Oral Metolazone and Intermittent Intravenous Furosemide V... | NCT00904488

Status Module

Name	Class
University of Illinois at Chicago	OTHER
Virginia Commonwealth University	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Addition of PO Thiazide Diuretic	Active Comparator	Addition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide.	Drug: Addition of oral Metolazone
IV furosemide dose escalation	Active Comparator	Current IV furosemide dose will be escalated to 2-2.5 x current dose, given as either IV bolus or continuous infusion over 24 hours.	Drug: Furosemide dose escalation

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Addition of oral Metolazone	Drug	Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide	Addition of PO Thiazide Diuretic

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)	Net fluid output = fluid output during 24-48 hours after randomization - fluid intake during 24-48 hours after randomization. A negative value means that daily fluid intake was less than the daily fluid output.	24-48 hours

Secondary Outcomes

Measure	Description	Time Frame
Daily Net Fluid Output on Days 1, 3, and 4	Daily net fluid output = daily fluid output - daily intake. A negative value means that daily fluid intake was less than the daily fluid output.	0-24, 48-72, 72-96 hrs
Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Greater than or equal to 18 years of age
Hospitalized for acute decompensated heart failure (ADHF) secondary to fluid overload as defined by the presence of at least
- 1 symptom (e.g. dyspnea, orthopnea, paroxysmal nocturnal dyspnea) AND
- 1 sign (e.g. rales on auscultation, > 2+ peripheral or presacral> edema, hepatomegaly, ascites, jugular vein distension > 7 cm, pulmonary vascular congestion on chest radiography)
Inadequate response to IV diuretics and requiring additional diuresis as determined by primary medical team
Received less than six doses of IV furosemide OR enrolled within 72 hours of hospital admission
Anticipated need for intravenous diuretic therapy for at least 48 hours
Able to provide informed consent

Exclusion Criteria:

Receiving a continuous infusion loop diuretic during current hospital visit
Substantial diuretic response to pre-randomization diuretic dosing such that higher doses of diuretic would be contraindicated (based on judgement of patient's primary team)
Planned or ongoing intravenous vasoactive therapy (e.g. inotrope, vasodilator) or mechanical support (e.g. intra-aortic balloon pump, ventricular assist device) for ADHF during this hospitalization
Planned elective admission for elective placement/revision of a cardiovascular device (e.g. defibrillator, biventricular pacemaker) during this hospitalization or such within the preceding 7 days
Systolic blood pressure < 90 mmHg
Serum creatinine > 3 mg/dL at baseline or renal replacement therapy including ultrafiltration
Serum potassium < 3.5 mEq/L (3.0 - 3.4 mEq/L allowed if supplemental potassium is being administered)
Serum magnesium < 1.6 mg/dL (1.4 - 1.5 mg/dL allowed if supplemental magnesium is being administered)
Acute coronary syndrome or hemodynamically significant arrhythmias causing worsening HF
Severe, uncorrected primary cardiac valvular disease, acute myocarditis, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, complex congenital heart disease
Primary pulmonary hypertension with right sided heart failure
Use of iodinated radiocontrast material in prior 72 hours or planned within the next 48 hours
Enrollment or planned enrollment in another randomized clinical trial during hospitalization

Name	Affiliation	Role
Jo E. Rodgers, PharmD	University of North Carolina, Chapel Hill	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
UNC_Chapel Hill		Chapel Hill	North Carolina	27599	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Furosemide Dose Escalation	Furosemide dose escalation given either as IV bolus (2-2.5 x current dose) or continuous infusion (2-2.5 x current dose administered over previous 24 hours)
FG001	IVB Loop and PO Thiazide Diuretic

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
BG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0005 BG0016 BG00211

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-1454.60± 1339.53 OG001-1322.83± 1738.30

Secondary

Daily Net Fluid Output on Days 1, 3, and 4

Daily net fluid output = daily fluid output - daily intake. A negative value means that daily fluid intake was less than the daily fluid output.

If diuretic therapy is changed to the oral route before a scheduled efficacy endpoint is to be measured (e.g.72 or 96 hour net output), then that endpoint will not be obtained.

Posted

Mean

Standard Deviation

ml/day

0-24, 48-72, 72-96 hrs

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)

Data were not collected at all time points for all subjects, and were only analyzed when available. Data not analyzed on days when diuretics were held or discontinued.

Posted

Mean

Standard Deviation

ml/mg furosemide received

0-24, 24-48, 48-72, 72-96 hrs

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Daily Weight

Data were not collected for all subjects at all time points, and were only analyzed when available

Posted

Mean

Standard Deviation

Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Patient Global Assessment Scale

Scale range: 1-5 Which of the following best describes your overall health state today?

= markedly worse
= worse
= neither better nor worse
= better
= markedly better

Data were not collected at all time points, and were only analyzed when available.

Posted

Mean

Standard Deviation

units on a scale

Baseline, 24, 48, 72, 96 hrs

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Physician Global Assessment Scale

Scale range: 1-5 Which of the following best describes the patient's overall health state today?

= markedly worse
= worse
= neither better nor worse
= better
= markedly better

Data were not collected at all time points, and were only analyzed when available.

Posted

Mean

Standard Deviation

units on a scale

Baseline, 24, 48, 72, 96 hours

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)

Patients will be considered a treatment failure if they require additional diuretic (including crossover to the alternative study arm) or require IV vasoactive drug therapy (e.g. vasodilators including nitroglycerin or inotropes) as deemed appropriate/necessary by their medical team.

Posted

Count of Participants

Participants

0-96 hours

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Time to Return to Baseline Weight

Weight was not collected in all subjects every day.

Posted

Mean

Standard Deviation

Days

0-96 hours

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Length of Hospitalization

Data not available in all subjects.

Posted

Mean

Standard Deviation

Days

Assessed till hospital discharge, an average of 1 week (longest 29 days)

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

30-day All-cause Mortality

Posted

Count of Participants

Participants

30 days

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Rehospitalization at 30 Days

30-day follow up data (except for mortality) were not collected in 2 participants

Posted

Count of Participants

Participants

30 days

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic

30-day follow up data (except for mortality) were not collected in 2 participants

Posted

Count of Participants

Participants

30 days

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Secondary

Blood Urea Nitrogen (BUN)

Posted

Mean

Standard Deviation

mg/dL

Baseline, 24, 48, 72, 96 hours

ID	Title	Description
OG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)
OG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Furosemide Dose Escalation	IV furosemide dose escalation via either intravenous bolus (2-2.5 x current dose) or continuous infusion furosemide (Furosemide 2-2.5 x current dose administered over previous 24 hours)	0	5	0	5	2	5
EG001	IVB Loop and PO Thiazide Diuretic	Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide continued at current dose)	0	6	0	6	6	6

Other Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
critically low potassium (< 3.5 mmol/L) while receiving study therapy	Cardiac disorders	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected6 at risk
critically low magnesium (< 1.6 mg/dL) while receiving study therapy	Cardiac disorders	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected6 at risk
Hypotension	Cardiac disorders	Systematic Assessment		EG0008 events2 affected5 at risk EG00132 events6 affected6 at risk
Hypotension resulting in holding antihypertensive doses	Cardiac disorders	Systematic Assessment	Reported as number of subjects affected/total at risk. Count of occurrence is total number of doses of antihypertensives being held.	EG0000 events0 affected5 at risk EG0018 events1 affected6 at risk

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D052999	Quinazolinones
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D013424	Sulfanilamides
D000814	Aniline Compounds
D000588	Amines