Aronson 2010

Methods	Study design: randomised, prospective, double‐blind trial Setting/location: Walter Reed Army Medical Center (WRAMC) in Washington Study period: 24 months (2004‐6) Sample size calculation: a sample size of 27 participants per treatment group was planned, assuming a 73% cure rate for ThermoMed (TM), 99% for SSG, controlling for a probability of a type I error at alpha = 0.05 and was predicted to have 80% power to determine a 26% difference in outcome.
Participants	Type of Leishmania: L major Inclusion criteria: eligible participants were Department of Defense healthcare beneficiaries with parasitologically confirmed cutaneous leishmaniasis. At Walter Reed Army Medical Center (WRAMC) in Washington. All participants were likely infected in Iraq or Kuwait. All were treatment naive. Exclusion criteria: 20 lesions; pregnancy, lactation; hypersensitivity to pentavalent antimonials or local anaesthetic; serious medical illness; lesion in proximity to mucous membranes, face, or cartilage; implanted metallic devices; unwillingness to avoid procreation for at least 2 months N randomised: 56, IVSSG: 28. Localised TM device heat treatment: 28 Participants with clinical failure at 2 months were offered cross‐over treatment. Afer 2 months: SSG: 29 (−1, +3), TM: 25 (−3, +1). Withdrawals: 2. TM: 1 (lesion not amenable to heat), SSG: 1 (not confirmed L major) N assessed: 54 (96.43%) completed treatment: TM: 27 (96.43%), SSG: 27 (96.43%). 53 (94.64%) completed 12 months follow‐up: TM: 27 (96.43%), SSG: 26 (92.86%) Median age (range): TM: 25 years (20‐53); SSG: 24 years (18‐57) Sex: TM: males: 28 (100%), SSG: males: 27 (96%), females: 1 (4%) Baseline data: Mean number of lesions (range): TM: 2 (1‐14), SSG: 3 (1‐17) Mean duration of lesions (range): TM: 126 days (45–231), SSG: 138 days (50–270) Amastigotes present (%): TM: 22 (79), SSG: 18 (64) Culture isoenzyme L major* (%): TM: 12/23 (52), SSG: 12/24 (50) L major spp PCR positive: TM: 28 (100), SSG: 27 (96) Complicated leishmaniasis, presence of significant regional adenopathy or subcutaneous nodules (%): TM: 5 (18), SSG: 8 (29) Location of the target lesion: TM: head and neck 11 (12%), arms 40 (43%), legs 27 (29%), back 11 (12%), chest 5 (5%). SSG: head and neck 6 (6%), arms 65 (67%), legs 14 (14%), back 3 (3%), chest 9 (9%) MSL (range): TM: 155 mm² (9–1014), SSG: 110 mm² (9–1720)
Interventions	Type of interventions: Group 1: quote: "Localized ThermoMed (TM) device heat treatment: one treatment session using the ThermoMed Model 1.8 device (TM). Prior to thermotherapy, each lesion was cleansed, anaesthestized, moistened, and overlying eschar was removed. 2 trained physicians performed TM treatments. TheTM probe was placed on the skin, covering the lesion with 50uCTM treatments applied for 30 s in a grid fashion extending 4 mm into border skin. The lesion size determined the number of applications. Each lesion was then covered with a dressing (Coverlet, Beiersdorf‐Jobst, Wilton CT) that was changed daily." Group 2: IVSSG 20 mg/kg/d for 10 doses (GlaxoSmithKline, UK) Duration of intervention: TM: 1 session. SSG: 10 days. Co‐interventions: participants randomised to thermotherapy received oral antibiotics for secondary bacterial infections of the leishmaniasis lesion(s) prior to treatment. SSG arm participants were treated concurrently with antibiotics. Follow‐up: 2, 6, and 12–24 months post‐treatment.
Outcomes	Clinical cure of the lesions: clinical cure was defined as complete epithelialisation or visually healed at 2 ± 1 month after completion of therapy and no reactivation in 12 months after the start of treatment. Clinical failure was less than complete epithelialisation or visually not healed at 2 ± 1 month after treatment completion. Relapse failure was defined as skin lesion persistence at the treatment site or elsewhere in the period up to 12 months after start of therapy, regardless of appearance at 2 ± 1 month after treatment completion Laboratory cure of the lesions: microbiological cure: they looked for an eradication of the infection Time to healing: survival analysis of time to healing for the 2 treatment arms Adverse effects: toxicity profile Time points reported: 2, 6, 12 months. Toxicity profile: daily physician evaluations
Notes	Study funding sources: this trial was supported by Walter Reed Army Medical Center, The North Atlantic Regional Medical Command, and the US Army Medical and Materiel Development Agency. 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	The statistician (RH) generated the randomisation plan in blocks of 4 subjects using www.randomization.com. The research pharmacist made assignments using the randomisation plan in sequential order.
Allocation concealment (selection bias)	Low risk	The allocation sequence was unavailable to investigators until completion of the trial
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Sequential photographs were independently assessed by blinded leishmaniasis experts, who were clinicians experienced in the treatment of CL, with a tiebreaker assessment when needed.
Incomplete outcome data (attrition bias) All outcomes	Low risk	2/56 withdrawals. An ITT analysis was performed
Selective reporting (reporting bias)	Low risk	Clinical Trial Registration: ClinicalTrials.gov NCT 00884377; all prespecified outcomes were reported
Other bias	Low risk	Other items assessed correctly reported