Van der Veen 2007.

Study characteristics
Methods	2‐arm, double‐blind, parallel‐group RCT, with 6 to 12 weeks duration of treatment and 1‐year duration of follow‐up
Participants	Location: patients referred from across Netherlands Setting of recruitment and treatment: tertiary medical centre, University Medical Center Utrecht, February 2003 till June 2006, single site Sample size: Number randomised: 50 in intervention, 51 in comparison Number completed: 47 in intervention versus 49 in comparison at 12 weeks and 44 in intervention, 46 in comparison at 1 year Participant (baseline) characteristics: Age: 1 to 12, median 4 years Gender (F/M): 47(47%)/54 (53%) Main diagnosis: COM which failed conventional management (topical/short term systemic antibiotics) High‐risk population: no Cleft palate (or other craniofacial malformation): excluded Down syndrome: excluded Indigenous groups (Australian Aboriginals/Greenland natives): none Immunocompromised: excluded Diagnosis method: Confirmation of perforated tympanic membrane: yes, otomicroscope Presence of mucopurulent discharge: unclear Duration of symptoms (discharge): median 8 months in intervention, 5 months in placebo group (3 to 116 months) Other important effect modifiers: Alternative diagnosis of ear discharge: not reported Number who have previously had grommets inserted: 91 (90%), participants with grommets still in place at inclusion: 61 (60.4%) Number who have had previous ear surgery (tympanoplasty and/or mastoidectomy): 12/101 (12%) Number who had previous antibiotic treatment for CSOM: 91/101 (90%) Inclusion criteria: Age between 1 and 12 years Documented otorrhoea for more than 3 months Exclusion criteria: Cholesteatoma Known immunodeficiency other than for IgA or IgG subclasses Down syndrome, craniofacial anomalies Cystic fibrosis, primary ciliary dyskinesia Continuous use of antibiotics for 6 weeks in the past 6 months
Interventions	Intervention (n = 50): trimethoprim/sulfamethoxazole 18 mg/kg, administered orally, 2 times per day Comparator group(n = 51): placebo, administered orally, 2 times per day Concurrent treatment: The interventions were used for 6 weeks if patients were cured at the 6‐week follow‐up, but continued to 12 weeks if there was still otorrhoea at the 6‐week follow‐up. Parents were to restart study medications if symptoms recurred between 6 and 12 weeks. At baseline and if otorrhoea was present at the 6‐week and 12‐week follow‐up visits, topical antibiotics with hydrocortisone was prescribed in addition to study medications for 7 to 10 days. This was hydrocortisone/bacitracin/colistin ear drops before July 2004 and hydrocortisone/neomycin polymyxin B ear drops after that.
Outcomes	Outcomes of interest in the review: Primary outcomes: Resolution of ear discharge or "dry ear" (whether otoscopically confirmed or not) measured after 4 weeks. Otoscopically confirmed. Health‐related quality of life using a validated questionnaire Secondary outcomes: Hearing measured as the pure tone average of air conduction thresholds across 4 frequencies tested (at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz) of the affected ear Serious complications, including intracranial complications (such as otitic meningitis, lateral sinus thrombosis and cerebellar abscess) and extracranial complications (such as mastoid abscess, postauricular fistula and facial palsy), and death Ototoxicity; measured as 'suspected ototoxicity' as reported by the studies where available, and as the number of people with the following symptoms that may be suggestive of ototoxicity: Sensorineural hearing loss Balance problems/dizziness/vertigo Tinnitus
Funding sources	Grant 01‐235 Health Care Insurance Council Netherlands
Declarations of interest	None declared
Notes	Unit of randomisation: person Methods for reporting outcomes of patients with bilateral disease: not stated Clinical trials.gov registration: NCT00189098. Data extraction used data from published papers and the results shown on this website.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated randomization list was prepared by an independent data manager." Comment: computer‐generated randomisation used.
Allocation concealment (selection bias)	Low risk	Quote: "A computer‐generated randomization list was prepared by an independent data manager and sent to the hospital pharmacist..." "At entry into the trial, the investigator responsible for seeing the study participants allocated the next available number on the randomization list and the corresponding box with blinded suspension to each participant. The investigators remained blinded to the randomization until the end of the study." Comment: concealment is adequate.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "the hospital pharmacist, who then provided numbered boxes with bottles filled with a blinded suspension of either trimethoprim/sulfamethoxazole or placebo, with identical taste, bottle appearance, and fluid appearance." Comment: blinding should be adequate.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Investigators remained blinded to the randomisation until the end of the study." Comment: study was open‐label for 12 weeks to 1 year.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: loss to follow‐up and exclusion of analysis was clearly documented, and the percentages were small and balanced across groups (6/50 versus 5/51 in 1 year).
Selective reporting (reporting bias)	High risk	Comment: quality of life measures (6‐item Chronic Otitis Media questionnaire, Child Health Questionnaire, VAS) were measured but not fully reported. Results for hearing only presented as graphs. Records on https://clinicaltrials.gov/ct2/show/NCT00189098 showed that the secondary outcome was use of other systemic or topical antibiotics or undergoing surgery, but these outcomes were not reported in the papers.

CSOM: chronic suppurative otitis media; F: female; M: male; RCT: randomised controlled trial; WHO: World Health Organization