Chief Investigator: Dr Kay Wang Senior Trial Manager: Tricia Carver The early use of Antibiotics in at Risk CHildren with InfluEnza www.archiestudy.com Twitter: @archiestudy 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 Please make sure your colleagues are aware of which patients we are looking for.

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.

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

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

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

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

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.

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

Recruitment tip 1 Ask parents and children to read the study information leaflets before the baseline appointment Patients can go to www.archiestudy.com 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 (www.archiestudy.com) where they can watch our introductory video clips and download our study information leaflets.

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 activities in red represent CRFs which can be completed online. Would encourage you to do this as it will reduce the likelihood of you entering incorrect data by mistake and reduce the amount of paperwork you have to archive. If you do wish to complete a paper copy, please enter this online as soon as possible – the study team will be happy to talk you through this if necessary. The forms listed in black, including the consent form, must be completed on paper. The study pack includes instructions on how to complete these and a prepaid envelopes.

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.

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.

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.

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

Thank you for listening E-mail: archie@phc.ox.ac.uk Tel: 01865 617842 Funded by NIHR Programme Grant for Applied Research RP-PG-1210-12012