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

Primary Purpose

Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure Acute

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Metolazone Oral Tablet
Chlorothiazide Injection
Sponsored by
University of Virginia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Loop diuretics, Heart failure, Diuretic resistance, Thiazide diuretics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Virginia Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Metolazone

Chlorothiazide

Arm Description

Metolazone 5 mg by mouth once daily for 2 days

Chlorothiazide 500 mg IV once daily for 2 days

Outcomes

Primary Outcome Measures

Net urine output at 24 hours
Milliliters of urine output minus the oral plus intravenous intake

Secondary Outcome Measures

Net urine output at 48 hours
Milliliters of urine output minus the oral plus IV intake
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
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
Weight change
Change in documented weight in kg at 48 hours after starting metolazone or chlorothiazide

Full Information

First Posted
April 16, 2018
Last Updated
February 10, 2021
Sponsor
University of Virginia
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1. Study Identification

Unique Protocol Identification Number
NCT03574857
Brief Title
Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance
Official Title
Prospective Comparison of Metolazone Versus Chlorothiazide for Acute Decompensated Heart Failure With Diuretic Resistance
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
January 1, 2021 (Actual)
Study Completion Date
January 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure Acute, Cardiovascular Diseases
Keywords
Loop diuretics, Heart failure, Diuretic resistance, Thiazide diuretics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metolazone
Arm Type
Active Comparator
Arm Description
Metolazone 5 mg by mouth once daily for 2 days
Arm Title
Chlorothiazide
Arm Type
Active Comparator
Arm Description
Chlorothiazide 500 mg IV once daily for 2 days
Intervention Type
Drug
Intervention Name(s)
Metolazone Oral Tablet
Other Intervention Name(s)
Zaroxolyn
Intervention Description
Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO
Intervention Type
Drug
Intervention Name(s)
Chlorothiazide Injection
Other Intervention Name(s)
Diuril
Intervention Description
Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV
Primary Outcome Measure Information:
Title
Net urine output at 24 hours
Description
Milliliters of urine output minus the oral plus intravenous intake
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Net urine output at 48 hours
Description
Milliliters of urine output minus the oral plus IV intake
Time Frame
48 hours
Title
Net fluid balance over 12 hours
Description
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
Time Frame
24 hours
Title
Net fluid balance over 24 hours
Description
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
Time Frame
48 hours
Title
Weight change
Description
Change in documented weight in kg at 48 hours after starting metolazone or chlorothiazide
Time Frame
48 hours
Other Pre-specified Outcome Measures:
Title
Electrolyte disturbances
Description
Frequency of hypokalemia, hypomagnesemia, hyponatremia
Time Frame
48 hours
Title
Worsening renal function
Description
increase in serum creatinine greater that 0.5 mg/dL from the patient's baseline value on the day of the first dose of chlorothiazide or metolazone
Time Frame
48 hours
Title
Hospital length of stay
Description
Number of days hospitalized
Time Frame
Assessed until hospital discharge, an average of 7 days
Title
ICU length of stay
Description
Number of days patient is located in an ICU
Time Frame
Assessed until hospital discharge, an average of 7 days
Title
In-hospital mortality
Description
Incidence of in-hospital mortality
Time Frame
Assessed until hospital discharge, an average of 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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