A randomized, controlled, non-inferiority, multicenter trial of systemic versus intralesional treatment with meglumine antimoniate for cutaneous leishmaniasis in Brazil.

Abstract

Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL), despite its high toxicity. Uncontrolled studies suggest that intralesional infiltration of MA (IL-MA) may be non-inferior in efficacy and safer than systemic (S-MA). Multicenter, randomized, controlled, open-label, phase III clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared to S-MA (10 to 20 mg Sb5+/kg/day, 20 days) for CL. Primary and secondary outcomes were respectively definitive cure at day 180 and epithelialization rate at day 90 of treatment. A non-inferiority margin of 20% was used to estimate the minimum sample. A two-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AE) were monitored according to The DAIDS AE Grading. This study evaluated 135 patients. The cure rates (confidence interval 95%) of IL-MA and S-MA treatment were respectively 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP), and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were respectively 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP, and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AE in IL-MA and S-MA groups were respectively: clinical 45.6%, 80.6%; laboratory 26.5%, 73.1%; EKG 8.8%, 25.4%. Ten participants in the S-MA and one in the IL-MA group were discontinued due to severe or persistent AEs. IL-MA provides similar cure rate and results in less toxicity compared to S-MA in CL patients. IL-MA may be used as first line therapy for CL.