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

Duke University

Status and phase: Completed; Phase 3

Conditions: Heart Failure

Treatments: Drug: Furosemide-Q12 hour bolus; Drug: Furosemide-High Intensification; Drug: Furosemide-Continuous Infusion; Drug: Furosemide-Low Intensification

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00577135

U01HL084904-01 (U.S. NIH Grant/Contract)

Pro00017634

Details and patient eligibility

About

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.

Full 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.

Enrollment: 308 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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308 participants in 4 patient groups

Q12 hour bolus

Experimental group

Description:

Furosemide-Q12 hour bolus

Treatment:

Drug: Furosemide-Low Intensification

Drug: Furosemide-High Intensification

Continuous Infusion

Experimental group

Description:

Furosemide-Continuous Infusion

Treatment:

Drug: Furosemide-Low Intensification

Drug: Furosemide-High Intensification

Low Intensification

Experimental group

Description:

Furosemide-Low Intensification

Treatment:

Drug: Furosemide-Continuous Infusion

Drug: Furosemide-Q12 hour bolus

High Intensification

Experimental group

Description:

Furosemide-High Intensification

Treatment:

Drug: Furosemide-Continuous Infusion

Drug: Furosemide-Q12 hour bolus