Loock 2012.

Study characteristics
Methods	Three‐arm, partially blinded, parallel‐group RCT, with up to 8 weeks duration of treatment and follow‐up
Participants	Location: South Africa, Cape Town, 1 site Setting of recruitment and treatment: otology clinic of the ENT outpatient clinic, Tygerberg Hospital; September 2007 to June 2010 Sample size: 159 Number randomised: 53 in ciprofloxacin group, 54 in acetic acid group, 52 in boric acid group (single administration) Number completed: 45 in ciprofloxacin group, 44 in acetic acid group, 49 in boric acid group (single administration) Participant (baseline) characteristics: Age: average 25 to 26 years (90% range: 20 to 34) Gender (F/M): 55.3%/44.7% Main diagnosis: otorrhoea because of active mucosal COM High‐risk population: no Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: none (exclusion criteria) Diagnosis method: Confirmation of perforated tympanic membrane: yes (ear cleaning until perforation was visible (see concurrent treatment section)). Perforation size at baseline was: 35% acetic acid group; 28% boric acid powder group; 35% ciprofloxacin group. Presence of mucopurulent discharge: not reported Duration of symptoms (discharge): not reported Other important effect modifiers: Alternative diagnosis of ear discharge: 0% Number who have previously had grommets inserted: none (exclusion criterion) Number who have had previous ear surgery: none (exclusion criterion) Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Aged over 6 years of age presenting with otorrhoea because of active mucosal COM Exclusion criteria: Cholesteatoma Signs of tuberculous otitis media Systemic immunosuppressive disease (e.g. diabetes mellitus, HIV/AIDS) Grommets (ventilation tubes) Aural polyp A history of previous middle ear surgery Local ear treatment or systemic antibiotics within the previous week
Interventions	Topical antibiotics (n = 53): ciprofloxacin, ear drops (no concentration given), 6 drops, 2 times per day for an unspecified period (likely to be 4 weeks) Topical antiseptics (acetic acid) (n = 54): 1% acetic acid, ear drops, 6 drops, 2 times per day for an unspecified period (likely to be 4 weeks) Topical antiseptics (boric acid)(n = 52): boric acid powder, single administration. After ear toilet and flushing of the middle ear and Eustachian tube with 6 drops of saline, the clinician 'tapped' boric acid powder into the external ear canal using a 50 mL 'urological' syringe with a wide mouth, an aural speculum and ambient light and compacted the boric acid powder into the external ear canal using an 'ear bud' until the external ear canal was filled with powder. The patient was instructed not to disturb the boric acid powder and to keep the ear dry. Concurrent treatment: Aural toileting: at the first visit the clinician performed ear toilet by syringing the ear using a naked eye and ambient light only, a 50 mL syringe with a Luer lock and an angled 1 mm diameter suction tip, a clean technique and clean body‐temperature tap water, with or without dry mopping, until the perforation was clearly visible. Participants were advised not to get water into the ear. No details of other additional treatments were listed. In all cases, ear drops were 'pumped' down the Eustachian tube using tragal pressure, 6 drops/twice per day.
Outcomes	Outcomes of interest in the review: Primary outcomes: Resolution of ear discharge ("dry ear"), measured after 4 weeks. Unclear if otoscopically confirmed. Ear pain (otalgia) or discomfort or local irritation Secondary outcomes: Hearing (measured as change in hearing threshold from baseline or at end point) Serious complications, including intracranial complications (such as otitic meningitis, lateral sinus thrombosis and cerebellar abscess), extracranial complications (such as mastoid abscess, postauricular fistula and facial palsy) and death
Funding sources	"Funding for purchase of the ciprofloxacin eardrops, audiological services and patient follow‐up visits was obtained through research funds generously provided by the ENT Society of South Africa. Funding for the microbiological investigations was generously sponsored by the National Health Laboratory Service of South Africa (NHLS)." "… the investigator received no sponsorship or incentive from manufacturers of any of the treatments used."
Declarations of interest	"There was no conflict of interest …"
Notes	Unit of randomisation: person Methods for including patients with bilateral disease: not stated This was a 3‐arm trial, but only 2 arms (acetic acid and boric acid) are relevant for this review. Although some results are given at 8 weeks, these are only for the participants who failed initial treatment. Therefore only the 4‐week results are presented.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated randomised series (Randomisation.com) generated for three groups in 30‐patient blocks …" Comment: appropriate sequence generation
Allocation concealment (selection bias)	Low risk	Quote: "A computer‐generated randomised series …was kept by a pharmacist at a distant site. This pharmacist supplied sequential opaque dispensing envelopes, numbered in advance according to the randomised sequence, containing the allocated treatment. These envelopes were held by the research nurse, who gave the sealed envelope containing the allocated treatment to the investigator after the patient had been enrolled in the trial." Comment: allocation code only revealed after enrolment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "The nurse would then supply the sequentially numbered envelope pre‐prepared by the pharmacist containing the allocated treatment. Each envelope contained an identical unlabelled bottle with one of: 1% acetic acid eardrops; ciprofloxacin eardrops; or normal saline with an added instruction to administer boric acid powder." Comment: although bottles were identical and unlabelled, it is possible to find out the allocated treatment because one of the groups had an additional powder, and it is possible that the acetic acid drops have a characteristic smell
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "At follow‐up, another clinician, unaware of the treatment allocation and hence 'blind' as far as possible, assessed the activity of the ear. Unavoidably, remnants of boric acid powder at times interfered with blinding of this clinician’s assessment…. The main outcome measure was whether the clinician judged the perforation to be inactive (dry), active (wet) or 'moist'." Comment: blinding of outcome assessment was attempted, but it is possible that for some patients the treatment used could be guessed
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: loss to follow‐up was 10/54 (18.5%), 3/49 (5.8%) and 8/53 (15.1%) at the assessment at 4 weeks. The paper states that no participant withdrew but the reasons for loss to follow‐up were not provided.
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available from clinicaltrial.gov or from the South African registry of clinical trials. The outcomes planned in the methods section were presented in the results, even where there was a reason that the outcome was not possible to report. Results of the audiometric tests were not well presented.