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

NCT ID: NCT00577135

Last Updated: 2018-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 308 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-02-28

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Q12 hour bolus

Furosemide-Q12 hour bolus

Group Type: EXPERIMENTAL

Furosemide-Low Intensification

Intervention Type: DRUG

1x oral dose

Furosemide-High Intensification

Intervention Type: DRUG

2.5x oral dose

Continuous Infusion

Furosemide-Continuous Infusion

Group Type: EXPERIMENTAL

Furosemide-Low Intensification

Intervention Type: DRUG

1x oral dose

Furosemide-High Intensification

Intervention Type: DRUG

2.5x oral dose

Low Intensification

Furosemide-Low Intensification

Group Type: EXPERIMENTAL

Furosemide-Q12 hour bolus

Intervention Type: DRUG

Q12 hours bolus

Furosemide-Continuous Infusion

Intervention Type: DRUG

Continuous infusion

High Intensification

Furosemide-High Intensification

Group Type: EXPERIMENTAL

Furosemide-Q12 hour bolus

Intervention Type: DRUG

Q12 hours bolus

Furosemide-Continuous Infusion

Intervention Type: DRUG

Continuous infusion

Interventions

Furosemide-Q12 hour bolus

Q12 hours bolus

Intervention Type: DRUG

Furosemide-Continuous Infusion

Continuous infusion

Intervention Type: DRUG

Furosemide-Low Intensification

1x oral dose

Intervention Type: DRUG

Furosemide-High Intensification

2.5x oral dose

Intervention Type: DRUG

Other Intervention Names

Loop diuretics; Loop diuretic; Loop diuretic; loop diuretic

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kerry L. Lee, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Eugene Braunwald, MD

Role: STUDY_CHAIR

Harvard University

Locations

Morehouse School of Medicine

Atlanta, Georgia, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Minnesota Heart Failure Network

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University Medical Center

Durham, North Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Health Sciences Center

Murray, Utah, United States

University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, United States

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

United States; Canada

References

Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.

Reference Type: RESULT

PMID: 21366472 (View on PubMed)

Rasoul D, Zhang J, Farnell E, Tsangarides AA, Chong SC, Fernando R, Zhou C, Ihsan M, Ahmed S, Lwin TS, Bateman J, Hill RA, Lip GY, Sankaranarayanan R. Continuous infusion versus bolus injection of loop diuretics for acute heart failure. Cochrane Database Syst Rev. 2024 May 22;5(5):CD014811. doi: 10.1002/14651858.CD014811.pub2.

Reference Type: DERIVED

PMID: 38775253 (View on PubMed)

Kelly JP, Cooper LB, Gallup D, Anstrom KJ, Chen HH, Redfield MM, O'Connor CM, Mentz RJ, Hernanadez AF, Felker GM. Implications of Using Different Definitions on Outcomes in Worsening Heart Failure. Circ Heart Fail. 2016 Aug;9(8):e003048. doi: 10.1161/CIRCHEARTFAILURE.116.003048.

Reference Type: DERIVED

PMID: 27514750 (View on PubMed)

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Reference Type: DERIVED

PMID: 26927285 (View on PubMed)

Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW. Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF). Circ Heart Fail. 2015 Jul;8(4):741-8. doi: 10.1161/CIRCHEARTFAILURE.114.001957. Epub 2015 Jun 3.

Reference Type: DERIVED

PMID: 26041600 (View on PubMed)

Mentz RJ, Stevens SR, DeVore AD, Lala A, Vader JM, AbouEzzeddine OF, Khazanie P, Redfield MM, Stevenson LW, O'Connor CM, Goldsmith SR, Bart BA, Anstrom KJ, Hernandez AF, Braunwald E, Felker GM. Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure. JACC Heart Fail. 2015 Feb;3(2):97-107. doi: 10.1016/j.jchf.2014.09.003. Epub 2014 Oct 31.

Reference Type: DERIVED

PMID: 25543972 (View on PubMed)

Kociol RD, McNulty SE, Hernandez AF, Lee KL, Redfield MM, Tracy RP, Braunwald E, O'Connor CM, Felker GM; NHLBI Heart Failure Network Steering Committee and Investigators. Markers of decongestion, dyspnea relief, and clinical outcomes among patients hospitalized with acute heart failure. Circ Heart Fail. 2013 Mar;6(2):240-5. doi: 10.1161/CIRCHEARTFAILURE.112.969246. Epub 2012 Dec 18.

Reference Type: DERIVED

PMID: 23250981 (View on PubMed)

Shah RV, McNulty S, O'Connor CM, Felker GM, Braunwald E, Givertz MM. Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heart failure: an analysis from diuretic optimization strategies in acute heart failure. Am Heart J. 2012 Dec;164(6):862-8. doi: 10.1016/j.ahj.2012.08.019. Epub 2012 Oct 29.

Reference Type: DERIVED

PMID: 23194486 (View on PubMed)

Other Identifiers

U01HL084904-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00017634

Identifier Type: -

Identifier Source: org_study_id