Injectable paromomycin for visceral leishmaniasis in India
Injectable paromomycin for visceral leishmaniasis in India
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DOI：
10.1056/nejmoa066536
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发表时间：
2007-06-21
影响因子：
158.5
通讯作者：
Li, X.
中科院分区：
文献类型：
--
作者：
Sundar, Shyam;Jha, T. K.;Li, X.
背景：内脏利什曼病（黑热病）影响南亚、非洲和巴西的大量农村、资源贫乏的人群。需要安全、有效和负担得起的新疗法。我们进行了一项随机、对照、3期开放标签研究，比较巴龙霉素（一种氨基糖苷类药物）与阿替霉素B（印度比哈尔邦目前的治疗标准）。巴龙霉素（502例）以每公斤体重11毫克的剂量每天肌肉注射21天，或阿替霉素B（165例）以每公斤体重1毫克的剂量每隔一天静脉注射30天。治疗结束后6个月评估最终治愈情况;安全性评估包括每日临床评价和每周实验室和听力测定评价。采用非劣效性检验比较6个月的治愈率，选择的非劣效性界值为10个百分点。结果：巴龙霉素非劣效于阿替霉素B（最终治愈率，94.6% vs. 98.8%;差异，4.2个百分点; 97.5%置信区间上限，6.9; P3乘以正常范围上限）;一过性可逆性耳毒性（2% vs. 0，P=0.20）和注射部位疼痛（55% vs. 0，P
Background: Visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in South Asia, Africa, and Brazil. Safe, effective, and affordable new therapies are needed. We conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care in Bihar, India.Methods: In four treatment centers for visceral leishmaniasis, 667 patients between 5 and 55 years of age who were negative for the human immunodeficiency virus and had parasitologically confirmed visceral leishmaniasis were randomly assigned in a 3:1 ratio to receive paromomycin (502 patients) at a dose of 11 mg per kilogram of body weight intramuscularly daily for 21 days or amphotericin B (165 patients) at a dose of 1 mg per kilogram intravenously every other day for 30 days. Final cure was assessed 6 months after the end of treatment; safety assessments included daily clinical evaluations and weekly laboratory and audiometric evaluations. Noninferiority testing was used to compare 6-month cure rates, with a chosen margin of noninferiority of 10 percentage points.Results: Paromomycin was shown to be noninferior to amphotericin B (final cure rate, 94.6% vs. 98.8%; difference, 4.2 percentage points; upper bound of the 97.5% confidence interval, 6.9; P3 times the upper limit of the normal range); transient reversible ototoxicity (2% vs. 0, P=0.20); and injection-site pain (55% vs. 0, P