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: University of North Carolina, Chapel Hill

Official(s) and/or principal investigator(s):
Jo E. Rodgers, PharmD, Principal Investigator, Affiliation: 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: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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: 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

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
Last updated: February 9, 2015