Cardiovascular Diseases, Heart Failure, Heart Failure Acute, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Loop diuretics, Heart failure, Diuretic resistance, Thiazide diuretics
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.
Interventions
DRUGMetolazone Oral Tablet
Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO
DRUGChlorothiazide Injection
Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net urine output at 24 hours | 24 hours | Milliliters of urine output minus the oral plus intravenous intake |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed