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Anaesthetic–analgesic ear drops to reduce antibiotic consumption in children with acute otitis media: the CEDAR RCT

Research output: Contribution to journalArticle

Original languageEnglish
Number of pages74
JournalHealth Technology Assessment
DOIs
DateAccepted/In press - 1 Jun 2018
DatePublished (current) - 3 Jul 2019

Abstract

Design: Individually randomised, three arm (active, placebo and no drop) superiority trial with cost effectiveness analysis and nested qualitative evaluation. Two control groups (recommended by the 2006 Cochrane Review): no drop (usual care) and placebo. Setting: Primary care (including GP practices, Children's Emergency Departments, Walk-in Centres and Out of Hours providers) Target population: Children aged 6m to 10y with ear pain due to acute (including recurrent) otitis media (AOM). Trial inclusion criteria (all criteria must be met): 1) Aged =6 months to <10 years 2) Presenting within 1 week of suspected AOM onset (other preceding respiratory tract infection symptoms may be longer) 3) Parent/legal guardian available to give consent 4) Parent-reported ear pain in 24 hours pre-enrolment (unless child too young to report pain) 5) GP-ascertained otoscopic evidence of acute tympanic membrane inflammation (operationalised as per our previous trial6 as: erythema with dullness or cloudiness; or bulging) 6) Clinician willing to use a NICE-recommended 'no' antibiotic prescribing strategy or a 'delayed' antibiotic prescribing strategy (until at least the next day) for the AOM and other elements of the underlying acute respiratory tract infection. NICE recommends a 'no' or 'delayed' antibiotic prescribing strategy for most immune-competent children with acute otitis media. 7) Parent able to give ear drops. 8) Parent willing in principle to use ear drops before antibiotics and to wait before giving delayed antibiotics until the next day. 9) Parent able to report the child's ear pain. 10) Parent able and willing to complete Symptom Diary and receive regular follow-up telephone calls today and for up to 7 more days (or until child has been free of ear pain without medicines for two days running). Observational study inclusion criteria (all criteria must be met): 11) Aged =6 months to <10 years 12) Presenting within 1 week of suspected AOM onset (other preceding respiratory tract infection symptoms may be longer) 13) Parent/legal guardian available to give immediate written or (if not present) telephone consent, and to provide written consent within 24 hours 14) Parent-reported ear pain in 24 hours pre-enrolment (unless child too young to report pain) 15) GP-ascertained otoscopic evidence of acute tympanic membrane inflammation (operationalised as per our previous trial6 as: erythema with dullness or cloudiness; or bulging) 16) No evidence of immunodeficiency. 17) GP wishes to use a same day antibiotic strategy for AOM or for other elements of the underlying acute respiratory tract infection (reason to be recorded). 18) Parent does not want to use ear drops (reason to be recorded). 19) Parent does not want to take part in the RCT (reason to be recorded). 20) Parent able to report the child's ear pain. 21) Parent able and willing to complete Symptom Diary and receive regular follow-up telephone calls today and for up to 7 more days (or until child has been free of ear pain without medicines for two days running) Trial exclusion criteria (presence of any warrants exclusion): 1) Child requires immediate hospitalisation 2) Child requires same day oral antibiotic treatment for AOM or other elements of the underlying acute respiratory tract infection (assess these children for observational study eligibility). NICE recommends same day antibiotic treatment for: 2.1) Child younger than 2 years with bilateral otitis media 2.2) Otorrhoea (discharge from the ear) 2.3) Child systemically very unwell 2.4) Child has symptoms and signs suggestive of serious illness and/or complications (particularly mastoiditis) 2.5) Child is at high risk of serious complications because of pre-existing comorbidity. NICE guidelines recommend the following children are excluded: 2.5.1) Child has significant heart, lung, renal, liver or neuromuscular disease 2.5.2) Child has immunosuppression 2.5.3) Child has cystic fibrosis 2.5.4) Child born prematurely NB: children with other conditions who are at higher risk of AOM (e.g. Down's Syndrome, cleft palate) may take part if the Responsible Clinician feels that they meet the inclusion criteria above) 3) Child requires same day oral antibiotics for another (non AOM) infection 4) Suspected or confirmed perforation (due to theoretical and unconfirmed risk of ototoxicity from active drops) 5) Known sensitivity to trial medicine 6) Child has proven alternative source(s) of pain 7) GP-ascertained otoscopic appearances consistent with fever (e.g. pink drum only) 8) Child has normal ear drum on examination 9) Child has otitis externa or other disorder of the outer ear or tympanic membrane for which CEDAR ear drops should not be prescribed 10) Child has a hearing aid 11) Diagnosis more suggestive of otitis media with effusion (glue ear) 12) Child has taken part in any research involving medicines within the last 30 days, or any other research within the last 90 days Observational study exclusion criteria (presence of any warrants exclusion): 1) Child requires immediate hospitalisation 2) Child has proven alternative source(s) of pain 3) GP-ascertained otoscopic appearances consistent with fever (e.g. pink drum alone) 4) Child has normal ear drum on examination 5) Child has otitis externa or other disorder of the outer ear or tympanic membrane 6) Child has a hearing aid 7) Diagnosis more suggestive of otitis media with effusion (glue ear) 8) Child taking part in the CEDAR RCT 9) Child has taken part in any other research within the last 90 days Health technology: Oil based benzocaine (local anaesthetic) with phenazone (analgesic) ear drops given to affected ear(s) every 1 to 2 hours until pain relieved. Rescue analgesia permitted and measured. Measurement of costs and outcomes: Primary outcome: 1.1 Any antibiotic consumed by day 7 (measured using daily symptom diary with telephone support calls during week 1), where day 0 is the day of randomisation; Key secondary outcome: 2.1 Ear pain over first 24 hours post randomisation using the parent completed, validated numerical rating scale successfully used in our previous trial6 (symptom diary with telephone support call in first three days). Other secondary outcomes: 2.2. Time taken before antibiotics started 2.3. Daily symptom severity (until illness resolution i.e. child free of ear pain without need for rescue analgesia for two consecutive days, expected by 8 days for most children17) including episodes of distress/crying, disturbed sleep, interference with normal activity, appetite, fever and hearing problems 2.4. Child completed Faces Pain Scale-Revised (FPS-R [Hicks et al 2001], for children aged =5 years) 2.5. Adverse events (symptom diary) 2.6. Ear drop and rescue analgesia consumption (symptom diary) 2.7. Parent satisfaction with, and opinion of, treatment allocation and future intention to use drops (with/without prior GP consultation if drops were to become available over-the-counter) at 7 days 2.8. Preference based quality of child life measured (baseline, 24 hours, 7 days and 3 months post randomisation) using CHU-9D18 (for children age =5 years) 2.9. NHS costs up to 7 days after randomisation (symptom diary) and contacts to 3 months (primary care medical notes review) 2.10. Child's school/nursery absences, parent lost productivity and other expenses up to 7 days after randomisation (symptom diary) 2.11. Child's quality of life (OMQ-14,19 modified for children <3 years) at baseline and 3 months after randomisation (postal questionnaire). 2.12. Qualitative outcomes to assess acceptability, barriers and adherence, a purposeful sample of parents and clinicians will be asked to participate in qualitative interviews to explore experiences of, and attitudes to AOM and its treatment. Sample size: Assume 90% power, alpha 0.05: primary comparison - 109 to 121 children needed in each of active and no drop groups to detect 20% reduction in antibiotic consumption from 80% to 90%; key secondary comparison - difference of 1.0 on pain numerical rating scale (using SD 2.5 from previous RCT) - 133 children in each of the active and placebo drop groups. With 20% attrition, 167 per arm, 501 total. Project timetables: Start January 2015, recruit June 2015 to May 2017 (internal pilot to February 2016), data analysis, writing and dissemination to March 2018. Team expertise: We are 4 academic GPs; ENT Professor; a Senior RF Statistics; a Professor of Health Economics; a PPI expert; a Consultant in Paediatric Anaesthesia; a Consultant in Paediatric Emergency Medicine; a Professor of Academic Nursing; and Qualitative Researcher.

    Structured keywords

  • BRTC

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via the National Institute for Health Research at https://doi.org/10.3310/hta23340 . Please refer to any applicable terms of use of the publisher.

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