Layegh 2009

Methods	Study design: randomised, prospective, double‐blind trial Setting/location: Dermatology Clinic of Qaem Hospital in Mashad, Iran Study period: 10 months Sample size calculation: to detect a 22% difference in the cure rate between cryotherapy and ILMA groups and assuming a 57% cure rate in the cryotherapy group, with a 65% power and a 10% 2‐sided type I error, 40 persons were needed in each group. The 79 participants who met our criteria were randomly divided into 2 groups: 40 participants received cryotherapy and 39 participants received ILMA
Participants	Type of Leishmania: L tropica Inclusion criteria: positive direct skin smears for CL, were ≤ 13 years of age, had visited the dermatology clinic from September 2006 through June 2007, and had lesions with a duration of < 12 weeks to exclude any natural self‐healing during follow‐up Exclusion criteria: > 13 years of age, had a lesion history > 3 months, allergic to antimonial drugs, simultaneously using any other therapeutic method N randomised: 79. Cryotherapy: 40, ILMA: 39 Withdrawals: 7: cryotherapy group: 4, ILMA: 3 N assessed: 72 (91.14%): cryotherapy group: 36 (90%), ILMA: 36 (92.31%) Mean (SD) age: 6.8 years (3.4) in cryotherapy group and 6.2 years (3.4) in ILMA group Sex (male/female): cryotherapy: 18/22; ILMA: 20/19 Baseline data: Mean number of lesions (SD): cryotherapy: 1.9 (1.02); ILMA: 1.4 (0.76) Location of lesions by site: Head and neck: cryotherapy: 24, ILMA: 31 Upper limb (hand): cryotherapy: 10, ILMA: 13 Lower limbs (foot): cryotherapy: 4, ILMA: 3 Type of lesion: Papule/plaque: cryotherapy: 35, ILMA: 37 Nodule: cryotherapy: 2, ILMA: 3 Ulcer: cryotherapy: 1, ILMA: 2 Mean duration of lesions (SD): cryotherapy: 11.2 weeks (11.8); ILMA: 12.1 weeks (18.4)
Interventions	Type of interventions: Group 1: cryotherapy group: liquid nitrogen (−195°C) was applied twice to the lesion. Each cycle was 10–15 s of freezing time with a thawing interval of 20 s. Care was taken to ensure that freezing reached up to a few millimetres within the healthy skin surrounding the lesion Group 2: ILMA (Glucantime; Specia, Paris, France) in a volume of 0.5–2 cm³ was injected into each lesion until the lesion was completely infiltrated (blanched) Duration of intervention: 6 weeks
Outcomes	Clinical cure: complete cure was defined as full re‐epithelialisation; disappearance of oedema, induration, and other signs of inflammation; and a negative direct skin smear result. Score: Complete improvement (full re‐epithelialisation of the lesions and a negative direct skin smear result), Significant improvement (decrease in induration size > 75%), Partial improvement (decrease in induration size between 50% and 75%, Slight improvement (decrease in induration size between 25% and 50% No improvement (decrease in induration size < 25%) Time to healing Adverse effects Time points reported: at the end of treatment and 6 months (clinical cure); at 4, 5 and 6 weeks (time to healing); at the end of treatment, after 6 weeks (adverse effects)
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)	Unclear risk	Comment: insufficient detail was reported about the method used to generate the allocation sequence.
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open trial
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Open trial; lesions of all participants were photographed.
Incomplete outcome data (attrition bias) All outcomes	Low risk	4 participants in the cryotherapy group and 3 participants in the ILMA group were excluded because they received 2 medications simultaneously, did not complete the treatment course, did not visit the clinic for follow‐up 6 months later, or changed their address and were lost to follow‐up
Selective reporting (reporting bias)	Low risk	Protocol not available; not registered; however, pre‐specified outcomes of the review were reported
Other bias	Low risk	Other items assessed correctly reported