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

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.

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 Criteria:
Inclusion Criteria:

1. Greater than or equal to 18 years of age
2. 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)
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