Jaffary 2014b

Methods	Study design: randomised parallel clinical trial Setting/location: Skin Diseases and Leishmaniasis Research Center (SDLRC), Isfahan, Iran Study period: not described Sample size calculation: not described
Participants	Type of Leishmania: not described Inclusion criteria: 6‐60 years old, with positive results of leishmaniasis smear test Exclusion criteria: size of lesion > 3 cm, > 5 lesions, lesion duration > 12 weeks, lesion located on the eyelid or < 2 cm away from the eye, pregnant or lactating N randomised: 165, 55 in each of 3 treatment groups Withdrawals: 7; 3 (5.5%), participants were in the concentrated boiled extract group and 2 (3.6%) participants in the other groups withdrew from the study due to the allergic reaction to the medications N assessed: 158. Concentrated boiled extract of Cassia fistula: 52; hydroalcoholic extract of C fistula: 53; ILMA: 53 Mean (SD) age: boiled extract of C fistula: 20.6 years (12.4); hydroalcoholic extract of C fistula: 19.8 years (11.5); ILMA: 22.9 years (13.6) Sex (n,(%)): boiled extract of C fistula: male: 35 (63.6), female: 20 (36.4); hydroalcoholic extract of C fistula: male: 29 (52.7), female: 26 (47.3); ILMA: male: 25 (45.5), female: 30 (54.5) Baseline data: Location of lesions (n(%)): Concentrated boiled extract of C fistula: foot 9 (16.4), hand 25 (45.5), trunk 5 (9.1), head and neck 8 (14.5), hand and foot 8 (14.5). Hydroalcoholic extract of C fistula: foot 11 (20), hand 23 (41.8), trunk 6 (11), head and neck 10 (18.2), hand and foot 5 (9.1). ILMA: foot 8 (14.5), hand 24 (43.6), trunk 5 (9.1), head and neck 11 (20), hand and foot 7 (12.7) Mean number of lesions (SD): Concentrated boiled extract of C fistula: 1.8 (1.13) Hydroalcoholic extract of Cassia fistula: 1.72 (0.98) ILMA: 2.03 (1.07) Kind of lesions (n(%)): Concentrated boiled extract of C fistula: nodule 23 (41.8), papule 17 (30.9), papule and nodule 15 (27.3) Hydroalcoholic extract of C fistula: nodule 30 (54.5), papule 11 (20), papule and nodule 14 (25.5) ILMA: nodule 39 (70.9), papule 5 (9.1), papule and nodule 11 (20)
Interventions	Type of interventions: Group 1: concentrated boiled extract of C fistula. 500 g of C fistula was powdered and then mixed with water with ratio of 1:3, then boiled for 30 minutes and concentrated by distillation in vacuum condition. Group 2: hydroalcoholic extract of Cassia fistula on the lesions. 500 g of C fistula was powdered and mixed with 70% ethanol with ratio of 1:3, then placed in a percolator. After 48 hours, extraction was performed. The extract was then concentrated using distillation in vacuum condition. Group 3: ILMA. 0.5‐2 mL twice a week Duration of intervention: until complete resolution of the lesion (complete epithelialisation) or for a maximum duration of 4 weeks. Follow‐up: 3 months after completing the project, they were examined every month to assess the recurrence of the lesions
Outcomes	Clinical and parasitological cure: lesions were considered completely cured (improvement), if the participants achieved both clinical and parasitological resolutions (negative results of direct smear). Participants were considered resistant to the treatment, if no clinical changes were observed in the lesion or it was worsened. Time to healing: comparison of complete cure time of the cutaneous Leishmaniasis lesions between 3 groups Adverse effects: allergic reaction to the medications Time points reported: week 1, 2, 3, 4, 16, complete cure
Notes	Study funding sources: the study was self‐funded Possible conflicts of interest: there was no conflict of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The participants were randomly allocated to 3 groups using table of random numbers.
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Different administration of treatments: 2 groups: apply the extract‐soaked gauze; third group: ILMA
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons (allergic reaction to the medications) of withdrawals were similar and small in 2 of the groups 3.5% (3/28) in concentrated boiled group vs 3.6% (2/28) in the other groups.
Selective reporting (reporting bias)	Low risk	The study published reports our primary outcomes: cured and adverse effects
Other bias	High risk	Sample size calculation and reporting of Leishmania spp involved was not correctly reported