Publication:
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

Issued Date

2013-06-08

Resource Type

Article

ISSN

17561833

DOI

10.1136/bmj.f3039

Other identifier(s)

2-s2.0-84878821350

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

BMJ (Online). Vol.346, No.7911 (2013)

Suggested Citation

Endang Rahayu Sedyaningsih, Moh Suhud Malik, Vivi Setiawaty, Trihono Trihono, Erlina Burhan, Tjandra Yoga Aditama, Prijanti Z. Soepandi, Lia G. Partakusuma, Agung P. Sutiyoso, Ika Priatni, Hadi Jusuf, Emmy Hermiyanti Pranggono, Arto Yuwono Soeroto, Djatnika Setiabudi, Dadang Hudaya Somasetia, Sri Sudarwati, Tini T. Maskoen, Yovita Hartantri, Ida Parwati, Sardikin Giriputro, Dewi Murniati, Sondang Maryutka Sirait, Tony Soetanto, Sri Sulastri, Rismali Agus, Adria Rusli, Sila Wiweka, Steve Wignall, Kevin Baird, Iko Safika, Chariya Sangsajja, Weerawat Manosuthi, Patama Sutha, Chareon Chuchottaworn, Piamlarp Sansayunh, Kittima Bangpattanasiri, Walter R.J. Taylor, Kasia Stepniewska, Caroline Fukuda, Niklas Lindegardh, Nicholas White, Nick Day, Tawee Chotpitayasunondh, Piyarat Suntarattiwong, Umaporn Chantbuddhiwet, Supichaya Netsawang, Kulkanya Chokephaibulkit, Nirun Vanprapar, Wasana Prasitsuebsai, Orasri Wittawatmongkol, Thanomsak Anekthananon, Winai Ratanasuwan, Yong Rongrungruang, Pilaipan Puthavathana, Paul A. Tambyah, Yee Sin Leo, Dale Fisher, Louis Chai, Lawrence Lee, Raymond Lin, Ngo Ngoc Quang Minh, Truong Huu Khanh, Le Phan Kim Thoa, Le Anh Tuan, Tran Thi My Dung, Lam Thi Thuy Ha, Le Minh Qui, Le Quoc Thinh, Nguyen Ngoc Tu Anh, Tran Anh Tuan, Trinh Hong Nhien, Bui Pham Phuong, Phan Tu Qui, Tieu Chau Thy, Bui Xuan Vu, Le Binh Bao Tinh, Dang Thi Thanh, Vo Phuong Khanh, Do Chau Viet, Tran Thi Thuy, Vo Quoc Bao, Le Nguyen Nhat Trung, Ho Thi Kim Thoa, Tran Thi Ngoc Anh, Tran Thi Thu Loan, Tran Quynh Huong, Nguyen Thi Hanh Le, Ho Lu Viet, Ha Manh Tuan, Nguyen Thi Thanh Ha, Nguyen Van Vinh Chau, Nguyen Thanh Truong, Le Thi Thu Thao, Nguyen Thanh Phong, Pham Tran Dieu Hien, Pham Thi Hai Men, Cao Thi Tam, Tran Vinh Diet, Nguyen Van Hao 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 (Online). Vol.346, No.7911 (2013). doi:10.1136/bmj.f3039 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32300

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Thesis

Title

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

Author(s)

Endang Rahayu Sedyaningsih
 Moh Suhud Malik
 Vivi Setiawaty
 Trihono Trihono
 Erlina Burhan
 Tjandra Yoga Aditama
 Prijanti Z. Soepandi
 Lia G. Partakusuma
 Agung P. Sutiyoso
 Ika Priatni
 Hadi Jusuf
 Emmy Hermiyanti Pranggono
 Arto Yuwono Soeroto
 Djatnika Setiabudi
 Dadang Hudaya Somasetia
 Sri Sudarwati
 Tini T. Maskoen
 Yovita Hartantri
 Ida Parwati
 Sardikin Giriputro
 Dewi Murniati
 Sondang Maryutka Sirait
 Tony Soetanto
 Sri Sulastri
 Rismali Agus
 Adria Rusli
 Sila Wiweka
 Steve Wignall
 Kevin Baird
 Iko Safika
 Chariya Sangsajja
 Weerawat Manosuthi
 Patama Sutha
 Chareon Chuchottaworn
 Piamlarp Sansayunh
 Kittima Bangpattanasiri
 Walter R.J. Taylor
 Kasia Stepniewska
 Caroline Fukuda
 Niklas Lindegardh
 Nicholas White
 Nick Day
 Tawee Chotpitayasunondh
 Piyarat Suntarattiwong
 Umaporn Chantbuddhiwet
 Supichaya Netsawang
 Kulkanya Chokephaibulkit
 Nirun Vanprapar
 Wasana Prasitsuebsai
 Orasri Wittawatmongkol
 Thanomsak Anekthananon
 Winai Ratanasuwan
 Yong Rongrungruang
 Pilaipan Puthavathana
 Paul A. Tambyah
 Yee Sin Leo
 Dale Fisher
 Louis Chai
 Lawrence Lee
 Raymond Lin
 Ngo Ngoc Quang Minh
 Truong Huu Khanh
 Le Phan Kim Thoa
 Le Anh Tuan
 Tran Thi My Dung
 Lam Thi Thuy Ha
 Le Minh Qui
 Le Quoc Thinh
 Nguyen Ngoc Tu Anh
 Tran Anh Tuan
 Trinh Hong Nhien
 Bui Pham Phuong
 Phan Tu Qui
 Tieu Chau Thy
 Bui Xuan Vu
 Le Binh Bao Tinh
 Dang Thi Thanh
 Vo Phuong Khanh
 Do Chau Viet
 Tran Thi Thuy
 Vo Quoc Bao
 Le Nguyen Nhat Trung
 Ho Thi Kim Thoa
 Tran Thi Ngoc Anh
 Tran Thi Thu Loan
 Tran Quynh Huong
 Nguyen Thi Hanh Le
 Ho Lu Viet
 Ha Manh Tuan
 Nguyen Thi Thanh Ha
 Nguyen Van Vinh Chau
 Nguyen Thanh Truong
 Le Thi Thu Thao
 Nguyen Thanh Phong
 Pham Tran Dieu Hien
 Pham Thi Hai Men
 Cao Thi Tam
 Tran Vinh Diet
 Nguyen Van Hao

Other Contributor(s)

Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia
 Persahabatan Hospital
 Rumah Sakit Hasan Sadikan Bandung
 Sulianto Saroso Hospital Jakarta
 Eijkman Oxford Clinical Research Unit
 Bamrasnaradura Infectious Disease Institute
 Chest Disease Institute Nonthaburi
 Mahidol Oxford Research Unit Bangkok
 Queen Sirikit National Institute of Child Health
 Mahidol University
 National University Hospital, Singapore
 Children's Hospital 1
 Children's Hospital 2
 UCL
 National Hospital for Tropical Diseases

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. Registration: Clinical Trials NCT00298233.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/32300

Collections

Scopus 2011-2015