Principi 1989.

Methods	Allocation: randomised Design: parallel groups, double‐blind
Participants	Number: 100 children (93 included in analysis at 6 months) Age (mean): unknown (range 9 months to 5 years) Gender: 55% boys, 45% girls Duration of OME prior at baseline (mean): unknown Laterality of disease at baseline (%): 81% bilateral disease Setting: tertiary care, Milan, Italy Eligibility criteria: 1. Children aged 9 months to 5 years 2. Unilateral or bilateral OME documented by otoscopy and tympanometry (type B tympanogram) 3. 3 or more AOM episodes in the prior 6 months as confirmed by otoscopy and tympanometry with the last episode occurring between 15 days and 2 months prior to enrolment Exclusion criteria: cleft palate, Down syndrome, immunodeficiency, history or allergic reactions to any of the study drugs
Interventions	Intervention group: amoxicillin 20 mg/kg/day once daily for 6 months; n = 34 Intervention group 2: TMP‐SMX 12 mg/kg/day once daily for 6 months; n = 33 Comparator group: placebo once daily for 6 months; n = 33 Use of additional interventions: AOM episodes were treated with cefaclor (prophylaxis was discontinued) for 10 days. If acute signs persisted tympanocentesis was performed and another antimicrobial drug was prescribed based on the sensitivity of the isolated pathogen. If another infectious disease requiring antibiotic treatment occurred, prophylaxis was stopped and the more appropriate treatment instituted. A child was discharged from the study in case of 2 AOM episodes within a 2‐month period.
Outcomes	Primary outcome: complete resolution of OME at 6 months based on otoscopy and tympanometry (type A, C1 or C2 tympanogram) Secondary outcome: adverse effects and AOM at 6 months
Funding sources	No information provided
Declaration of interest	No information provided
Notes	Participants lost to follow‐up total: 7/100 children (7%) Participants lost to follow‐up in antibiotic group: 3/67 children (4%) Participants lost to follow‐up in control group: 4/33 children (12%) 1 child in each antibiotic group had no OME at randomisation
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method not described
Allocation concealment (selection bias)	Unclear risk	Method not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "... the placebo was similar in appearance to one of the active drugs."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind. Primary outcome based on objective tympanometry.
Incomplete outcome data (attrition bias) All outcomes	High risk	7% of children lost to follow‐up; 4% in antibiotic group versus 12% in placebo group
Selective reporting (reporting bias)	Unclear risk	No protocol available; insufficient information to permit a judgement of low or high risk
Other bias	High risk	Baseline characteristics: balanced Did not perform ITT analysis No formal sample size calculations were performed Use of co‐interventions: antibiotic treatment in case of AOM episodes or other infectious disease requiring antibiotic treatment Compliance with treatment: compliance with medication was good in 97% (32/33) of children with amoxicillin, in 94% (31/33) of those receiving sulfamethoxazole and trimethoprim, and in 97% (29/30) of children who received placebo