Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance

Study Overview
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Brief Summary
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The primary objective of the study is to compare efficacy of metolazone and chlorothiazide as add-on therapy in patients refractory to loop diuretics with heart failure with a reduced ejection fraction (HFrEF). This will be a single-center randomized pilot study.

Official Title
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Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance

Conditions
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Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure Acute, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Metolazone Oral Tablet
* Drug: Chlorothiazide Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Admitted for acute decompensated HF with left ventricular ejection fraction (LVEF) <40% Refractory fluid overload: Unresponsive (<500 mL net negative over previous 24 hours) AND ineffective diuresis (determined by HF team) to moderate intensity push or low intensity continuous infusion loop diuretic (80 mg IV furosemide or equivalent bumetanide dose of 4 mg) English or Spanish-speaking subjects Willing and able to comply with study procedures Exclusion Criteria: Baseline thiazide use prior to admission or prior to study enrollment Renal replacement therapies (RRT) or glomerular filtration rate (GFR) <30 mL/min at the time of enrollment Pregnant women Cognitive impairment Prisoners Left ventricular assist devices (LVAD) or temporary mechanical circulatory support devices History of cardiac transplant Reported allergy to thiazides No enteral access or unable to take medications enterally Palliative diuretics Systolic blood pressure (SBP) <90 mm Hg prior to randomization Patients receiving concomitant lithium therapy

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metolazone<br>Metolazone 5 mg by mouth once daily for 2 days | Drug: Metolazone Oral Tablet<br>* Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO<br>* Other names: Zaroxolyn;|
| Active Comparator: Chlorothiazide<br>Chlorothiazide 500 mg IV once daily for 2 days | Drug: Chlorothiazide Injection<br>* Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV<br>* Other names: Diuril;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net urine output at 24 hours | Milliliters of urine output minus the oral plus intravenous intake | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net urine output at 48 hours | Milliliters of urine output minus the oral plus IV intake | 48 hours | 
| Net fluid balance over 12 hours | the net fluid balance over 12 and 24 hours prior to the addition of metolazone or chlorothiazide compared to the 12 hours after addition of the study drug | 24 hours | 
| Net fluid balance over 24 hours | Net fluid balance over 24 hours prior to the addition of metolazone or chlorothiazide compared to the 24 hours after addition of the study drug | 48 hours | 
| Weight change | Change in documented weight in kg at 48 hours after starting metolazone or chlorothiazide | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Loop diuretics, Heart failure, Diuretic resistance, Thiazide diuretics