Firooz 2006

Methods	Study design: randomised controlled trial Setting/location: Mashad, Iran Study period: 18 months Sample size calculation: 45 participants per treatment group were needed to have 80% power to detect a significant difference in the expected cure rate of 50% in the vehicle group and the desired cure rate of 80% in the imiquimod‐treated group at week 8 with a type Ierror level of 0.05. To compensate for 20% estimated dropout, 54 participants would be required in each group.
Participants	Type of Leishmania: L tropica endemic in the area Inclusion criteria: parasitologically proven cases of CL based on positive smear or culture, otherwise healthy participants Exclusion criteria: pregnant or lactating women, duration of the lesions > 6 months, number of lesions > 5, any lesions > 5 cm, history of any standard course of treatment with antimonials, history of allergy to antimonials, serious systemic illnesses, participation in any drug trials in the last 60 days N participants randomised (lesions): 119 (252). 59 (128) participants in the imiquimod group and 60 (124) in the vehicle group Withdrawals: 30 participants. Imiquimod group (n = 17): 9 lost to follow‐up, 4 inadequate efficacy, 3 protocol deviation, 1 consent withdrawal. Vehicle group (n = 13): 9 lost to follow‐up, 2 inadequate efficacy, 2 protocol deviation N assessed: 89. 42 participants in the imiquimod group and 47 in the vehicle group Mean (SD) age: 27.0 years (SD 1, range 12‐60). Imiquimod group: 7.4 years (13); vehicle group: 6.5 years (12) Sex: approximately 50%‐55% of the participants were female (35/59 in the imiquimod group, and 31/60 in the vehicle group) Baseline data: Lesions were mainly located on the upper extremities (66.3%) and around 15% to 17% on the face and lower extremities Location of lesions (n (%)): face: imiquimod group: 20 (15.6), vehicle group: 19 (15.3); trunk: imiquimod group: 1 (0.8); vehicle group: 1 (0.8); upper extremity: imiquimod group: 85 (66.4); vehicle group: 82 (66.1); lower extremity: imiquimod group: 22 (17.2); vehicle group: 22 (17.7) Imiquimod group: MNL: 2.2. MDLBT: 13 weeks. MSL: 174 mm² Vehicle group: MNL: 2.0. MDLBT: 13.2 weeks. MSL: 237 mm²
Interventions	Type of interventions: Group 1: imiquimod cream 5% + IMMA Group 2: vehicle + IMMA Duration of intervention: imiquimod and vehicle 3 times per week for 28 days, IMMA 20 mg/kg/d for 14 days Duration of follow‐up: 20 weeks after initiation of treatment
Outcomes	Primary outcome: percentage of participants 'cured' 3.5 months after treatment. Clinical cure of the participants, defined as more than 75% reduction in the size of lesions compared with baseline Secondary outcomes: the relapse rate (defined as a reappearance of lesions at the site or periphery of previously healed lesions or an increase in the size of lesions after initial improvement) was assessed 16 weeks after the end of treatment Adverse effects Time points reported: at the end of the treatment period (week 4) and 4 weeks later Intention‐to‐treat analysis of rates of complete re‐epithelialisation, clinical cure, and clinical improvement at weeks 4, 8,and 20 after initiation of treatment
Notes	Study funding sources: this study was supported by the Small Grants Scheme for Operational Research in Tropical and Other Communicable Diseases from the Joint World Health Organization Eastern Mediterranean Region Division of Communicable Diseases and the Special Program for Research and Training in Tropical Diseases. Possible conflicts of interest: the funding source was involved in the study design, in the writing of the manuscript, and in the decision to submit the manuscript for publication, but not in the collection, analysis, or interpretation of data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomly divided into 2 groups according to a list made by a simple randomisation block design"
Allocation concealment (selection bias)	Low risk	Quote: "The randomisation allocation concealment was performed by sending the randomisation numbers in envelopes to a pharmacist who was responsible for giving the assigned treatment after each eligible patient was enrolled."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Treatment unlikely to be blinded. This study was a single‐blind trial.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "To keep the trial blinded, the physicians who were responsible for evaluation of patients were uninvolved in the process of allocation and drug dispensing and were unaware of the drug used by the patients."
Incomplete outcome data (attrition bias) All outcomes	High risk	Withdrawals: 30/119 (25.2%); no ITT analyses performed
Selective reporting (reporting bias)	Low risk	All relevant outcomes reported
Other bias	Unclear risk	There was not enough information in the publication to assess if there were other biases present.