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

2. 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.

3. 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?

4. Recruitment plan 650 ‘at risk’ children with influenza-like illness
Winter Season 2015/2016, 2016/2017 October to March/April depending on circulation of ILI
Target: 2-5 recruits per site per season

5. Identifying Eligible Patients
EMIS database search available at
Flag appropriate patients that are identified
Posters & leaflets available for waiting room, use in flu clinics.

6. 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.

7. Recruitment timeframe
Same day if possible
Following (working) day if still 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.

8. 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.

9. Recruitment tip 1
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.

10. Recruitment tip 2
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.

11. 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.

12. Data Entry Eligibility assessment – entered at www.archie.com
Randomization – online via Sortition
Baseline, Follow Up & Safety – paper CRF’s posted to Oxford for data entry

13. 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
(Consent for additional throat swabs)

14. Safety Reporting
Common side effects (diarrhoea, thrush, vomiting, nausea) that are clinically mild/moderate do not require reporting. Severe side effects do
Usual Safety reporting otherwise applies e.g. an overnight stay in hospital requires an SAE report.

15. Follow-up throat swabs (optional)
If the child’s parent agreed to them having follow-up throat swabs, the study team will remind you when these are due and send you the kits you need to obtain these swabs.
3, 6 and 12 months (+/- 2 weeks)
Study team will send swab extra swab kits and remind you to contact patient when swabs are due

16. Summary of study 3m + Day 1 Day 7 Day 14 Day 21 Day 28
Enrolment and randomisation
Medical notes review (all children)
Follow-up throat swabs (optional)
Return weekly diaries (parent ± child)

17. Primary Outcome Re-consultation within 28 days of study entry
Extracted from Medical Notes at GP surgery 3m+ from study entry.

18. 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.

19. Reimbursement Service support costs Research costs
region specific via CRN
Research costs
Reimbursed annually by study team
£16.48 per child recruited into trial
£25.48 per child recruited into trial + follow-up throat swabs

20. Site training Videos on the ARCHIE web site
Video 1 – eligibility assessment and recruitment tips
Video 2 – baseline assessment consent and clinical details
Video 3 – baseline assessment study medication and contact card
Video 4 – questionnaires, diaries and arranging follow ups
Video 5 – follow up assessment and adverse event reporting

21. Before you recruit .. Complete contract and send it to Oxford
Complete delegation logs and send the access requirements to Oxford (for log-in details)
Train all staff & return training logs
CV’s and GCP certificates
Receive ‘green light’ form from Oxford
Then go …..

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