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

Phase 3

Completed

Conditions: Heart Failure

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

Registration Number: NCT00577135

Lead Sponsor: Duke University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 308

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Q12 hour bolus	Furosemide-Low Intensification	Furosemide-Q12 hour bolus
Q12 hour bolus	Furosemide-High Intensification	Furosemide-Q12 hour bolus
Continuous Infusion	Furosemide-Low Intensification	Furosemide-Continuous Infusion
Continuous Infusion	Furosemide-High Intensification	Furosemide-Continuous Infusion
Low Intensification	Furosemide-Q12 hour bolus	Furosemide-Low Intensification
Low Intensification	Furosemide-Continuous Infusion	Furosemide-Low Intensification
High Intensification	Furosemide-Q12 hour bolus	Furosemide-High Intensification
High Intensification	Furosemide-Continuous Infusion	Furosemide-High Intensification

Primary Outcome Measures

Name	Time	Method
Patient Well Being, as Determined by a Visual Analog Scale	Measured at 72 hours	Global Visual Analog Scale Scale Range 0-7200; higher score is better
Change in Serum Creatinine	Measured at baseline and 72 hours

Secondary Outcome Measures

Name	Time	Method
Change in Weight	baseline and 96 hours
Proportion of Patients Free of Congestion	Measured at 72 hours
Change in Uric Acid	baseline and Day 60
Dyspnea VAS	72 hours	Dyspnea Visual Analog Scale Scale Range 0-7200; higher score is better
Change in B-type Natriuretic Peptide	baseline and 72 hours	Change in NTproBNP
Patient Well Being, as Determined by a Visual Analog Scale	48 hours	Global Visual Analog Scale Scale Range 0-4800; higher score is better
Change in NTproBNP	baseline and Day 60
Presence of Cardiorenal Syndrome	Within 72 hours
Treatment Failure	Within 72 hours	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	Through 72 hours
Dyspnea, as Determined by Visual Analog Scales	Measured at 24 hours	Global Visual Analog Scale Scale Range 0-2400; higher score is better
Change in Serum Creatinine	baseline and day 60
Change in Cystatin C	baseline and day 60

Trial Locations

Locations (9): Morehouse School of Medicine
🇺🇸
Atlanta, Georgia, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Vermont - Fletcher Allen Health Care
🇺🇸
Burlington, Vermont, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Minnesota Heart Failure Network
🇺🇸
Minneapolis, Minnesota, United States
University of Utah Health Sciences Center
🇺🇸
Murray, Utah, United States
Montreal Heart Institute
🇨🇦
Montreal, Quebec, Canada
Baylor College of Medicine
🇺🇸
Houston, Texas, United States