Oseltamivir Randomised Controlled Efficacy Trial

Summary

Background In preparation for a global influenza pandemic, there is an urgent need for representative data from populations and settings where the pandemic is most likely to arise. There are no data on oseltamivir efficacy from Asian urban slum populations concerning duration of illness and viral shedding, nor whether efficacy depends on starting treatment \< 48 hours or ≥ 48 hours after illness onset. Finally, there are no data on the capacity of the drug, in such settings, to affect household and community transmission rates. Aims and Objectives This proposal aims to compare the duration of clinical illness among patients treated with oseltamivir vs placebo \< 48 hours and ≥ 48 hours after illness onset. It will compare the duration of viral shedding among all treatment groups vs placebo, risk of transmission to household contacts by treatment group and whether neuraminidase inhibitor use creates resistance. Secondarily it aims to measure the effect on influenza. Design and Methods A double-blind placebo controlled clinical trial design among a population in an urban slum under current influenza disease burden surveillance will be enrolled. Infection status will be confirmed by rRT-PCR. Patients ≥ 1 year old will be randomised to \< 48 hour and ≥ 48 hour treatment arms. Family members and neighbours will also be assessed by PCR and a basic reproductive number calculated (R0). Relevance These findings will address whether oseltamivir can affect illness duration and severity, affect transmission, incidence and resistance in high risk urban Asian settings where a pandemic is most likely to arise.

Timeline

Start

2008-05

Primary completion

2011-03

Completion

2011-03

Publications

• Background Abdullah Brooks W, Terebuh P, Bridges C, Klimov A, Goswami D, Sharmeen AT, Azim T, Erdman D, Hall H, Luby S, Breiman RF. Influenza A and B infection in children in urban slum, Bangladesh. Emerg Infect Dis. 2007 Oct;13(10):1507-8. doi: 10.3201/eid1310.070368. No abstract available.
• Background Abdullah Brooks W, Erdman D, Terebuh P, Klimov A, Goswami D, Sharmeen AT, Azim T, Luby S, Bridges C, Breiman R. Human metapneumovirus infection among children, Bangladesh. Emerg Infect Dis. 2007 Oct;13(10):1611-3. doi: 10.3201/eid1310.070337.
• Background Brooks WA, Breiman RF, Goswami D, Hossain A, Alam K, Saha SK, Nahar K, Nasrin D, Ahmed N, El Arifeen S, Naheed A, Sack DA, Luby S. Invasive pneumococcal disease burden and implications for vaccine policy in urban Bangladesh. Am J Trop Med Hyg. 2007 Nov;77(5):795-801.
• Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Trujillo A, Barnes J, Azim T, Bresee J, Luby SP, Brooks WA. Effects of oseltamivir treatment of index patients with influenza on secondary household illness in an urban setting in Bangladesh: secondary analysis of a randomised, placebo-controlled trial. Lancet Infect Dis. 2015 Jun;15(6):654-62. doi: 10.1016/S1473-3099(15)70041-1. Epub 2015 Mar 16.
• Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Azim T, Bresee J, Luby SP, Brooks WA. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect Dis. 2014 Feb;14(2):109-18. doi: 10.1016/S1473-3099(13)70267-6. Epub 2013 Nov 22.

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Indications