Trial of Miltefosine in Cutaneous Leishmaniasis (Brazil)

Study Overview
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Brief Summary
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The hypothesis of this trial is that the therapeutic activity and safety of oral miltefosine in Brazilian patients with cutaneous leishmaniasis is similar or superior to the intravenous standard treatment (meglumine antimoniate - Glucantime®).

Official Title
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Clinical Trial to Assess Efficacy and Safety of Orally Administered Miltefosine in Brazilian Patients With Cutaneous Leishmaniasis Compared to the Standard Care as Active Control

Conditions
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Treatment of Cutaneous Leishmaniasis in Brazil.

Intervention / Treatment
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* Drug: Miltefosine.
* Drug: Meglumine antimoniate.
* Drug: Miltefosine.
* Drug: Meglumine antimoniate.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed (untreated) cutaneous leishmaniasis with localized lesions and visualization of amastigotes in tissue samples or a positive culture or diagnosed by polymerase chain reaction (PCR) methods or by intradermal skin testing (Montenegro test). Number of lesions: 1 to 5 ulcerative lesions. Lesion´s diameter: 1 to 5 cm. Disease duration: up to three months. Exclusion Criteria: Safety concerns: Thrombocyte count <30 x 109/l Leukocyte count <1 x 109/l Hemoglobin <5 g/100 ml ASAT, ALAT, AP >3 times upper limit of normal range Bilirubin >2 times upper limit of normal range Serum creatinine or BUN >1.5 times upper limit of normal range Evidence of serious underlying disease (cardiac, renal, hepatic or pulmonary) Immunodeficiency or antibody to HIV Any non-compensated or uncontrolled condition, such as active tuberculosis, malignant disease, severe malaria, HIV, or other major infectious diseases Lactation, pregnancy (to be determined by adequate test) or inadequate contraception in females of childbearing potential for treatment period plus 2 months Lack of suitability for the trial: Negative parasitology (aspirate/smear)or negative Montenegro test Any history of prior anti-leishmania therapy Any condition which compromises ability to comply with the study procedures Concomitant serious infection other than cutaneous Administrative reasons: Lack of ability or willingness to give informed consent (patient and/or parent / legal representative) Anticipated non-availability for study visits/procedures

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.1<br>Cutaneous leishmaniasis patients in Manaus-Amazonas randomized to receive Miltefosine. | Drug: Miltefosine.<br>* Miltefosine: Capsules containing 10 mg or 50 mg miltefosine; administered orally for 28 days at dosage of 2.5 mg/kg body weight per day.<br>* Other names: Impavido.;|
| Active Comparator: 1.2<br>Cutaneous leishmaniasis patients in Manaus-Amazonas randomized to receive Meglumine antimoniate (standard treatment). | Drug: Meglumine antimoniate.<br>* Meglumine antimoniate administered by intravenous route for 20 days at the dosage of 20mg/kg/day.<br>* Other names: Glucantime.;|
| Experimental: 2.1<br>Cutaneous leishmaniasis patients in Corte de Pedra-Bahia randomized to receive Miltefosine. | Drug: Miltefosine.<br>* Miltefosine: Capsules containing 10 mg or 50 mg miltefosine; administered orally for 28 days at dosage of 2.5 mg/kg body weight per day.<br>* Other names: Impavido.;|
| Active Comparator: 2.2<br>Cutaneous leishmaniasis patients in Corte de Pedra-Bahia randomized to receive Meglumine antimoniate (standard treatment). | Drug: Meglumine antimoniate.<br>* Meglumine antimoniate administered by intravenous route for 20 days at the dosage of 20mg/kg/day.<br>* Other names: Glucantime.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure rate or complete cicatrization of the ulcer. | Bidirectional measurements of ulcers will be taken of the patients' lesions at the initial visit, and at each follow-up visit with standardized caliper. The area involved will be calculated as the product of the two measurements. All lesions will be categorized as either active or healed (cured) at follow-up visits. Only lesions with complete re-epithelialization, without raised borders, infiltrations or crusts will be considered healed. Evaluation of the lesions will be performed by 2 clinicians who will be unaware of the group assignment of all patients. | 6 months after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inicial cure rate or complete cicatrization of the ulcer. | Bidirectional measurements of ulcers will be taken of the patients' lesions at the initial visit, and at each follow-up visit with standardized caliper. The area involved will be calculated as the product of the two measurements. All lesions will be categorized as either active or healed (cured) at follow-up visits. Only lesions with complete re-epithelialization, without raised borders, infiltrations or crusts will be considered healed. Evaluation of the lesions will be performed by 2 clinicians who will be unaware of the group assignment of all patients. | 2 months after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous leishmaniasis, Miltefosine, Meglumine antimoniate, L. braziliensis, L. guyanensis