Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate versus Oseltamivir for Treatment of Influenza: A Double-Blind, Randomized, Noninferiority Clinical Trial
Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate versus Oseltamivir for Treatment of Influenza: A Double-Blind, Randomized, Noninferiority Clinical Trial
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DOI：
10.1086/656802
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发表时间：
2010-11-15
影响因子：
11.8
通讯作者：
Ohashi, Yasuo
中科院分区：
文献类型：
--
作者：
Watanabe, Akira;Chang, Shan-Chwen;Ohashi, Yasuo
背景资料。一种长效神经氨酸酶抑制剂辛酸拉奈米韦单次给药，在非临床研究中已被证明对流感感染有效。本研究评价辛酸拉奈米韦治疗成人流感的临床疗效。一项双盲随机对照试验研究了辛酸拉奈米韦是否不逊于奥司他韦。共有1003名20岁、发热症状不超过36小时的流感患者被随机分为3组，分别接受辛酸拉奈米韦40毫克、辛酸拉奈米韦20毫克或奥司他韦。第1天吸入辛酸拉奈米韦1次，口服奥司他韦75 mg，每日2次，疗程5天。主要终点是病情缓解的时间。共有996名患者纳入初步分析(40毫克辛酸拉奈米韦，n=334；20毫克辛酸拉奈米韦，n=326；和奥司他韦，n=336)。辛酸拉奈米韦40 mg组、辛酸拉奈米韦20 mg组和奥司他韦组的中位缓解时间分别为73.0、85.8和73.6小时。辛酸拉奈米韦与奥司他韦的差值分别为-0.6h(95%可信区间，-9.9~6.9h)和12.2 h(95%可信区间，-1.5~17.2 h)。95%可信区间的上限小于预先指定的非劣势边际(18h)。辛酸拉奈米韦40 mg组患者第3天排出病毒的比例明显低于奥司他韦组(P=006)。一次吸入辛酸拉奈米韦可有效治疗季节性流感，包括由奥司他韦耐药病毒引起的成人流感。
Background. A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, against influenza infection has been proven effective in nonclinical studies. This study evaluated the clinical efficacy of laninamivir octanoate for the treatment of adult influenza patients.Methods. A double-blind, randomized controlled trial examined whether laninamivir octanoate was noninferior to oseltamivir. A total of 1003 patients aged >= 20 years with febrile influenza symptoms for no more than 36 h were randomized to receive either 40 mg of laninamivir octanoate, 20 mg of laninamivir octanoate, or oseltamivir. Laninamivir octanoate was inhaled once on day 1, and oseltamivir (75 mg) was administered orally twice daily for 5 days. The primary end point was the time to illness alleviation.Results. A total of 996 patients were included in the primary analysis (40-mg laninamivir octanoate, n = 334; 20-mg laninamivir octanoate, n = 326; and oseltamivir, n = 336). The median time to illness alleviation in the 40-mg laninamivir octanoate, 20-mg laninamivir octanoate, and oseltamivir groups was 73.0, 85.8, and 73.6 h, respectively. The difference between laninamivir octanoate and oseltamivir was -0.6 h (95% confidence interval, -9.9 to 6.9 h) for the 40-mg group and 12.2 h (95% confidence interval, -1.5 to 17.2 h) for the 20-mg group. The upper limits of the 95% confidence intervals were less than the prespecified noninferiority margin (18 h). The proportion of patients shedding virus at day 3 was significantly lower in the 40-mg laninamivir octanoate group than in the oseltamivir group (P = 006).Conclusions. A single inhalation of laninamivir octanoate is effective for the treatment of seasonal influenza, including that caused by oseltamivir-resistant virus, in adults.