Sambe 1977.

Study characteristics
Methods	2‐arm, double‐blind, multicentre, parallel‐group RCT with 14 days of treatment and follow‐up
Participants	Location: Japan, 73 sites Setting of recruitment and treatment: otolaryngology departments of university and general hospitals Sample size: Number randomised: 302 in group A, 301 in group B Number completed: 213 in group A, 215 in group B Participant characteristics: Age: mean age and absolute range not reported; participants greater than 15 years old, with a subset of participants greater than 71 years old Gender (F/M): 205 (48.0%)/223 (52.0%) Main diagnosis: chronic suppurative otitis media High‐risk population: not reported 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: yes  Duration of symptoms (discharge): not reported Other important effect modifiers: Alternative diagnosis of ear discharge: unclear Number who have previously had grommets inserted: unclear Number who have had previous ear surgery: unclear Number who had previous antibiotic treatment for CSOM: unclear Inclusion criteria: Patients with suppurative otitis media Adult patients (15 years or older) with tympanic membrane perforation Exclusion criteria: Lack of ear discharge Pregnancy or breastfeeding Drug allergy Liver or renal disease Mastoiditis, petrous apicitis or cholesteatoma Post‐ear surgery (except myringoplasty)
Interventions	Group A (n = 302 participants): oral pipemidic acid, 500 mg 4 times a day (2000 mg per day) for 14 days Group B (n = 301 participants): oral aminobenzylpenicillin, 500 mg 4 times a day (2000 mg a day) for 14 days Concurrent treatment: none reported
Outcomes	Outcomes of interest in the review: Primary outcomes: Complete resolution of ear discharge, measured at between 1 week to 2 weeks Ear pain (otalgia)
Funding sources	No information provided
Declarations of interest	No information provided
Notes	Unit of randomisation: person Methods for including patients bilateral disease: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information on methods used for randomisation.
Allocation concealment (selection bias)	Unclear risk	Comment: the allocation code was separate from physicians and participants until the end of the trial. However, no information was provided on the methods to keep allocation concealed (e.g. sealed opaque envelopes etc.).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: participants and personnel were blinded to group allocation, with efforts made to ensure the treatment were indistinguishable.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: the randomisation sequence was kept separate from the outcome assessors until the code was broken at the end of the trial.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: high proportion of missing outcome data, which may have significant impact on the results.
Selective reporting (reporting bias)	Unclear risk	Comment: no study protocol available.