Condition category
Respiratory
Date applied
11/12/2013
Date assigned
11/12/2013
Last edited
16/07/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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

Trial website

http://www.archiestudy.com

Contact information

Type

Scientific

Primary contact

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 number

2013-002822-21

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

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

Trial setting

GP practices

Trial 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

Phase

Not Applicable

Drug names

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 trial start date

02/12/2013

Overall trial 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

Patient

Age group

Child

Gender

Both

Target number of participants

Planned Sample Size: 650; UK Sample Size: 650; Description: randomised 1:1

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 (clinician’s 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

United Kingdom

Trial participating centre

Nuffield Department of Primary Care Health Sciences
Oxford
OX2 6GG
United Kingdom

Trial 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
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/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 (www.archiestudy.com) in 2019/20

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/09/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2018 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/29769256

Publication citations

Additional files

Editorial Notes

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.