Stahl 2014

Methods	Study design: single‐centre, 3‐armed, open label, randomised, controlled, phase IIb trial Setting/location: Leishmania and Malaria Centre (LMC) of the Provincial Balkh Civil Hospital Mazar‐e‐Sharif (Afghanistan) Study period: November 2010 to March 2011 (15 months) Sample size calculation: the sample size calculation was based on the per protocol (PP) analysis, defined as all participants evaluable with respect to the primary endpoint
Participants	Type of Leishmania: in 44/69 participants analysed, 28 (64%) lesions were infected with L tropica and 16 (36%) with L major Inclusion criteria: CL lesions with Leishmania‐positive Giemsa smears without prior CL treatment Exclusion criteria: age < 12 years; more than one skin lesion (to exclude intra‐individual variations in this phase IIb analysis); lesion age > 3 months; lesions located on eye lids, lips or nose; drug addiction; coinfection with Mycobacterium tuberculosis, HIV, or diabetes N randomised: 87 participants: group 1, 24 (27.5%), group 2, 32 (36.8%), and group 3, 31 (35.6%) Withdrawals: lost after registration: group 2, 3; group 3, 3. Not followed up for the full treatment period: SSG, 1; group 2, 6; group 3, 3. Mixed treatment: group 3, 2 N assessed: 81 (93.10%). group 1: 24; group 2: 29; group 3: 28 Mean age: 29 years (95% CI 25–33) Sex (male/female): 32 (46%)/37 (54%) Baseline data: comparable in all 3 regimens
Interventions	Type of interventions: Group 1: intradermal injections of 0.6 mL SSG according to a protocol used by Zeglin 2009 Group 2: aseptic MWT with 0.045% DAC N‐055 following a single initial superficial wound debridement with HF‐EC, which was performed under local anaesthesia after wound cleansing and disinfection with gauzes soaked in physiological saline solution containing 320 ppm chlorine dioxide (pH 5.5 acidified 0.09% DAC N‐055) for 15 min Group 3: MWT with 0.045% DAC N‐055 alone Duration of intervention: for all groups: daily treatments (with the exception of Fridays) during the first week, followed by topical treatments at the centre twice a week until the end of week 4 and thereafter once a week until wound closure In group 1, the SSG treatment was discontinued after week 4. In groups 2 and 3, participants dressed their lesion themselves after week 4 with the topical NaClO₂‐basic‐crème between their visits at the centre until lesion closure
Outcomes	Primary outcome was the ratio of closed versus open wounds at day 75 (D75) in the PP analysis for each regimen Speed of healing: not reported in Methods Adverse effects: not reported in Methods 6 visits were scheduled in the first week, 2 visits per week from weeks 2 to 4, and 1 visit per week thereafter until complete wound closure. Follow‐up visits were required once a month until day 180 after treatment start
Notes	The funders had no role in study design, data collection, data analysis, and interpretation, decision to publish, or preparation of the manuscript. KWS and HCS are members of the Board and CB is a member of the non‐profit NGO Waisenmedizin PACEM e.V. promoting access to essential medicine
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Each patient was randomly assigned to one of the 3 regimens by the random allocation generator in the computer‐based Leishmedoc system."
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study was described as open and no blinding was done
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "the present trial could not be conducted as either a double or a single blinded trial due to the physical nature of the applied interventions"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "The intention‐to‐treat analysis (ITT) is solely added as additional information. Patients that could not be evaluated were patients that were lost immediately after registration before treatment started. 81 out of 87 patients (93.1%) were suitable for the ITT and 69 (79.3%) for the PP analysis"
Selective reporting (reporting bias)	Low risk	Clinicaltrials.gov ID: NCT00996463. Registered: 15 October 2009
Other bias	Low risk	Other items assessed correctly reported