The early use of antibiotics for at risk children with influenza

ISRCTN	ISRCTN70714783
DOI	https://doi.org/10.1186/ISRCTN70714783
Clinical Trials Information System (CTIS)	2013-002822-21
Protocol serial number	15212
Sponsor	University of Oxford (UK)
Funder	National Institute for Health Research

Submission date: 11/12/2013
Registration date: 11/12/2013
Last edited: 19/04/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Dr Sharon Tonner
Scientific

Clinical Trials Unit
Nuffield Department of Primary Care Health Sciences
ROQ
Woodstock Road
Oxford
OX2 6GG
United Kingdom

Email	sharon.tonner@phc.ox.ac.uk

Study information

Primary study design	Interventional
Study design	Double-blind randomised placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	The early use of Antibiotics for at Risk CHildren with InfluEnza in primary care (ARCHIE): a double-blind randomised placebo-controlled trial
Study acronym	ARCHIE
Study objectives	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
Health condition(s) or problem(s) studied	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
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Co-amoxiclav
Primary outcome measure(s)	Proportion of children re-consulting due to clinical deterioration within 28 days of study entry
Key secondary outcome measure(s)	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
Completion date	01/05/2019

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	12 Years
Sex	All
Target sample size at registration	650
Total final enrolment	271
Key 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
Key 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
Date of first enrolment	01/10/2014
Date of final enrolment	20/04/2018

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Nuffield Department of Primary Care Health Sciences

Oxford
OX2 6GG
United Kingdom

80 active sites (most of them GP practices) - please see study website (www.archiestudy.com) for complete list of recruiting centres

-
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		18/03/2021	22/03/2021	Yes	No
Protocol article	protocol	16/05/2018		Yes	No
HRA research summary			28/06/2023	No	No
Other publications	Economic analysis	15/04/2022	19/04/2022	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

19/04/2022: Publication reference added.
31/03/2021: IPD sharing statement added.
22/03/2021: Publication reference added.
16/07/2018: The intention to publish date was changed from 01/05/2020 to 30/09/2020.
13/07/2018: The recruitment end date was changed from 25/04/2018 to 20/04/2018.
18/05/2018: Publication reference added.
09/08/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2016 to 25/04/2018.
2. The overall trial end date was changed from 01/05/2017 to 01/05/2019.
3. The publication and dissemination plan and IPD sharing statement was added.