Background:

Acute otitis media (AOM) is a common reason for primary care consultations and antibiotic prescribing in children. Options for improved pain control may influence antibiotic prescribing and consumption.

Objective:

The Children’s Ear Pain Study (CEDAR) investigated whether or not providing anaesthetic–analgesic ear drops reduced antibiotic consumption in children with AOM. Secondary objectives included pain control and cost-effectiveness.

Design:

A multicentre, randomised, parallel-group (two-group initially, then three-group) trial.

Setting:

Primary care practices in England and Wales.

Participants:

1- to 10-year-old children presenting within 1 week of suspected AOM onset with ear pain during the preceding 24 hours and not requiring immediate antibiotics. Participating children were logged into the study and allocated using a remote randomisation service.

Interventions:

Two-group trial – unblinded comparison of anaesthetic–analgesic ear drops versus usual care. Three-group trial – blinded comparison of anaesthetic–analgesic ear drops versus placebo ear drops and unblinded comparison with usual care.

Main outcome measures:

The primary outcome measure was parent-reported antibiotic use by the child over 8 days following enrolment. Secondary measures included ear pain at day 2 and NHS and societal costs over 8 days.

Results:

Owing to a delay in provision of the placebo drops, the recruitment period was shortened and most participants were randomly allocated to the two-group study (n = 74) rather than the three-group study (n = 32). Comparing active drops with usual care in the combined two-group and three-group studies, 1 out of 39 (3%) children allocated to the active drops group and 11 out of 38 (29%) children allocated to the usual-care group consumed antibiotics in the 8 days following enrolment [unadjusted odds ratio 0.09, 95% confidence interval (CI) 0.02 to 0.55; p = 0.009; adjusted for delayed prescribing odds ratio 0.15, 95% CI 0.03 to 0.87; p = 0.035]. A total of 43% (3/7) of patients in the placebo drops group consumed antibiotics by day 8, compared with 0% (0/10) of the three-group study active drops groups (p = 0.051). The economic analysis of NHS costs (£12.66 for active drops and £11.36 for usual care) leads to an estimated cost of £5.19 per antibiotic prescription avoided, but with a high degree of uncertainty. A reduction in ear pain at day 2 in the placebo group (n = 7) compared with the active drops group (n = 10) (adjusted difference in means 0.67, 95% CI –1.44 to 2.79; p = 0.51) is consistent with chance. No adverse events were reported in children receiving active drops.

Limitations:

Estimated treatment effects are imprecise because the sample size target was not met. It is not clear if delayed prescriptions of an antibiotic were written prior to randomisation. Few children received placebo drops, which hindered the investigation of ear pain.

Conclusions:

This study suggests that reduced antibiotic use can be achieved in children with AOM by combining a no or delayed antibiotic prescribing strategy with anaesthetic–analgesic ear drops. Whether or not the active drops relieved ear pain was not established.

Future work:

The observed reduction in antibiotic consumption following the prescription of ear drops requires replication in a larger study. Future work should establish if the effect of ear drops is due to pain relief.

Trial registration:

Current Controlled Trials ISRCTN09599764.

Funding:

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 34. See the NIHR Journals Library website for further project information. Alastair D Hay was funded by a NIHR Research Professorship (funding identifier NIHR-RP-02-12-012).

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 13/88/13. The contractual start date was in January 2015. The draft report began editorial review in January 2018 and was accepted for publication in June 2018. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Alastair D Hay and William Hollingworth are members of the Health Technology Assessment Clinical Trials Board. Chris Metcalfe is a member of a clinical trials unit in receipt of National Institute for Health Research (NIHR) support funding. Desmond Nunez is an author of a related Cochrane review protocol. Paul Little is the Director of the NIHR Programme Grants for Applied Research programme and a member of the NIHR Journals Library Board.