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Trial in closure.


ALIC4E aims to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity and so the clinical and cost effectiveness of adding antiviral agents to best usual primary care of people suffering from influenza-like illness (ILI).

why this is important

Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with co-morbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies.


ALIC4E is a European multi-national, multi-centre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial (RCT). Initial trial arms will be best usual primary care, and best usual primary care plus treatment with oseltamivir for five days. The ALIC4E trial has now closed. By the final recruiting season 21 primary-care networks in 15 European countries were open to recruitment (Poland, Lithuania, Greece, Denmark, UK, Belgium, the Netherlands, France, Spain, Czech Republic, Sweden, Norway, Hungary, Switzerland, Ireland). Total recruitment reached 3226 and primary outcome data was available for 3059 of these participants (94.8%)

benefits to the patient and nhs

Provide more evidence and support GPs when deciding whether to prescribe oseltamivir to patients with ILI depending on the benefit they may receive.



This study will determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity. It will also investigate the clinical cost and effectiveness of the addition of antivirals to usual care initially oseltamivir, but the adaptive design will allow the addition of new antiviral throughout the 3 years of the trial. The study will also look at sub-groups and how they respond to different treatments allowing analysis throughout the trial. The trial will also test a new point of care test for influenza. A qualitative research component will review barriers to recruitment in infectious disease research.

Infectious diseases are a major threat to human wellbeing and economic and social development. Influenza, a highly contagious virus, causes a common respiratory infection with local and systemic symptoms. Patients with influenza can develop complications such as pneumonia, otitis media, encephalopathy or other secondary bacterial infections. Annual influenza epidemics cause substantial morbidity and mortality and the 2009 H1N1 influenza outbreak was defined as a pandemic by the World Health Organisation (WHO). The ALIC4E  trial will be delivered as  work package (WP) 4 of the Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium grant. PREPARE is a European Commission funded network for the rapid and efficient delivery of harmonised, large-scale clinical research studies on infectious diseases (ID).

PREPARE aims to develop the capability to rapidly implement prospective clinical research during pandemics to provide real-time evidence to inform the clinical management of patients and for informing public health responses to outbreaks.

Study Design: Open adaptive-platform randomised design trial
Sponsor: University of Oxford   
Ethical Approval:  REC No: 15/SC/0138
Chief Investigator: Professor Chris Butler, University of Oxford
Contact Details:

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