Miltefosine and GM-CSF in Cutaneous Leishmaniasis

Hospital Universitário Professor Edgard Santos

Status and phase: Completed; Phase 3

Conditions: Cutaneous Leishmaniasis

Treatments: Drug: Sbv; Drug: Miltefosine plus GM-CSF; Drug: Miltefosine plus placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03023111

Mil GM CL-2017

Details and patient eligibility

About

Cutaneous leishmaniasis (CL) standard treatment is done with parenteral pentavalent antimony (Sbv) at the dose of 15-20mg / kg per day for 20 days. However, therapeutic failure has been described in up to 50% of patients, and the long period of 60 to 90 days required for healing of the ulcerated lesion indicate the need for alternative drugs. Currently the alternatives include other parenteral drugs such as pentamidine and amphotericin B, whose use is limited either by toxicity or because, as with Sbv, the parenteral route hinders adherence and regularity of treatment in the rural area. Recent studies by our group indicate that oral miltefosine is the most effective drug for the treatment of patients with CL caused by L. (V.) guyanensis and L. (V.) braziliensis in Brazil, with a cure rate of 71.4% and 75% respectively. CL pathogenesis is associated with intense inflammatory infiltrate and tissue damage. Previous trials associating GM-CSF to Sbv improved the cure rate of CL caused by L. (V.) braziliensis. The objective of this trial is to evaluate the therapeutic response to the use of miltefosine associated to GM-CSF in the treatment of CL caused by L. (V.) braziliensis in an endemic region in Bahia and Ceará, and by L. (V.) guyanensis in the Amazon region.

Enrollment: 300 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Untreated ulcerative cutaneous leishmaniasis, with laboratory diagnosis obtained through at least one of the following tests: direct examination of the lesion, positive culture or PCR for Leishmania.
2. Age: 18 to 65 years;
3. Sex: male and female patients;
4. Presence of at least 1 ulcerated lesion at any location;
5. Presence of a maximum of 3 ulcerated lesions;
6. Diameter of lesions varying between 1 and 5 cm;
7. Clinical evolution of the disease of not less than 1 month and not more than 3 months.

Exclusion criteria

1. Evidence of severe underlying disease (cardiac, renal, hepatic, pulmonary) or malignant disease;
2. Patients with immunodeficiency or HIV carriers;
3. Serious protein and / or caloric malnutrition;
4. Active and uncontrolled infectious-contagious disease such as tuberculosis, leprosy, systemic fungal disease (histoplasmosis, paracoccidioidomycosis) or any other similar condition;
5. Women who are pregnant or breastfeeding;
6. Allergy to Sbv or miltefosine;
7. Previous treatment for leishmaniasis;
8. Lack of capacity or willingness to provide informed consent (patient and / or parent / legal representative); Absence of availability for the visits or to comply with the study procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 3 patient groups

Sbv

Active Comparator group

Description:

Meglumine antimoniate (Glucantime): Dosage: 20 mg / kg / day, intravenously, during 20 days.

Treatment:

Drug: Sbv

Miltefosine plus placebo

Experimental group

Description:

Miltefosine (28 days / 2.5mg / Kg / day at a maximum dose of 150mg / day orally) + Topical placebo (gel cream, 2 times a day for 28 days)

Treatment:

Drug: Miltefosine plus placebo

Miltefosine plus GM-CSF

Experimental group

Description:

Miltefosine (28 days / 2.5mg / kg / day at a maximum dose of 150mg / day orally) + Topical GM-CSF (0.01% gel cream, 2 times a day for 28 days)

Treatment:

Drug: Miltefosine plus GM-CSF