Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure (The DOSE-AHF Study)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00577135
First received: December 18, 2007
Last updated: July 15, 2014
Last verified: April 2013
  Purpose

Heart failure is a disorder in which the heart does not pump blood adequately. This can lead to several serious problems, including reduced blood flow throughout the body, congestion of blood in the veins and lungs, and fluid accumulation in various organs and limbs. Diuretics are often used to address the problem of fluid accumulation, but the optimal dose and the amount of time over which to administer each dose are unclear. This study will compare high and low doses of diuretics administered over longer and shorter periods of time to determine the safest and most effective combination.


Condition Intervention Phase
Heart Failure
Drug: Furosemide-Q12 hour bolus
Drug: Furosemide-Continuous Infusion
Drug: Furosemide-Low Intensification
Drug: Furosemide-High Intensification
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Patient Well Being, as Determined by a Visual Analog Scale [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: No ]
    Global Visual Analog Scale Scale Range 0-7200; higher score is better

  • Change in Serum Creatinine [ Time Frame: Measured at baseline and 72 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in Weight [ Time Frame: baseline and 96 hours ] [ Designated as safety issue: No ]
  • Proportion of Patients Free of Congestion [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: No ]
  • Dyspnea, as Determined by Visual Analog Scales [ Time Frame: Measured at 24 hours ] [ Designated as safety issue: No ]
    Global Visual Analog Scale Scale Range 0-2400; higher score is better

  • Change in Serum Creatinine [ Time Frame: baseline and 24 hours ] [ Designated as safety issue: Yes ]
  • Change in Cystatin C [ Time Frame: baseline and 72 hours ] [ Designated as safety issue: No ]
  • Change in Serum Creatinine [ Time Frame: baseline and 48 hours ] [ Designated as safety issue: Yes ]
  • Change in Serum Creatinine [ Time Frame: baseline and 96 hours ] [ Designated as safety issue: Yes ]
  • Change in Serum Creatinine [ Time Frame: baseline and day 7 ] [ Designated as safety issue: Yes ]
  • Change in Serum Creatinine [ Time Frame: baseline and day 60 ] [ Designated as safety issue: Yes ]
  • Patient Well Being, as Determined by a Visual Analog Scale [ Time Frame: Measured at 24 hours ] [ Designated as safety issue: No ]
    Global Visual Analog Scale Scale Range 0-2400; higher score is better

  • Patient Well Being, as Determined by a Visual Analog Scale [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Global Visual Analog Scale Scale Range 0-4800; higher score is better

  • Dyspnea VAS [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Dyspnea Visual Analog Scale Scale Range 0-4800; higher score is better

  • Dyspnea VAS [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Dyspnea Visual Analog Scale Scale Range 0-7200; higher score is better

  • Change in Cystatin C [ Time Frame: baseline and day 7 ] [ Designated as safety issue: No ]
  • Change in Cystatin C [ Time Frame: baseline and day 60 ] [ Designated as safety issue: No ]
  • Change in Uric Acid [ Time Frame: baseline and 72 hours ] [ Designated as safety issue: No ]
  • Change in Uric Acid [ Time Frame: baseline and day 7 ] [ Designated as safety issue: No ]
  • Change in Uric Acid [ Time Frame: baseline and Day 60 ] [ Designated as safety issue: No ]
  • Change in B-type Natriuretic Peptide [ Time Frame: baseline and 72 hours ] [ Designated as safety issue: No ]
    Change in NTproBNP

  • Change in NTproBNP [ Time Frame: baseline and Day 7 ] [ Designated as safety issue: No ]
  • Change in NTproBNP [ Time Frame: baseline and Day 60 ] [ Designated as safety issue: No ]
  • Presence of Cardiorenal Syndrome [ Time Frame: Within 72 hours ] [ Designated as safety issue: No ]
  • Treatment Failure [ Time Frame: Within 72 hours ] [ Designated as safety issue: No ]
    Treatment failure is defined as the patient met cardiorenal syndrome endpoint, worsening or persistent heart failure endpoint, patient died, or there was clinical evidence of overdiuresis requiring intervention within first 72 hours after randomization

  • Net Fluid Loss [ Time Frame: Through 24 hours ] [ Designated as safety issue: No ]
  • Net Fluid Loss [ Time Frame: Through 48 hours ] [ Designated as safety issue: No ]
  • Net Fluid Loss [ Time Frame: Through 72 hours ] [ Designated as safety issue: No ]

Enrollment: 308
Study Start Date: February 2008
Study Completion Date: February 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Q12 hour bolus
Furosemide-Q12 hour bolus
Drug: Furosemide-Low Intensification
1x oral dose
Other Name: Loop diuretic
Drug: Furosemide-High Intensification
2.5x oral dose
Other Name: loop diuretic
Experimental: Continuous Infusion
Furosemide-Continuous Infusion
Drug: Furosemide-Low Intensification
1x oral dose
Other Name: Loop diuretic
Drug: Furosemide-High Intensification
2.5x oral dose
Other Name: loop diuretic
Experimental: Low Intensification
Furosemide-Low Intensification
Drug: Furosemide-Q12 hour bolus
Q12 hours bolus
Other Name: Loop diuretics
Drug: Furosemide-Continuous Infusion
Continuous infusion
Other Name: Loop diuretic
Experimental: High Intensification
Furosemide-High Intensification
Drug: Furosemide-Q12 hour bolus
Q12 hours bolus
Other Name: Loop diuretics
Drug: Furosemide-Continuous Infusion
Continuous infusion
Other Name: Loop diuretic

Detailed Description:

Heart failure is a common disorder in which the heart cannot pump enough blood to meet the needs of the rest of the body. Heart failure symptoms include shortness of breath, swelling, and fatigue. Standard treatment for the swelling associated with heart failure includes the use of diuretic medications, such as furosemide, which cause urination and the removal of excess fluids in the body. Although furosemide has been used to treat heart failure patients for many years, it is still unclear how much of the drug to use, and over what time period the drug should be given. This study will evaluate whether furosemide treatment is safer and more effective when the drug is given in high doses versus low doses and in two to three separate doses versus one continuous infusion.

Participants in this study will begin study procedures within the first 24 hours of their hospital admission for heart failure. Participants will be randomly assigned to receive one of the following four treatments: high dose furosemide via continuous intravenous (IV) infusion and placebo every 12 hours via IV bolus; low dose furosemide via continuous IV infusion and placebo every 12 hours via IV bolus; high dose furosemide every 12 hours via IV bolus and placebo via continuous IV infusion; and low dose furosemide every 12 hours via IV bolus and placebo via continuous IV infusion. Each participant will receive treatment for the first 72 hours of his or her hospital stay. Participants will answer questionnaires and undergo physical examinations and blood tests during the first 96 hours of hospitalization and again before hospital discharge or on Day 7, if that occurs first. Participants will be asked to return to their doctors 60 days following hospital discharge to evaluate their responses to treatment.

  Eligibility

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

Inclusion Criteria:

  • Prior clinical diagnosis of heart failure that was treated with daily oral loop diuretics for at least 1 month
  • Current diagnosis of heart failure, as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
  • Daily oral dose of furosemide between 80 mg and 240 mg (or equivalent)
  • Identified within 24 hours of hospital admission
  • Current treatment plan includes IV loop diuretics for at least 48 hours

Exclusion Criteria:

  • Brain natriuretic peptide (BNP) less than 250 mg/mL or N-terminal prohormone brain natriuretic peptide (NT-proBNP) less than 1000 mg/mL
  • Received IV vasoactive treatment or ultra-filtration therapy for heart failure since initial presentation
  • Treatment plan during current hospitalization includes IV vasoactive treatment or ultra-filtration for heart failure
  • Substantial diuretic response to pre-randomization diuretic dosing such that higher doses of diuretics would be medically inadvisable
  • Systolic blood pressure less than 90 mm Hg
  • Serum creatinine level greater than 3.0 mg/dL at baseline or currently undergoing renal replacement therapy
  • Hemodynamically significant arrhythmias
  • Acute coronary syndrome within 4 weeks prior to study entry
  • Active myocarditis
  • Hypertrophic obstructive cardiomyopathy
  • Severe stenotic valvular disease
  • Restrictive or constrictive cardiomyopathy
  • Complex congenital heart disease
  • Constrictive pericarditis
  • Non-cardiac pulmonary edema
  • Clinical evidence of digoxin toxicity
  • Need for mechanical hemodynamic support
  • Sepsis
  • Terminal illness (other than heart failure) with expected survival time of less than 1 year
  • History of adverse reaction to the study drugs
  • Use of IV iodinated radiocontrast material within 72 hours prior to study entry or planned during hospitalization
  • Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
  • Inability to comply with planned study procedures
  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: NCT00577135

Locations
United States, Georgia
Morehouse School of Medicine
Atlanta, Georgia, United States, 30310
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Minnesota Heart Failure Network
Minneapolis, Minnesota, United States, 55415
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Sciences Center
Murray, Utah, United States, 84107
United States, Vermont
University of Vermont - Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T - 1C8
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Kerry L. Lee, PhD Duke Clinical Research Institute
Study Chair: Eugene Braunwald, MD Harvard University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00577135     History of Changes
Other Study ID Numbers: Pro00017634, U01HL084904-01, U01 HL084904-01, 523
Study First Received: December 18, 2007
Results First Received: January 23, 2013
Last Updated: July 15, 2014
Health Authority: United States: Federal Government

Keywords provided by Duke University:
Loop Diuretics
Furosemide
Fluid Overload
Cardio Renal Failure

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

ClinicalTrials.gov processed this record on September 29, 2014