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Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

NCT ID: NCT03746002

Last Updated: 2021-10-22

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-01

Study Completion Date

2020-01-10

Brief Summary

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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

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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.

Conditions

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Fluid Overload Heart Failure Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, randomized, open-label, active control pilot study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Metolazone 60 minutes prior to furosemide

Intervention Type DRUG

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.

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)

Group Type ACTIVE_COMPARATOR

Metolazone concurrently with furosemide

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Zaroxolyn Zaroxolyn

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Maryland, Baltimore

OTHER

Sponsor Role lead

Responsible Party

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Brent Reed

Associate Professor, Pharmacy Practice and Science

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Brent Reed, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Locations

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University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med. 2017 Nov 16;377(20):1964-1975. doi: 10.1056/NEJMra1703100. No abstract available.

Reference Type BACKGROUND
PMID: 29141174 (View on PubMed)

Jentzer JC, DeWald TA, Hernandez AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34. doi: 10.1016/j.jacc.2010.06.034.

Reference Type BACKGROUND
PMID: 21029871 (View on PubMed)

Grosskopf I, Rabinovitz M, Rosenfeld JB. Combination of furosemide and metolazone in the treatment of severe congestive heart failure. Isr J Med Sci. 1986 Nov;22(11):787-90.

Reference Type BACKGROUND
PMID: 3793436 (View on PubMed)

Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991 May 15;114(10):886-94. doi: 10.7326/0003-4819-114-10-886.

Reference Type BACKGROUND
PMID: 2014951 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HP-00082982

Identifier Type: -

Identifier Source: org_study_id