Ejaz 2014

Methods	Study design: randomised controlled trial Setting/location: Pakistan at dermatology departments of Combined Military Hospital, Kharian Camtonment, Combines Military Hospital, Quetta and Combined Military Hospital, Muzaffarabad Study period: January 2008 to December 2010 (35 months) Sample size calculation: assuming equal‐sized groups, keeping the equivalence trial design, standardised difference of 0.05 and power at 90%, sample size was calculated as 150 participants in each arm using Altman nomogram. A total of 300 participants were needed for the study and 24 extra participants were recruited to cater for dropouts.
Participants	Type of Leishmania: not described Inclusion criteria: men and women over 18 years of age having parasitologically proven CL requiring systemic therapy, willing for admission to hospital for the study and regular follow‐up visits, and consenting not to use any other treatment for CL during trial Exclusion criteria: pregnant, compromised immune system (i.e. diabetics or cancer patients), diffuse cutaneous or visceral leishmaniasis, complete or incomplete treatment with antimony compounds in the last 3 months, history of hepatic, renal, or cardiovascular disease N randomised: 324. Group 1: 151; group 2: 173 Withdrawals: not described N assessed: 324 (100%) Age: mean 27.9 years (SD 6.5), range 17‐48 years Sex: all were male soldiers Baseline data: most participants (39.2%) had a single lesion, but one participant had 15 lesions. Maximum lesions were found on exposed parts of body, arms and legs accounted for 42.3% and 47.2% of lesions respectively. Plaques were the most common morphological pattern seen (82.7%). Mean (SD) size of lesions at baseline was 28.8 mm (16.1). Group 1: 29.7 mm (16.4); group 2: 28 mm (15.8). Mean induration at baseline was 17.5 mm (11.6). Group 1: 17.7 mm (11.5); group 2: 18 mm (12.8)
Interventions	Type of interventions: Group 1: IMMA (Glucantime, Lot No. 888, Aventis Laboratories, France) 20 mg/kg/d until clinical resolution or for 28 days maximum Group 2: IMMA 10 mg/kg/d + oral allopurinol (Zyloric – 300, Batch No. 2ZMAF, GlaxoSmithKline Pakistan Limited) 20 mg/kg/d Duration of intervention: 28 days maximum
Outcomes	Successful treatment: was defined as complete re‐epithelialisation of the ulcer and disappearance of the induration, or reduction of more than 50% of the ulcer and the indurations areas in relation to the last clinical evaluation Adverse effects: serious adverse event was defined as life‐threatening, or prolongation of existing hospitalisation, or causing persistent or significant disability. Non‐serious adverse effects, not qualifying the above criteria were clinically judged by the investigator to be definitely related, probably related, possibly related, or not related to the trial medication. Time points reported: follow‐up phase lasted 6 months
Notes	Study funding sources: none reported Possible conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple randomisation through a random number table and allocation ratio being 1:1.
Allocation concealment (selection bias)	Unclear risk	"Randomisation sequence generation and allocation of medicine was done by lead investigators at the three research set ups" Comment: no information on the method of allocation concealment was provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded from the treatment groups; however, it is not clear how this was done. No placebo was provided.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "There were 18 dropouts due to various complications, 9 belonging to each group" Comment: ITT analyses were performed.
Selective reporting (reporting bias)	Unclear risk	Protocol not available. The trial was registered with www.anzctr.org.au and the registration number is ACTRN12607000295448. Some outcomes registered in the protocol were not reported: successful treatment; therapeutic failure; reactivation
Other bias	Unclear risk	There was not enough information in the publication to assess if there were other biases present.