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

NCT ID: NCT00904488

Last Updated: 2018-03-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2017-11-14

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.

Conditions

Acute Decompensated Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Addition of PO Thiazide Diuretic

Addition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide.

Group Type: ACTIVE_COMPARATOR

Addition of oral Metolazone

Intervention Type: DRUG

Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide

IV furosemide dose escalation

Current IV furosemide dose will be escalated to 2-2.5 x current dose, given as either IV bolus or continuous infusion over 24 hours.

Group Type: ACTIVE_COMPARATOR

Furosemide dose escalation

Intervention Type: DRUG

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)

Interventions

Addition of oral Metolazone

Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide

Intervention Type: DRUG

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)

Intervention Type: DRUG

Other Intervention Names

Zaroxolyn; Lasix

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jo E. Rodgers, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

UNC_Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

08-1292

Identifier Type: -

Identifier Source: org_study_id