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BMJ Open. 2018 Jul 12;8(7):e021032. doi: 10.1136/bmjopen-2017-021032.

Antivirals for influenza-Like Illness? A randomised Controlled trial of Clinical and Cost effectiveness in primary CarE (ALIC4 E): the ALIC4 E protocol.

Author information

1
The Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
2
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
3
Berry Consultants, Austin, Texas, USA.
4
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
5
Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
6
Institute for Public Health, University of Copenhagen, Copenhagen, Denmark.
7
Department of Family Medicine and Community Nursing, Medical University of Bialystok, Bialystok, Poland.
8
Centre for General Practice, Department of Primary and Interdisciplinary Care (ELIZA), University of Antwerp, Antwerp, Belgium.
9
Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
10
Ely Bridge Surgery, Ely, UK.
11
Department of General Practice, Royal College of Surgeons in Ireland School of Medicine, Dublin, Ireland.
12
Department of Family Medicine and Primary Health Care, Ghent University, Ghent, Belgium.
13
Department of Population Medicine, Cardiff University School of Medicine, Cardiff, UK.
14
University of Basel, Basel, Switzerland.
15
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
16
Department of Family and Community Medicine, Medical University of Lodz, Lodz, Poland.
17
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
18
Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
19
Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway.
20
Primary Care and Population Science, University of Southampton, Southampton, UK.
21
SERGAS, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
22
Primary Healthcare Centre Jaume I, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
23
Drug Research Centre LLC, Balatonfüred, Hungary.
24
Institute of General Practice, First Faculty of Medicine, Charles University, Prague, Czech Republic.
25
JSC Mano Seimos Gydytojas, Klaipėda, Lithuania.
26
Närhälsan, Research and Development Primary Health Care, Region Västra Götaland, Research and Development Center Södra Älvsborg, Borås, Sweden.
27
Department of Public Health and Community Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
28
Department of Pulmonology, Hospital Clínic de Barcelona, Universitat de Barcelona and IDIBAPS, Barcelona, Spain.
29
Department of Public Health, University Hospital of Nice, Nice, France.
30
Department of Teaching and Research in General Practice, University of Côte d'Azur, Nice, France.
31
Clinic of Social and Family Medicine, University of Crete, Heraklion, Greece.
#
Contributed equally

Abstract

INTRODUCTION:

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 comorbidity 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.

METHODS AND ANALYSIS:

Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (<12, 12-64 and >64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms.

ETHICS AND DISSEMINATION:

Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations.

TRIAL REGISTRATION NUMBER:

ISRCTN27908921; Pre-results.

KEYWORDS:

adaptive clinical trial; cost-benefit analysis; influenza; oseltamivir; primary healthcare

PMID:
30002007
PMCID:
PMC6089276
DOI:
10.1136/bmjopen-2017-021032
[Indexed for MEDLINE]
Free PMC Article

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