Trial Outcomes & Findings for Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing (NCT NCT03746002)

NCT ID: NCT03746002

Last Updated: 2021-10-22

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 3 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2021-10-22

Participant Flow

Participant milestones

Measure	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) 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 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) 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.
Overall Study STARTED	1	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

Baseline characteristics by cohort

Measure	Metolazone Pre-dosing n=1 Participants 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 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 Concurrent Dosing n=2 Participants 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) 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.	Total n=3 Participants Total of all reporting groups
Age, Continuous	39 years STANDARD_DEVIATION NA • n=5 Participants	66 years STANDARD_DEVIATION 7.1 • n=7 Participants	57 years STANDARD_DEVIATION 16.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Left ventricular ejection fraction	50 % STANDARD_DEVIATION NA • n=5 Participants	53 % STANDARD_DEVIATION 10.6 • n=7 Participants	51.7 % STANDARD_DEVIATION 7.6 • n=5 Participants
Serum creatinine	1 mg/dL STANDARD_DEVIATION NA • n=5 Participants	2.1 mg/dL STANDARD_DEVIATION 0.6 • n=7 Participants	1.8 mg/dL STANDARD_DEVIATION 0.8 • n=5 Participants
Serum sodium	138 mmol/L STANDARD_DEVIATION NA • n=5 Participants	142 mmol/L STANDARD_DEVIATION 6.4 • n=7 Participants	140.3 mmol/L STANDARD_DEVIATION 4.9 • n=5 Participants
Systolic blood pressure	134 mm Hg STANDARD_DEVIATION NA • n=5 Participants	132 mm Hg STANDARD_DEVIATION 17 • n=7 Participants	132.7 mm Hg STANDARD_DEVIATION 12 • n=5 Participants
Total daily dose loop diuretic prior to admission (in oral furosemide equivalents)	100 mg/day STANDARD_DEVIATION NA • n=5 Participants	140 mg/day STANDARD_DEVIATION 28.3 • n=7 Participants	126.7 mg/day STANDARD_DEVIATION 30.6 • n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
24-Hour Urine Output	2030 mL Standard Deviation 1626.3	5650 mL Standard Deviation NA This group only had one participant so standard deviation does not apply.

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Change in Total Body Weight	-.6 kg Standard Deviation 1.1	-8.5 kg Standard Deviation NA This group only had one participant so standard deviation does not apply.

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Change in Serum Creatinine	0.45 mg/dL Standard Deviation 0.28	0.38 mg/dL Standard Deviation NA This group only had one participant so standard deviation does not apply.

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Acute Kidney Injury	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Hypokalemia	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Hypomagnesemia	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and at 12 to 23 hours after metolazone dose

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

Outcome measures

Measure	Metolazone Concurrent Dosing n=2 Participants 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) 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.	Metolazone Pre-dosing n=1 Participants 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 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.
Hyponatremia	0 Participants	0 Participants

Adverse Events

Metolazone Pre-dosing

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Metolazone Concurrent Dosing

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Metolazone Pre-dosing n=1 participants at risk 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 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 Concurrent Dosing n=2 participants at risk 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) 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.
Renal and urinary disorders Acute kidney injury	100.0% 1/1 • Number of events 1 • 24 hours after metolazone dose (no greater than 48 hours after enrollment)	50.0% 1/2 • Number of events 1 • 24 hours after metolazone dose (no greater than 48 hours after enrollment)

Additional Information

Brent Reed

University of Maryland School of Pharmacy

Phone: 410-706-1452

Email: breed@rx.umaryland.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place