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

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00577135

Purpose

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.

Condition	Intervention	Phase
Heart Failure	Drug: Furosemide Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Factorial Assignment, Safety/Efficacy Study
Official Title:	Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Furosemide

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Patient well being, as determined by a visual analog scale [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Change in serum creatinine [ Time Frame: Measured at baseline and after 72 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Weight loss [ Time Frame: Measured at 24, 48, 72, and 96 hours ] [ Designated as safety issue: No ]
Proportion of patients free of congestion [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: No ]
Change in the bivariate relationship of creatinine versus weight loss [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: Yes ]
Dyspnea, as determined by visual analog scales [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
Patient global assessment, as determined by visual analog scales [ Time Frame: Measured at 24 and 48 hours ] [ Designated as safety issue: No ]
Change in serum creatinine [ Time Frame: Measured at baseline, Hours 24, 48, and 96, and Days 7 and 60 ] [ Designated as safety issue: Yes ]
Change in cystatin C [ Time Frame: Measured at baseline, 72 hours, and Days 7 and 60 ] [ Designated as safety issue: No ]
Worsening or persistent heart failure, defined as a need for rescue therapy [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Development of cardio-renal syndrome, defined as an increase in the serum creatinine level greater than 0.3 mg/dl [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: Yes ]
Net fluid loss [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
Time from study entry to discharge during index hospitalization [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
Death or total days hospitalized for heart failure [ Time Frame: Measured over the 60 days following study entry ] [ Designated as safety issue: No ]
Death or re-hospitalization [ Time Frame: Measured at Day 60 ] [ Designated as safety issue: No ]

Estimated Enrollment:	300
Study Start Date:	February 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive high dose furosemide administered via IV bolus every 12 hours and placebo via continuous IV infusion.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
2: Experimental Participants will receive high dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
3: Experimental Participants will receive low dose furosemide administered via IV bolus every 12 hours and placebo via continuous infusion.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.
4: Experimental Participants will receive low dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.	Drug: Furosemide High intensification (2.5 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion; low intensification (1 x oral dose) IV furosemide by either Q12 hours bolus or continuous infusion Drug: Placebo To maintain blinding, all participants will receive placebo (a salt solution) via the method to which they were not assigned to receive furosemide.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577135

Locations

United States, Georgia
Morehouse School of Medicine	Recruiting
Atlanta, Georgia, United States, 30310
Contact: Elizabeth Ofili, MD 404-752-1970 eofili@msm.edu
Contact: Brenda Lankford, RN, PhD 404-756-1377 blankford@msm.edu
Principal Investigator: Elizabeth Ofili, MD
Sub-Investigator: Anekwe Onwuanyi, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lynne W. Stevenson, MD 617-732-7406 lstevenson@partners.org
Contact: Jerry Cornish jcornish@partners.org
Principal Investigator: Lynne W. Stevenson, MD
Sub-Investigator: Michael Givertz, MD
Sub-Investigator: Marc Semigran, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Margaret M. Redfield, MD 507-284-1281 redfield.margaret@mayo.edu
Contact: Jilian Foxen 919-284-1281 foxen.jilian@mayo.edu
Principal Investigator: Margaret M. Redfield, MD
Sub-Investigator: John Burnett, MD
Sub-Investigator: Horng Chen, MD
Minnesota Heart Failure Network	Recruiting
Minneapolis, Minnesota, United States, 55415
Contact: Steven R. Goldsmith, MD 612-347-2875 srg_hcmc@yahoo.com
Contact: Shari Mackedanz, RN, BSN 612-347-5195 shari.mackedanz@co.hennepin.mn.us
Principal Investigator: Steven R. Goldsmith, MD
Sub-Investigator: Bradley Bart, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27705
Contact: Christopher O'Connor, MD 919-880-6787 oconn002@mc.duke.edu
Contact: Renee Story 919-681-3398 story003@mc.duke.edu
Principal Investigator: Christopher O'Conner, MD
Sub-Investigator: Michael Felker, MD, MHS
Sub-Investigator: Larry Allen, MD
Sub-Investigator: Joseph Rogers, MD
Sub-Investigator: Carmelo Milano, MD
United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Douglas Mann, MD 713-798-0285 dmann@bcm.tmc.edu
Contact: Mary Soliz 713-798-0270 msoliz@bcm.tmc.edu
Principal Investigator: Doug Mann, MD
Sub-Investigator: Anita Deswal, MD, MPH
United States, Utah
University of Utah Health Sciences Center	Recruiting
Murray, Utah, United States, 84107
Contact: David Bull, MD 801-585-3936 david.bull@hsc.utah.edu
Contact: Bev Campbell 801-408-5715 bev.campbell@intermountainmail.org
Principal Investigator: David Bull, MD
Sub-Investigator: Dean Li, MD
Sub-Investigator: Dale Renlund, MD
United States, Vermont
University of Vermont - Fletcher Allen Health Care	Recruiting
Burlington, Vermont, United States, 05401
Contact: Martin LeWinter, MD 802-847-2879 martin.lewinter@vtmednet.org
Contact: Michaelanne Rowen, RN 802-847-4746 michaelanne.rowen@vtmednet.org
Principal Investigator: Martin LeWinter, MD
Sub-Investigator: Markus Meyer, MD
Sub-Investigator: Richard Pratley, MD
Sub-Investigator: Peter VanBuren, MD
Canada, Quebec
Montreal Heart Institute	Recruiting
Montreal, Quebec, Canada, H1T - 1C8
Contact: Jean Rouleau, MD 514-343-6351 jean.rouleau@umontreal.ca
Contact: Mady Benhaim 514-376-3330 ext 3935 mady.benhaim@umontreal.ca
Principal Investigator: Jean Rouleau, MD
Sub-Investigator: Normand Racine, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Kerry L. Lee, PhD	Duke University
Study Chair:	Eugene Braunwald, MD	Harvard University

More Information

No publications provided

Responsible Party:	Duke Clinical Research Institute ( Kerry L. Lee, PhD )
Study ID Numbers:	523, U01 HL084904-01
Study First Received:	December 18, 2007
Last Updated:	February 23, 2009
ClinicalTrials.gov Identifier:	NCT00577135 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Loop Diuretics
Furosemide
Fluid Overload
Cardio Renal Failure

Additional relevant MeSH terms:

Heart Failure
Heart Diseases
Molecular Mechanisms of Pharmacological Action
Diuretics
Physiological Effects of Drugs
Cardiovascular Agents
Furosemide

Pharmacologic Actions
Membrane Transport Modulators
Natriuretic Agents
Therapeutic Uses
Cardiovascular Diseases
Sodium Potassium Chloride Symporter Inhibitors

ClinicalTrials.gov processed this record on November 05, 2009