Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial
Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial
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DOI：
10.1016/s0140-6736(10)62050-8
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发表时间：
2011-02-05
期刊：
影响因子：
168.9
通讯作者：
Modabber, Farrokh
中科院分区：
文献类型：
--
作者：
Sundar, Shyam;Sinha, Prabhat Kumar;Modabber, Farrokh
背景内脏利什曼病需要改进的治疗方法。我们评估了三种可能的短程联合治疗与印度标准单药治疗相比的疗效和安全性。（隔日输注1 mg/kg阿替霉素B，持续30天，总剂量15 mg/kg）与三种药物组合进行比较（单次注射5 mg/kg脂质体阿替霉素B和7天50 mg口服米替福新或单次10天11 mg/kg肌肉注射巴龙霉素;或米替福新和巴龙霉素各10天）在印度比哈尔邦的两个医院进行的开放标签、平行组、非劣效性、随机对照试验中。由试验统计员使用计算机生成的列表，将5-60岁经寄生虫学证实的内脏利什曼病患者随机分配至4种治疗之一。在治疗结束时（联合治疗15天;标准治疗31天）以及45天和6个月后进行临床评估。主要终点是确定性治愈（定义为无内脏利什曼病的体征或症状，并且寄生虫学治愈至末次随访）。按意向治疗和符合方案进行分析。ClinicalTrials.gov在2008年6月至2009年7月期间，634名患者被分配使用阿替霉素B（n=157）、阿替霉素B脂质体与米替福新（n=160）或巴龙霉素（n =158）或米替福新和巴龙霉素（n=159）。618例患者属于符合方案人群。每组有2例复发。意向治疗人群中6个月时确定治愈的人数为146人（治愈率93.0%; CI 87.5-96.3）对于阿替西霉素B，156（97.5%; 93.3-99.2）对于脂质体阿霉素B和米替福新，154（97.5%; 93.24-99.2），米替福新和巴龙霉素为157（98-7%; 95.1-99.8）。在意向治疗人群和符合方案人群中，所有联合治疗均非劣效于标准治疗。在组合组的患者有较少的不良事件比那些分配的标准treatment.Interpretation内脏利什曼病的组合治疗是有效的和安全的，并减少治疗的持续时间，从而鼓励坚持和减少耐药寄生虫的出现。
Background Improved treatment approaches are needed for visceral leishmaniasis. We assessed the efficacy and safety of three potential short-course combination treatments compared with the standard monotherapy in India.Methods Standard treatment (1 mg/kg amphotericin B infusion on alternate days for 30 days, total dose 15 mg/kg) was compared with three drug combinations (single injection of 5 mg/kg liposomal amphotericin B and 7-day 50 mg oral miltefosine or single 10-day 11 mg/kg intramuscular paromomycin; or 10 days each of miltefosine and paromomycin) in an open-label, parallel-group, non-inferiority, randomised controlled trial in two hospital sites in Bihar, India. Patients aged 5-60 years with parasitologically confirmed visceral leishmaniasis were randomly assigned one of the four treatments by the trial statistician by use of a computer-generated list. Clinical assessments were done at the end of treatment (15 days on combination treatment; 31 days for standard treatment) and after 45 days and 6 months. The primary endpoint was definitive cure (defined as no sign or symptom of visceral leishmaniasis and parasitologically cured to the last follow-up). Analyses were done both by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00696969.Findings Between June, 2008, and July, 2009, 634 patients were assigned amphotericin B (n=157), liposomal amphotericin B with miltefosine (n=160) or paromomycin (n=158), or miltefosine and paromomycin (n=159). 618 patients were in the per-protocol population. There were two relapses in each group. The numbers with definitive cure at 6 months for the intention-to-treat population were 146 (cure rate 93.0%; CI 87.5-96.3) for amphotericin B, 156 (97.5%; 93.3-99.2) for liposomal amphotericin B and miltefosine, 154 (97.5%; 93.24-99.2) for liposomal amphotericin B and paromomycin, and 157(98-7%; 95.1-99.8) for miltefosine and paromomycin. All combinations were non-inferior to the standard treatment, in both the intention-to-treat and per-protocol populations. Patients in the combination groups had fewer adverse events than did those assigned standard treatment.Interpretation Combination treatments for visceral leishmaniasis are efficacious and safe, and decrease the duration of therapy, thereby encouraging adherence and reducing emergence of drug-resistant parasites.