A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

摘要 引言：鉴于传统一线抗利什曼病药物的毒性与给药途径限制，黏膜利什曼病（mucosal leishmaniasis, ML）的临床治疗难度较高。米替福新（miltefosine）是一款用于利什曼病治疗的口服制剂，但目前巴西地区尚无其应用于ML治疗的相关研究数据。本研究作为一项先导临床试验，旨在对比米替福新与五价锑剂（pentavalent antimonial）治疗ML的临床疗效。

方法：本研究采用随机平行分组临床试验设计。试验组给予米替福新1.3~2 mg/kg/日（两粒胶囊），疗程28天；对照组给予葡甲胺锑酸盐（meglumine antimoniate, N-MA）静脉输注，以五价锑（SbV）计剂量为20 mg/kg/日，疗程30天。本研究设置双重疗效终点：最终终点为治疗4年后病灶完全愈合；早期终点为治疗后90天时的病灶愈合情况。

结果：本研究共纳入40例患者，两组各20例。经意向治疗分析（intention-to-treat analysis）结合多变量模型测算，治疗后90天时，米替福新组患者的治愈概率较N-MA组高2.08倍（95%置信区间（confidence interval, CI）=1.03~4.18）。在最终终点的分析中，两组患者的治愈概率无显著统计学差异（相对风险（relative risk）=0.66；95%CI=0.33~1.32）。不良反应方面，两组间差异主要集中于胃肠道反应，该类不良反应在米替福新组中发生率更高。

结论：米替福新具备口服给药的便捷性优势，且长期随访结果显示其临床治愈率可观，有望成为ML治疗的潜在替代方案。