This randomized, open label, multi-centre, non-inferiority study aims to compare that the combination of thermotherapy (one application, 50⁰C for 30) and 3 weeks of miltefosine (2.5 mg/kg/day for 21 days orally) (here after referred to as combination), is non-inferior to the current recommended first line treatments, meglumine antimoniate (20 mg/kg/day for 20 days parenterally) or miltefosine monotherapy (2.5 mg/kg/day for 28 days orally), for uncomplicated CL cases in the New World.~Primary Objective~• To determine the non-inferior efficacy of the combination in comparison to the standard first line treatment (meglumine antimoniate) and/or to miltefosine monotherapy as measured by the percentage of patients with initial clinical cure at Day 90.~Secondary objectives~Assess the proportion of patients who show clinical improvement at D90 (have more or equal of 75% and less than 100% re-epithelization) and achieve 100% re-epithelization at D105 (late responders).~Assess the proportion of relapses at D180.~Assess the safety and tolerability profile for each regimen (percentage of treatment discontinuation, frequency and severity, causality with each study drug and seriousness of Adverse Events (AEs)).~Assess the time to achieve 100% re-epithelialization/ flattening of ulcerated/ non ulcerated lesions by Leishmania species.~A computer-generated randomization code will be used for patient treatment allocation to one of the three arms indicated and utilizing a 1:1:1 allocation ratio.~Patients assigned to the combination treatment will start treatment at Day 1 and have a follow-up visit on 24 hours to assess safety of thermotherapy. Hereafter, these patients are required to return at Days 7, 14, 21, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy.In Brazil, women of childbearing potential are required to also return on D120 and D150 to perform blood pregnancy tests. Women with irregular menstrual cycle, should return for blood pregnancy tests every two weeks until D150.~Patients assigned to the meglumine antimoniate treatment are required to come at Days 1, 7, 14, 21, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy.~Patients assigned to the miltefosine monotherapy are required to come at Days 1, 7, 14, 21, 28, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy. In Brazil, women of childbearing potential are required to also return on D120 and D150 to perform blood pregnancy tests. Women with irregular menstrual cycle, should return for blood pregnancy tests every two weeks until D150.~Patients who have 100% re-epithelization at D90 are declared cured and appointed to come to their D180 assessment. If at D90 re-epithelization of the ulcer(s) is more or equal to 75% but less than 100%, patients will be defined as having clinical improvement and will be asked to return to D105 for a late responder assessment.
This study evaluates if the combination of thermotherapy (one application, 50⁰C for 30) and 3 weeks of miltefosine is safe and have a comparable cure rate with the current recommended first line treatments comprising meglumine antimoniate for 3 weeks or miltefosine monotherapy for 4 weeks, for the treatment of uncomplicated cutaneous leishmaniasis cases in the New World.