Damoiseaux 2000.

Methods	Randomised ‐ yes, computerised 2 block randomisation Concealment of allocation ‐ adequate Double‐blind ‐ yes Intention‐to‐treat (ITT) ‐ yes Loss to follow‐up ‐ described Design ‐ parallel
Participants	N ‐ 240 children (N = 212 children included in analysis) Age ‐ between 6 months and 2 years Setting ‐ general practice; 53 general practitioners (GPs) in the Netherlands Inclusion criteria ‐ acute otitis media (AOM) defined as infection of the middle ear of acute onset and a characteristic eardrum picture (injection along the handle of the malleus and the annulus of the tympanic membrane or a diffusely red or bulging eardrum) or acute otorrhoea. In addition 1 or more symptoms of acute infection (fever, recent earache, general malaise, recent irritability) Exclusion criteria ‐ antibiotic treatment < 4 weeks prior to randomisation, contraindication for amoxicillin, comprised immunity, craniofacial abnormalities, Down's syndrome or being entered in this study before Baseline characteristics ‐ slight imbalance in the prevalence of recurrent AOM, regular attendance at a daycare centre and parental smoking; logistic regression was used to adjust for these imbalances
Interventions	Tx ‐ amoxicillin suspension 40 mg/kg/day 3 times daily for 10 days; N = 117 (N = 107 included in analysis for short‐term outcome) C ‐ matching placebo suspension for 10 days; N = 123 (N = 105 included in analysis for short‐term outcome) Use of additional medication ‐ all children received decongestive nose drops for 7 days; analgesics (paracetamol, children < 1 year: 120 mg suppository, > 1 year: 240 mg suppository) was allowed
Outcomes	Primary outcome ‐ persistent symptoms at day 4: assessed by the doctor and defined as persistent earache, fever > 38 °C, crying or being irritable. Additionally, prescription of another antibiotic because of clinical deterioration before the first follow‐up visit was to be considered a persistent symptom Secondary outcomes ‐ (a) clinical treatment failure at day 11 (i.e. persistent fever, earache, crying, being irritable or no improvement of tympanic membrane (including perforation); (b) duration of fever, pain or crying; (c) mean number of doses analgesics given; (d) adverse effects mentioned in diaries; (e) percentage of children with middle‐ear effusion at 6 weeks (i.e. combined otoscopy and tympanometry) Follow‐up visits at the GP's clinic were scheduled at day 4 and 11; home visit at 6 weeks by the researcher collecting data of symptoms, referrals and both otoscopy and tympanometry was performed Parents were instructed to keep a symptom diary for 10 days
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised 2 block randomisation
Allocation concealment (selection bias)	Low risk	Randomisation was carried out independently of the investigators; randomisation code was kept in pharmacy of the University Medical Centre Utrecht
Other bias	Low risk	ITT analysis ‐ yes, baseline characteristics ‐ slight imbalance, logistic regression was used to adjust for imbalances in prognostic factors
Blinding of participants and personnel (performance bias)	Low risk	Placebo suspension with same taste and appearance as amoxicillin
Incomplete outcome data (attrition bias)	Unclear risk	Loss to follow‐up/exclusion from analysis (received other antibiotics or had grommets inserted) ‐ treatment: N = 10 (9%) and placebo: N = 18 (15%). However, for primary analysis of symptoms at day 4 all randomised patients were included