after publication upon request and local institutional approval.
• IPD Sharing Time Frame: Following publication of manuscript
• IPD Sharing Access Criteria: Written request and local institutional approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No