Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

Fluid Overload Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03746002
• Other study ID #: HP-00082982
• Status: Terminated
• Phase: Phase 4
• Start date: January 1, 2019
• Est. completion date: January 10, 2020

Study information

• Verified date: September 2021
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: January 10, 2020
• Est. primary completion date: January 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

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:

• Metolazone prescribed prior to admission

• Receipt of continuous intravenous infusion of furosemide

• Cirrhosis or end stage renal disease

• Non-English speaking patients

Related Conditions & MeSH terms

• Fluid Overload
• Heart Failure
• Heart Failure Acute

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Maryland Medical Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & 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. Review. Erratum in: N Engl J Med. 2018 Feb 1;378(5):492. — View Citation

Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991 May 15;114(10):886-94. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-Hour Urine Output	Total measured urine output in milliliters produced after metolazone dose is given	24 hours
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	Baseline and at 12 to 23 hours after metolazone dose
Secondary	Change in Serum Creatinine	Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose	Baseline and at 12 to 23 hours after metolazone dose
Secondary	Acute Kidney Injury	Portion of patients with increase in serum creatinine by = 0.3 mg/dL or = 50% from baseline	Baseline and at 12 to 23 hours after metolazone dose
Secondary	Hypokalemia	Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given	Baseline and at 12 to 23 hours after metolazone dose
Secondary	Hypomagnesemia	Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given	Baseline and at 12 to 23 hours after metolazone dose
Secondary	Hyponatremia	Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given	Baseline and at 12 to 23 hours after metolazone dose