青蒿琥酯-阿莫地喹和青蒿琥酯-甲氟喹固定剂量组合治疗利比里亚宁巴县 6-59 个月儿童无并发症恶性疟的疗效：一项开放性随机非劣效性试验。
Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.
机构信息
Epicentre, 75011 Paris, France.
出版信息
Malar J. 2013 Jul 17;12:251. doi: 10.1186/1475-2875-12-251.
BACKGROUND
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce.
METHODS
An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured.
RESULTS
The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017).
CONCLUSIONS
Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
背景
及时发现抗疟药物耐药性的发展，对抗疟治疗的前瞻性疗效监测至关重要。在利比里亚宁巴县，对 6 至 59 个月龄儿童进行了青蒿琥酯-阿莫地喹（ASAQ）固定剂量复方（FDC）与青蒿素-哌喹（AL）的体内疗效比较，该地区恶性疟原虫疟疾流行，疗效数据稀缺。
方法
一项开放标签、随机对照非劣效性试验比较了 300 例 6 至 59 个月龄无并发症恶性疟儿童中 ASAQ FDC（ASAQ Winthrop®）与 AL（Coartem®）的基因分型调整第 42 天治愈率。纳入时间为 2008 年 12 月至 2009 年 5 月。随机（1:1）为 3 天口服观察方案（ASAQ：每天一次；AL：每天两次，与高脂肪食物一起服用）。还测量了第 7 天去乙基阿莫地喹和青蒿琥酯的血药浓度。
结果
基因分型调整的第 42 天治愈率估计值分别为 97.3%[95%CI：91.6-99.1]（ASAQ）和 94.2%[88.1-97.2]（AL）（Kaplan-Meier 生存估计值）。第 42 天治愈率的差异为-3.1%[上限 95%CI：1.2%]。这些结果在按方案人群中第 42 天治愈的患者比例上得到了确认。第 3 天时，寄生虫清除率为 100%（ASAQ）和 99.3%（AL）。无再感染的概率分别为 0.55[95%CI：0.46-0.63]（ASAQ）和 0.66[0.57-0.73]（AL）（p=0.017）。
结论
ASAQ 和 AL 均具有高度疗效，ASAQ 非劣效于 AL。在这一高度流行地区，两个治疗组的再感染率均较高。2010 年，ASAQ FDC 在利比里亚被采用为国家一线治疗药物。建议进行持续的疗效监测。
试验注册
方案在当前对照试验（Current Controlled Trials）中注册，标识符为 ISRCTN51688713、ISRCTN40020296。
Zotero 插件