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.
REGISTRATION: Clinical Trials NCT00298233.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:346 |
|---|---|
| Enthalten in: |
BMJ (Clinical research ed.) - 346(2013) vom: 30. Mai, Seite f3039 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
South East Asia Infectious Disease Clinical Research Network [VerfasserIn] |
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| Links: |
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| Themen: |
20O93L6F9H |
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| Anmerkungen: |
Date Completed 06.08.2013 Date Revised 21.10.2021 published: Electronic ClinicalTrials.gov: NCT00298233 CommentIn: BMJ. 2013;346:f3449. - PMID 23723458 Citation Status MEDLINE |
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| doi: |
10.1136/bmj.f3039 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM227938526 |
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| 100 | 0 | |a South East Asia Infectious Disease Clinical Research Network |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza |b double blind randomised controlled trial |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.08.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00298233 | ||
| 500 | |a CommentIn: BMJ. 2013;346:f3449. - PMID 23723458 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza | ||
| 520 | |a DESIGN: Double blind randomised trial | ||
| 520 | |a SETTING: Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam | ||
| 520 | |a PARTICIPANTS: Patients aged ≥ 1 year admitted to hospital with confirmed severe influenza | ||
| 520 | |a INTERVENTIONS: Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital | ||
| 520 | |a REGISTRATION: Clinical Trials NCT00298233 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Oseltamivir |2 NLM | |
| 650 | 7 | |a 20O93L6F9H |2 NLM | |
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