Khatami 2013

Methods	Study design: randomised, assessor‐blind, controlled clinical trial Setting/location: Kashan, Tehran, Iran Study period: September 2008 to April 2010 (19 months) Sample size calculation: 56 lesions per treatment group were needed to have 80% power to detect a significant difference in the expected cure rate of 60% in the ILMA alone group and the desired cure rate of 85% in the ILMA and either silver or non‐silver dressing‐treated group at week 10 with a type I error level of 0.05. Compensating for a 20% loss‐to‐follow‐up, recruiting 68 (round up to 70) lesions per treatment group looked reasonable.
Participants	Type of Leishmania: L major Inclusion criteria: parasitologically confirmed cases of CL based on positive smear and/or culture; otherwise healthy subjects on the basis of medical history; age of 12‐60 years; willingness to participate in the study and signing the informed consent form (by the participant or his/her parent/guardian in cases younger than 18 years). Exclusion criteria: pregnant or lactating women; duration of lesion more than 3 months; number of lesions more than 5; ulcer size greater than 5 cm in largest diameter; history of receiving full course standard treatment (antimonials); history of allergy to MA or silver; serious systemic illnesses (as judged by the physician); participation in any drug trials in the last 60 days; indication for systemic treatment with MA; presence of secondary bacterial infection of the lesion according to clinical appearance N randomised: 83 participants (158 lesions) ILMA: 26 participants (45 lesions); ILMA + non‐silver dressing: 26 participants (53 lesions); ILMA + silver dressing: 31 participants (60 lesions) Withdrawals: 10 participants (18 lesions) N assessed: 73 (140 lesions) Mean (SD) age: 28.81 years (14.45). ILMA: 32.88 years (12.92); ILMA + non‐silver dressing: 30.31 years (15.41); ILMA + silver dressing: 24.13 years (13.97) Sex: male 39; ILMA: male 8; ILMA + non‐silver dressing: male 11; ILMA + silver dressing: male 20 Baseline data: Mean duration of lesions (SD): 7.951 weeks (2.67); ILMA: 8.31 weeks (2.86); ILMA + non‐silver dressing: 8.46 weeks (2.15); ILMA + silver dressing: 7.23 weeks (2.82) Mean number of lesions (SD): 1.90 (1.21); ILMA: 1.77 (1.34); ILMA + non‐silver dressing: 2.00 (1.47); ILMA + silver dressing: 1.94 (1.12) Induration area median (IQR): 169 mm² (79‐433); ILMA: 270 mm² (120‐557); ILMA + non‐silver dressing: 156 mm² (67‐490); ILMA + silver dressing: 141 mm² (48‐346). Ulceration area median (IQR): 6 mm² (1‐25); ILMA: 8 mm² (2‐37); ILMA + non‐silver dressing: 6 mm² (0‐15); ILMA + silver dressing: 6 mm² (0‐24)
Interventions	Type of interventions: Group 1: eligible participants were randomly allocated into 2 groups and treated for 6 weeks with either: Weekly injections of ILMA combined with application of a non‐silver dressing (AtraumanH, Hartmann, CMC Consumer Medical Care GmbH, Germany) on the lesions, or Weekly injections of ILMA combined with application of a silver containing dressing (AtraumanH Ag, Hartmann, CMC Consumer Medical Care GmbH, Germany) on the lesions. Group 2: weekly injections of ILMA (GlucantimeH; Rhodia Laboratories, Rhone‐Poulenc, France) alone Duration of intervention: 6 weeks
Outcomes	Clinical cure (complete healing defined as more than 75% reduction, clinical improvement defined as 50%–75% reduction, and no response to treatment defined as less than 50% reduction in the size of the lesion compared with baseline) Relapse: 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 5 months after the termination of treatment Adverse effects: itching and burning, exudation, oedema, and dermatitis Time points reported: oucomes were assessed at the end of the treatment period (end of week 6), then at 4 weeks and 5 months after the last treatment session
Notes	Study funding sources: the budget of the research project has been provided by the Vice‐Chancellery of Research of Tehran University of Medical Sciences. Possible conflicts of interest: the authors have declared that no competing interests exist.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A random sequence generated by using the online software Random Sequence Generator, which is available at URL: www.random.org [22]. It was done by an investigator with no clinical involvement in the trial. R. Talaee was responsible for enrolment of the patients."
Allocation concealment (selection bias)	Low risk	Quote: "The method for randomisation concealment was to use sequentially numbered, opaque, sealed envelopes (SNOSE). The envelopes were kept in a safe box, which was only accessible to A. Khatami who was responsible for assigning the patients to the interventions."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not stated
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "An assessor who was blinded to the type of treatment visited the patients at weekly intervals during the treatment period and 1‐ month and 5 months after the last treatment session"
Incomplete outcome data (attrition bias) All outcomes	Low risk	An intent‐to‐treat analysis was performed at 2 time points (end of the treatment period (day 42) and one month later (day 72)). The numbers of and the reasons for withdrawals were not significantly different between the 3 groups: 11% ILMA group; 19% ILMA + non‐silver and 6.45% ILMA + silver
Selective reporting (reporting bias)	Low risk	Comment: all relevant outcomes were reported
Other bias	Low risk	Other items assessed correctly reported