1. Chief Investigator: Dr Kay Wang Senior Trial Manager: Tricia Carver
The early use of Antibiotics in at Risk CHildren with InfluEnza
Chief Investigator: Dr Kay Wang
Senior Trial Manager: Tricia Carver

2. Research questions
Does early antibiotic use in ‘at risk’ children with influenza-like illness reduce the likelihood of re-consultation due to clinical deterioration?
What impact might early antibiotic use have on antimicrobial resistance?
Is early antibiotic use cost effective?

3. Recruitment plan 650 ‘at risk’ children with influenza-like illness
Winters 2014/5 and 2015/6 (+/- 2016/7)
October to March
Bulk of recruitment during peak influenza season (December/January)
Target: 8 recruits per site per season (2 per month)

4. Patients to consider for ARCHIE
‘At risk’ children aged 6 months to 12 years
Cough AND fever (fever reported as symptom or temperature 37.9°C or higher during consultation)
Within 5 days of symptom onset
No known contraindication to co-amoxiclav
Does not require immediate antibiotics or hospitalisation
Please make sure your colleagues are aware of which patients we are looking for.

5. Archie is more ill than usual when he just gets a cold or flu………
We are not looking for children who just have a simple cough or cold whom clinicians are confident will get better by themselves. Neither are we looking for children who are so unwell that they need immediate antibiotics or hospitalisation. We are looking for children who are somewhere in between those two ends of the spectrum because these are the children we feel most uncertain about whether to prescribe antibiotics.
………………but I’m not sure if he is ill enough to need antibiotics.

6. Summary of study 3m + Day 1 Day 7 Day 14 Day 21 Day 28
Enrolment and randomisation

7. Summary of study 3m + Day 1 Day 7 Day 14 Day 21 Day 28
Enrolment and randomisation

8. Summary of study 3m + Day 1 Day 7 Day 14 Day 21 Day 28
Enrolment and randomisation
Return weekly diaries (parent ± child)

9. Summary of study 3m + Day 1 Day 7 Day 14 Day 21 Day 28
Enrolment and randomisation
Medical notes review
(ARCHIE trial coordinators)
Return weekly diaries (parent ± child)

10. Recruitment timeframe
Same day if possible
Following (working) day if still meet eligibility criteria
Complete eligibility assessment form on the same day as the baseline appointment
Ideally, we would like you to recruit children on the same day as they present, but if they present later in the day, we would still be happy for you to recruit them the following day. In those circumstances, please only complete our eligibility assessment form on the day that you see the child for their baseline assessment.

11. Study enrolment (face to face)
Receptionist
Triage nurse
Clinician
Introduce the study
Initial eligibility assessment (healthcare professionals)
Eligibility criteria and information leaflets available from
Make your whole team aware about the ARCHIE study and that we are looking for:
‘at risk’ children (i.e. with underlying medical condition)
aged 6 months to 12 years inclusive
presenting with influenza/influenza-like illness (i.e. cough and fever)
Within 5 days of symptom onset
Ask anyone in your team who might encounter potential participants to introduce our study and direct children and parents to our study website ( for more information. This may include receptionists as well as healthcare professionals e.g. triage nurses and clinicians. The healthcare professional who first sees the child may also wish to do an initial eligibility assessment. Full lists of our study inclusion and exclusion criteria are on our website.
Please also make sure your colleagues know who the ‘ARCHIE study recruiters’ are at your recruiting site so that they can direct children and parents who express an interest in taking part towards these individuals.
Study enrolment (face to face)
Full eligibility assessment
Baseline assessment

12. Recruitment tip 1
Ask parents and children to read the study information leaflets before the baseline appointment
Patients can go to to:
Watch video clips about the study
Download study information leaflets
Read our Frequently Asked Questions
To save you time and help patients familiarise themselves with the study before they attend for their face to face consultation, direct them to the ARCHIE study website ( where they can watch our introductory video clips and download our study information leaflets.

13. Baseline appointment (day 1)
To be completed by healthcare professional
Eligibility assessment
Consent +/- assent
Baseline clinical assessment
Randomise and allocate study medication
Contact card
To be completed by parent/guardian ± child
Contact information form
Questionnaires (two for parent, one for child)
Study diaries
This slide summarises the activities and CRFs which you and the child’s parent/guardian will need to complete during the baseline appointment (day 1 of the study).
The items in red will need to be done online. The eligibility can initially be done on paper, but will eventually need to be entered on line. The randomization must be done online at the time of entering the study. If you are unable to access the online system please call the trial office ( ) and they can randomize on your behalf.
The study pack includes instructions on how to complete these and a prepaid envelopes.
Please remember to place an ID sticker on each form and on the diaries you give the parents.
We do not intend for for children who have not been recruited from a secondary care site to consent for follow-up throat swabs.

14. Recruitment tip 2
Use the armpit thermometer provided to take the child’s temperature, and show the parent how to use it at the same time
The study pack also contains an armpit thermometer, which you can give to parents to measure their child’s temperature when they are at home. If you like, please feel free to use this to measure the child’s temperature during the baseline appointment. This might also be a good opportunity to show the parent and child how to use the thermometer.

15. Recruitment tip 3
While you prepare the child’s study medication, ask the parent and child to:
Complete the contact information form
Complete the study questionnaires
Look through the Diary – Instructions and Overview
Another tip which might save you time is to ask the parent and child to complete their contact information form and study questionnaires while you are preparing their study medication. They can also look through the instructions in the front of the study diary which explain how to complete it.

16. Study medication Co-amoxiclav 400/57 or matching placebo
Randomisation system accessible via website
Key instructions for parents:
Keep medication refrigerated once reconstituted
Give first dose as soon as possible (consider during baseline appointment)
Can repeat dose if child vomits within 30 minutes of dose
Give child maximum of 10 doses
Discard leftover medication
Medication comes in dry powder form.
A repeated dose due to vomiting does not count towards the total of 10 doses.

17. Follow-up assessments
Telephone follow-ups
Week 1 (day 7 to 10)
Week 2 (day 14 to 17)
Objectives
Safety monitoring
Reminders to complete and return diaries
No need to ask consent for follow-up throat swabs for children who have not been recruited from a GP surgery
Please draw a line through item 8 on the consent form to indicate you do not wish to consent the patient for the follow-up throat swabs.
However, if you are recruiting a participant you see regularly in a clinic you may decide to participate in the follow-up swabs.

18. Thank you for listening
Tel:
Funded by NIHR Programme Grant for Applied Research RP-PG

19. FAQ- reconsultation
Q: What is the procedure if a child reconsults because they are unwell while they are still taking their study medication? A: The clinician should assess and manage the child as they would based on their usual clinical practice. This may include issuing a prescription for antibiotics if the clinician considers that antibiotic treatment is indicated. The BNF states that the standard dose of co-amoxiclav can be doubled* when treating severe infections. The study medication dosing regimen in ARCHIE is based on the BNF standard dosing regimen. The child can therefore continue taking their study medication unless there is a reason to stop it (e.g. suspected allergic reaction).
In the ARCHIE study, children randomised to the co-amoxiclav arm will receive the standard dose of co-amoxiclav based on the their age +/- weight.
The BNF states that the standard dose of co-amoxiclav can be doubled when treating severe infections. Therefore, in most cases, even if the child had been randomised to the co-amoxiclav arm of the trial, issuing a prescription for co-amoxiclav while the child is still taking their study medication is unlikely to be problematic.
It would be advisable, however, to exercise caution in children with underlying conditions which may compromise the excretion or metabolism of co-amoxiclav, and in children whose weight is less than 6kg (the lowest weight for which standard dosing instructions are available). In these children, an alternative antibiotic should be considered if antibiotic treatment is felt to be indicated
*caution advised in children with underlying conditions which may compromise the excretion or metabolism of co-amoxiclav, and in children weighting less than 6kg. In these children, an alternative antibiotic should be considered.