title: Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.
abstract: BACKGROUND
  In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events.
  
  
  METHODS
  The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients.
  
  
  CONCLUSIONS
  The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure.
authors.affiliation: Advocate Heart Institute, Naperville, IL. Electronic address: mariarosa.Costanzo@advocatehealth.com.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Costanzo
authors.affiliation: Division of Nephrology, University of Pennsylvania Medical Center, Philadelphia, PA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Negoianu
authors.affiliation: Division of Cardiology, University of California at Los Angeles, Los Angeles, CA.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: San Diego Cardiac Center, Sharp Memorial Hospital, San Diego, CA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Jaski
authors.affiliation: Division of Cardiology, Department of Medicine, Hennepin County Medical Center, Minneapolis MN.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Bart
authors.affiliation: Heart Failure Recovery & Research Program, Scripps Clinic, San Diego, CA.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Heywood
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Nabut
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schollmeyer
mesh_terms: D000368:Aged; D004232:Diuretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D004232:Diuretics