Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure - Full Text View

Sponsor:	The University of North Carolina, Chapel Hill
Collaborators:	Western University of Health Sciences University of Illinois University of Southern California University of Kentucky University of Wisconsin, Madison University of Michigan
Information provided by:	The University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT00904488

Purpose

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	Intervention	Phase
Acute Decompensated Heart Failure	Drug: Intravenous Bolus Furosemide and Oral Metolazone Drug: Intravenous Continuous Infusion Furosemide	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines Heart Failure

Drug Information available for: Furosemide Metolazone

U.S. FDA Resources

Further study details as provided by The University of North Carolina, Chapel Hill:

Primary Outcome Measures:

Daily net fluid output [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Patient Global Assessment Scale [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Daily urine output (mL urine out per mg furosemide received) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Need for additional or alternative diuretic (crossover) or IV vasoactive therapy (study failure) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Death, rehospitalization, and unscheduled visit for HF to an emergency department or outpatient clinic [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Critically low potassium (< 3.5 mmol/L) and magnesium (< 1.6 mg/dL) concentrations [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
Change in blood urea nitrogen or creatinine [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Total number of times antihypertensive doses are held due to low blood pressure [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	160
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
IVB Loop and PO Thiazide Diuretic: Active Comparator 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
IV Continuous Infusion Loop Diuretic: Active Comparator 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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Greater than or equal to 18 years of age
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)
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00904488

Contacts

Contact: Jo E. Rodgers, PharmD	919-962-2249	jerodgers@unc.edu
Contact: J. H. Patterson, PharmD	919-962-0072	hpatterson@unc.edu

Locations

United States, North Carolina
UNC_Chapel Hill	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jo E. Rodgers, PharmD 919-962-2249 jerodgers@unc.edu
Contact: J. H. Patterson, PharmD 919-962-0072 hpatterson@unc.edu

Sponsors and Collaborators

The University of North Carolina, Chapel Hill

Western University of Health Sciences

University of Illinois

University of Southern California

University of Kentucky

University of Wisconsin, Madison

University of Michigan

Investigators

Principal Investigator:

Jo E. Rodgers, PharmD

The University of North Carolina, Chapel Hill

More Information

No publications provided

Responsible Party:	University of North Carolina-Chapel Hill ( Jo E. Rodgers/Clinical Associate Professor )
Study ID Numbers:	08-1292
Study First Received:	May 17, 2009
Last Updated:	January 21, 2010
ClinicalTrials.gov Identifier:	NCT00904488 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by The University of North Carolina, Chapel Hill:

Acute Decompensated Heart Failure
Diuretics

Additional relevant MeSH terms:

Metolazone
Heart Failure
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Diuretics
Physiological Effects of Drugs
Cardiovascular Agents
Antihypertensive Agents

Furosemide
Pharmacologic Actions
Membrane Transport Modulators
Natriuretic Agents
Therapeutic Uses
Cardiovascular Diseases
Sodium Potassium Chloride Symporter Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010