Clinical trial NCT00904488: Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Decompensated Heart Failure
Keywords: Acute Decompensated Heart Failure
Diuretics
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
name: Virginia Commonwealth University
First posted: 2009-05-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)
timeFrame: 24-48 hours
Secondary outcomes:
measure: Daily Net Fluid Output on Days 1, 3, and 4
timeFrame: 0-24, 48-72, 72-96 hrs
measure: Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)
timeFrame: 0-24, 24-48, 48-72, 72-96 hrs
measure: Daily Weight
timeFrame: Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs
measure: Patient Global Assessment Scale
timeFrame: Baseline, 24, 48, 72, 96 hrs
measure: Physician Global Assessment Scale
timeFrame: Baseline, 24, 48, 72, 96 hours
measure: Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)
timeFrame: 0-96 hours
measure: Time to Return to Baseline Weight
timeFrame: 0-96 hours
measure: Length of Hospitalization
timeFrame: Assessed till hospital discharge, an average of 1 week (longest 29 days)
measure: 30-day All-cause Mortality
timeFrame: 30 days
measure: Rehospitalization at 30 Days
timeFrame: 30 days
measure: Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic
timeFrame: 30 days
measure: Blood Urea Nitrogen (BUN)
timeFrame: Baseline, 24, 48, 72, 96 hours
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC_Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jo E. Rodgers, PharmD
role: PRINCIPAL_INVESTIGATOR
References: