Ramos 2003.

Study characteristics
Methods	6‐arm, open‐label, parallel‐group RCT, with 7‐day duration of treatment and 10 days of follow‐up; follow‐up to 3 days after finishing the treatment
Participants	Location: Spain Setting of recruitment and treatment: 3 ENT departments of 3 tertiary hospitals Sample size: 300 patients Number randomised: 50 in each group Number completed: 50 in each group Participant (baseline) characteristics: Age (mean, range): 5 to 73, n = 36 (12%) were children (< 14 years) Gender (F/M): 134 (44.7%)/166 (55.3%) Main diagnosis: chronic ear discharge, which comprised the following groups: Simple chronic otitis media (n = 128): no lesions of the ossicular chain, erosion of the tympanic frame, absence of tympanosclerosis and no evidence of cholesteatoma Chronic otitis media with osteolysis (OMCO) (n = 57): osteolytic lesions and alterations of the mucosa of medium type, types of pansclerosis, granulomatous lesions, atelectasis or marginal perforation, without signs of cholesteatoma Chronic cholesteatoma (n = 42): signs of infection of middle cholesteatoma Chronic otorrhoea in operated ears (n = 73): radical mastoidectomy (n = 40), tympanoplasty infection (n = 21), transtympanic grommets (n = 12) 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 had otoscopic examination at baseline; 62.3% had perforation confirmed (marginal perforation: 1.43% non‐marginal perforation: 42% attical perforation) Presence of mucopurulent discharge: otoscopic examination Duration of symptoms (discharge): "for more than 6 weeks or sporadically with 3 or more episodes in the last year" Other important effect modifiers Alternative diagnosis of ear discharge: cholesteatoma (n = 42) Number who have previously had grommets inserted: 12 Number who have had previous ear surgery: 73 Number who had previous antibiotic treatment for CSOM: 65.6% (n = 197) Inclusion criteria: Chronic otorrhoea, meaning that those cases presenting permanent, unilateral or bilateral, otorrhoea for more than 6 weeks, or sporadically, as long as it has manifested 3 or more episodes in the last year, regardless of the origin and morphological changes Exclusion criteria: Pregnant women Patients with renal and/or hepatic impairment patients who had undergone topical or systemic antibiotic treatment during the 48 hours prior to the start of the study Patients with mycotic infections Patients who had concomitant treatment with theophylline or antacids, which include magnesium hydroxide or aluminium hydroxide in the formulation
Interventions	Group A (n = 50): oral ciprofloxacin 500 mg 12‐hourly PLUS topical ciprofloxacin 0.2% 0.5 mL, 8‐hourly for 7 days Group B(n = 50): topical ciprofloxacin 0.3% PLUS fluocinolone 0.5 mL, 8‐hourly for 7 days Group C(n = 50): topical ciprofloxacin 0.5%, 0.5 mL, 8‐hourly for 7 days Group D (n = 50): topical ciprofloxacin 0.2%, 0.5 mL, 8‐hourly for 7 days Group E (n = 50): topical polymyxin 10,000 IU, neomycin 0.0035 g, hydrocortisone 0.00025 g, 8‐hourly for 7 days Group F (n = 50): oral ciprofloxacin 500 mg, 12‐hourly for 7 days Concurrent treatment: not reported
Outcomes	Outcomes of interest in the review: Primary outcome: Resolution of ear discharge ("dry ear"), unclear whether otoscopically confirmed, at 1 to 2 weeks Secondary outcomes: Hearing: hearing tests at time of diagnosis, at 8 days and at 15 days Suspected ototoxicity Suspected ototoxicity: diagnosed with audiogram (specific definition not stated, but study reports 0/125 patients had ototoxicity from treatment) Balance problems/dizziness/vertigo: not reported Tinnitus: not reported
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: "patients were randomly allocated into 6 groups" Comment: insufficient information about the sequence generation. In addition, the study stated that children were not randomised to oral ciprofloxacin: unclear how this was done.
Allocation concealment (selection bias)	Unclear risk	Quote: "patients were randomly allocated into 6 groups" Comment: insufficient information about allocation concealment. There is no information about how they maintained allocation concealment but did not randomise children to ciprofloxacin.
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 is impossible without the use of placebo.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comment: no information provided regarding who assessed the outcomes. For subjective outcomes (otoscopy examinations) the knowledge of treatment group may influence the results.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 2 patients on oral treatment were reported as withdrawn due to gastrointestinal adverse events. Unclear from which group this was and whether these patients were counted in the percentages reported. The percentage of withdrawal is small.
Selective reporting (reporting bias)	Unclear risk	Comment: audiogram was performed at baseline and end of treatment, but not reported