BMJ:双倍剂量达菲治疗重症流感或无优势

　　一项来自东南亚的研究表明，使用双倍剂量的奥司他韦（达菲）治疗重症流感住院患者，与标准剂量相比，并无病毒学或临床优势。该研究结果2013年5月30日在线发表于BMJ。

　　该研究在2007年4月到2010年2月期间，纳入326名重症流感患者（主要是15岁以下的儿童），将其分为两组，一组接受标准剂量（75mg，一日两次，儿童剂量当量），另外一组接受双倍剂量（150mg，一日两次，儿童剂量当量）的奥司他韦。两组均进行为期5天的治疗。研究人员采集鼻咽拭子检测其病毒水平。其他评估结果还包括死亡、移送重症监护、辅助呼吸（机械通气）。

　　结果显示，5日后并未发现不同剂量的两个治疗组之间在病毒水平、死亡率和不良事件发生率上有所不同。研究者也强调，可供重症流感患者选择的治疗方法“仍需拓展”，希望未来这方面的研究能够带来更有效的治疗方法或更好的药物联合。  

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
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.