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

Condition(s) targeted: Heart Failure

Intervention: Furosemide (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

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

Official(s) and/or principal investigator(s):
Kerry L. Lee, PhD, Principal Investigator, Affiliation: Duke University
Eugene Braunwald, MD, Study Chair, Affiliation: Harvard University

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.

Official title: Diuretic Optimal Strategy Evaluation in Acute Heart Failure (The DOSE-AHF Study)

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Factorial Assignment, Safety/Efficacy Study

Primary outcome:

Patient well being, as determined by a visual analog scale

Change in serum creatinine

Secondary outcome:

Weight loss

Proportion of patients free of congestion

Change in the bivariate relationship of creatinine versus weight loss

Dyspnea, as determined by visual analog scales

Patient global assessment, as determined by visual analog scales

Change in serum creatinine

Change in cystatin C

Worsening or persistent heart failure, defined as a need for rescue therapy

Development of cardio-renal syndrome, defined as an increase in the serum creatinine level greater than 0.3 mg/dl

Net fluid loss

Time from study entry to discharge during index hospitalization

Death or total days hospitalized for heart failure

Death or re-hospitalization

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Morehouse School of Medicine, Atlanta, Georgia 30310, United States; Recruiting
Elizabeth Ofili, MD, Phone: 404-752-1970, Email: eofili@msm.edu
Brenda Lankford, RN, PhD, Phone: 404-756-1377, Email: blankford@msm.edu
Elizabeth Ofili, MD, Principal Investigator
Anekwe Onwuanyi, MD, Sub-Investigator

Brigham and Women's Hospital, Boston, Massachusetts 02115, United States; Recruiting
Lynne W. Stevenson, MD, Phone: 617-732-7406, Email: lstevenson@partners.org
Jerry Cornish, Email: jcornish@partners.org
Lynne W. Stevenson, MD, Principal Investigator
Michael Givertz, MD, Sub-Investigator
Marc Semigran, MD, Sub-Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Margaret M. Redfield, MD, Phone: 507-284-1281, Email: redfield.margaret@mayo.edu
Jilian Foxen, Phone: 919-284-1281, Email: foxen.jilian@mayo.edu
Margaret M. Redfield, MD, Principal Investigator
John Burnett, MD, Sub-Investigator
Horng Chen, MD, Sub-Investigator

Minnesota Heart Failure Network, Minneapolis, Minnesota 55415, United States; Recruiting
Steven R. Goldsmith, MD, Phone: 612-347-2875, Email: srg_hcmc@yahoo.com
Shari Mackedanz, RN, BSN, Phone: 612-347-5195, Email: shari.mackedanz@co.hennepin.mn.us
Steven R. Goldsmith, MD, Principal Investigator
Bradley Bart, MD, Sub-Investigator

Duke University Medical Center, Durham, North Carolina 27705, United States; Recruiting
Christopher O'Connor, MD, Phone: 919-880-6787, Email: oconn002@mc.duke.edu
Renee Story, Phone: 919-681-3398, Email: story003@mc.duke.edu
Christopher O'Conner, MD, Principal Investigator
Michael Felker, MD, MHS, Sub-Investigator
Larry Allen, MD, Sub-Investigator
Joseph Rogers, MD, Sub-Investigator
Carmelo Milano, MD, Sub-Investigator

Montreal Heart Institute, Montreal, Quebec H1T - 1C8, Canada; Recruiting
Jean Rouleau, MD, Phone: 514-343-6351, Email: jean.rouleau@umontreal.ca
Mady Benhaim, Phone: 514-376-3330, Ext: 3935, Email: mady.benhaim@umontreal.ca
Jean Rouleau, MD, Principal Investigator
Normand Racine, MD, Sub-Investigator

Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Douglas Mann, MD, Phone: 713-798-0285, Email: dmann@bcm.tmc.edu
Mary Soliz, Phone: 713-798-0270, Email: msoliz@bcm.tmc.edu
Doug Mann, MD, Principal Investigator
Anita Deswal, MD, MPH, Sub-Investigator

University of Utah Health Sciences Center, Murray, Utah 84107, United States; Recruiting
David Bull, MD, Phone: 801-585-3936, Email: david.bull@hsc.utah.edu
Bev Campbell, Phone: 801-408-5715, Email: bev.campbell@intermountainmail.org
David Bull, MD, Principal Investigator
Dean Li, MD, Sub-Investigator
Dale Renlund, MD, Sub-Investigator

University of Vermont - Fletcher Allen Health Care, Burlington, Vermont 05401, United States; Recruiting
Martin LeWinter, MD, Phone: 802-847-2879, Email: martin.lewinter@vtmednet.org
Michaelanne Rowen, RN, Phone: 802-847-4746, Email: michaelanne.rowen@vtmednet.org
Martin LeWinter, MD, Principal Investigator
Markus Meyer, MD, Sub-Investigator
Richard Pratley, MD, Sub-Investigator
Peter VanBuren, MD, Sub-Investigator

Starting date: February 2008
Ending date: December 2009
Last updated: February 23, 2009