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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Furosemide-Q12 hour bolus
Furosemide-Continuous Infusion
Furosemide-Low Intensification
Furosemide-High Intensification
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Loop Diuretics, Furosemide, Fluid Overload, Cardio Renal Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Morehouse School of Medicine
  • Brigham and Women's Hospital
  • Minnesota Heart Failure Network
  • Mayo Clinic
  • Duke University Medical Center
  • Baylor College of Medicine
  • University of Utah Health Sciences Center
  • University of Vermont - Fletcher Allen Health Care
  • Montreal Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Q12 hour bolus

Continuous Infusion

Low Intensification

High Intensification

Arm Description

Furosemide-Q12 hour bolus

Furosemide-Continuous Infusion

Furosemide-Low Intensification

Furosemide-High Intensification

Outcomes

Primary Outcome Measures

Patient Well Being, as Determined by a Visual Analog Scale
Global Visual Analog Scale Scale Range 0-7200; higher score is better
Change in Serum Creatinine

Secondary Outcome Measures

Change in Weight
Proportion of Patients Free of Congestion
Dyspnea, as Determined by Visual Analog Scales
Global Visual Analog Scale Scale Range 0-2400; higher score is better
Change in Serum Creatinine
Change in Cystatin C
Change in Serum Creatinine
Change in Serum Creatinine
Change in Serum Creatinine
Change in Serum Creatinine
Patient Well Being, as Determined by a Visual Analog Scale
Global Visual Analog Scale Scale Range 0-2400; higher score is better
Patient Well Being, as Determined by a Visual Analog Scale
Global Visual Analog Scale Scale Range 0-4800; higher score is better
Dyspnea VAS
Dyspnea Visual Analog Scale Scale Range 0-4800; higher score is better
Dyspnea VAS
Dyspnea Visual Analog Scale Scale Range 0-7200; higher score is better
Change in Cystatin C
Change in Cystatin C
Change in Uric Acid
Change in Uric Acid
Change in Uric Acid
Change in B-type Natriuretic Peptide
Change in NTproBNP
Change in NTproBNP
Change in NTproBNP
Presence of Cardiorenal Syndrome
Treatment Failure
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
Net Fluid Loss
Net Fluid Loss

Full Information

First Posted
December 18, 2007
Last Updated
February 5, 2018
Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00577135
Brief Title
Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure (The DOSE-AHF Study)
Official Title
Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Loop Diuretics, Furosemide, Fluid Overload, Cardio Renal Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
308 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Q12 hour bolus
Arm Type
Experimental
Arm Description
Furosemide-Q12 hour bolus
Arm Title
Continuous Infusion
Arm Type
Experimental
Arm Description
Furosemide-Continuous Infusion
Arm Title
Low Intensification
Arm Type
Experimental
Arm Description
Furosemide-Low Intensification
Arm Title
High Intensification
Arm Type
Experimental
Arm Description
Furosemide-High Intensification
Intervention Type
Drug
Intervention Name(s)
Furosemide-Q12 hour bolus
Other Intervention Name(s)
Loop diuretics
Intervention Description
Q12 hours bolus
Intervention Type
Drug
Intervention Name(s)
Furosemide-Continuous Infusion
Other Intervention Name(s)
Loop diuretic
Intervention Description
Continuous infusion
Intervention Type
Drug
Intervention Name(s)
Furosemide-Low Intensification
Other Intervention Name(s)
Loop diuretic
Intervention Description
1x oral dose
Intervention Type
Drug
Intervention Name(s)
Furosemide-High Intensification
Other Intervention Name(s)
loop diuretic
Intervention Description
2.5x oral dose
Primary Outcome Measure Information:
Title
Patient Well Being, as Determined by a Visual Analog Scale
Description
Global Visual Analog Scale Scale Range 0-7200; higher score is better
Time Frame
Measured at 72 hours
Title
Change in Serum Creatinine
Time Frame
Measured at baseline and 72 hours
Secondary Outcome Measure Information:
Title
Change in Weight
Time Frame
baseline and 96 hours
Title
Proportion of Patients Free of Congestion
Time Frame
Measured at 72 hours
Title
Dyspnea, as Determined by Visual Analog Scales
Description
Global Visual Analog Scale Scale Range 0-2400; higher score is better
Time Frame
Measured at 24 hours
Title
Change in Serum Creatinine
Time Frame
baseline and 24 hours
Title
Change in Cystatin C
Time Frame
baseline and 72 hours
Title
Change in Serum Creatinine
Time Frame
baseline and 48 hours
Title
Change in Serum Creatinine
Time Frame
baseline and 96 hours
Title
Change in Serum Creatinine
Time Frame
baseline and day 7
Title
Change in Serum Creatinine
Time Frame
baseline and day 60
Title
Patient Well Being, as Determined by a Visual Analog Scale
Description
Global Visual Analog Scale Scale Range 0-2400; higher score is better
Time Frame
Measured at 24 hours
Title
Patient Well Being, as Determined by a Visual Analog Scale
Description
Global Visual Analog Scale Scale Range 0-4800; higher score is better
Time Frame
48 hours
Title
Dyspnea VAS
Description
Dyspnea Visual Analog Scale Scale Range 0-4800; higher score is better
Time Frame
48 hours
Title
Dyspnea VAS
Description
Dyspnea Visual Analog Scale Scale Range 0-7200; higher score is better
Time Frame
72 hours
Title
Change in Cystatin C
Time Frame
baseline and day 7
Title
Change in Cystatin C
Time Frame
baseline and day 60
Title
Change in Uric Acid
Time Frame
baseline and 72 hours
Title
Change in Uric Acid
Time Frame
baseline and day 7
Title
Change in Uric Acid
Time Frame
baseline and Day 60
Title
Change in B-type Natriuretic Peptide
Description
Change in NTproBNP
Time Frame
baseline and 72 hours
Title
Change in NTproBNP
Time Frame
baseline and Day 7
Title
Change in NTproBNP
Time Frame
baseline and Day 60
Title
Presence of Cardiorenal Syndrome
Time Frame
Within 72 hours
Title
Treatment Failure
Description
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
Time Frame
Within 72 hours
Title
Net Fluid Loss
Time Frame
Through 24 hours
Title
Net Fluid Loss
Time Frame
Through 48 hours
Title
Net Fluid Loss
Time Frame
Through 72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kerry L. Lee, PhD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eugene Braunwald, MD
Organizational Affiliation
Harvard University
Official's Role
Study Chair
Facility Information:
Facility Name
Morehouse School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30310
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Minnesota Heart Failure Network
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health Sciences Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Vermont - Fletcher Allen Health Care
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T - 1C8
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
21366472
Citation
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.
Results Reference
result
PubMed Identifier
27514750
Citation
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.
Results Reference
derived
PubMed Identifier
26927285
Citation
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.
Results Reference
derived
PubMed Identifier
26041600
Citation
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.
Results Reference
derived
PubMed Identifier
25543972
Citation
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.
Results Reference
derived
PubMed Identifier
23250981
Citation
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.
Results Reference
derived
PubMed Identifier
23194486
Citation
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.
Results Reference
derived

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

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