Gyde 1978.

Methods	Two‐arm, double‐blind, cross‐over RCT, with unclear duration of treatment (up to 3 weeks) and 12 months duration of follow‐up
Participants	Location: Canada, unclear number of sites Setting of recruitment and treatment: unclear. Outpatient department, published in 1978. Sample size: 91 people (100 ears) Number randomised: 50 ears in gentamycin, 50 ears in trimethoprim, sulphacetamide and polymixin B combination (TSP) Number completed: 50 ears in gentamycin, 50 ears in TSP Participant (baseline) characteristics: Age: mean group 1: 25.8 years; mean group 2: 32.7 years Gender (F/M): 46 (41%)/66 (59%) Main diagnosis: otorrhoea High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: unclear Presence of mucopurulent discharge: not reported Duration of symptoms (discharge): not reported Other important effect modifiers: Alternative diagnosis of ear discharge: otitis externa: 24 (21%); sub‐acute otitis media: 18 (16%); postoperative infections: 13 (12%) Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Adult or child with otorrhoea due to bacterial infection with: External otitis Chronic otitis media Sub‐acute otitis media with perforation of ear drum Postoperative infection of the mastoid cavity or after tympanostomy Exclusion criteria: Known allergy to one of the ingredients Pregnant/breastfeeding Infants less than 2 months old Cases of non‐bacterial otorrhoea Patients given high‐dose corticosteroids Patients unable to attend follow‐up Potentially complicated cases (e.g. cholesteatoma) Patients who had previously received an ototoxic therapy No treatment with antibiotics within 2 weeks of start of the trial
Interventions	Intervention (n = 50 ears): trimethoprim (1 mg/mL), sulphacetamide (5 mg/mL) and polymyxin B (10,000 units/mL) (Burroughs Wellcome Ltd), ear drops, 8 drops/12 hours. Duration of treatment: up to 3 weeks (average treatment time for those with 'success' was 16.4 days). Comparator group (n = 50 ears): gentamycin (Garamycin), 0.3% (3mg/mL), ear drops, 8 drops/12 hours. Duration of treatment: up to 3 weeks (average treatment time for those with 'success' was 22.8 days). Concurrent treatment: aural toileting: dry mopping and suction cleaning before each treatment. No details on method. No further details on any other treatment.
Outcomes	Outcomes of interest in the review: Primary outcomes: Resolution of ear discharge or "dry ear" (whether otoscopically confirmed or not) measured at between 2 to 4 weeks. Unclear if otoscopically confirmed. Ear pain (otalgia) or discomfort or local irritation 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. If this is not available, the pure‐tone average of the thresholds measured will be reported. Ototoxicity: this was 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	No information provided
Declarations of interest	No information provided
Notes	Unit of randomisation: person Methods for reporting outcomes of patients with bilateral disease: it does not appear that any consideration of the correlation of results between ears has been taken into account. If there was a treatment failure 'ears' were transferred to the alternative groups. These results have not been included in the analysis. If an ear was not dry on review at 6 months, treatment for 3 weeks with the alternative treatment was completed with review after 6 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: (translated) "We used the method minimisation technique of Taves to allocate the patients to the treatment groups using the type of infection as the principal criterium." Comment: references are given to support the method of participant selection
Allocation concealment (selection bias)	Low risk	Comment: if the Taves method of minimisation was used correctly, it is unlikely that the allocating physician could have predicted the treatment group to which the patient would have been allocated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "double‐blinded study" Comment: no further information provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "double‐blinded study" Comment: no further information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: it appears that all of the participants who started the trial were accounted for in the results
Selective reporting (reporting bias)	Low risk	Comment: no protocol was identified on the WHO clinical trials registry