Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)
Overview
- Phase
- Phase 3
- Intervention
- Furosemide-Low Intensification
- Conditions
- Heart Failure
- Sponsor
- Duke University
- Enrollment
- 308
- Locations
- 9
- Primary Endpoint
- Patient Well Being, as Determined by a Visual Analog Scale
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility 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
Arms & Interventions
Q12 hour bolus
Furosemide-Q12 hour bolus
Intervention: Furosemide-Low Intensification
Q12 hour bolus
Furosemide-Q12 hour bolus
Intervention: Furosemide-High Intensification
Continuous Infusion
Furosemide-Continuous Infusion
Intervention: Furosemide-Low Intensification
Continuous Infusion
Furosemide-Continuous Infusion
Intervention: Furosemide-High Intensification
Low Intensification
Furosemide-Low Intensification
Intervention: Furosemide-Q12 hour bolus
Low Intensification
Furosemide-Low Intensification
Intervention: Furosemide-Continuous Infusion
High Intensification
Furosemide-High Intensification
Intervention: Furosemide-Q12 hour bolus
High Intensification
Furosemide-High Intensification
Intervention: Furosemide-Continuous Infusion
Outcomes
Primary Outcomes
Patient Well Being, as Determined by a Visual Analog Scale
Time Frame: Measured at 72 hours
Global Visual Analog Scale Scale Range 0-7200; higher score is better
Change in Serum Creatinine
Time Frame: Measured at baseline and 72 hours
Secondary Outcomes
- 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, as Determined by Visual Analog Scales(Measured at 24 hours)
- Change in Serum Creatinine(baseline and day 60)
- Change in Cystatin C(baseline and day 60)
- Patient Well Being, as Determined by a Visual Analog Scale(48 hours)
- Dyspnea VAS(72 hours)
- Change in B-type Natriuretic Peptide(baseline and 72 hours)
- Change in NTproBNP(baseline and Day 60)
- Presence of Cardiorenal Syndrome(Within 72 hours)
- Treatment Failure(Within 72 hours)
- Net Fluid Loss(Through 72 hours)