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

NCT00577135 | Completed Phase 3 Results DMC

• 2 other identifiers: Pro00017634U01HL084904-01
• Study Type: interventional
• Target: 308
• Locations: 2 countries
• Sites: 9

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.

Conditions

Heart Failure

Keywords

Loop Diuretics; Furosemide; Fluid Overload; Cardio Renal Failure

Outcome Measures

Primary Outcomes (2)

• Patient Well Being, as Determined by a Visual Analog Scale

  Global Visual Analog Scale Scale Range 0-7200; higher score is better

  Measured at 72 hours

• Change in Serum Creatinine

  Measured at baseline and 72 hours

Secondary Outcomes (26)

• Change in Weight

  baseline and 96 hours

• Proportion of Patients Free of Congestion

  Measured at 72 hours

• Dyspnea, as Determined by Visual Analog Scales

  Measured at 24 hours

• Change in Serum Creatinine

  baseline and 24 hours

• Change in Cystatin C

  baseline and 72 hours

Study Arms (4)

Q12 hour bolus

EXPERIMENTAL

Furosemide-Q12 hour bolus

Drug: Furosemide-Low Intensification; Drug: Furosemide-High Intensification

Continuous Infusion

EXPERIMENTAL

Furosemide-Continuous Infusion

Drug: Furosemide-Low Intensification; Drug: Furosemide-High Intensification

Low Intensification

EXPERIMENTAL

Furosemide-Low Intensification

Drug: Furosemide-Q12 hour bolus; Drug: Furosemide-Continuous Infusion

High Intensification

EXPERIMENTAL

Furosemide-High Intensification

Drug: Furosemide-Q12 hour bolus; Drug: Furosemide-Continuous Infusion

Interventions

Furosemide-Q12 hour bolus DRUG

Q12 hours bolus

Also known as: Loop diuretics

High Intensification; Low Intensification

Furosemide-Continuous Infusion DRUG

Continuous infusion

Also known as: Loop diuretic

High Intensification; Low Intensification

Furosemide-Low Intensification DRUG

1x oral dose

Also known as: Loop diuretic

Continuous Infusion; Q12 hour bolus

Furosemide-High Intensification DRUG

2.5x oral dose

Also known as: loop diuretic

Continuous Infusion; Q12 hour bolus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (9)

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Minnesota Heart Failure Network

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Murray, Utah, 84107, United States

Location

University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Montreal Heart Institute

Montreal, Quebec, H1T - 1C8, Canada

Location

Related Publications (8)

• 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.

  PMID: 21366472 RESULT

• 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.

  PMID: 38775253 DERIVED

• 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.

  PMID: 27514750 DERIVED

• de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dube MP. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. Pharmacogenomics J. 2017 Mar;17(2):192-200. doi: 10.1038/tpj.2016.4. Epub 2016 Mar 1.

  PMID: 26927285 DERIVED

• 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.

  PMID: 26041600 DERIVED

• 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.

  PMID: 25543972 DERIVED

• 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.

  PMID: 23250981 DERIVED

• 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.

  PMID: 23194486 DERIVED

MeSH Terms

Conditions

Heart Failure; Edema

Interventions

Sodium Potassium Chloride Symporter Inhibitors

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs

Results Point of Contact

• Title: Jeff Sharp
• Organization: Duke University

jeff.sharp@dm.duke.edu

919.668.7086

Study Officials

• Kerry L. Lee, PhD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

• Eugene Braunwald, MD

  Harvard University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: December 19, 2007
• Study Start: February 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: February 1, 2010
• Last Updated: March 6, 2018
• Results First Posted: May 27, 2013

Record last verified: 2013-04

Locations

US (8); CA (1)