The deferasirox-AmBisome therapy for mucormycosis (Defeat Mucor) study: A randomized, double-blinded, placebo-controlled trial

Brad Spellberg, Ashraf S. Ibrahim, Peter V. Chin-Hong, Dimitrios P. Kontoyiannis, Michele I. Morris, John R. Perfect, David Fredricks, Eric P. Brass

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

Objectives: 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=0.1). 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.

Original languageEnglish (US)
Article numberdkr375
Pages (from-to)715-722
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • Antifungal
  • Combination therapy
  • Fungal infections
  • Mould infections

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'The deferasirox-AmBisome therapy for mucormycosis (Defeat Mucor) study: A randomized, double-blinded, placebo-controlled trial'. Together they form a unique fingerprint.

  • Cite this

    Spellberg, B., Ibrahim, A. S., Chin-Hong, P. V., Kontoyiannis, D. P., Morris, M. I., Perfect, J. R., Fredricks, D., & Brass, E. P. (2012). The deferasirox-AmBisome therapy for mucormycosis (Defeat Mucor) study: A randomized, double-blinded, placebo-controlled trial. Journal of Antimicrobial Chemotherapy, 67(3), 715-722. [dkr375]. https://doi.org/10.1093/jac/dkr375