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

Acute Decompensated Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00904488
• Other study ID #: 08-1292
• Status: Terminated
• Phase: Phase 4
• First received: May 17, 2009
• Last updated: February 13, 2018
• Start date: October 2008
• Est. completion date: November 14, 2017

Study information

• Verified date: January 2018
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: November 14, 2017
• Est. primary completion date: May 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• Addition of oral Metolazone
Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide
• Furosemide dose escalation
Furosemide dose escalation via either IV bolus (2-2.5 x current dose) or continuous infusion (2-2.5 x current dose administered over previous 24 hours)

Locations

Country	Name	City	State
United States	UNC_Chapel Hill	Chapel Hill	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	University of Illinois at Chicago, Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)	Net fluid output = fluid output during 24-48 hours after randomization - fluid intake during 24-48 hours after randomization. A negative value means that daily fluid intake was less than the daily fluid output.	24-48 hours
Secondary	Daily Net Fluid Output on Days 1, 3, and 4	Daily net fluid output = daily fluid output - daily intake. A negative value means that daily fluid intake was less than the daily fluid output.	0-24, 48-72, 72-96 hrs
Secondary	Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)		0-24, 24-48, 48-72, 72-96 hrs
Secondary	Daily Weight		Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs
Secondary	Patient Global Assessment Scale	Scale range: 1-5 Which of the following best describes your overall health state today?; = markedly worse; = worse; = neither better nor worse; = better; = markedly better	Baseline, 24, 48, 72, 96 hrs
Secondary	Physician Global Assessment Scale	Scale range: 1-5 Which of the following best describes the patient's overall health state today?; = markedly worse; = worse; = neither better nor worse; = better; = markedly better	Baseline, 24, 48, 72, 96 hours
Secondary	Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)	Patients will be considered a treatment failure if they require additional diuretic (including crossover to the alternative study arm) or require IV vasoactive drug therapy (e.g. vasodilators including nitroglycerin or inotropes) as deemed appropriate/necessary by their medical team.	0-96 hours
Secondary	Time to Return to Baseline Weight		0-96 hours
Secondary	Length of Hospitalization		Assessed till hospital discharge, an average of 1 week (longest 29 days)
Secondary	30-day All-cause Mortality		30 days
Secondary	Rehospitalization at 30 Days		30 days
Secondary	Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic		30 days
Secondary	Blood Urea Nitrogen (BUN)		Baseline, 24, 48, 72, 96 hours