Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
N Engl J Med. 2010 Feb 11;362(6):504-12. doi: 10.1056/NEJMoa0903627.
Some 50% of patients with visceral leishmaniasis (kala-azar) worldwide live in the Indian state of Bihar. Liposomal amphotericin B is an effective treatment when administered in short courses. We wanted to determine whether the efficacy of a single infusion of liposomal amphotericin B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of amphotericin B deoxycholate.
In this open-label study, we randomly assigned 412 patients in a 3:1 ratio to receive either liposomal amphotericin B (liposomal-therapy group) or amphotericin B deoxycholate (conventional-therapy group). Liposomal amphotericin B (at a dose of 10 mg per kilogram of body weight) was given once, and patients were discharged home 24 hours later. Amphotericin B deoxycholate, which was administered in 15 infusions of 1 mg per kilogram, was given every other day during a 29-day hospitalization. We determined the cure rate 6 months after treatment.
A total of 410 patients--304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group--had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group.
A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number, NCT00628719.)
全世界约有 50%的内脏利什曼病（黑热病）患者生活在印度比哈尔邦。当短疗程使用时，两性霉素 B 脂质体是一种有效的治疗方法。我们想确定单次输注两性霉素 B 脂质体的疗效是否不如常规的两性霉素 B 去氧胆酸盐的肠外治疗。
在这项开放标签研究中，我们将 412 名患者按照 3:1 的比例随机分配，分别接受两性霉素 B 脂质体（脂质体治疗组）或两性霉素 B 去氧胆酸盐（常规治疗组）治疗。两性霉素 B 脂质体（剂量为 10 毫克/千克体重）单次给药，24 小时后患者出院回家。两性霉素 B 去氧胆酸盐，剂量为 1 毫克/千克体重，每两天给药一次，共 29 天。我们在治疗后 6 个月确定治愈率。
共有 410 名患者（脂质体治疗组 304 名患者中的 304 名（100%）和常规治疗组 108 名患者中的 106 名（98%））在第 30 天出现明显的治愈反应。两组 6 个月的治愈率相似：脂质体治疗组为 95.7%（95%置信区间 [CI]，93.4 至 97.9），常规治疗组为 96.3%（95% CI，92.6 至 99.9）。脂质体治疗组的不良反应为输液相关发热或寒战（40%）和贫血或血小板减少症加重（2%）；常规治疗组的不良反应为发热或寒战（64%）、贫血加重（19%）和低钾血症（2%）。两组均无 1%以上的患者发生肾毒性或肝毒性。
单次输注两性霉素 B 脂质体并不劣于且费用低于常规的两性霉素 B 去氧胆酸盐治疗。（临床试验.gov 编号，NCT00628719。）
