Results of a double-blind, placebo-controlled trial in patients with culture-confirmed invasive candidiasis, treated with a human recombinant antibody to hsp90 and liposomal amphotericin B

Abstract number: 1133_205

Matthews R.C.

Objectives:  

To determine whether combination therapy with a human recombinant antibody to hsp90 (Mycograb) plus a lipid preparation of amphotericin B was superior to monotherapy with liposomal amphotericin B.

Methods:  

This was a prospective, double-blind, randomised, comparative study of the efficacy and safety of a 5 day course of Mycograb (1 mg/kg iv) plus liposomal amphotericin B versus placebo (saline iv) plus liposomal amphotericin B in adult hospitalised patients with culture-confirmed deep-seated candidiasis. Patients were stratified on the basis of their germ tube test result. Efficacy was assessed on the basis of clinical and mycological response at Day 10, Candida-attributable mortality (28 days after last dose of study drug) and speed of culture-confirmed resolution of the infection. The primary efficacy variable was overall response at Day 10 i.e. clinical and mycological resolution of the infection. There were 137 patients in the modified ITT population, recruited from 10 European countries and 2 US Centres.

Results:  

A complete overall response was obtained in 48% (29/61) of the placebo group compared to 84% (47/56) of the Mycograb-treated group (p < 0.001). The following secondary efficacy criteria were also met: clinical response (52% versus 86%, p < 0.001), mycological response (54% versus 89%, p < 0.001), Candida-attributable mortality (18% versus 4%, P < 0.025), and rate of culture-confirmed clearance of the infection, being over twice as fast in the Mycograb-treated group (P 0.001). Mycograb was well-tolerated.

Conclusion:  

Combining Mycograb with amphotericin B produced a highly statistically significant improvement in outcome in patients with culture-confirmed invasive candidiasis, mirroring the synergy observed between these two drugs in pre-clinical studies. This is the first time a double blind, placebo controlled trial has shown synergy between two antifungals in the treatment of invasive candidiasis.