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Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

Primary Purpose

Fluid Overload, Heart Failure Acute

Status

Terminated

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Metolazone 60 minutes prior to furosemide

Metolazone concurrently with furosemide

About this trial

This is an interventional treatment trial for Fluid Overload focused on measuring diuretic, metolazone, furosemide

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Maryland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Metolazone Pre-dosing

Metolazone Concurrent Dosing

Arm Description

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 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)

Outcomes

Primary Outcome Measures

24-Hour Urine Output

Total measured urine output in milliliters produced after metolazone dose is given

Secondary Outcome Measures

Change in Total Body Weight

Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose

Change in Serum Creatinine

Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose

Acute Kidney Injury

Portion of patients with increase in serum creatinine by ≥ 0.3 mg/dL or ≥ 50% from baseline

Hypokalemia

Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given

Hypomagnesemia

Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given

Hyponatremia

Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given

Full Information

NCT ID

NCT03746002

First Posted

November 15, 2018

Last Updated

September 25, 2021

Sponsor

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT03746002

Brief Title

Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

Official Title

Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing With Furosemide: a Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Terminated

Why Stopped

Insufficient rate of patient enrollment/accrual.

Study Start Date

January 1, 2019 (Actual)

Primary Completion Date

January 10, 2020 (Actual)

Study Completion Date

January 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fluid Overload, Heart Failure Acute

Keywords

diuretic, metolazone, furosemide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Prospective, randomized, open-label, active control pilot study

Masking

None (Open Label)

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metolazone Pre-dosing

Arm Type

Active Comparator

Arm Description

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)

Arm Title

Metolazone Concurrent Dosing

Arm Type

Active Comparator

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

Metolazone 60 minutes prior to furosemide

Other Intervention Name(s)

Zaroxolyn

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Metolazone concurrently with furosemide

Other Intervention Name(s)

Zaroxolyn

Intervention Description

Primary Outcome Measure Information:

Title

24-Hour Urine Output

Description

Total measured urine output in milliliters produced after metolazone dose is given

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Change in Total Body Weight

Description

Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose

Time Frame