Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial
Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial
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DOI：
10.1371/journal.pntd.0002613
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发表时间：
2014-01-01
影响因子：
3.8
通讯作者：
Hailu, Asrat
中科院分区：
文献类型：
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作者：
Khalil, Eltahir A. G.;Weldegebreal, Teklu;Hailu, Asrat
背景资料：包括单剂量AmBisome（R）在内的抗利什曼病药物方案可能适用于东非有症状的内脏利什曼病（VL）患者，但合适的单剂量尚不清楚。方法：一项采用适应性设计的多中心、开放标签、非劣效性、随机对照试验，比较单剂量和多剂量AmBisome（R）治疗东非VL的有效性和安全性。主要疗效终点为6个月时的确定性治愈（DC）。在第1 - 5、14和21天，具有寄生虫学证实的非重度VL的症状患者接受单剂量的AmBisome（R）7.5mg/kg体重或多剂量，7次3mg/kg。如果在40或80例患者开始治疗后30天进行的中期分析显示，在5%的显著性水平下，单次给药的寄生虫清除率显著低于多次给药，则单次剂量增加2.5 mg/kg。在一个子集的患者，寄生虫清除率测定定量逆转录酶（qRT）PCR.Principal调查结果：试验终止后，第三次中期分析，因为这两个方案的疗效低。基于意向治疗人群，多次给药（n = 63）和单次给药（n = 21）的DC分别为85%（95%CI 73 - 93%）、40%（95%CI 19 - 64%）和58%（95%CI 41 - 73%）。或10 mg/kg（n = 40）。qRT-PCR表明早在第3天多次给药的寄生虫清除率更高。安全性数据与药物标签一致。结论：测试的AmBisome（R）方案不适用于整个东非的VL治疗。尚未确定最佳单次给药方案。
Background: Anti-leishmanial drug regimens that include a single dose AmBisome (R) could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.Methodology: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome (R) for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome (R) 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2.5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR.Principal Findings: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95% CI 73-93%), 40% (95% CI 19-64%), and 58% (95% CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7.5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label.Conclusions: The tested AmBisome (R) regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.