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=0.01). 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 withdeferasirox 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.
RCT Entities:
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 diabeticmice 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: Maureen M Roden; Theoklis E Zaoutis; Wendy L Buchanan; Tena A Knudsen; Tatyana A Sarkisova; Robert L Schaufele; Michael Sein; Tin Sein; Christine C Chiou; Jaclyn H Chu; Dimitrios P Kontoyiannis; Thomas J Walsh Journal: Clin Infect Dis Date: 2005-07-29 Impact factor: 9.079
Authors: J R Boelaert; M de Locht; J Van Cutsem; V Kerrels; B Cantinieaux; A Verdonck; H W Van Landuyt; Y J Schneider Journal: J Clin Invest Date: 1993-05 Impact factor: 14.808
Authors: Livio Pagano; Oliver A Cornely; Alessandro Busca; Morena Caira; Simone Cesaro; Cristiana Gasbarrino; Corrado Girmenia; Werner J Heinz; Raoul Herbrecht; Cornelia Lass-Flörl; Annamaria Nosari; Leonardo Potenza; Zdenek Racil; Volker Rickerts; Donald C Sheppard; Arne Simon; Andrew J Ullmann; Caterina Giovanna Valentini; Jörg Janne Vehreschild; Anna Candoni; Maria J G T Vehreschild Journal: Haematologica Date: 2013-05-28 Impact factor: 9.941
Authors: Guanpingsheng Luo; Teclegiorgis Gebremariam; Hongkyu Lee; Samuel W French; Nathan P Wiederhold; Thomas F Patterson; Scott G Filler; Ashraf S Ibrahim Journal: Antimicrob Agents Chemother Date: 2013-05-06 Impact factor: 5.191
Authors: Joana Cortez; Bruno Costa Gomes; Andrea Speidel; Conceição Peixoto; Elina Selicka; Cristina Valente; Paulo Figueiredo; António Vieira Journal: Med Mycol Case Rep Date: 2013-03-14