Miltefosine and GM-CSF in Cutaneous Leishmaniasis

Phase 3

Completed

• Conditions: Cutaneous Leishmaniasis
• Interventions: Drug: Miltefosine plus placebo; Drug: Sbv; Drug: Miltefosine plus GM-CSF

• Registration Number: NCT03023111
• Lead Sponsor: Hospital Universitário Professor Edgard Santos

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-27
• Study First Submitted QC: 2017-01-17
• Study First Posted: 2017-01-18
• Study Start: 2017-06-30
• Primary Completion: 2019-08-09
• Study Completion: 2020-02-14
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-03
• Last Update Posted: 2020-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Miltefosine plus placebo	Miltefosine plus placebo	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)
Sbv	Sbv	Meglumine antimoniate (Glucantime): Dosage: 20 mg / kg / day, intravenously, during 20 days.
Miltefosine plus GM-CSF	Miltefosine plus GM-CSF	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)

Primary Outcome Measures

Name	Time	Method
Final cure rate or complete cicatrization of the ulcer	6 months after the end of treatment	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. 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.

Secondary Outcome Measures

Name	Time	Method
Initial cure rate or initial cicatrization of the ulcer	2 months after the end of treatment	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. 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.
Healing time	Up to 2 months after the end of treatment	Time (in days) to achieve complete cicatrization will be recorded.
Clinical and laboratory adverse events	During treatment and through study completion, an average of 1 year	Clinical and laboratory adverse events will be recorded and graded according to the Common Terminology Criteria for Adverse Event (CTCAE) of the National Cancer Institute

Trial Locations

Locations (2)

Corte de Pedra Health Post; 🇧🇷 Presidente Tancredo Neves, Bahia, Brazil

Fundação de Medicina Tropical do Amazonas; 🇧🇷 Manaus, Amazonas, Brazil