Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03746002
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fluid Overload; Heart Failure Acute	Drug: Metolazone 60 minutes prior to furosemide; Drug: Metolazone concurrently with furosemide	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, randomized, open-label, active control pilot studyProspective, randomized, open-label, active control pilot study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing With Furosemide: a Pilot Study
• Actual Study Start Date: Jan 1, 2019
• Actual Primary Completion Date: Jan 10, 2020
• Actual Study Completion Date: Jan 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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)	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.; Other Names: Zaroxolyn
Active Comparator: 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)	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.; Other Names: Zaroxolyn

Outcome Measures

Primary Outcome Measures

1. 24-Hour Urine Output [24 hours]

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

Secondary Outcome Measures

1. Change in Total Body Weight [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

2. Change in Serum Creatinine [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

3. Acute Kidney Injury [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

4. Hypokalemia [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

5. Hypomagnesemia [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

6. Hyponatremia [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland Medical Center	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

• Principal Investigator: Brent Reed, PharmD, University of Maryland, College Park

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 14, 2018

More Information

Publications

• 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.
• 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.
• 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.
• 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.

• Responsible Party: Brent Reed, Associate Professor, Pharmacy Practice and Science, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03746002
• Other Study ID Numbers: HP-00082982
• First Posted: Nov 19, 2018
• Last Update Posted: Oct 22, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Brent Reed, Associate Professor, Pharmacy Practice and Science, University of Maryland, Baltimore: diuretic; metolazone; furosemide
• Additional relevant MeSH terms: Heart Failure; Metolazone; Furosemide

Study Results

Participant Flow

Arm/Group Title	Metolazone Pre-dosing	Metolazone Concurrent Dosing
Arm/Group Description	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 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.
Period Title: Overall Study
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Metolazone Pre-dosing	Metolazone Concurrent Dosing	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	1	2	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39 (NA)	66 (7.1)	57 (16.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 50%	1 33.3%
Male	1 100%	1 50%	2 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 50%	1 33.3%
White	1 100%	1 50%	2 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Left ventricular ejection fraction (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	50 (NA)	53 (10.6)	51.7 (7.6)
Serum creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1 (NA)	2.1 (0.6)	1.8 (0.8)
Serum sodium (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	138 (NA)	142 (6.4)	140.3 (4.9)
Systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	134 (NA)	132 (17)	132.7 (12)
Total daily dose loop diuretic prior to admission (in oral furosemide equivalents) (mg/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/day]	100 (NA)	140 (28.3)	126.7 (30.6)

Outcome Measures

1. Primary Outcome

Title	24-Hour Urine Output
Description	Total measured urine output in milliliters produced after metolazone dose is given
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Mean (Standard Deviation) [mL]	2030 (1626.3)	5650 (NA)

2. Secondary Outcome

Title	Change in Total Body Weight
Description	Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Mean (Standard Deviation) [kg]	-.6 (1.1)	-8.5 (NA)

3. Secondary Outcome

Title	Change in Serum Creatinine
Description	Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Mean (Standard Deviation) [mg/dL]	0.45 (0.28)	0.38 (NA)

4. Secondary Outcome

Title	Acute Kidney Injury
Description	Portion of patients with increase in serum creatinine by ≥ 0.3 mg/dL or ≥ 50% from baseline
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Count of Participants [Participants]	1 100%	1 50%

5. Secondary Outcome

Title	Hypokalemia
Description	Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	1 50%

6. Secondary Outcome

Title	Hypomagnesemia
Description	Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	1 50%

7. Secondary Outcome

Title	Hyponatremia
Description	Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given
Time Frame	Baseline and at 12 to 23 hours after metolazone dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metolazone Concurrent Dosing	Metolazone Pre-dosing
Arm/Group Description	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 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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	24 hours after metolazone dose (no greater than 48 hours after enrollment)
Arm/Group Title	Metolazone Pre-dosing		Metolazone Concurrent Dosing
Arm/Group Description	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 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.
All Cause Mortality
	Metolazone Pre-dosing		Metolazone Concurrent Dosing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Serious Adverse Events
	Metolazone Pre-dosing		Metolazone Concurrent Dosing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Metolazone Pre-dosing		Metolazone Concurrent Dosing
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/2 (50%)
Renal and urinary disorders
Acute kidney injury	1/1 (100%)	1	1/2 (50%)	1

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.