Addis Ababa University, Addis Ababa, Ethiopia.
PLoS Negl Trop Dis. 2010 Oct 26;4(10):e709. doi: 10.1371/journal.pntd.0000709.
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment.
Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified.
The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.
内脏利什曼病（VL）是发展中国家的一个主要卫生问题。未经治疗的疾病是致命的，现有的治疗方法既昂贵又常常有毒性，而且耐药性正在增加。需要改进的治疗方案。在印度，硫酸巴龙霉素被证明是一种有效且毒性低的一线治疗药物。
这是一项在东非进行的 3 臂、多中心、开放标签、随机对照临床试验，旨在比较 VL 的三种治疗方案：15 毫克/公斤/天的硫酸巴龙霉素（PM）治疗 21 天与 20 毫克/公斤/天的葡萄糖酸锑钠（SSG）治疗 30 天；以及两种剂量方案联合治疗 17 天。主要疗效终点是治疗后 6 个月时从寄生虫清除的组织吸出物判断治愈。
总共在苏丹（2 个地点）、肯尼亚（1 个）和埃塞俄比亚（2 个）的五个中心纳入了每个臂 135 名患者，当时由于疗效不佳，PM 臂不得不停止。该试验继续使用较高剂量的 PM 以及 PM 和 SSG 联合治疗臂。这些结果将在以后报告。治疗组的基线患者特征相似。PM 的总体治愈率明显低于 SSG（63.8%与 92.2%；差异 28.5%，95%CI 18.8%至 38.8%，p<0.001）。PM 的疗效在各中心之间存在差异，在苏丹（14.3%和 46.7%）明显低于肯尼亚（80.0%）和埃塞俄比亚（75.0%和 96.6%）。未发现 PM 有重大安全性问题。
PM 15 毫克/公斤/天治疗 21 天的疗效不足，尤其是在苏丹。更高剂量和联合治疗的疗效需要进一步研究。
