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Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure

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ClinicalTrials.gov Identifier: NCT00904488
Recruitment Status : Terminated (Difficult recruitment)
First Posted : May 19, 2009
Last Update Posted : September 25, 2017
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Acute Decompensated Heart Failure Drug: Intravenous Bolus Furosemide and Oral Metolazone Drug: Intravenous Continuous Infusion Furosemide Phase 4

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2008
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: IVB Loop and PO Thiazide Diuretic
Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide dose left to discretion of primary medical team)
Drug: Intravenous Bolus Furosemide and Oral Metolazone
Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide
Other Name: Lasix, Zaroxolyn
Active Comparator: IV Continuous Infusion Loop Diuretic
Transition from intravenous bolus to continuous infusion furosemide (Furosemide dose left to discretion of primary medical team)
Drug: Intravenous Continuous Infusion Furosemide
Transition from intravenous bolus to continuous infusion furosemide
Other Name: Lasix

Outcome Measures

Primary Outcome Measures :
  1. Daily net fluid output [ Time Frame: 48 hours ]

Secondary Outcome Measures :
  1. Patient Global Assessment Scale [ Time Frame: 48 hours ]
  2. Daily urine output (mL urine out per mg furosemide received) [ Time Frame: 48 hours ]
  3. Need for additional or alternative diuretic (crossover) or IV vasoactive therapy (study failure) [ Time Frame: 48 hours ]
  4. Death, rehospitalization, and unscheduled visit for HF to an emergency department or outpatient clinic [ Time Frame: 30 days ]
  5. Critically low potassium (< 3.5 mmol/L) and magnesium (< 1.6 mg/dL) concentrations [ Time Frame: 48 hours ]
  6. Change in blood urea nitrogen or creatinine [ Time Frame: 48 hours ]
  7. Number of hypotensive episodes defined as systolic blood pressure below 85 mmHg or greater than 10 mmHg below baseline (whichever is greater) [ Time Frame: 48 hours ]
  8. Total number of times antihypertensive doses are held due to low blood pressure [ Time Frame: 48 hours ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Greater than or equal to 18 years of age
  2. Hospitalized for 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)
  3. Inadequate response to IV diuretics and requiring additional diuresis as determined by primary medical team
  4. Received less than six doses of IV furosemide OR enrolled within 72 hours of hospital admission
  5. Anticipated need for intravenous diuretic therapy for at least 48 hours
  6. Able to provide informed consent

Exclusion Criteria:

  1. Receiving a continuous infusion loop diuretic during current hospital visit
  2. 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)
  3. 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
  4. 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
  5. Systolic blood pressure < 90 mmHg
  6. Serum creatinine > 3 mg/dL at baseline or renal replacement therapy including ultrafiltration
  7. Serum potassium < 3.5 mEq/L (3.0 - 3.4 mEq/L allowed if supplemental potassium is being administered)
  8. Serum magnesium < 1.6 mg/dL (1.4 - 1.5 mg/dL allowed if supplemental magnesium is being administered)
  9. Acute coronary syndrome or hemodynamically significant arrhythmias causing worsening HF
  10. Severe, uncorrected primary cardiac valvular disease, acute myocarditis, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, complex congenital heart disease
  11. Primary pulmonary hypertension with right sided heart failure
  12. Use of iodinated radiocontrast material in prior 72 hours or planned within the next 48 hours
  13. Enrollment or planned enrollment in another randomized clinical trial during hospitalization
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00904488

United States, North Carolina
UNC_Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
University of Illinois at Chicago
Virginia Commonwealth University
Principal Investigator: Jo E. Rodgers, PharmD University of North Carolina, Chapel Hill
More Information

Responsible Party: Jo Rodgers, PharmD, Clinical Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00904488     History of Changes
Other Study ID Numbers: 08-1292
First Posted: May 19, 2009    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Keywords provided by Jo Rodgers, PharmD, University of North Carolina, Chapel Hill:
Acute Decompensated Heart Failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Sodium Chloride Symporter Inhibitors