Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

NCT03746002 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: HP-00082982
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Fluid Overload; Heart Failure Acute

Keywords

diuretic; metolazone; furosemide

Outcome Measures

Primary Outcomes (1)

• 24-Hour Urine Output

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

  24 hours

Secondary Outcomes (6)

• Change in Total Body Weight

  Baseline and at 12 to 23 hours after metolazone dose

• Change in Serum Creatinine

  Baseline and at 12 to 23 hours after metolazone dose

• Acute Kidney Injury

  Baseline and at 12 to 23 hours after metolazone dose

• Hypokalemia

  Baseline and at 12 to 23 hours after metolazone dose

• Hypomagnesemia

  Baseline and at 12 to 23 hours after metolazone dose

Study Arms (2)

Metolazone Pre-dosing

ACTIVE COMPARATOR

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)

Drug: Metolazone 60 minutes prior to furosemide

Metolazone Concurrent Dosing

ACTIVE COMPARATOR

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)

Drug: Metolazone concurrently with furosemide

Interventions

Metolazone 60 minutes prior to furosemide 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.

Also known as: Zaroxolyn

Metolazone Pre-dosing

Metolazone concurrently with furosemide 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.

Also known as: Zaroxolyn

Metolazone Concurrent Dosing

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Metolazone prescribed prior to admission
• Receipt of continuous intravenous infusion of furosemide
• Cirrhosis or end stage renal disease
• Non-English speaking patients

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (4)

• 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.

  PMID: 29141174 BACKGROUND

• 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.

  PMID: 21029871 BACKGROUND

• 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.

  PMID: 3793436 BACKGROUND

• 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.

  PMID: 2014951 BACKGROUND

MeSH Terms

Conditions

Edema

Interventions

Metolazone; Furosemide

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfanilamides; Aniline Compounds; Amines

Limitations and Caveats

This study was terminated early due to slow enrollment, resulting in an inadequate sample size.

Results Point of Contact

• Title: Brent Reed
• Organization: University of Maryland School of Pharmacy

breed@rx.umaryland.edu

410-706-1452

Study Officials

• Brent Reed, PharmD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Pharmacy Practice and Science

Model Details: Prospective, randomized, open-label, active control pilot study

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 19, 2018
• Study Start: January 1, 2019
• Primary Completion: January 10, 2020
• Study Completion: January 10, 2020
• Last Updated: October 22, 2021
• Results First Posted: October 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)