Antivirals for influenza-like illness? Are they effective?
| ISRCTN | ISRCTN27908921 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN27908921 |
| EudraCT/CTIS number | 2014-004471-23 |
| Secondary identifying numbers | 19749 |
- Submission date
- 21/10/2015
- Registration date
- 22/10/2015
- Last edited
- 18/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
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?
Dr Emily Bongard
emily.bongard@phc.ox.ac.uk
Contact information
Public
Primary Care Clinical Trials Unit
Nuffield Department of Primary Care Health Sciences
Radcliffe Primary Care
Radcliffe Observatory Quarter
Woodstock Road
Oxford
OX2 6GG
United Kingdom
| Phone | +44 (0)1865 289296 |
|---|---|
| emily.bongard@phc.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) |
| Study 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(s) | 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: Ethics Committee of the General Hospital, Prague, 12/12/2015, ref: 2354/15 S-MEK |
| 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 | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Oseltamivir |
| Primary outcome measure | 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 study start date | 01/02/2014 |
| Overall study end date | 31/01/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | Planned Sample Size: 675; UK Sample Size: 675. 464 participants were recruited in the UK and 3266 worldwide. |
| Total final enrolment | 464 |
| 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 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 | 13/04/2018 |
Locations
Countries of recruitment
- Belgium
- Croatia
- Czech Republic
- Denmark
- England
- France
- Greece
- Hungary
- Ireland
- Lithuania
- Netherlands
- Norway
- Poland
- Spain
- Sweden
- Switzerland
- United Kingdom
- Wales
Study participating centres
Witney
OX28 6JS
United Kingdom
Oxford
OX1 4RP
United Kingdom
Wokingham
RG40 1XS
United Kingdom
Aston Clinton
Aylesbury
HP22 5LB
United Kingdom
Eynsham
Witney
OX29 4QB
United Kingdom
Didcot
OX11 7JH
United Kingdom
Faringdon
SN7 7YU
United Kingdom
Pangbourne
Reading
RG8 7DP
United Kingdom
Yorkley
Lydney
GL15 4RS
United Kingdom
121 Swindon Road
Cheltenham
GL50 4DP
United Kingdom
Horton Road
Gloucester
GL1 3PX
United Kingdom
Waterlooville
P07 7AH
United Kingdom
Wareham
BH20 4PG
United Kingdom
Cowplain
Waterlooville
PO8 8DL
United Kingdom
Alton
GU34 1RJ
United Kingdom
Weymouth
DT3 6SA
United Kingdom
Salisbury
SP1 1DX
United Kingdom
Winchester
SO22 6EL
United Kingdom
Cardiff
CF24 1AG
United Kingdom
Dinas Powys
CF64 4JT
United Kingdom
Cardiff
CF5 2DY
United Kingdom
Cardiff
CF14 2FD
United Kingdom
Llanedeyrn
Cardiff
CF23 3PN
United Kingdom
Barry
CF63 1BA
United Kingdom
Barry
CF63 4AR
United Kingdom
Amersfoort
3817 KJ
Netherlands
Crete
70003
Greece
Athenry
Galway
-
Ireland
Basel
CH-4057
Switzerland
Basel
H-4031
Switzerland
Nice
06200
France
Alingsås
SE-441 50
Sweden
Hoboken
2660
Belgium
Barcelona
08036
Spain
Rødovre
2610
Denmark
Stokke
38160
Norway
Kossuth Lajos str. 20
Balatonfured
-
Hungary
Prague
186 00
Czech Republic
Zagreb
10 000
Croatia
Sponsor information
Hospital/treatment centre
Research Services
Clinical Trials and Research Governance
Headley Way
Headington
Oxford
OX3 9DU
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Results and Publications
| Intention to publish date | 30/06/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication of a trial protocol in 2018 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. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Protocol article | protocol | 12/07/2018 | 17/10/2019 | Yes | No |
| Results article | results | 04/01/2020 | 17/12/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | Conditional versus non-conditional incentives to maximise return of participant completed questionnaires in clinical trials: a cluster randomised study within a trial | 07/11/2023 | 18/11/2024 | Yes | No |
Editorial Notes
18/11/2024: Publication reference added.
17/12/2019: The following changes have been made:
1. Publication reference added.
2. The EU-CTR results link has been added to the basic results summary.
3. The Participant inclusion criteria: Target number of participants has been changed from "Planned Sample Size: 675; UK Sample Size: 675" to "Planned Sample Size: 675; UK Sample Size: 675. 464 participants were recruited in the UK and 3266 worldwide." This information has been added from the EU-CTR record.
17/10/2019: Publication reference added.
13/07/2018: The recruitment end date was changed from 31/03/2018 to 13/04/2018.
19/06/2018: Contact details updated and IPD sharing statement added.
14/06/2018: The ethics approval details were updated and Croatia was removed from the countries of recruitment.
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.
