Plain English Summary
Background and study aims
Flu (influenza) and flu-like illness are among the most common reasons why parents and carers take children to see a doctor or nurse in winter. Flu is a viral infection that just causes a mild cough or cold in most children. However, when some children get flu, they develop bacterial infections, such as chest or ear infections, which can make them feel even more unwell. 'At risk' children with underlying medical conditions such as asthma and diabetes are particularly prone to becoming more unwell from bacterial infections if they get flu. The aim of this study is to find out whether giving an antibiotic called co-amoxiclav to 'at risk' children within 5 days of them becoming ill with flu or flu-like illness might:
1. Help stop them from developing bacterial infections and becoming more unwell
2. Help them get better more quickly
3. Affect how well antibiotics work against similar infections in future
Who can participate?
'At risk' children between 6 months and 12 years of age, who see a doctor or nurse within the first five days of developing flu or flu-like illness. 'At risk' children include children with medical conditions such as asthma, diabetes, cancer, cerebral palsy, Down's syndrome, heart problems, kidney problems and liver problems. 'At risk' children also include children under 2 years of age who were born prematurely.
What does the study involve?
A healthcare professional gains consent for each child to take part in the study from a parent or guardian. The healthcare professional then records some details about the child's flu-like illness. A nose swab and, if possible, a throat swab is taken from each child. Each child is randomly allocated to either receive an antibiotic (co-amoxiclav) or a placebo (dummy). Parents and guardians are asked to give children one dose of medication twice a day for five days and to fill in a study diary. Parents and guardians are asked if they would be willing for their child to have further optional throat swabs after 3, 6 and 12 months.
What are the possible benefits and risks of participating?
This study will help to work out whether giving antibiotics to 'at risk' children early on when they have flu or flu-like illness is worthwhile. It may also help the government plan how to use antibiotics during future flu epidemics or pandemics (which is when lots of people get flu all at once). The study medication may help children get better more quickly and/or prevent them from becoming more unwell from a bacterial infection. However, this is not known for sure until the end of the study.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
Recruitment will take place over three winters (2015/6, 2016/7 and 2017/8). Each winter will be defined as October to March/April inclusive
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Kay Wang
kay.wang@phc.ox.ac.uk
Study website
Contact information
Type
Scientific
Contact name
Dr Sharon Tonner
ORCID ID
Contact details
Clinical Trials Unit
Nuffield Department of Primary Care Health Sciences
ROQ
Woodstock Road
Oxford
OX2 6GG
United Kingdom
-
sharon.tonner@phc.ox.ac.uk
Additional identifiers
EudraCT/CTIS number
2013-002822-21
IRAS number
ClinicalTrials.gov number
Protocol/serial number
15212
Study information
Scientific title
The early use of Antibiotics for at Risk CHildren with InfluEnza in primary care (ARCHIE): a double-blind randomised placebo-controlled trial
Acronym
ARCHIE
Study hypothesis
In 'at risk' children with influenza, early use of antibiotics reduces the likelihood of subsequent re-consultation due to clinical deterioration during the same illness episode.
Ethics approval(s)
NRES Committee North West - Liverpool East, ref:13/NW/0621, First MREC approval date 10/10/2013, ref: 13/NW/0621
Study design
Double-blind randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
GP practice
Study type
Treatment
Patient information sheet
Patient information can be found at: http://www.phctrials.ox.ac.uk/studies/archie
Condition
Influenza and influenza-like illness
Intervention
Co-amoxiclav 400/57 or matching placebo for 5 days.
Follow Up Length: 12 month(s).
Study Entry: Single Randomisation only.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Co-amoxiclav
Primary outcome measure
Proportion of children re-consulting due to clinical deterioration within 28 days of study entry
Secondary outcome measures
1. Duration of fever from time of study entry
2. Duration of symptoms from time of study entry
3. Proportion of children prescribed medication (e.g. antibiotics, steroids) and/or requiring further investigations (e.g. chest X-ray) within 28 days of study entry
4. Proportion of children in whom adverse events are reported within 28 days of study entry
5. Proportion of children who are hospitalised or die within 28 days of study entry
Other outcome measures:
6. Health-related quality of life measured using the EQ-5D-Y and EQ-5D-Y proxy on days 1, 4, 7, 14 and 28
7. Healthcare resource utilisation and parental/informal care costs within 28 days of study entry
8. Minimum inhibitory concentrations (MICs) of alpha-haemolytic streptococci (including Streptococcus pneumoniae), Haemophilus influenzae and Staphylococcus aureus in relation to a representative range of antibiotics 3 months, 6 months and 12 months after study entry
9. Proportion of ampicillin-resistant alpha-haemolytic streptococci (including Streptococcus pneumoniae), Haemophilus influenzae and Staphylococcus aureus 12 months after study entry
10. Prevalence of alpha-haemolytic streptococci (including Streptococcus pneumoniae), Haemophilus influenzae and Staphylococcus aureus at 12 months after study entry
Overall study start date
02/12/2013
Overall study end date
01/05/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 09/08/2017:
1. Male and female, aged 6 months to 12 years inclusive
2. In 'at risk' category, including:
2.1. Aged under 2 years and born prematurely
2.2. Respiratory/renal conditions
2.3. Cardiac conditions/cancer/cerebral palsy
2.4. Hepatic/haematological conditions
2.5. Immunodeficiency
2.6. Endocrine/metabolic conditions
3. Presenting with influenza-like illness (i.e., cough and fever) during influenza season
4. Presenting within 5 days of symptom onset
5. Permanently registered at a general practice in UK
6. Parent/guardian able to complete study diary and questionnaires
Previous inclusion criteria:
1. Male and female, aged 6 months to 12 years inclusive
2. In 'at risk' category, including:
2.1. Aged under 2 years and born prematurely
2.2. Respiratory/renal conditions
2.3. Cardiac conditions/cancer/cerebral palsy
2.4. Hepatic/haematological conditions
2.5. Immunodeficiency
2.6. Endocrine/metabolic conditions
3. Presenting with influenza-like illness (i.e., cough and fever) during influenza season
4. Presenting within 5 days of symptom onset
5. Permanently registered at a general practice in England
6. Parent/guardian able to complete study diary and questionnaires
Participant type(s)
Patient
Age group
Child
Lower age limit
6 Months
Upper age limit
12 Years
Sex
Both
Target number of participants
Planned Sample Size: 650; UK Sample Size: 650; Description: randomised 1:1
Total final enrolment
271
Participant exclusion criteria
Current exclusion criteria as of 09/08/2017:
1. Known contraindication to co-amoxiclav
2. Child given antibiotics for treatment of an acute infection within the last 72 hours
3. Child requires immediate antibiotics (clinician’s judgement)
4. Child requires immediate hospital admission for treatment of an influenza-related complication (clinician’s judgement)
5. Child has been observed on hospital ward or ambulatory care unit for longer than 24 hours
6. Presence of any reason to prevent healthcare professional from obtaining nasal swab
7. Child with known cystic fibrosis
8. Child previously entered into the ARCHIE study
9. Child has been involved in another medicinal trial within the last 90 days
Previous exclusion criteria:
1. Known contraindication to co-amoxiclav
2. Child given antibiotics within the last 72 hours
3. Child requires immediate antibiotics or hospital admission (clinicians judgement)
4. Presence of any reason to prevent healthcare professional from obtaining high nasal swab
5. Child with known cystic fibrosis
6. Child previously entered into the ARCHIE study
7. Child has been involved in another medicinal trial within the last 90 days
Recruitment start date
01/10/2014
Recruitment end date
20/04/2018
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
Nuffield Department of Primary Care Health Sciences
Oxford
OX2 6GG
United Kingdom
Study participating centre
80 active sites (most of them GP practices) - please see study website (www.archiestudy.com) for complete list of recruiting centres
-
United Kingdom
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Joint Research Office
Block 60
Churchill Hospital
Oxford
OX3 7LE
England
United Kingdom
Sponsor type
University/education
Website
ROR
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
1. The protocol will be published in 2017/18
2. The results will be published in a peer-reviewed journal and disseminated to the public and patient groups via the study website (http://www.archiestudy.com) in 2019/20
Intention to publish date
30/09/2020
Individual participant data (IPD) sharing plan
The trial protocol, statistical analysis plan and de-identified participant-level data collected for the trial are available on request. Research data requests should be submitted to the corresponding author Kay Wang (kay.wang@phc.ox.ac.uk) for consideration by the research team.
IPD sharing plan summary
Available on request
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Protocol article | protocol | 16/05/2018 | Yes | No | |
Results article | 18/03/2021 | 22/03/2021 | Yes | No | |
Other publications | Economic analysis | 15/04/2022 | 19/04/2022 | Yes | No |
HRA research summary | 28/06/2023 | No | No |