Nassiri‐Kashani 2005

Methods	Study design: randomised controlled trial Setting/location: Iran Study period: October 2000 to February 2001 (5 months) Sample size calculation: to detect a clinically relevant difference of at least 25% between placebo (35% estimated response rate) and itraconazole (60% estimated response rate) in the primary outcome parameter with a power of 90% and a 2‐sided type I error of 5%, a total of 164 subjects (82 in each group) were required. To compensate for dropouts, 20% more participants were enrolled in each group (in total 200 participants).
Participants	Type of Leishmania: L major Inclusion criteria: aged 12‐60 years; presence of parasitologically confirmed lesion(s) of CL; healthiness on the basis of physical examination, medical history, and the results of blood biochemistry and haematology, carried out < 2 weeks before the start of the trial Exclusion criteria: women of child‐bearing age without adequate effective contraception, pregnant or breastfeeding, duration of lesions > 45 days, presence of lesions on the face or near the mucous membranes, > 5 lesions, any lesion with a diameter > 3 cm, history of any systemic antileishmanial therapy, known hypersensitivity/allergy to itraconazole, receiving any drug with known interaction with itraconazole N randomised: 200 Withdrawals: 42 in total. 17 in the Itraconozale group and 25 in the placebo group N assessed: 158 Age: not described Baseline imbalances: comparable with regard to age, sex, and duration of the lesions Group 1: mean number of lesions: 2.5, mean size of lesions: 7.76 mm Group 2: mean number of lesions: 2.2, mean size of lesions: 8.58 mm Duration of < 45 days
Interventions	Type of interventions: Group 1: itraconazole 200 mg once daily Group 2: placebo Duration of intervention: 8 weeks
Outcomes	Healing rates: for clinical assessment a 5‐point scoring system was employed: cure (complete re‐epithelialisation of all of the lesions), moderate improvement (more than 50% reduction in the size of the lesions), mild improvement (less than 50% reduction in the size of the lesions), no change, and worsening Adverse effects: at each visit, all of the participants were asked about any adverse effects. Time points reported: after completion of treatment (8 weeks), and at the end of the 3 months follow‐up (healing rates)
Notes	Study funding sources: supported by a grant from Janssen‐Cilag Pharmaceuticals Inc. Possible conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation sequence was generated from a random number table"
Allocation concealment (selection bias)	Low risk	Quote: "Concealed from the investigator until the data entry was completed and the data bank was locked"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Patients were randomly allocated to receive either itraconazole in the form of two 100‐mg capsules or identical placebo capsules once daily for 8 weeks." Comment: we think the outcome is unlikely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Imbalance in numbers and reasons for missing data across intervention groups (17% itraconozale group; 25% placebo group). Comment: the results for the defaulters were not excluded from the statistical analysis. We think missing outcome data likely to be related to true outcome.
Selective reporting (reporting bias)	Low risk	The study protocol is not available, but it is clear that the published reports include all expected outcomes.
Other bias	Low risk	Other items assessed correctly reported