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

Health Technol Assess. 2019 Jul;23(34):1-48. doi: 10.3310/hta23340.

Abstract

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).

Keywords: ANALGESICS; ANTIBACTERIAL AGENTS; CHILD; EAR ACHE; OTITIS MEDIA.

Plain language summary

Ear infections are common in children < 10 years of age, with 40% of these children suffering from an ear infection at least once per year. During the infection, germs multiply in the confined space of the middle ear, resulting in a build-up of pressure that pushes on and stretches the ear drum. This causes severe pain and distress to the child, which in turn leads to disrupted family life. Although there is world-class evidence showing that antibiotics do not help, and the National Institute for Health and Care Excellence advises against their use, > 85% of UK children with middle ear infections (acute otitis media) are prescribed an antibiotic, which is a higher percentage than for any other childhood infection. Antibiotics do not treat the child’s pain and, in most cases, they do not help to treat the infection (because many ear infections are caused by viruses that do not respond to antibiotics), but they can cause side effects (such as diarrhoea) and increase the problem of antibiotic resistance, which is a major public health concern. The Children’s Ear Pain Study (CEDAR) wanted to find out whether or not painkilling ear drops [benzocaine–phenazone otic solution (Auralgan®) currently manufactured by Pfizer Consumer Healthcare(Pfizer Inc., New York, NY USA)] can, by treating children’s ear pain, reduce the number of parents giving their children antibiotics for acute otitis media. Children were given the painkilling drops, placebo (dummy) drops or usual care. The study found that, if the children were given the painkilling drops, significantly fewer of them were given antibiotics. Unfortunately, there were not enough children who took part in the study to change advice on how doctors treat ear infections. However, these results suggest that ear drops help reduce unnecessary antibiotic use and should be investigated in a further larger study.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Analgesics / therapeutic use*
  • Anesthetics / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cost-Benefit Analysis
  • England
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Otitis Media / drug therapy*
  • Pain / drug therapy*
  • Wales

Substances

  • Analgesics
  • Anesthetics
  • Anti-Bacterial Agents

Associated data

  • ISRCTN/ISRCTN09599764