Efficacy and Safety of Amphotericin B Emulsion versus Liposomal Formulation in Indian Patients with Visceral Leishmaniasis: A Randomized, Open-Label Study

BackgroundIndia is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).MethodsIn this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.FindingsA total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.ConclusionsABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.Trial Registrationwww.clinicaltrials.govNCT00876824

背景：印度占全球内脏利什曼病（visceral leishmaniasis, VL）总患病人群的60%。当前作为VL主要治疗方案的长期口服药物（如米替福新）及肠外给药药物，正面临耐药性攀升、疗效减退、依从性欠佳及安全性隐患等问题。本研究团队评估了替代治疗方案的疗效与安全性，即单次输注预制型两性霉素B脂质乳剂（ABLE），并与脂质体两性霉素B（LAmB）进行对照。
方法：本项多中心、开放标签研究共纳入500名VL患者，按3:1的比例随机分配至两组，分别接受15 mg/kg单次输注的ABLE（n=376）或LAmB（n=124）。研究终点包括初始治愈（第30/45天）、临床改善（第30天）以及长期明确治愈（第180天）。
结果：ABLE组共计326例（86.7%）、LAmB组共计122例（98.4%）患者完成本研究。ABLE组95.9%的患者实现初始治愈，LAmB组为100%（p=0.028；95%置信区间：-0.0663，-0.0150）。两组临床改善率相当：ABLE组为98.9%，LAmB组为98.4%。ABLE组明确治愈率为85.9%，LAmB组为98.4%。两组输液相关发热（分别为37.2%与32.3%）及寒战（分别为18.4%与18.5%）发生率无显著差异。ABLE组治疗相关严重不良事件发生率（0.3%）低于LAmB组（1.6%）。ABLE组共出现2例死亡事件，其中1例可能与研究药物相关。两组均未观察到肾毒性与肝毒性。
结论：15 mg/kg单次输注ABLE疗效良好且耐受性优异。结合本研究人群的人口统计学特征，单剂量治疗在依从性、成本及临床适用性方面均具备显著优势。
试验注册：www.clinicaltrials.gov NCT00876824