Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

Phase 4

Terminated

Interventions: Drug: Metolazone 60 minutes prior to furosemide
Drug: Metolazone concurrently with 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Metolazone Pre-dosing	Metolazone 60 minutes prior to furosemide	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 Concurrent Dosing	Metolazone concurrently with furosemide	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)

Primary Outcome Measures

Name	Time	Method
24-Hour Urine Output	24 hours	Total measured urine output in milliliters produced after metolazone dose is given

Secondary Outcome Measures

Name	Time	Method
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
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
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