Jebran 2014

Methods	Study design: randomised, prospective, double‐blind trial Setting/location: Leishmania Clinic of the German Medical Service (GMS), Darwaze‐e‐Lahory, 1st district, Kabul, Afghanistan Study period: 36 months (2004‐7) Sample size calculation: sample size was calculated based on the primary outcome (i.e. complete wound healing). A number of 40 participants each was calculated to be necessary to obtain a power of 80% (significance level 5%). A presumed dropout rate of 20% led to a minimum total enrolment of 100 participants
Participants	Type of Leishmania: L tropica Inclusion criteria: male or female participants of the GMS Clinic; 5 years of age or older; with non‐ulcerated (papule/nodule) or ulcerated lesions (ulcer with or without crust); presence of at least one parasitologically confirmed CL lesion and no prior history of leishmaniasis and/or anti‐parasitic treatment Exclusion criteria: participants below age 5; with the presence of CL lesion(s) on or immediately adjacent to the nose, lips or eyes; pregnancy, or serious co morbidities N randomised: 135. Group 1: 73; group 2: 62 Withdrawals: due to protocol breach: group 1, n = 14; group 2, n = 8. Lost to follow‐up: group 1, n = 21; group 2, n = 22 N assessed: 113 (83.7%): group 1: 59 (80.82%); group 2: 54 (87.09%). Mean age (range): group 1: 18.62 years (5‐66); group 2: 18.16 years (6‐63) Sex (male/female): 93/42; group 1: n = 51/22; group 2: n = 42/20. Baseline data: Lesion type: group 1: papule or nodule: 24, ulcer: 49; group 2: papule or nodule: 17, ulcer: 45 Location of the target lesion: group 1: 22 face, 2 shoulder/neck, 42 upper extremity, 7 lower extremity; group 2: 14 face, 0 shoulder/neck, 44 upper extremity, 4 lower extremity MLDBT (range): group 1: 2.92 months (1‐12); group 2: 2.61 months (1‐9) Giemsa smear: group 1: G0 (no amastigotes (AM)): 2, G 1 (1–10 AM): 49, G2 (11–100 AM): 7, G3 (> 100 AM): 15; group 2: G0 (no AM): 0, G 1 (1–10 AM): 40, G2 (11–100 AM): 11, G3 (> 100 AM): 11 Parasite load in the 1st biopsy (Leishmania per gram tissue): mean (SEM): group 2: 9.14 (2.85) × 107; group 2: 1.54 (0.83) × 108. Wound surface after EC treatment: mean (SEM): group I: 347.9 mm³ (23.39); group 2: 391.9 mm³ (27.80)
Interventions	Type of interventions: Group 1: superficial coagulation and removal of lesion tissue was performed using bipolar high‐frequency electrocauterisation (EC; also termed high‐frequency electrocoagulation) with the help of the electrosurgical Mini Cutter HMC 80 HF. After EC, a polyacrylate hydrogel with freshly prepared 0.045% (w/w) pharmaceutical sodium chlorite (sodium chlorosum, DAC N‐055) gel was applied to the lesions, daily Group 2: superficial coagulation and removal of lesion tissue was performed using bipolar high‐frequency electrocauterisation (EC; also termed high‐frequency electrocoagulation) with the help of the electrosurgical Mini Cutter HMC 80 HF. After EC, a polyacrylate hydrogel without DAC N‐055 Duration of intervention: time to wound closure Co‐interventions: systemic antibiotics were only given if bacteria were detected and the wound infection was severe. Neither local nor systemic antifungal therapy was allowed to exclude anti‐protozoal effects on the Leishmania infection
Outcomes	Primary outcome ‐ time to wound closure (days): the time needed for complete epithelialisation of the lesion wound was defined and photodocumented. Secondary outcome ‐ microbiological cure: the parasite load (Leishmania/g) of the lesions was taken prior to electrocauterisation (1st time), after wound closure (2nd) and after 6 months (3rd) Adverse effects: such as bacterial or fungal superinfections of the wounds, the formation or scars and the rate of re‐ulcerations were monitored during the treatment and follow‐up period
Notes	Possible conflicts of interest: not described Study funding sources: this study was supported by the German‐Academic Exchange Service (travel grants to KWS, AFJ and FM), the Senior Expert Service (travel grants to KWS) and the Interdisciplinary Center of Clinical Research at the Universitätsklinikum Erlangen (IZKF, project A49 to US and CB). The founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "subjects were randomly assigned with the help of a GMS computer at a ratio of 1:1"
Allocation concealment (selection bias)	Unclear risk	Quote: "RS and KWS were responsible for the enrolment of the patients and their assignment to the treatment groups." Comment: not further information was provided regarding the method for allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The participants, the medical personnel treating and evaluating the patients, the investigators analysing the clinical course of treated lesions, as well as the lab members performing the parasitological analyses were blinded. The preparation of the two different gels (marked as jelly A and B), which could not be visually distinguished, was performed by a technician who was not involved in the treatment of patients".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The participants, the medical personnel treating and evaluating the patients, the investigators analysing the clinical course of treated lesions, as well as the lab members performing the parasitological analyses were blinded. The preparation of the two different gels (marked as jelly A and B), which could not be visually distinguished, was performed by a technician who was not involved in the treatment of patients".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	14 participants of group 1 and 8 participants of group 2 were retrospectively excluded due to deviations from the study protocol. For the follow‐up analysis, 6 months after wound healing, only 70 participants could be included, as 21 participants of group I and 22 participants of group II did not observe their appointments.
Selective reporting (reporting bias)	Low risk	Main outcomes were included. Trial was registered at clinicaltrial.gov: NCT00947362
Other bias	Low risk	Other items assessed correctly reported