A Study of Ultra High Dose Diuretics to Treat Heart Failure

Study Overview
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Brief Summary
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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.

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

Conditions
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Heart Failure; With Decompensation

Intervention / Treatment
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* Drug: Bumetanide
* Drug: Furosemide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultra-high dose diuretic group<br>Subjects with decompensated heart failure requiring hospitalization will receive IV bumetanide. | Drug: Bumetanide<br>* 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.<br>* Other names: Ultra-high dose diuretic;|
| Active Comparator: Standard dose diuretic group<br>Subjects with decompensated heart failure requiring hospitalization will receive IV furosemide. | Drug: Furosemide<br>* 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.<br>* Other names: Standard dose diuretic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Output | The total volume of urine produced in liters (L) 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 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 device at Baseline and 24 hours after initiation of intravenous diuretic. | Baseline, 24 hours | 
| Change in Iothalamate glomerular filtration rate (GFR) | Renal or kidney function was measured by GFR determined by iothalamate clearance. Iothalamate GFR will be measured at Baseline and 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 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 | 
| 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 |