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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 1, 2021

Interventions

  • Drug: Metolazone Oral Tablet
    • Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO
  • Drug: Chlorothiazide Injection
    • Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV

Arms, Groups and Cohorts

  • Active Comparator: Metolazone
    • Metolazone 5 mg by mouth once daily for 2 days
  • Active Comparator: Chlorothiazide
    • Chlorothiazide 500 mg IV once daily for 2 days

Clinical Trial Outcome Measures

Primary Measures

  • Net urine output at 24 hours
    • Time Frame: 24 hours
    • Milliliters of urine output minus the oral plus intravenous intake

Secondary Measures

  • Net urine output at 48 hours
    • Time Frame: 48 hours
    • Milliliters of urine output minus the oral plus IV intake
  • Net fluid balance over 12 hours
    • Time Frame: 24 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
  • Net fluid balance over 24 hours
    • Time Frame: 48 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
  • Weight change
    • Time Frame: 48 hours
    • Change in documented weight in kg at 48 hours after starting metolazone or chlorothiazide

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Virginia
  • Provider of Information About this Clinical Study
    • Principal Investigator: Emily Burns, Principle Investigator – University of Virginia

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