Fluid Overload, Heart Failure Acute
Conditions
Keywords
diuretic, metolazone, furosemide
Brief summary
The purpose of this study is to examine whether administering metolazone 60 minutes prior to furosemide increases urine output compared with administering metolazone and furosemide concomitantly. Participants will have equal chance of being assigned to each group.
Detailed description
Diuretic resistance is common among patients with acute decompensated heart failure, and one strategy for overcoming this phenomenon is sequential nephron blockade with loop plus thiazide-type diuretics. Metolazone is an oral thiazide-type diuretic commonly used for this purpose. Due to its delayed absorption, some clinicians suggest that metolazone be given 30-60 minutes prior to the loop diuretic. However, the efficacy and safety of such a strategy has not been investigated despite its added complexity. The purpose of this study is to investigate whether pre-dosing with metolazone confers a difference in efficacy and safety compared to administering it at the same time as furosemide.
Interventions
DRUGMetolazone 60 minutes prior to furosemide
All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide.
DRUGMetolazone concurrently with furosemide
All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, randomized, open-label, active control pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Admission within 48 hours for acute decompensated heart failure with at least one symptom and one sign of volume overload * Receipt of loop diuretic prior to admission * Plan to administer furosemide 120 - 160 mg IV bolus twice daily over the next 24 hours with additional diuresis deemed necessary * If patient is concurrently administered intravenous vasodilator or inotrope, the dose of vasodilator or inotrope must be stable for 6 hours prior to enrollment with a plan to continue the same dose for the 24 hour duration of this study
Exclusion criteria
* Metolazone prescribed prior to admission * Receipt of continuous intravenous infusion of furosemide * Cirrhosis or end stage renal disease * Non-English speaking patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-Hour Urine Output | 24 hours | Total measured urine output in milliliters produced after metolazone dose is given |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hyponatremia | Baseline and at 12 to 23 hours after metolazone dose | Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given |
| Change in Total Body Weight | Baseline and at 12 to 23 hours after metolazone dose | Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose |
| Hypomagnesemia | Baseline and at 12 to 23 hours after metolazone dose | Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given |
| Acute Kidney Injury | Baseline and at 12 to 23 hours after metolazone dose | Portion of patients with increase in serum creatinine by ≥ 0.3 mg/dL or ≥ 50% from baseline |
| Hypokalemia | Baseline and at 12 to 23 hours after metolazone dose | Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given |
| Change in Serum Creatinine | Baseline and at 12 to 23 hours after metolazone dose | Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metolazone Pre-dosing Metolazone 5 mg by mouth administered 60 minutes prior to furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after)
Metolazone 60 minutes prior to furosemide: All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide. | 1 |
| Metolazone Concurrent Dosing Metolazone 5 mg by mouth administered at the same time as furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after)
Metolazone concurrently with furosemide: All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide. | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Metolazone Pre-dosing | Metolazone Concurrent Dosing | Total |
|---|---|---|---|
| Age, Continuous | 39 years | 66 years STANDARD_DEVIATION 7.1 | 57 years STANDARD_DEVIATION 16.4 |
| Left ventricular ejection fraction | 50 % | 53 % STANDARD_DEVIATION 10.6 | 51.7 % STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Serum creatinine | 1 mg/dL | 2.1 mg/dL STANDARD_DEVIATION 0.6 | 1.8 mg/dL STANDARD_DEVIATION 0.8 |
| Serum sodium | 138 mmol/L | 142 mmol/L STANDARD_DEVIATION 6.4 | 140.3 mmol/L STANDARD_DEVIATION 4.9 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
| Systolic blood pressure | 134 mm Hg | 132 mm Hg STANDARD_DEVIATION 17 | 132.7 mm Hg STANDARD_DEVIATION 12 |
| Total daily dose loop diuretic prior to admission (in oral furosemide equivalents) | 100 mg/day | 140 mg/day STANDARD_DEVIATION 28.3 | 126.7 mg/day STANDARD_DEVIATION 30.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 1 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
24-Hour Urine Output
Total measured urine output in milliliters produced after metolazone dose is given
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metolazone Concurrent Dosing | 24-Hour Urine Output | 2030 mL | Standard Deviation 1626.3 |
| Metolazone Pre-dosing | 24-Hour Urine Output | 5650 mL | — |
Secondary
Acute Kidney Injury
Portion of patients with increase in serum creatinine by ≥ 0.3 mg/dL or ≥ 50% from baseline
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metolazone Concurrent Dosing | Acute Kidney Injury | 1 Participants |
| Metolazone Pre-dosing | Acute Kidney Injury | 1 Participants |
Secondary
Change in Serum Creatinine
Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metolazone Concurrent Dosing | Change in Serum Creatinine | 0.45 mg/dL | Standard Deviation 0.28 |
| Metolazone Pre-dosing | Change in Serum Creatinine | 0.38 mg/dL | — |
Secondary
Change in Total Body Weight
Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metolazone Concurrent Dosing | Change in Total Body Weight | -.6 kg | Standard Deviation 1.1 |
| Metolazone Pre-dosing | Change in Total Body Weight | -8.5 kg | — |
Secondary
Hypokalemia
Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metolazone Concurrent Dosing | Hypokalemia | 0 Participants |
| Metolazone Pre-dosing | Hypokalemia | 1 Participants |
Secondary
Hypomagnesemia
Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metolazone Concurrent Dosing | Hypomagnesemia | 0 Participants |
| Metolazone Pre-dosing | Hypomagnesemia | 1 Participants |
Secondary
Hyponatremia
Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given
Time frame: Baseline and at 12 to 23 hours after metolazone dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metolazone Concurrent Dosing | Hyponatremia | 0 Participants |
| Metolazone Pre-dosing | Hyponatremia | 0 Participants |