Miltefosine and GM-CSF in Cutaneous Leishmaniasis

Cutaneous Leishmaniasis Clinical Trial

Official title:

Miltefosine and GM-CSF in Cutaneous Leishmaniasis: a Randomized and Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03023111
• Other study ID #: Mil GM CL-2017
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2017
• Est. completion date: February 14, 2020

Study information

• Verified date: April 2020
• Source: Hospital Universitário Professor Edgard Santos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: February 14, 2020
• Est. primary completion date: August 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cutaneous Leishmaniasis
• Leishmaniasis
• Leishmaniasis, Cutaneous

Intervention

Drug:
• Sbv
Standard treatment for CL, parenteral drug used during 20 days.
• Miltefosine plus placebo
Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. Placebo gel cream will be used topically.
• Miltefosine plus GM-CSF
Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. GM-CSF gel cream will be used topically.

Locations

Country	Name	City	State
Brazil	Fundação de Medicina Tropical do Amazonas	Manaus	Amazonas
Brazil	Corte de Pedra Health Post	Presidente Tancredo Neves	Bahia

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitário Professor Edgard Santos	Oswaldo Cruz Foundation

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final cure rate or complete cicatrization of the ulcer	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.	6 months after the end of treatment
Secondary	Initial cure rate or initial cicatrization of the ulcer	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.	2 months after the end of treatment
Secondary	Healing time	Time (in days) to achieve complete cicatrization will be recorded.	Up to 2 months after the end of treatment
Secondary	Clinical and laboratory adverse events	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	During treatment and through study completion, an average of 1 year