de Miguel 1999.

Study characteristics
Methods	5‐arm, non‐blinded, parallel‐group RCT, with 7 days duration of treatment and 15 days duration of follow‐up
Participants	Location: Canary Islands, Spain Setting of recruitment and treatment: general hospital, published in 1999 Sample size: 125 Number randomised: 25 in group A, 25 in group B, 25 in group C, 25 in group D, 25 in group E Number completed: 25 in group A, 25 in group B, 25 in group C, 25 in group D, 25 in group E Participant (baseline) characteristics: Age (mean, range): 39.6 years, 6 to 83, but 17/125 of participants were children Gender (F/M): 56 (44.8%)/69 (55.2%) Main diagnosis: chronic otitis media, which comprised the following groups: Simple chronic otitis media ‐ no osteitic changes, tympanosclerosis or cholesteatoma (n = 45) Osteitic chronic otitis media ‐ with changes to the ossicular chain and some permanent alterations in the mucosa (tympanosclerosis or chronic granulomatosis) (n = 32) Cholesteatomatous chronic otitis media (n = 17) Post‐surgery cases (n = 31) 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: all patients had otoscopy under microscopy at entry. 51.2% had "non‐marginal tympanic perforation". The involvement of the ossicular chain in the otological microscopic examination was found in 43.2% of the patients. Presence of mucopurulent discharge: 113/125 (90.4%), 89/125 (71.2%) with odorous discharge Duration of symptoms (discharge): not reported Other important effect modifiers Alternative diagnosis of ear discharge: cholesteatoma (n = 17) Patients with discharge after operation: unclear type/reason for operations (n = 31) Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: at least 31/125 (24.8%), reasons and type of surgery not reported Number who had previous antibiotic treatment for CSOM: 79/125 (63.2%) Inclusion criteria: Patients (adults and children) with chronic otitis media, presenting with chronic otorrhoea as major symptom. Diagnostic criteria not reported. Exclusion criteria: not reported
Interventions	Group A(n = 25): oral ciprofloxacin, 500 mg/12 hours for 7 days Group B(n = 25): topical ciprofloxacin 0.2%, 3 ear drops/8 hours for 7 days Group C(n = 25): topical ciprofloxacin 0.5%, 3 ear drops/8 hours for 7 days Group D (n = 25): topical ciprofloxacin 0.2%, 3 ear drops/8 hours for 7 days and oral ciprofloxacin, 500 mg/12 hours for 7 days simultaneously Group E (n = 25): topical polymixin B + neomycin + hydrocortisone, 3 ear drops/8 hours for 7 days Concurrent treatment: all patients had aspiration and cleaning of ear secretions before beginning treatment; analgesics and antipyretics
Outcomes	Outcomes of interest in the review: Primary outcome: Resolution of ear discharge at 1 to 2 weeks. Unclear if otoscopically confirmed. Secondary outcomes: Hearing: hearing tests at time of diagnosis, at 8 days and at 15 days Suspected ototoxicity
Funding sources	No information provided
Declarations of interest	No information provided
Notes	Unit of randomisation: person Methods for including patients with bilateral disease: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "125 patients were analysed for two years attending to health system with chronic otorrhea as the mean symptom" Comment: insufficient information about the sequence generation process to permit judgement
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were randomized to five therapeutic groups" Comment: insufficient information about allocation concealment method provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: no information provided about blinding method or use of placebo. The treatment arms involved different dosage forms (oral versus ear drops) – blinding of these interventions impossible without use of placebo.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comment: no information provided regarding to who assessed the outcomes. For subjective outcomes (otoscopy examinations, hearing test or adverse events) it is probable that the knowledge of treatment group has influenced the results.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: no dropouts or missing data reported; no statements about missing data
Selective reporting (reporting bias)	Unclear risk	Comment: insufficient information to permit judgement of 'low risk' or 'high risk'; protocol for trial not available