Esposito 1990.

Study characteristics
Methods	3‐arm, non‐blinded, single‐centre, parallel‐group RCT, with 5 to 10 days of treatment and 24 hours and 14 days follow‐up after end of treatment
Participants	Location: Naples, Italy Setting of recruitment and treatment: Clinic of Infectious Diseases and Otolaryngology, University of Naples Sample size: Number randomised: 20 in each intervention Number completed: 20 in each intervention Participant (baseline) characteristics: Age: mean 38 years Gender (F/M): 29 (48%)/31 (52%) Main diagnosis: mild or moderate "chronic OM in the acute stage" High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: "no patients had diabetes or any other comorbidities" Diagnosis method: Confirmation of perforated tympanic membrane: not reported Presence of mucopurulent discharge: not reported Duration of symptoms (discharge): not specified Other important effect modifiers: Alternative diagnosis of ear discharge: not reported 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: 38/60 (63%) had at least 5 days of antibiotics and did not respond Inclusion criteria: "Mild to moderate chronic OM in acute stage without cholesteatoma or mastoiditis" Exclusion criteria: Younger than 18 years old
Interventions	Topical plus systemic ciprofloxacin (n = 20): topical ciprofloxacin, 3 drops (250 µg/ml in saline solution) locally twice a day, PLUS oral ciprofloxacin 250 mg twice a day Topical ciprofloxacin (n = 20): topical ciprofloxacin, 3 drops (250 µg/ml in saline solution) locally twice a day Oral ciprofloxacin (n = 20): oral ciprofloxacin 250 mg twice a day All interventions given for at least 5 days. Those not cured at 5 days carried on up to 10 days. Concurrent treatment: no other treatment or use of aural toileting was mentioned.
Outcomes	Outcomes of interest in the review: Primary outcomes: Resolution of ear discharge at 1 week (5 to 11 days) and 2 to 4 weeks (19 to 24 days) Secondary outcomes: Suspected ototoxicity (audiometric and vestibular function)
Funding sources	"The ciprofloxacin tablets and powder used in this study were kindly provided by Bayer Italia Spa, Milan, Italy"
Declarations of interest	No information provided
Notes	Topical ciprofloxacin was prepared from ciprofloxacin powder in sterile saline and tested for stability and activity for 10 days. No information about inclusion of patients with bilateral disease.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Ciprofloxacin was randomly administered according to the following schedules ..." Comment: randomisation method not clearly specified. 38/60 patients were previously unsuccessfully treated with at least 5 days of antibiotics – unclear how this was distributed across groups. 12/20 in the oral ciprofloxacin only group had Pseudomonas versus 8/20 in other groups.
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Group A (20 patients), 250 mg orally twice a day; group (20 patients), 3 drops containing 250ug/mL of ciprofloxacin in saline solution locally twice a day; and group C (20 patients), both the previous treatments twice a day." Comment: participants were most likely not to be blinded as the routes of administration (oral versus topical) are different among groups and it is not mentioned that placebo was used.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "Patients were clinically examined before, during (every 2‐3 days) and after the therapy" Comment: not specified who assessed the outcomes or that the assessment method was specifically standardised. "Cure" "improvement" and "failure" seem to be more of a subjective judgement.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no dropout cases were reported. All of the patients randomised are presented in the results of the study.
Selective reporting (reporting bias)	High risk	Comment: there is no protocol for the trial on clinicaltrials.gov or the EU register of clinical trials. Some of the results mentioned in the methods section are not fully presented in the results section. "Cure" or resolution of discharge is only reported at one time point, most likely 14 days after end of treatment. The other time point, 24 hours after end of treatment (i.e. 6 to 11 days), was not reported.