Double-blind randomised trial of co-amoxiclav versus placebo for persistent otitis media with effusion in general practice

Lancet. 1996 Sep 14;348(9029):713-6. doi: 10.1016/s0140-6736(96)02511-1.

Abstract

Background: The treatment of persistent otitis media with effusion (OME) remains controversial, but this condition is the commonest reason for children to require ear, nose, and throat (ENT) surgery. Trials of antibiotics are inconclusive, are often weak methodologically, and have not been done in general practice. Our aim was a trial of an antibiotic for OME in such a population.

Methods: 433 children, aged 6 months to 6 years, with OME from 57 general practices entered a 3-month watchful waiting period. Of 223 (52%) with persistent bilateral OME, 162 were randomised double-blind to receive co-amoxiclav suspension (20 mg/kg amoxicillin, 5 mg/kg clavulanate potassium) or matching placebo, orally three times a day for 14 days. All cases also received xylometazoline 0.25% decongestant nosedrops thrice daily. Of the 61 not randomised, 13 children were referred to an ENT surgeon and parents refused consent in 48 cases. The main outcome measures were persistent OME in both ears and in one or both ears, as assessed clinically and by tympanometry. Analysis was by intention-to-treat.

Findings: 79 children in the treatment group and 70 in the placebo group were analysed for efficacy. 3 withdrew in the co-amoxiclav group (2 lost to follow-up, 1 due to side-effects); 6 withdrew in the placebo group (5 and 1, respectively). In addition, 4 tympanograms were uninterpretable in the controls. Compliance was over 90% in both groups. Persistent OME in both ears and in one or both ears were found at significantly lower rates in the co-amoxiclav group than in the controls at the 2-week follow-up: 53 vs 84% and 77 vs 93%, respectively. Odds ratios adjusted for sex, history of adenoidectomy, and upper respiratory tract infection at follow-up were 0.25 (95% CI 0.11, 0.58, p = 0.001) and 0.30 (0.10, 0.89, p = 0.03), respectively. Parents of children in the co-amoxiclav group reported significantly more side-effects than those of control children (44 vs 22%, p = 0.03). Side-effects were mostly gastrointestinal and mild.

Interpretation: Our study in a general-practice setting confirmed the positive short-term effect of antibiotic treatment for persistent middle-ear infection. Before referral to an ENT surgeon, children with persistent OME presenting to general practitioners could be considered for such treatment, depending on the individual child and possible adverse sequelae.

Publication types

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

MeSH terms

  • Amoxicillin / therapeutic use
  • Amoxicillin-Potassium Clavulanate Combination
  • Child
  • Child, Preschool
  • Clavulanic Acids / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Multivariate Analysis
  • Odds Ratio
  • Otitis Media with Effusion / drug therapy*
  • Placebos
  • Treatment Outcome

Substances

  • Clavulanic Acids
  • Placebos
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin