A Study of Ultra High Dose Diuretics to Treat Heart Failure

Ultra High Dose Diuretic Strategy for Management of Acute Decompensated Heart Failure - A Randomized, Double-Blind Pilot Trial

The purpose of this study is to determine the safety and effectiveness of ultrahigh dose diuretics compared to standard dose diuretics over 24 hours in patients with decompensated heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure; With Decompensation
• Intervention / Treatment: Drug: Bumetanide; Drug: Furosemide

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of decompensated heart failure receiving intravenous diuretics
• Ability to provide informed consent

Exclusion Criteria:

• Patients on home inotrope medications
• Patients with Chronic Kidney disease stage V and end stage renal failure on dialysis
• Patients lacking the capacity to consent for themselves
• Known pregnancy or breastfeeding mothers
• Complex congenital heart disease
• Allergy to furosemide or bumetanide
• Respiratory failure requiring non-invasive ventilation (CPAP/BiPAP) or invasive mechanical ventilatory support at the time of randomization
• Hypotension with systolic blood pressure <80 mm Hg at the time of randomization
• Acute coronary syndrome
• Sustained Ventricular tachycardia requiring treatment in the last 48 hours
• Patients weighing ≤ 40 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultra-high dose diuretic group; Subjects with decompensated heart failure requiring hospitalization will receive IV bumetanide.	Drug: Bumetanide; Bumetanide will be administered via intravenous (IV) infusion at a dose of 12.5 mg two times a day (BID) for 2 doses total within 24 hours.; Other Names: Ultra-high dose diuretic
Active Comparator: Standard dose diuretic group; Subjects with decompensated heart failure requiring hospitalization will receive IV furosemide.	Drug: Furosemide; Furosemide will be administered via intravenous (IV) infusion at usual doses (twice the home dose of oral daily diuretic in furosemide equivalents) administered as 2 doses total within 24 hours. Furosemide equivalents will be considered as follows (40 mg of intravenous furosemide = 1 mg oral bumetanide or 40 mg of torsemide or 80 mg of oral furosemide consistent with prior literature). The lowest dose of furosemide administered during the study will be 40 mg IV two times a day (BID) and the maximum dose will be 100 mg IV BID.; Other Names: Standard dose diuretic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Output	The total volume of urine produced in milliliters (mL) over 24 hours after initiation of intravenous diuretic.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in NT-proBNP	Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Urine Sodium Excretion	Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Peripheral Vein Pressure	Peripheral vein pressure (mm Hg) will be recorded from existing IV lines through pressure transducer monitoring at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Cardiac Output	Cardiac output (L/min) is the total volume of blood moved by the heart per minute and will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in E/e'	E/e' will be assessed using echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. It is defined as the ratio of peak early diastolic mitral inflow velocity (E) and peak early diastolic mitral annular velocity (e').	Baseline, 24 hours
Change in Apnea-hypopnea Index	The apnea-hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep which is an indicator of severity of sleep apnea AHI will be measured using a Watch Pat or Nox device at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Iohexol Glomerular Filtration Rate (GFR)	Renal or kidney function was measured by GFR determined by Iohexol clearance. Iohexol GFR will be measured at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Estimated Right Ventricular (RV) Systolic Pressure	Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Right Atrial (RA) Pressure	RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Left Atrial (LA) Strain	LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Left Ventricular (LV) Global Longitudinal Strain	LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours
Change in Right Ventricular (RV) Global Longitudinal Strain	RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.	Baseline, 24 hours

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Yogesh Reddy, M.B.B.S, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Actual): October 8, 2024
• Study Completion (Actual): October 8, 2024

Study Registration Dates

• First Submitted: September 7, 2023
• First Submitted That Met QC Criteria: September 7, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Natriuretic Agents; Sulfur Compounds; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Aniline Compounds; Amines; Benzene Derivatives; Acids, Carbocyclic; Sulfonamides; Sulfanilamides; Sulfones; Aminobenzoates; Benzoates; meta-Aminobenzoates; Furosemide; Bumetanide; Diuretics
• Other Study ID Numbers: 23-005262

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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