Dastgheib 2012

Methods	Study design: prospective randomised controlled trial Setting/location: dermatology clinic in Saadi Hospital, an academic center in Fars Province, Iran Study period: December 2008 to March 2010 (15 months) Sample size calculation: not described
Participants	Type of Leishmania: L major Inclusion criteria: participants that presented with skin lesions suspicious of CL, not receiving any previous treatment, positive for leishmaniasis with direct smears Exclusion criteria: pregnant and nursing women; children < 12 years old; lesions on the face; disease for more than 3 months; more than 5 active lesions; participants with any serious systemic disease or previous history of sensitivity to MA, allopurinol, or azithromycin; any difficulty in laboratory results before initial treatment (CBC diff, LFT, BUN, Cr); those who refused to sign the written informed consent form N randomised: 86 participants Withdrawals: 14 participants (6 in azithromycin + allopurinol group and 8 IMMA group) one lost follow‐up because of adverse effect N assessed: 71 participants (36 azithromycin + allopurinol group and 35 IMMA group) Mean age (SD; range): 38.2 years (12.6); range 16‐64. Azithromycin + allopurinol group: 39.7 years (12.6); IMMA: 36.8 years (12.8) Sex: 28 females and 53 males (azithromycin + allopurinol group: 13 females and 23 males; IMMA group: 15 females and 20 males Baseline data: most participants in azithromycin + allopurinol group had more than 3 lesions (72.3%) and in the IMMA group most participants also had more than 3 lesions (65.8%)
Interventions	Type of interventions: Group 1: azithromycin capsules (Tehran Chemie Pharmaceutical Company, Tehran, Iran) at a daily dose of 10 mg/kg (maximum dose of 500 mg) + allopurinol tablets (Hakim Pharmaceutical Company, Tehran, Iran) at a daily dose of 10 mg/kg (maximum doses 800 mg) Group 2: IMMA (Aventis Laboratories, France) at a dose of 20 mg/kg of antimony Duration of intervention: group 1, 2 months; group 2, 20 days. Co‐interventions: in case of any secondary bacterial infection, participants were with oral cephalexin for 10 days after which the antileishmanial was administered
Outcomes	Cure rate, assessed as follows: Complete response: complete re‐epithelialisation and relief of induration Partial response: more than 50% re‐epithelialisation and decrease of induration and size of lesion No response: < 50% decrease of induration and size of lesion or worsening of lesion was considered as no response Adverse effects Time points reported: 2 months after completing treatment
Notes	Study funding sources: funded by deputy of research, Shiraz University of Medical Sciences Possible conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A total of 71 participants who met the inclusion criteria in the trial were randomly divided into two treatment groups according to simple even and odd number allocation"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not stated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "Fourteen of 86 patients dropped out due to poor compliance (six patients in the combination therapy and eight in the Glucantime group). The number and reason for their withdrawal were almost the same in both treatment groups. One patient also developed GI complications and headache while taking the combination therapy of azithromycin and allopurinol; therefore, overall 71 subjects completed the study." Comment: no ITT analyses were performed. However, withdrawals accounted for <20% and were homogeneous among the treatment groups.
Selective reporting (reporting bias)	Low risk	Our primary outcomes (cure and adverse effects) were described in Methods and reported in Results
Other bias	Unclear risk	There was not enough information in the publication to assess if there were other biases present.