A Study of Ultra High Dose Diuretics to Treat Heart Failure

• ClinicalTrials.gov Identifier: NCT06036914
• Recruitment Status: Enrolling by invitation
• First Posted: September 14, 2023
• Last Update Posted: March 27, 2024
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Yogesh Reddy, Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Heart Failure; With Decompensation	Drug: Bumetanide; Drug: Furosemide	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Ultra High Dose Diuretic Strategy for Management of Acute Decompensated Heart Failure - A Randomized, Double-Blind Pilot Trial
• Actual Study Start Date: November 27, 2023
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

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 Name: 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 Name: Standard dose diuretic

Outcome Measures

Primary Outcome Measures :

1. Urine Output [ Time Frame: 24 hours ]
   The total volume of urine produced in liters (L) over 24 hours after initiation of intravenous diuretic.

Secondary Outcome Measures :

1. Change in Body Weight [ Time Frame: Baseline, 24 hours ]
   Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic.
2. Change in NT-proBNP [ Time Frame: Baseline, 24 hours ]
   Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic.
3. Change in Urine Sodium Excretion [ Time Frame: Baseline, 24 hours ]
   Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic.
4. Change in apnea-hypopnea index [ Time Frame: Baseline, 24 hours ]

   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.

5. Change in Iohexol glomerular filtration rate (GFR) [ Time Frame: Baseline, 24 hours ]
   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.
6. Change in Peripheral Vein Pressure [ Time Frame: Baseline, 24 hours ]
   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.
7. Change in Cardiac Output [ Time Frame: Baseline, 24 hours ]
   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.
8. Change in estimated Right Ventricular (RV) systolic pressure [ Time Frame: Baseline, 24 hours ]
   Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
9. Change in Right Atrial (RA) pressure [ Time Frame: Baseline, 24 hours ]
   RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
10. Change in Left Atrial (LA) strain [ Time Frame: Baseline, 24 hours ]
    LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
11. Change in Left Ventricular (LV) global longitudinal strain [ Time Frame: Baseline, 24 hours ]
    LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
12. Change in Right Ventricular (RV) global longitudinal strain [ Time Frame: Baseline, 24 hours ]
    RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
13. Change in E/e' [ Time Frame: Baseline, 24 hours ]
    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').

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

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

More Information

• Responsible Party: Yogesh Reddy, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT06036914
• Other Study ID Numbers: 23-005262
• First Posted: September 14, 2023
• Last Update Posted: March 27, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; Furosemide; Bumetanide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action