Shamsi Meymandi 2011

Methods	Study design: randomised, prospective, double‐blind trial Setting/location: dermatology clinic and leishmaniasis research centre of Afzalipour hospital of Kerman, province of Iran Study period: 21 months Sample size calculation: not described
Participants	Type of Leishmania: L tropica Inclusion criteria: aged 7–60 years, confirmed CL Exclusion criteria:chronic systemic disease (such as renal failure, myocarditis, hepatitis and pancreatitis), immune suppression, breastfeeding, pregnancy, sporotrichoid and lupoid forms, maximum diameter of lesions > 3 cm, disease duration more than 1 year, more than 2 lesions present, history of sensitisation to MA,facial and joint lesions, receiving other specific anti Leishmania therapies N randomised: 191. Group 1: 96, group 2: 95 Withdrawals: group 1: 16 (14: no follow‐up, 2 enrolled in other treatment), group 2: 15 (8 no follow‐up, 4 enrolled in other treatment, 3 did not adhere to treatment schedule) N assessed: 160 (83.77%). Group 1: participants: 80 (83.33%), group 2: participants: 80 (84.21%) Age: range 7‐60 years Sex (male/female): Randomised patients: group 1: 50(52%)/46 (48%), group 2 39 (41%)/56 (59%). Assessed patients: group 1: 42 (50%)/38 (46%); group 2: 31 (39%)/49 (61%) Baseline data (N lesions): group 1: 80, GB: 80 Locationof the target lesion: Group 1: head and neck 1 (1.3%), upper limb 68 (85%), lower limb 7 (8.8%), trunk 4 (5%) Group 2: head and neck 5 (6.3%), upper limb 64 (80%), lower limb 10 (12.5%), trunk 1 (1.3%) Type of lesions: Group 1: plaque or ulcerated plaque 33 (40.5%), nodule or ulcerated nodule 47 (59.5) Group 2: plaque or ulcerated plaque 25 (31.3%), nodule or ulcerated nodule 55 (68.7%) Case type: New, group 1: 67 (83.3%); group 2: 69 (86.3%) Recurrence, group 1: 0 (0%); group 2: 1 (1.3%) Failure of previous treatment, group 1: 8 (10%); group 2: 0 (0%) Missed previous treatment, group 1: 5 (6.3%); group 2: 10 (12.5%)
Interventions	Type of interventions: Group 1: CO₂ laser. Lesions were locally anaesthetised by injection of 2% lidocaine. The CO₂ laser (6–8 W continuous wave) was applied to the lesions and an area 2–3 mm² around it. The procedure was repeated until the ulcer bed turned brown (maximum 3–5 times) Group 2: participants were treated with combined cryotherapy (biweekly) and ILMA (weekly). Cryotherapy with liquid nitrogen was performed using dipstick technique. Then ILMA (Amp 1.5 gr in 5 Ml solution) was injected in lesions Duration of intervention: 16 weeks
Outcomes	Clinical cure of the lesions: defined as complete re‐epithelialisation of 100% (± scar), complete flattening of induration Laboratory cure of the lesions: negative smear of the lesions compared with baseline Cure rate based on weeks of follow‐up Adverse effects of 2 types of treatments Time points reported: weeks 2, 6, 12 and 16
Notes	Study funding sources: not reported Possible conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was generated by the use of a randomisation Table. A simple block randomisation list with block size of 4 was prepared by a member of the study.
Allocation concealment (selection bias)	Unclear risk	Quote: "The randomisation allocation concealment was performed by sending the randomisation number in envelopes to a member who was responsible for giving the assigned treatment after each eligible patient was enrolled. The recruited patients were referred to this member to receive their assigned treatments." Comment: unclear because no mention of opaque and numbered envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open trial
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgment
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There were 31 withdrawals (16/96 (16.7%) in the ILMA + cryotherapy and 15/95 (15.8%) in the CO₂ laser group) Comment: no ITT analyses were performed. However, withdrawals accounted for < 20% and were homogeneous among the treatment groups.
Selective reporting (reporting bias)	Unclear risk	Protocol not available. Not registered. Some pre‐specified outcomes were reported. Data on individuals not presented. Conflicting data is presented between the abstract and the tables
Other bias	Unclear risk	There was not enough information in the publication to assess if there were other biases present.