Asilian 1995

Methods	Study design: randomised controlled trial Setting/location: 8 primary health centres around Borkhar, north of Isfahan, Iran Study period: 14 months Sample size calculation: not described
Participants	Type of Leishmania: infections here were thought to be caused entirely by L major parasites, although there is probably some L tropica infection within the city of Isfahan Inclusion criteria: 2 years or older, single lesion that was parasitologically positive, < 5 cm in diameter, at least 3 cm from the eyes, lesion present < 4 months Exclusion criteria: pregnant or nursing mothers, previously treated for leishmaniasis, intercurrent illness or a history of allergy to aminoglycoside N randomised: 251, aminosidine group: 126 (134 lesions); placebo group: 125 (134 lesions) Withdrawals: not described N assessed: aminosidine group: 123 lesions; placebo group: 123 lesions Age (years): aminosidine group: < 15 years: 114, >15 years: 12; placebo group: < 15 years: 105, > 15 years: 20 Sex (male/female): aminosidine group: 64/62; placebo group: 67/58 Baseline data: 12 to 17 participants had papular lesions; 12 to 16 nodular; 76 to 79 nodule‐ulcerative; 11 to 12 flat‐ulcerative, and 13 to 20 plaque‐like lesions. Site of lesion: aminosidine group: limb: 82, head: 35, trunk: 9; placebo group: limb: 90, head: 28, trunk: 7 PR (15% aminosidine and 10% urea): MNL: 1, MDLBT: 1.5 weeks Vehicle: MNL: 1, MDLBT: < 4 weeks
Interventions	Type of interventions: Group 1: paromomycin (PR) (15% aminosidine and 10% urea) in petroleum ointment twice a day Group 2: vehicle Duration of intervention: 14 days Co‐interventions: additional treatment, usually parenteral antimony, was given if lesions were judged to have worsened (25 participants in the PR‐treated group and 28 in the placebo group) Duration of follow‐up: 105 days after starting treatment
Outcomes	Healing rates: percentage of participants 'cured' 2.5 months after treatment. Definite cure was defined as complete epithelialisation on days 45 or 105 Adverse effects Tertiary outcomes: microbiological or histopathological cure of skin lesion Time points reported: 15, 45, 105 days
Notes	Study funding sources: this work was supported in part by he UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR) and Isfahan University of Medical Sciences Possible conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation of treatment was carried out in Geneva (Switzerland) but did not state how that was done.
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Identical ointment tubes were numbered and allocated to consecutive eligible participants.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups (16 drops out of 251, 10%)
Selective reporting (reporting bias)	Unclear risk	The study protocol is not available, but it is clear that the published reports include all expected outcomes, including those that were pre‐specified
Other bias	High risk	Sample size calculation and reporting of Leishmania spp involved was not correctly reported