Back to resultsOral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure
Primary Purpose
Acute Decompensated Heart Failure
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Addition of oral Metolazone
Furosemide dose escalation
Sponsored by
About this trial
This is an interventional treatment trial for Acute Decompensated Heart Failure focused on measuring Acute Decompensated Heart Failure, Diuretics
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
Sites / Locations
- UNC_Chapel Hill
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Addition of PO Thiazide Diuretic
IV furosemide dose escalation
Arm Description
Addition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)
Daily Weight
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
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
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.
Time to Return to Baseline Weight
Length of Hospitalization
30-day All-cause Mortality
Rehospitalization at 30 Days
Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic
Blood Urea Nitrogen (BUN)
Full Information
NCT ID
NCT00904488
First Posted
May 17, 2009
Last Updated
February 13, 2018
Sponsor
University of North Carolina, Chapel Hill
Collaborators
University of Illinois at Chicago, Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT00904488
Brief Title
Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure
Official Title
Addition of Oral Metolazone to Intermittent Intravenous Furosemide Versus Transition to Continuous Infusion Furosemide in Acute Decompensated Heart Failure Patients Experiencing an Inadequate Response to Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
Difficult recruitment
Study Start Date
October 2008 (Actual)
Primary Completion Date
May 28, 2016 (Actual)
Study Completion Date
November 14, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
University of Illinois at Chicago, Virginia Commonwealth University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this prospective, randomized, open-label study is to compare two diuretic strategies in patients with acute decompensated heart failure (ADHF): the addition of an oral thiazide diuretic to intravenous bolus (IVB) loop diuretic will be compared to transition from IVB to continuous infusion (CI) loop diuretic.
Detailed Description
Patients hospitalized for ADHF secondary to fluid overload and who are experiencing an inadequate response to IVB furosemide and require additional diuresis will be enrolled. Patients will be randomized to one of two treatment arms: the addition of oral metolazone to continued IVB furosemide versus transition from IVB to CI furosemide. A suggested algorithm for initial dosing and titration of these two diuretic strategies will be provided. Baseline and daily data collection will include various efficacy and safety endpoints including daily net urine output and weight, patient and physician global assessment scale, length of stay, 30-day death or rehospitalization, vital signs, electrolytes, and renal function. Clinically meaningful efficacy and safety endpoints will be compared.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Decompensated Heart Failure
Keywords
Acute Decompensated Heart Failure, Diuretics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Addition of PO Thiazide Diuretic
Arm Type
Active Comparator
Arm Description
Addition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide.
Arm Title
IV furosemide dose escalation
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Addition of oral Metolazone
Other Intervention Name(s)
Zaroxolyn
Intervention Description
Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide
Intervention Type
Drug
Intervention Name(s)
Furosemide dose escalation
Other Intervention Name(s)
Lasix
Intervention Description
Furosemide dose escalation via either IV bolus (2-2.5 x current dose) or continuous infusion (2-2.5 x current dose administered over previous 24 hours)
Primary Outcome Measure Information:
Title
Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)
Description
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.
Time Frame
24-48 hours
Secondary Outcome Measure Information:
Title
Daily Net Fluid Output on Days 1, 3, and 4
Description
Daily net fluid output = daily fluid output - daily intake. A negative value means that daily fluid intake was less than the daily fluid output.
Time Frame
0-24, 48-72, 72-96 hrs
Title
Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)
Time Frame
0-24, 24-48, 48-72, 72-96 hrs
Title
Daily Weight
Time Frame
Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs
Title
Patient Global Assessment Scale
Description
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
Time Frame
Baseline, 24, 48, 72, 96 hrs
Title
Physician Global Assessment Scale
Description
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
Time Frame
Baseline, 24, 48, 72, 96 hours
Title
Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)
Description
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.
Time Frame
0-96 hours
Title
Time to Return to Baseline Weight
Time Frame
0-96 hours
Title
Length of Hospitalization
Time Frame
Assessed till hospital discharge, an average of 1 week (longest 29 days)
Title
30-day All-cause Mortality
Time Frame
30 days
Title
Rehospitalization at 30 Days
Time Frame
30 days
Title
Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic
Time Frame
30 days
Title
Blood Urea Nitrogen (BUN)
Time Frame
Baseline, 24, 48, 72, 96 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jo E. Rodgers, PharmD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC_Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
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Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure
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