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)

You should have by now Completed the search and identified those at risk (the ‘golden ticket’ sent with the flu jab reminder) Set up the read code (if you code symptoms and signs for flu and flu like illness) Set up a IT flag if you wish Used the videos on the web to train all staff involved

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

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 (all children) Follow-up throat swabs (optional) 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 eligibility criteria – Complete eligibility assessment form on the same day as the baseline appointment

Face to face consultation Full eligibility assessment Baseline assessment Consider booking longer appointment or appointment at end of surgery Telephone consultation Initial eligibility assessment Introduce study (information leaflets on Study website Screen prompt Apply Read code for ‘At risk of influenza-related complications’

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 – (Consent for additional throat swabs)

Follow-up throat swabs (optional) 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

Reimbursement Service support costs – Insert region specific details 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

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 Receive ‘green light’ form from Oxford Then go …..

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

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.