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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
University of Illinois at Chicago
Information provided by (Responsible Party):
Jo Rodgers, PharmD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00904488
First received: May 17, 2009
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Acute Decompensated Heart Failure
Drug: Intravenous Bolus Furosemide and Oral Metolazone
Drug: Intravenous Continuous Infusion Furosemide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Daily net fluid output [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patient Global Assessment Scale [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Daily urine output (mL urine out per mg furosemide received) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Need for additional or alternative diuretic (crossover) or IV vasoactive therapy (study failure) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Death, rehospitalization, and unscheduled visit for HF to an emergency department or outpatient clinic [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Critically low potassium (< 3.5 mmol/L) and magnesium (< 1.6 mg/dL) concentrations [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  • Change in blood urea nitrogen or creatinine [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
  • Number of hypotensive episodes defined as systolic blood pressure below 85 mmHg or greater than 10 mmHg below baseline (whichever is greater) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Total number of times antihypertensive doses are held due to low blood pressure [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: October 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IVB Loop and PO Thiazide Diuretic
Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide (Furosemide dose left to discretion of primary medical team)
Drug: Intravenous Bolus Furosemide and Oral Metolazone
Addition of oral metolazone 5 mg daily to continued intravenous bolus furosemide
Other Name: Lasix, Zaroxolyn
Active Comparator: IV Continuous Infusion Loop Diuretic
Transition from intravenous bolus to continuous infusion furosemide (Furosemide dose left to discretion of primary medical team)
Drug: Intravenous Continuous Infusion Furosemide
Transition from intravenous bolus to continuous infusion furosemide
Other Name: Lasix

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Greater than or equal to 18 years of age
  2. Hospitalized for 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00904488

Contacts
Contact: Jo E. Rodgers, PharmD 919-962-2249 jerodgers@unc.edu
Contact: J. H. Patterson, PharmD 919-962-0072 hpatterson@unc.edu

Locations
United States, North Carolina
UNC_Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jo E. Rodgers, PharmD    919-962-2249    jerodgers@unc.edu   
Contact: J. H. Patterson, PharmD    919-962-0072    hpatterson@unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
University of Illinois at Chicago
Investigators
Principal Investigator: Jo E. Rodgers, PharmD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Jo Rodgers, PharmD, Clinical Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00904488     History of Changes
Other Study ID Numbers: 08-1292
Study First Received: May 17, 2009
Last Updated: December 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Acute Decompensated Heart Failure
Diuretics

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Diuretics
Furosemide
Metolazone
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents

ClinicalTrials.gov processed this record on July 22, 2014