Romero Gustavo Adolfo Sierra, Costa Dorcas Lamounier, Costa Carlos Henrique Nery, de Almeida Roque Pacheco, de Melo Enaldo Viera, de Carvalho Sílvio Fernando Guimarães, Rabello Ana, de Carvalho Andréa Lucchesi, Sousa Anastácio de Queiroz, Leite Robério Dias, Lima Simone Soares, Amaral Thais Alves, Alves Fabiana Piovesan, Rode Joelle
Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, Distrito Federal, Brasil.
Universidade Federal do Piauí, Hospital de Doenças Tropicais Natan Portela, Teresina, Piauí, Brasil.
PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005706. doi: 10.1371/journal.pntd.0005706. eCollection 2017 Jun.
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.
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.
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).
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.
ClinicalTrials.gov NCT01310738.
在巴西，支持内脏利什曼病（VL）治疗建议的证据不足，迫切需要改进当前的治疗方法。联合用药可能是一种选择。
在巴西的五个地点进行了一项多中心、随机、开放标签、对照试验，以评估以下治疗方法的疗效和安全性：（i）两性霉素B去氧胆酸盐（AmphoB）（1mg/kg/天，共14天），（ii）脂质体两性霉素B（LAMB）（3mg/kg/天，共7天），以及（iii）LAMB（10mg/kg单剂量）加葡甲胺锑酸盐（MA）（20mg Sb⁺⁵/kg/天，共10天）的联合用药，与（iv）MA标准治疗（20mg Sb⁺⁵/kg/天，共20天）进行比较。年龄在6个月至50岁之间、确诊为VL且未感染HIV的患者被纳入该研究。主要疗效终点是6个月时的临床治愈。一项计划中的疗效和安全性中期分析导致试验中断。
378名患者被随机分配到四个治疗组：MA组（n = 112）、AmphoB组（n = 45）、LAMB组（n = 109）或LAMB加MA组（n = 112）。AmphoB的高毒性促使进行了一次非计划的中期安全性分析，该治疗组被排除。按照意向性分析方案，对其余332名患者的最终分析显示，MA组6个月时的治愈率为77.5%，LAMB组为87.2%，LAMB加MA组为83.9%，各试验组与对照（LAMB：9.7%；CI95% -0.28至19.68，p = 0.06；LAMB加MA：6.4%；CI95% -3.93至16.73；p = 0.222）之间无统计学显著差异。就治疗相关不良事件（AE）的发生率（p = 0.045）、出现至少一种严重AE的患者比例（p = 0.029）以及导致明确治疗中断的AE比例（p = 0.003）而言，LAMB单药治疗比MA更安全。
由于毒性较低且疗效可接受，LAMB作为VL的一线治疗比标准治疗更合适。ClinicalTrials.gov识别号：NCT01310738。
ClinicalTrials.gov NCT01310738。
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