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

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00577135

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 Drug: Placebo	Phase III

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:

MedlinePlus related topics: Heart Failure

Drug Information available for: Furosemide

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Patient well being, as determined by a visual analog scale [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Change in serum creatinine [ Time Frame: Measured at baseline and after 72 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Weight loss [ Time Frame: Measured at 24, 48, 72, 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 ]
Change in the bivariate relationship of creatinine versus weight loss [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: Yes ]
Dyspnea, as determined by visual analog scales [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
Patient global assessment, as determined by visual analog scales [ Time Frame: Measured at 24 and 48 hours ] [ Designated as safety issue: No ]
Change in serum creatinine [ Time Frame: Measured at baseline, Hours 24, 48, and 96, and Days 7 and 60 ] [ Designated as safety issue: Yes ]
Change in cystatin C [ Time Frame: Measured at baseline, 72 hours, and Days 7 and 60 ] [ Designated as safety issue: No ]
Worsening or persistent heart failure, defined as a need for rescue therapy [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Development of cardio-renal syndrome, defined as an increase in the serum creatinine level greater than 0.3 mg/dl [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: Yes ]
Net fluid loss [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
Time from study entry to discharge during index hospitalization [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Death or total days hospitalized for heart failure [ Time Frame: Measured over the 60 days following study entry ] [ Designated as safety issue: No ]
Death or re-hospitalization [ Time Frame: Measured at Day 60 ] [ Designated as safety issue: No ]

Estimated Enrollment:	300
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: 1 Participants will receive high dose furosemide administered via IV bolus every 12 hours and placebo via continuous IV infusion.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Other Name: Loop diuretics Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
Experimental: 2 Participants will receive high dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Other Name: Loop diuretics Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
Experimental: 3 Participants will receive low dose furosemide administered via IV bolus every 12 hours and placebo via continuous infusion.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Other Name: Loop diuretics Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
Experimental: 4 Participants will receive low dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Other Name: Loop diuretics Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.

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

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

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Kerry L. Lee, PhD	Duke Clinical Research Institute
Study Chair:	Eugene Braunwald, MD	Harvard University

More Information

Publications:

Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805.

Responsible Party:	Kerry L. Lee, PhD, Duke Clinical Research Institute
ClinicalTrials.gov Identifier:	NCT00577135 History of Changes
Other Study ID Numbers:	523, U01 HL084904-01
Study First Received:	December 18, 2007
Last Updated:	May 6, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

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 February 09, 2012