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

December 18, 2007
July 15, 2014
February 2008
January 2010   (final data collection date for primary outcome measure)
  • 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 ]
  • Efficacy measure will be patient reported global well being by visual analog scale (VAS) quantified as the area under the curve (AUC) over 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Safety measure will be change in serum creatinine from baseline to 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00577135 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Weight Loss: Weight loss will be measured over the 96-hour study period (at 24, 48, 72, and 96 hours from randomization). [ Time Frame: 96 hours ] [ Designated as safety issue: No ]
  • Proportion of Patients Free of Congestion at 72 hours: will be defined as JVP < 8 cm, no orthopnea, trace peripheral edema or less [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Change in the bivariate relationship of creatinine at 72 hours vs. weight loss at 72 hours. Visual and statistical assessment will reveal the "trade off" between change in weight and change in renal function. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
  • Dyspnea VAS AUC over 24, 48, and 72 hours [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • PGA VAS AUC over 24 and 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Change in Serum Creatinine from baseline to 24, 48, 96 hours, day 7/discharge, and 60 days [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
  • Change in Cystatin C from baseline to 72 hours, Day 7/discharge, and 60 days [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Worsening or persistent heart failure: defined as need for rescue therapy over 72 hours after randomization. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Development of Cardio-renal syndrome: defined as increase in serum creatinine > 0.3 mg/dl from randomization at any time point during 72 hours after randomization. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
  • Net fluid loss over study period: Assessed at 24, 48, and 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Time from randomization to discharge during index hospitalization [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Total days hospitalized for heart failure or deceased during the 60 days after randomization. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Death or rehospitalization (to include unscheduled clinic visits or ED visits) at 60 days. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure (The DOSE-AHF Study)
Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Heart Failure
  • Drug: Furosemide-Q12 hour bolus
    Q12 hours bolus
    Other Name: Loop diuretics
  • Drug: Furosemide-Continuous Infusion
    Continuous infusion
    Other Name: Loop diuretic
  • Drug: Furosemide-Low Intensification
    1x oral dose
    Other Name: Loop diuretic
  • Drug: Furosemide-High Intensification
    2.5x oral dose
    Other Name: loop diuretic
  • Experimental: Q12 hour bolus
    Furosemide-Q12 hour bolus
    Interventions:
    • Drug: Furosemide-Low Intensification
    • Drug: Furosemide-High Intensification
  • Experimental: Continuous Infusion
    Furosemide-Continuous Infusion
    Interventions:
    • Drug: Furosemide-Low Intensification
    • Drug: Furosemide-High Intensification
  • Experimental: Low Intensification
    Furosemide-Low Intensification
    Interventions:
    • Drug: Furosemide-Q12 hour bolus
    • Drug: Furosemide-Continuous Infusion
  • Experimental: High Intensification
    Furosemide-High Intensification
    Interventions:
    • Drug: Furosemide-Q12 hour bolus
    • Drug: Furosemide-Continuous Infusion

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
308
February 2010
January 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00577135
Pro00017634, U01HL084904-01, U01 HL084904-01, 523
Yes
Duke University
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Kerry L. Lee, PhD Duke Clinical Research Institute
Study Chair: Eugene Braunwald, MD Harvard University
Duke University
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP