Combination, Miltefosine Monotherapy & Antimonial Therapy for Cutaneous Leishmaniasis in New World
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|ClinicalTrials.gov Identifier: NCT04515186|
Recruitment Status : Recruiting
First Posted : August 17, 2020
Last Update Posted : March 25, 2021
|Condition or disease||Intervention/treatment||Phase|
|Cutaneous Leishmaniases||Drug: Meglumine Antimoniate Drug: Miltefosine Device: Thermotherapy machine||Phase 3|
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.
• 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||306 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of Thermotherapy in Combination With Miltefosine Compared to Meglumine Antimoniate and Miltefosine Monotherapy for the Treatment of New World Cutaneous Leishmaniasis: A Phase III, Open Label, Multicenter Randomized Trial|
|Actual Study Start Date :||January 26, 2021|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||March 30, 2023|
Active Comparator: Meglumine Antimoniate
Meglumine Antimoniate, 20 mg/kg/day for 20 days parenterally
Drug: Meglumine Antimoniate
Vials of a 5mL solution. Each vial contains 405 mg of Sb5+ corresponding to 8.1% Sb5+ (81 mg/mL).
Other Name: Glucantime®
Active Comparator: Miltefosine monotherapy
Miltefosine monotherapy 2.5 mg/kg/day for 28 days orally
50 mg capsule
Other Name: Impavido®
Experimental: Thermotherapy + miltefosine
Thermotherapy (one session, 50⁰C for 30" applications*) + miltefosine 2.5 mg/kg/day for 21 days orally.
50 mg capsule
Other Name: Impavido®
Device: Thermotherapy machine
Localized Current Field radio-frequency generating device
Other Name: ThermoMed™
- The proportion of initial clinical cure in each arm. [ Time Frame: Day 90 ]Defined for ulcerated lesions as 100% re-epithelialization of the ulcer(s) on D90 as compared to D1 and for non-ulcerated lesions as flattening and/or no signs of induration of the lesion(s) on D90 as compared to D1.
- The number of patients who fulfil the criteria for clinical improvement at D90 and late responders at D105. [ Time Frame: Days 90 and 105 ]
Clinical improvement is defined for ulcerated lesions as more than or equal to 75% but less than 100% re-epithelization of the ulcer(s) as compared to D1, and for non-ulcerated lesions as more than or equal to 75% but less than 100% of flattening and/ or signs of induration of the lesion(s) as compared to D1.
Late responders isdefined for ulcerated lesions as 100% re-epithelialization of the ulcer(s) on D105 compared to D1, and for non-ulcerated lesions as 100% of flattening and/or no signs of induration of the lesion(s) on D105 as compared to D1.
- The number of patients who fulfil the criteria of initial cure at D90 or late responders at D105 and have no relapse by D180 (final cure). [ Time Frame: Day 180 ]
- Percentage of treatment discontinuation, frequency, severity, causality with each study drug and seriousness of AEs by treatment group. [ Time Frame: Through study completion, i.e up to 6 months ]
- Proportion of lesions with 100% re-epithelialization/flattening at each measurement time point by Leishmania sp. [ Time Frame: Days 7, 14 and 21. At end of treatment (days 21 or 28), and at days 45, 63, 90, 105 and 180. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04515186
|Contact: Byron Aranaemail@example.com|
|Contact: Joelle Rodefirstname.lastname@example.org|
|Fundación Nacional de Dermatología||Not yet recruiting|
|Santa Cruz de la Sierra, Bolivia|
|Contact: Jaime Soto|
|Julio Muller University Hospital Federal University of Mato Grosso||Not yet recruiting|
|Contact: Marcia Hueb|
|Federal University of Bahia Immunology Department||Not yet recruiting|
|Contact: Paulo Machado|
|Instituto Conmemorativo Gorgas de Estudios de la Salud||Recruiting|
|Contact: Juan Miguel Pascale|
|Universidad Peruana Cayetano Heredia||Not yet recruiting|
|Contact: Alejandro Llanos-Cuentas|
|Principal Investigator:||Paulo Machado||Federal University of Bahia|
|Principal Investigator:||Marcia Hueb||Julio Muller University Hospital Federal University of Mato Grosso|
|Principal Investigator:||Alejandro Llanos-Cuentas||Universidad Peruana Cayetano Heredia|
|Principal Investigator:||Juan Miguel Pascale||Instituto Conmemorativo Gorgas de Estudios de la Salud|
|Principal Investigator:||Jaime Soto||Fundación Nacional de Dermatología|