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

Sponsor

University of Virginia (Other)

Overall Status

Terminated

CT.gov ID

NCT03574857

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Heart Failure With Reduced Ejection Fraction Heart Failure Acute Cardiovascular Diseases	Drug: Metolazone Oral Tablet Drug: Chlorothiazide Injection	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2018

Actual Primary Completion Date :

Jan 1, 2021

Actual Study Completion Date :

Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metolazone Metolazone 5 mg by mouth once daily for 2 days	Drug: Metolazone Oral Tablet Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO Other Names: Zaroxolyn
Active Comparator: Chlorothiazide Chlorothiazide 500 mg IV once daily for 2 days	Drug: Chlorothiazide Injection Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV Other Names: Diuril

Arm

Intervention/Treatment

Active Comparator: Metolazone

Metolazone 5 mg by mouth once daily for 2 days

Drug: Metolazone Oral Tablet

Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO

Other Names:

Zaroxolyn

Active Comparator: Chlorothiazide

Chlorothiazide 500 mg IV once daily for 2 days

Drug: Chlorothiazide Injection

Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV

Other Names:

Diuril

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Net urine output at 48 hours [48 hours]
Milliliters of urine output minus the oral plus IV intake
Net fluid balance over 12 hours [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 [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 [48 hours]
Change in documented weight in kg at 48 hours after starting metolazone or chlorothiazide

Other Outcome Measures

Electrolyte disturbances [48 hours]
Frequency of hypokalemia, hypomagnesemia, hyponatremia
Worsening renal function [48 hours]
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
Hospital length of stay [Assessed until hospital discharge, an average of 7 days]
Number of days hospitalized
ICU length of stay [Assessed until hospital discharge, an average of 7 days]
Number of days patient is located in an ICU
In-hospital mortality [Assessed until hospital discharge, an average of 7 days]
Incidence of in-hospital mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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