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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
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3039 (Published 30 May 2013)
Cite this as: BMJ 2013;346:f3039
Infectious diseases
Child health
Adult intensive care
Clinical trials (epidemiology)
Epidemiologic studies
More topics
Article
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South East Asia Infectious Disease Clinical Research Network
Correspondence to: J Farrar, SEAICRN Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City 5, Vietnam jfarrar@oucru.org
Accepted 7 May 2013
Abstract
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.
http://www.bmj.com/content/346/bmj....gn=Feed%253A+bmj%252Frecent+(Latest+from+BMJ)
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3039 (Published 30 May 2013)
Cite this as: BMJ 2013;346:f3039
Infectious diseases
Child health
Adult intensive care
Clinical trials (epidemiology)
Epidemiologic studies
More topics
Article
Related content
Article metrics
South East Asia Infectious Disease Clinical Research Network
Correspondence to: J Farrar, SEAICRN Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City 5, Vietnam jfarrar@oucru.org
Accepted 7 May 2013
Abstract
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.
http://www.bmj.com/content/346/bmj....gn=Feed%253A+bmj%252Frecent+(Latest+from+BMJ)