Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure (The DOSE-AHF Study)
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| ClinicalTrials.gov Identifier: NCT00577135 |
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Recruitment Status :
Completed
First Posted : December 19, 2007
Results First Posted : May 27, 2013
Last Update Posted : March 6, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Heart Failure | Drug: Furosemide-Q12 hour bolus Drug: Furosemide-Continuous Infusion Drug: Furosemide-Low Intensification Drug: Furosemide-High Intensification | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 308 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study) |
| Study Start Date : | February 2008 |
| Actual Primary Completion Date : | January 2010 |
| Actual Study Completion Date : | February 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Q12 hour bolus
Furosemide-Q12 hour bolus
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Drug: Furosemide-Low Intensification
1x oral dose
Other Name: Loop diuretic Drug: Furosemide-High Intensification 2.5x oral dose
Other Name: loop diuretic |
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Experimental: Continuous Infusion
Furosemide-Continuous Infusion
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Drug: Furosemide-Low Intensification
1x oral dose
Other Name: Loop diuretic Drug: Furosemide-High Intensification 2.5x oral dose
Other Name: loop diuretic |
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Experimental: Low Intensification
Furosemide-Low Intensification
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Drug: Furosemide-Q12 hour bolus
Q12 hours bolus
Other Name: Loop diuretics Drug: Furosemide-Continuous Infusion Continuous infusion
Other Name: Loop diuretic |
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Experimental: High Intensification
Furosemide-High Intensification
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Drug: Furosemide-Q12 hour bolus
Q12 hours bolus
Other Name: Loop diuretics Drug: Furosemide-Continuous Infusion Continuous infusion
Other Name: Loop diuretic |
- 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 ]
- Change in Weight [ Time Frame: baseline and 96 hours ]
- Proportion of Patients Free of Congestion [ Time Frame: Measured at 72 hours ]
- Dyspnea, as Determined by Visual Analog Scales [ Time Frame: Measured at 24 hours ]Global Visual Analog Scale Scale Range 0-2400; higher score is better
- Change in Serum Creatinine [ Time Frame: baseline and 24 hours ]
- Change in Cystatin C [ Time Frame: baseline and 72 hours ]
- Change in Serum Creatinine [ Time Frame: baseline and 48 hours ]
- Change in Serum Creatinine [ Time Frame: baseline and 96 hours ]
- Change in Serum Creatinine [ Time Frame: baseline and day 7 ]
- Change in Serum Creatinine [ Time Frame: baseline and day 60 ]
- Patient Well Being, as Determined by a Visual Analog Scale [ Time Frame: Measured at 24 hours ]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 ]Global Visual Analog Scale Scale Range 0-4800; higher score is better
- Dyspnea VAS [ Time Frame: 48 hours ]Dyspnea Visual Analog Scale Scale Range 0-4800; higher score is better
- Dyspnea VAS [ Time Frame: 72 hours ]Dyspnea Visual Analog Scale Scale Range 0-7200; higher score is better
- Change in Cystatin C [ Time Frame: baseline and day 7 ]
- Change in Cystatin C [ Time Frame: baseline and day 60 ]
- Change in Uric Acid [ Time Frame: baseline and 72 hours ]
- Change in Uric Acid [ Time Frame: baseline and day 7 ]
- Change in Uric Acid [ Time Frame: baseline and Day 60 ]
- Change in B-type Natriuretic Peptide [ Time Frame: baseline and 72 hours ]Change in NTproBNP
- Change in NTproBNP [ Time Frame: baseline and Day 7 ]
- Change in NTproBNP [ Time Frame: baseline and Day 60 ]
- Presence of Cardiorenal Syndrome [ Time Frame: Within 72 hours ]
- Treatment Failure [ Time Frame: 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 [ Time Frame: Through 24 hours ]
- Net Fluid Loss [ Time Frame: Through 48 hours ]
- Net Fluid Loss [ Time Frame: Through 72 hours ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00577135
| 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 | |
| Principal Investigator: | Kerry L. Lee, PhD | Duke Clinical Research Institute | |
| Study Chair: | Eugene Braunwald, MD | Harvard University |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00577135 |
| Other Study ID Numbers: |
Pro00017634 U01HL084904-01 ( U.S. NIH Grant/Contract ) |
| First Posted: | December 19, 2007 Key Record Dates |
| Results First Posted: | May 27, 2013 |
| Last Update Posted: | March 6, 2018 |
| Last Verified: | April 2013 |
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Loop Diuretics Furosemide Fluid Overload Cardio Renal Failure |
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Heart Failure Heart Diseases Cardiovascular Diseases Furosemide Diuretics |
Sodium Potassium Chloride Symporter Inhibitors Natriuretic Agents Physiological Effects of Drugs Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |