Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter,randomized,open label trial

Background: there is insufficient evidence to support visceral leishmaniasis (vl) treatment recommendations in brazil and an urgent need to improve current treatments. drug combinations may be an option. methods: a multicenter,randomized,open label,controlled trial was conducted in five sites in brazil to evaluate efficacy and safety of (i) amphotericin b deoxycholate (amphob) (1 mg/kg/day for 14 days),(ii) liposomal amphotericin b (lamb) (3 mg/kg/day for 7 days) and (iii) a combination of lamb (10 mg/kg single dose) plus meglumine antimoniate (ma) (20 mg sb+5/kg/day for 10 days),compared to (iv) standard treatment with ma (20 mg sb+5/kg/day for 20 days). patients,aged 6 months to 50 years,with confirmed vl and without hiv infection were enrolled in the study. primary efficacy endpoint was clinical cure at 6 months. a planned efficacy and safety interim analysis led to trial interruption. results: 378 patients were randomized to the four treatment arms: ma (n = 112),amphob (n = 45),lamb (n = 109),or lamb plus ma (n = 112). a high toxicity of amphob prompted an unplanned interim safety analysis and this treatment arm was dropped. per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for ma,87.2% for lamb,and 83.9% for lamb plus ma,without statistically significant differences between the experimental arms and comparator (lamb: 9.7%; ci95% -0.28 to 19.68,p = 0.06; lamb plus ma: 6.4%; ci95% -3.93 to 16.73; p = 0.222). lamb monotherapy was safer than ma regarding frequency of treatment-related adverse events (ae) (p = 0.045),proportion of patients presenting at least one severe ae (p = 0.029),and the proportion of aes resulting in definitive treatment discontinuation (p = 0.003). conclusions: due to lower toxicity and acceptable efficacy,lamb would be a more suitable first line treatment for vl than standard treatment. clinicaltrials.gov identification number: nct01310738. trial registration: clinicaltrials.gov nct01310738. © 2017 romero et al.