Efficacy and safety of low-dose pentavalent antimonial for treatment of cutaneous leishmaniasis by Leishmania (Viannia) braziliensis in Bahia, Brazil: a randomized clinical trial / Eficácia e segurança da dose baixa de antimonial pentavalente no tratamento da leishmaniose cutânea por Leishmania (Viannia) braziliensis em área endêmica da Bahia, Brasil : ensaio clínico randomizado

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

A randomized open-label clinical trial was conducted to assess the efficacy and safety of an intravenous dose of 5 mg/kg/day antimony-N-methyl-glucamine for 20 days compared with the conventional dose of 15mg/kg/day for 20 days for treatment of cutaneous leishmaniasis (CL) associated with L. (V.) braziliensis infection. This trial was registered with clinicaltrials.gov, number: NCT00317980. From January 2006 to January 2007 were enrollment 280 patients aged 7 to 50 years old, of both sexes with clinical and laboratory diagnosis of CL. The volunteers were randomly assigned to one of the two treatment groups. All patients presented with up to nine ulcerated cutaneous lesions with less than twenty weeks of disease evolution. Clinical cure was defined as complete healing of the lesions defined as complete epithelization plus absence of erythema, oedema, flaking, and regional adenitis or lymphangitis, three months after finishing the exposure to the drug. According to the per-protocol analysis (180 patients) the cure rate was 8.8% and 20.2% for the group receiving 5 mg/kg/d and 15mg/kg/d respectively, and the cure rate difference was 11.4% (upper limit of a 1-sided 95% IC = 20.3). The intention-to-treat analysis (280 patients) showed effectiveness rate of 9.3% and 18.6% for the group receiving 5 mg/ kg/d and 15mg/kg/d respectively, and the cure rate difference was 9.3% (upper limit of a 1-sided 95% IC = 16.2), confirming the findings of the per-protocol analysis. The dose of 5mg/kg/d was shown to be inferior than 15 mg/kg/d when the non-inferiority test was applied compared to the proposed a priori difference of 15%. Patients who received the 15 mg/kg/d dose experienced more adverse events compared with patients who received the low dose schedule. By the end of the second year of follow-up there were no patients diagnosed with mucosal disease. Patients who received low dose had a higher failure rate between the first 20 to 40 days of followup, 28.6% (95% CI 20.0 to 38.5) versus 7.9% (CI 95% 3.5 to 14.9) in the group receiving 15 mg/kg/d (p <0.001). Risk factors for early treatment failure identified in the final multivariate model were: exposition to the low dose schedule, to be female, to have lesions in the head and neck and the presence of intestinal parasites at the time of diagnosis of leishmaniasis. In conclusion, the incidence rate of cure of low dose was significantly lower than 15 mg/kg/d, and the number of adverse events was higher in the group receiving the standard dose.

ASSUNTO(S)

antimonial pentavalente antimony-n-methylglucamine ensaio clinico medicina leishmania braziliensis leishmaniasis cutaneous clinical trials low dose dose baixa leishmaniose cutânea leishmania braziliensis

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