Condition category
Infections and Infestations
Date applied
21/10/2015
Date assigned
22/10/2015
Last edited
31/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Influenza, also known as the flu, is caused by a common virus which attacks the nose, throat, sinuses and lungs (respiratory system). Sufferers usually also experience a high temperature (fever), aching muscles and tiredness, as their bodies work to fight the infection. Most people are able to recover from the flu within one or two weeks, as their immune systems are able to destroy the virus. However, in the very young, the elderly and those with pre-existing serious medical conditions, the flu can lead to serious complications and even death. These “at risk” people are routinely offered vaccinations (flu jab) to help prevent the flu, and anti-viral medicines such as oseltamivir (Tamiflu), to help their bodies to fight the flu virus. There are many other viruses which cause symptoms similar to the flu, and are known as influenza-like illnesses (ILI). Currently, there is no way of quickly testing whether someone with influenza-like illness actually has real flu. Current treatment options such as Tamiflu seem to work best when real flu is present, and so more effective ways of targeting flu treatment are needed. This study aims to find out whether adding antiviral treatment to best usual primary care is effective in reducing the time it takes for a person to return to usual daily activity. The study also aims to look at the link between the virus that a person is suffering from and the effectiveness of the antiviral treatment.

Who can participate?
All patients over one year old, who are experiencing a flu-like illness.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive standard care from their doctor (best primary care), such as advice about looking after themselves by drinking plenty of fluids and resting. Those in the second group receive the standard care from their doctor but are also given a dose of oseltamivir (Tamiflu) for a period of five days. Participants in both groups are asked to fill in a diary for two weeks so that their symptoms can be recorded. At day 14 and day 28, participants receive a follow-up phone call to find out whether their symptoms are gone and they are back to normal. Additionally, a group of participants will have a swab taken at the start of the study so that the virus they are suffering from can be identified in the lab to find out whether the anti-viral treatment works better for real flu or ILI.

What are the possible benefits and risks of participating?
There are no direct benefits for participants taking part in this study. There are some risks involved with taking Tamiflu, such as headache and nausea (feeling sick), however these will be closely monitored.

Where is the study run from?
25 health centres in England and Wales (UK) and 15 other European countries.

When is the study starting and how long is it expected to run for?
December 2015 to March 2018

Who is funding the study?
European Commission's Seventh Framework Programme (Belgium)

Who is the main contact?
Mrs Julie Allen
julie.allen@phc.ox.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mrs Julie Allen

ORCID ID

Contact details

Department of Primary Health Care
23-38 Hythe Bridge Street
Oxford
OX1 2ET
United Kingdom
+44 1865 617868
julie.allen@phc.ox.ac.uk

Additional identifiers

EudraCT number

2014-004471-23

ClinicalTrials.gov number

Protocol/serial number

19749

Study information

Scientific title

Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E)

Acronym

ALIC4E

Study hypothesis

The aim of this study is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity.

Ethics approval

1. UK: South Central - Oxford B Research Ethics Committee, 31/03/2015, ref: 15/SC/0138
2. Netherlands: METC UMC Utrecht, 23/12/2015, ref: 15-420
3. Greece: Scientific Council, 10/11/2015, ref: 8829
4. Lithuania: Lithuanian Bioethics Committee, Vilnius, 21/09/2015, ref: P-15-73
5. Ireland: Tallaght Hospital / St. James's Hospital Joint Research Ethics Committee (REC), 07/10/2015, ref: 2015-09-LIST35 (2)
6. Switzerland: Ethikkommission Nordwest- und Zentralschweiz (EKNZ), 09/12/2015, ref: EKNZ 2015-232
7. France: Comité de Protection des Personnes Sud-Mediterannee V, 09/09/2015, ref: 15.068
8. Sweden: Regionala Etikprövningsnämnden i Göteborg, 29/09/2015
9. Belgium: Ethisch comité UZA, 17/08/2015, ref: 15/27/283
10. Spain: Hospitla Clinic Barcelona, 15/12/2015, ref: HCB/2015/0854
11. Denmark: De Videnskabsetiske Komiteer, 05/11/2016, ref: H-15009261
12. Poland: Komisja Bioetyczna przy Uniwersytecie Medycznym w Łodzi, 06/06/2015, ref: RNN/227/15/KE
13. Poland: Komisja Bioetyczna przy Uniwersytecie Medycznym w Bialymstoku, 24/09/2015, ref: R-I-002/316/2015
14. Norway: Regionale komiteer for medisinsk og helsefaglig forskningsetikk Sør-Øst, 24/06/2015, ref: 2015/932/REK
15. Hungry: Medical Research Council, Ethics Committee For Clinical Pharmacology, 06/08/2015, ref: OGYI/23427-8/2015
16. Czech Republic - Pending
17. Croatia - Pending

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Influenza-like illness

Intervention

Participants are randomly allocated to one of two groups.

Group 1: Participants in the first group are given best primary care (standard practice)
Group 2: Participants in the first group are given oseltamivir in the standard dose for their age for five days, as well as best primary care (standard practice)

Participants in both groups are asked to complete a 2 week symptom diary and will receive follow up phone calls at days 2-­4, 14­-28 and after day 28.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Time to return to usual activity is determined using a symptom diary recorded between day 1-14 and a telephone call on days 14 and 28.

Secondary outcome measures

1. Cost effectiveness measures through health resource use and EQ-5D-5L - completed by the patient on Days 1-14
2. Number of hospital admissions, collected in a patient symptom diary on day 14 and day 28
3. Attendance hospital emergency care, or Out of Hours (OOH) centres with symptoms or complications and the reasons for them and the basis for diagnosis, such as pneumonia collected in the patient diary on days 1-14
4. Attendance at GP Practice, hospital emergency care, or Out of Hours (OOH) centres with ILI symptoms collected in the patient diary on days 1-14
5. Time to alleviation of ILI symptoms, measured using symptom scoring and VAS on days 1-14
6. Incidence of new or worsening symptoms measured using symptom scoring and VAS on days 1-14
7. Report of time to onset of symptom relief measured using symptom scoring and VAS on days 1-14
8. Duration of moderately severe or worse symptoms measured using symptom scoring and VAS on days 1-14
9. Use of over-the-counter medications and prescription medications, including antibiotics collected in symptom diary through direct questioning on days 1-14
10. Report of new cases if ILI within household collected in symptom diary through direct questioning on days 1-14
11. Patient reported self-management, medication use, rest and activity collected in symptom diary through direct questioning on days 1-14
12. Analysis of benefit according to age, illness duration, severity and co-morbidity measured is recorded using the patient symptom diary on days 1-14 and through a telephone interview on days 14 and 28

Overall trial start date

01/02/2014

Overall trial end date

31/01/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged at least one year old
2. Presenting with influenza-like illness* in primary care during a period of increased influenza activity.
3. Is able and willing to comply with all trial requirements
4. Participant or legal guardian(s) of a child is willing and able to give informed consent
5. Agrees not to take antiviral agents apart from study antiviral agents according to patient randomisation

*Sudden onset of self reported fever, with at least one respiratory symptom (cough, sore throat, running or congested nose) and one systematic symptom (headache, muscle ache, sweats or chills or tiredness), with a symptom duration of 72 hours or less.

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

Planned Sample Size: 675; UK Sample Size: 675

Participant exclusion criteria

1. Chronic renal failure e.g. known (recorded in GP clinical records) or estimated creatinine glomerular filtration rate of less than 60 mg/L
2. Condition or treatment associated with significant impaired immunity (e.g. long­term oral steroids, chemotherapy, or
immune disorder)
3. Those who in the opinion of the responsible clinician should be prescribed immediate antiviral treatment
4. Allergic to oseltamivir, or any other trial medication
5. Scheduled elective surgery or other procedures requiring general anaesthesia during the subsequent two weeks
6. Participant with life expectancy estimate by a clinician to be less than 6 months
7. Patient with severe hepatic impairment
8. Responsible clinician considers urgent hospital admission is required
9. Any other significant disease or disorder which, in the opinion of the responsible clinician, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or may affect the participant’s ability to participate in the trial
10. Involvement, including completion of any follow up procedures, in another clinical trial of an investigational medicinal product in the last 90 days
11. Previous ALIC4E trial participation
12. Patients unable to be randomised within 72 hours after onset of symptoms
13. Requirement for any live viral vaccine in the next 7 days

Recruitment start date

01/12/2015

Recruitment end date

31/03/2018

Locations

Countries of recruitment

Belgium, Croatia, Czech Republic, Denmark, France, Greece, Hungary, Ireland, Lithuania, Netherlands, Norway, Poland, Spain, Sweden, Switzerland, United Kingdom

Trial participating centre

Windrush Health Centre
Welch Way
Witney
OX28 6JS
United Kingdom

Trial participating centre

South Oxford Health Centre
Lake Street
Oxford
OX1 4RP
United Kingdom

Trial participating centre

Wokingham Medical Centre
23 Rose Street
Wokingham
RG40 1XS
United Kingdom

Trial participating centre

Aston Clinton Surgery
136 London Road Aston Clinton
Aylesbury
HP22 5LB
United Kingdom

Trial participating centre

Eynsham Medical Practice
Conduit Lane Eynsham
Witney
OX29 4QB
United Kingdom

Trial participating centre

Didcot Health Centre
Britwell Road
Didcot
OX11 7JH
United Kingdom

Trial participating centre

White Horse Medical Practice
Volunteer Way
Faringdon
SN7 7YU
United Kingdom

Trial participating centre

The Boathouse Surgery
Whitchurch Road Pangbourne
Reading
RG8 7DP
United Kingdom

Trial participating centre

Yorkley Health Centre
Bailey Hill Yorkley
Lydney
GL15 4RS
United Kingdom

Trial participating centre

Portland Practice
St Paul's Medical Centre 121 Swindon Road
Cheltenham
GL50 4DP
United Kingdom

Trial participating centre

London Medical Practice
Aspen Centre Horton Road
Gloucester
GL1 3PX
United Kingdom

Trial participating centre

Forest End Surgery
Forest End
Waterlooville
P07 7AH
United Kingdom

Trial participating centre

Wareham Surgery
Streche Road
Wareham
BH20 4PG
United Kingdom

Trial participating centre

Cowplain Practice
30 London Road Cowplain
Waterlooville
PO8 8DL
United Kingdom

Trial participating centre

Chawton Park Surgery
Chawton Park Road
Alton
GU34 1RJ
United Kingdom

Trial participating centre

Bridges Medical Centre
26 Commercial Road
Weymouth
DT3 6SA
United Kingdom

Trial participating centre

Three Swans Surgery
Rollestone Street
Salisbury
SP1 1DX
United Kingdom

Trial participating centre

Friarsgate Surgery
Stockbridge Road
Winchester
SO22 6EL
United Kingdom

Trial participating centre

Clifton Surgery
151-153 Newport Road
Cardiff
CF24 1AG
United Kingdom

Trial participating centre

Dinas Powys Medical Centre
75 Cardiff Road
Dinas Powys
CF64 4JT
United Kingdom

Trial participating centre

Llandaff and Pentyrch Surgery
19A High Street
Cardiff
CF5 2DY
United Kingdom

Trial participating centre

Llandaff North Medical Practice
99 Station Road
Cardiff
CF14 2FD

Trial participating centre

Llanedeyrn Health Centre
Maelfa Llanedeyrn
Cardiff
CF23 3PN

Trial participating centre

The Practice Of Health
31 Barry Road
Barry
CF63 1BA
United Kingdom

Trial participating centre

Waterfront Medical Practice
Heol Y Llongau
Barry
CF63 4AR

Trial participating centre

Huisartsenpraktijk Valk & Meijer
Leusderweg 272
Amersfoort
3817 KJ
Netherlands

Trial participating centre

Health Center of Agia Varvara
Agia Varvara Monofatsiou
Crete
70003
Greece

Trial participating centre

Turloughmore Medical Centre
Turloughmore Athenry
Galway
-
Ireland

Trial participating centre

Praxis Hammer
Bläsiring 160
Basel
CH-4057
Switzerland

Trial participating centre

Notfallstation Universitäts-Kinderspital
Spitalstrasse 33
Basel
H-4031
Switzerland

Trial participating centre

Mouille-Blanc Cécile
43 Avenue Henri Matisse
Nice
06200

Trial participating centre

Närhälsan Ängabo vårdcentral
Sundsbergsvägen 7
Alingsås
SE-441 50
Sweden

Trial participating centre

Praktijk Sorghvliedt
Lelieplaats 15
Hoboken
2660
Belgium

Trial participating centre

Centre Atenció Primària Casanova
C/ Rosselló 161
Barcelona
08036
Spain

Trial participating centre

Mit lægehus
Rødovre Centrum
Rødovre
2610
Denmark

Trial participating centre

Stokke legesenter, Nygaards alle 4A, 3160 Stokke, Norway
Nygaards alle 4A
Stokke
38160
Norway

Trial participating centre

Dr. Kun Gazda Melinda
H-8225 Szentkirályszabadja Kossuth Lajos str. 20
Balatonfured
-
Hungary

Trial participating centre

Ordinace PL Karlín, s.r.o.
Šaldova 504/24
Prague
186 00
Czech Republic

Trial participating centre

Practice Jelena Stanic
Kauzlaricev prilaz 7
Zagreb
10 000
Croatia

Sponsor information

Organisation

University of Oxford

Sponsor details

Research Services
Clinical Trials and Research Governance
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Seventh Framework Programme

Alternative name(s)

EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

Planned publication of a trial protocol in 2016 and a results paper in 2019. Findings of the trial will also be disseminated to all the recruiters and participants involved through flyers at the recruiting GP Practice.

Intention to publish date

30/06/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

31/05/2016: The ethics approval information and trial participating centres have been updated. 30/12/2015: Ethical approval and a trial participating centre (Huisartsenpraktijk Valk & Meijer) for the Netherlands has been added.