Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial.
Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial.
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DOI：
10.1136/bmj.f3039
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发表时间：
2013-05-30
期刊：
影响因子：
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通讯作者：
South East Asia Infectious Disease Clinical Research Network
中科院分区：
文献类型：
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作者：
South East Asia Infectious Disease Clinical Research Network
目的探讨重症流感患者使用高于批准剂量的奥司他韦治疗指南建议的有效性。设计双盲随机试验。设置在印度尼西亚，新加坡，泰国和越南的13家医院。参与者年龄≥1岁的确诊重症流感患者入院。口服奥司他韦，双倍剂量（150毫克，每天两次/儿科当量）与标准剂量（75毫克，每天两次/儿科当量）。主要结果测量第五天鼻和咽拭子中流感RNA的逆转录聚合酶链反应（RT-PCR）病毒状态。结果326例患者（包括246例（75.5%）<15岁儿童）中，165例和161例分别随机接受双倍或标准剂量奥司他韦治疗。其中，260人（79.8%）感染了甲型流感病毒（133人（40.8%）感染了甲型H3 N2，72人（22.1%）感染了甲型H1 N1-pdm 09，38人（11.7%）感染了季节性甲型H1 N1，17人（5.2%）感染了甲型H5 N1），53人（16.2%）感染了乙型流感病毒B。另外3.9%（13例）为快速抗原试验假阳性（RT-PCR阴性，恢复期血凝抑制滴度未升高）。治疗第5天RT-PCR阴性的患者比例相似：115/159（72.3%，95%置信区间64.9%至78.7%）倍剂量接受者vs 105/154（68.2%，60.5%至75.0%）标准剂量接受者;差异4.2%（-5.9至14.2）; P=0.42。在按病毒类型/亚型、年龄和随机化前疾病持续时间进行的亚组分析中，未发现病毒清除率存在差异。死亡率相似：双倍剂量接受者12/165（7.3%，4.2%至12.3%），标准剂量接受者9/161（5.6%，3.0%至10.3%）。双倍剂量组和标准剂量组之间的中位吸氧天数（3（四分位距2-5）v 3.5（2-7））、重症监护天数（4.5（3-6）v 5（2-11））和机械通气天数（2.5（1-16）v 8（1-16））无差异。没有重要的差异，耐受性被发现。结论有没有病毒学或临床优势与双倍剂量奥司他韦相比，标准剂量的严重流感患者入院治疗。注册临床试验NCT 00298233
Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (−5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233