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

NCT00904488 | Terminated Phase 4 Results

• 1 other identifier: 08-1292
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Decompensated Heart Failure

Keywords

Acute Decompensated Heart Failure; Diuretics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Daily Net Fluid Output on Days 1, 3, and 4

  0-24, 48-72, 72-96 hrs

• Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)

  0-24, 24-48, 48-72, 72-96 hrs

• Daily Weight

  Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs

• Patient Global Assessment Scale

  Baseline, 24, 48, 72, 96 hrs

• Physician Global Assessment Scale

  Baseline, 24, 48, 72, 96 hours

Study Arms (2)

Addition of PO Thiazide Diuretic

ACTIVE COMPARATOR

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

Drug: Addition of oral Metolazone

IV furosemide dose escalation

ACTIVE COMPARATOR

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.

Drug: Furosemide dose escalation

Interventions

Addition of oral Metolazone DRUG

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

Also known as: Zaroxolyn

Addition of PO Thiazide Diuretic

Furosemide dose escalation 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)

Also known as: Lasix

IV furosemide dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Greater than or equal to 18 years of age
• Hospitalized for acute decompensated heart failure (ADHF) secondary to fluid overload as defined by the presence of at least
• symptom (e.g. dyspnea, orthopnea, paroxysmal nocturnal dyspnea) AND
• sign (e.g. rales on auscultation, \> 2+ peripheral or presacral\> edema, hepatomegaly, ascites, jugular vein distension \> 7 cm, pulmonary vascular congestion on chest radiography)
• Inadequate response to IV diuretics and requiring additional diuresis as determined by primary medical team
• Received less than six doses of IV furosemide OR enrolled within 72 hours of hospital admission
• Anticipated need for intravenous diuretic therapy for at least 48 hours
• Able to provide informed consent

You may not qualify if:

• Receiving a continuous infusion loop diuretic during current hospital visit
• 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)
• 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
• 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
• Systolic blood pressure \< 90 mmHg
• Serum creatinine \> 3 mg/dL at baseline or renal replacement therapy including ultrafiltration
• Serum potassium \< 3.5 mEq/L (3.0 - 3.4 mEq/L allowed if supplemental potassium is being administered)
• Serum magnesium \< 1.6 mg/dL (1.4 - 1.5 mg/dL allowed if supplemental magnesium is being administered)
• Acute coronary syndrome or hemodynamically significant arrhythmias causing worsening HF
• Severe, uncorrected primary cardiac valvular disease, acute myocarditis, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, complex congenital heart disease
• Primary pulmonary hypertension with right sided heart failure
• Use of iodinated radiocontrast material in prior 72 hours or planned within the next 48 hours
• Enrollment or planned enrollment in another randomized clinical trial during hospitalization

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• University of Illinois at Chicago: collaborator
• Virginia Commonwealth University: collaborator

Study Sites (1)

UNC_Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

Metolazone; Furosemide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Dr. Jo Ellen Rodgers
• Organization: UNC Eshelman School of Pharmacy

jerodgers@unc.edu

(919) 962-2249

Study Officials

• Jo E. Rodgers, PharmD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2009
• First Posted: May 19, 2009
• Study Start: October 1, 2008
• Primary Completion: May 28, 2016
• Study Completion: November 14, 2017
• Last Updated: March 13, 2018
• Results First Posted: February 13, 2018

Record last verified: 2018-01

Locations

US (1)