Clinical trial NCT03023111: Miltefosine and GM-CSF in Cutaneous Leishmaniasis
Official title: Miltefosine and GM-CSF in Cutaneous Leishmaniasis: a Randomized and Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cutaneous Leishmaniasis
Keywords: Cutaneous leishmaniasis
miltefosine
cytokines
treatment
Lead sponsor: Hospital Universitário Professor Edgard Santos
Sponsor class: OTHER
Collaborators: name: Oswaldo Cruz Foundation
First posted: 2017-01-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Final cure rate or complete cicatrization of the ulcer
timeFrame: 6 months after the end of treatment
Secondary outcomes:
measure: Initial cure rate or initial cicatrization of the ulcer
timeFrame: 2 months after the end of treatment
measure: Healing time
timeFrame: Up to 2 months after the end of treatment
measure: Clinical and laboratory adverse events
timeFrame: During treatment and through study completion, an average of 1 year
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Fundação de Medicina Tropical do Amazonas
state: Amazonas
city: Presidente Tancredo Neves
country: Brazil
facility: Corte de Pedra Health Post
state: Bahia
Study officials:
affiliation: Federal University of Bahia
name: Paulo RL Machado, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Fernandes Figueira
name: Edgar M Carvalho, MD, PhD
role: STUDY_DIRECTOR
affiliation: Instituto Fernandes Figueira
name: Manoel Barral Neto, MD, PhD
role: STUDY_CHAIR
affiliation: Instituto Fernandes Figueira
name: Gerson Penna, MD, PhD
role: STUDY_CHAIR
References:
citation: Mendes L, Guerra JO, Costa B, Silva ASD, Guerra MDGB, Ortiz J, Doria SS, Silva GVD, de Jesus DV, Barral-Netto M, Penna G, Carvalho EM, Machado PRL. Association of miltefosine with granulocyte and macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis in the Amazon region: A randomized and controlled trial. Int J Infect Dis. 2021 Feb;103:358-363. doi: 10.1016/j.ijid.2020.11.183. Epub 2020 Nov 27.
citation: Machado PRL, Prates FVO, Boaventura V, Lago T, Guimaraes LH, Schriefer A, Corte TWF, Penna G, Barral A, Barral-Netto M, Carvalho EM. A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil. Clin Infect Dis. 2021 Oct 5;73(7):e2465-e2469. doi: 10.1093/cid/ciaa1337.