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

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?

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)

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

Archie is more ill than usual when he just gets a cold or flu……… ……………… but I’m not sure if he is ill enough to need antibiotics.

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

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

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

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

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

Study enrolment (face to face) Full eligibility assessment Baseline assessment Introduce the study Initial eligibility assessment (healthcare professionals) Eligibility criteria and information leaflets available from Triage nurse Clinician Receptionist

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

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

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

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

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

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

Reimbursement Service support costs – Insert region specific details Research costs – Reimbursed annually by study team – £16.48 per child recruited into trial

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

FAQ- online systems Online serviceUseHow to access (live systems*) WebsiteTraining, reference documents, and access to the other online systems. Log in by clicking on link in top right hand corner of front page. Additional links will appear under the ‘Randomise your patient’ section. SortitionRandomisation system which generates study medication ID to be allocated to participant Directly from website (Web Randomisation link) or from link in baseline assessment form* (randomisation page opens in a separate tab on the browser). OpenClinicaClinical database for entering CRF data Under ‘Randomise your patient’ there are links to ‘Eligibility Form’ and ‘Follow-up data collection’*. A link to the baseline assessment form* will appear once you have completed the eligibility form.

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). *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.