Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials
Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials
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DOI：
10.1016/s0140-6736(14)62449-1
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发表时间：
2015-05-02
期刊：
影响因子：
168.9
通讯作者：
Monto, Arnold S.
中科院分区：
文献类型：
--
作者：
Dobson, Joanna;Whitley, Richard J.;Monto, Arnold S.
背景尽管奥司他韦广泛使用，但其治疗流感的疗效仍存在疑问。我们的目的是做一个单独的患者数据荟萃分析的所有临床试验比较奥司他韦与安慰剂治疗季节性流感的成人症状缓解，并发症，和safety.Methods我们包括所有出版和未出版的罗氏赞助的随机安慰剂对照，双盲试验75毫克，每天两次奥司他韦在成人。奥司他韦治疗成人自然发生的流感样疾病的试验报告至少一项研究结果是合格的。我们还检索了Medline、PubMed、Embase、科克伦对照试验中心注册中心和ClinicalTrials.gov试验注册中心，以查找2014年1月1日之前发表的其他相关试验（检索最后更新日期为2014年11月27日）。我们分析了意向治疗感染人群、意向治疗人群和安全人群。主要结局是用加速失效时间方法分析的所有症状缓解时间。我们使用的风险比和Mantel-Haenszel方法来计算并发症，入院率和安全性outcome.Findings我们纳入了9项试验，包括4328例患者的数据。在意向性治疗感染人群中，我们注意到奥司他韦组与安慰剂组相比，所有症状缓解的时间缩短了21%（时间比0.79，95% CI 0.74-0.85;安慰剂组p7 h（差异-25.2 h，95% CI -36.2至-16.0）。对于意向治疗人群，估计的治疗效果减弱（时间比0>85），但仍然非常显著（中位差异-17至8小时）。在意向治疗感染人群中，我们注意到随机分组后48小时内需要抗生素治疗的下呼吸道并发症较少（风险比[RR] 0.56，95% CI 0.42-0.75; p=0.0001; 4.9%奥司他韦vs 8>7%安慰剂，风险差异为-3.8%，95%CI为-5.0至-2.2），并且因任何原因入院的患者也较少（RR 0.37，95% CI 0.17-0.81; p=0.013; 0.6%奥司他韦，1.7%安慰剂，风险差异-1.1%，95% CI -1.4至-0.3）。关于安全性，奥司他韦增加恶心风险（RR 1.60，95%CI 1.29-1.99; p
Background Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety.Methods We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes.Findings We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0.79, 95% CI 0.74-0.85; p7 h for placebo groups (difference -25.2 h, 95% CI -36.2 to -16.0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0>85) but remained highly significant (median difference -17>8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0.56, 95% CI 0.42-0.75; p=0.0001; 4.9% oseltamivir vs 8>7% placebo, risk difference -3.8%, 95% CI -5.0 to -2.2) and also fewer admittances to hospital for any cause (RR 0.37, 95% CI 0.17-0.81; p=0.013; 0.6% oseltamivir, 1.7% placebo, risk difference -1.1%, 95% CI -1.4 to -0.3). Regarding safety, oseltamivir increased the risk of nausea (RR 1.60, 95% CI 1.29-1.99; p