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

Condition(s) targeted: Acute Decompensated Heart Failure

Intervention: Intravenous Bolus Furosemide and Oral Metolazone (Drug); Intravenous Continuous Infusion Furosemide (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: The University of North Carolina, Chapel Hill

Official(s) and/or principal investigator(s):
Jo E. Rodgers, PharmD, Principal Investigator, Affiliation: The University of North Carolina, Chapel Hill

Overall contact:
Jo E. Rodgers, PharmD, Phone: 919-962-2249, Email: jerodgers@unc.edu

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.

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Daily net fluid output

Secondary outcome:

Patient Global Assessment Scale

Daily urine output (mL urine out per mg furosemide received)

Need for additional or alternative diuretic (crossover) or IV vasoactive therapy (study failure)

Death, rehospitalization, and unscheduled visit for HF to an emergency department or outpatient clinic

Critically low potassium (< 3.5 mmol/L) and magnesium (< 1.6 mg/dL) concentrations

Change in blood urea nitrogen or creatinine

Number of hypotensive episodes defined as systolic blood pressure below 85 mmHg or greater than 10 mmHg below baseline (whichever is greater)

Total number of times antihypertensive doses are held due to low blood pressure

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 one HF symptom (e. g., dyspnea) AND one HF sign (e. g., rales)

- Inadequate response to IV diuretics and requiring additional diuresis as determined

by primary medical team

- Identified within 24 hours of hospital admission

- Anticipated need for intravenous diuretic therapy for at least 48 hours

- Able to provide informed consent

Exclusion Criteria:

- Received greater than two intravenous bolus doses of loop diuretic or 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 cardiac transplantation or ventricular assist device

placement or work-up for either 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 intravenous

potassium is being administered)

- Serum magnesium < 1. 6 mg/dL (1. 4 - 1. 5 mg/dL allowed if supplemental intravenous

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 last 72 hours or planned during

hospitalization

- Enrollment or planned enrollment in another randomized clinical trial during

hospitalization

Jo E. Rodgers, PharmD, Phone: 919-962-2249, Email: jerodgers@unc.edu

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

Starting date: October 2008
Ending date: December 2010
Last updated: June 22, 2009