Clinical trial NCT03746002: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Fluid Overload
Heart Failure Acute
Keywords: diuretic
metolazone
furosemide
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2018-11-19
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, open-label, active control pilot study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 24-Hour Urine Output
timeFrame: 24 hours
Secondary outcomes:
measure: Change in Total Body Weight
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
measure: Change in Serum Creatinine
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
measure: Acute Kidney Injury
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
measure: Hypokalemia
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
measure: Hypomagnesemia
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
measure: Hyponatremia
timeFrame: Baseline and at 12 to 23 hours after metolazone dose
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland, College Park
name: Brent Reed, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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. doi: 10.7326/0003-4819-114-10-886.