title: The Deferasirox-AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial.
abstract: OBJECTIVE
  Host iron availability is fundamental to mucormycosis pathogenesis. The combination of liposomal amphotericin B (LAmB) and deferasirox iron chelation therapy synergistically improved survival in diabetic mice with mucormycosis. To determine the safety of combination deferasirox plus LAmB therapy for mucormycosis, a multicentred, placebo-controlled, double-blinded clinical trial was conducted.
  
  
  METHODS
  Twenty patients with proven or probable mucormycosis were randomized to receive treatment with LAmB plus deferasirox (20 mg/kg/day for 14 days) or LAmB plus placebo (NCT00419770, clinicaltrials.gov). The primary analyses were for safety and exploratory efficacy.
  
  
  RESULTS
  Patients in the deferasirox arm (n=11) were more likely than those in the placebo arm (n=9) to have active malignancy, neutropenia and corticosteroid therapy, and were less likely to receive concurrent non-study antifungal therapy. Reported adverse events and serious adverse events were similar between the groups. However, death was more frequent in the deferasirox than in the placebo arm at 30 days (45% versus 11%, P=0.1) and 90 days (82% versus 22%, P=0.01). Global success (alive, clinically stable, radiographically improved) for the deferasirox arm versus the placebo arm at 30 and 90 days, respectively, was 18% (2/11) versus 67% (6/9) (P=0.06) and 18% (2/11) versus 56% (5/9) (P=0.2).
  
  
  CONCLUSIONS
  Patients with mucormycosis treated with deferasirox had a higher mortality rate at 90 days. Population imbalances in this small Phase II study make generalizable conclusions difficult. Nevertheless, these data do not support a role for initial, adjunctive deferasirox therapy for mucormycosis.
authors.affiliation: Division of General Internal Medicine, Los Angeles Biomedical Research Institute, Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA. bspellberg@labiomed.org
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Peter V
authors.initials: PV
authors.lastname: Chin-Hong
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Michele I
authors.initials: MI
authors.lastname: Morris
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: David
authors.initials: D
authors.lastname: Fredricks
authors.forename: Eric P
authors.initials: EP
authors.lastname: Brass
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D000077588:Deferasirox; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009091:Mucormycosis / Q000188:drug therapy* / Q000401:mortality; D010919:Placebos / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000935:Antifungal Agents; D001565:Benzoates; D007502:Iron Chelating Agents; D010919:Placebos; D014230:Triazoles; C068538:liposomal amphotericin B; D000666:Amphotericin B; D000077588:Deferasirox