Miltefosine and GM-CSF in Cutaneous Leishmaniasis

NCT ID: NCT03023111

Last Updated: 2020-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-30
• Study Completion Date: 2020-02-14

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.

Conditions

Cutaneous Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sbv

Meglumine antimoniate (Glucantime):

Dosage: 20 mg / kg / day, intravenously, during 20 days.

Group Type: ACTIVE_COMPARATOR

Sbv

Intervention Type: DRUG

Standard treatment for CL, parenteral drug used during 20 days.

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)

Group Type: EXPERIMENTAL

Miltefosine plus placebo

Intervention Type: DRUG

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

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)

Group Type: EXPERIMENTAL

Miltefosine plus GM-CSF

Intervention Type: DRUG

Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. GM-CSF gel cream will be used topically.

Interventions

Sbv

Standard treatment for CL, parenteral drug used during 20 days.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Glucantime; Impavido plus placebo; Impavido plus GM-CSF

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oswaldo Cruz Foundation

OTHER

Sponsor Role: collaborator

Hospital Universitário Professor Edgard Santos

OTHER

Sponsor Role: lead

Responsible Party

Paulo Roberto Lima Machado

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paulo RL Machado, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Federal University of Bahia

Edgar M Carvalho, MD, PhD

Role: STUDY_DIRECTOR

Instituto Fernandes Figueira

Manoel Barral Neto, MD, PhD

Role: STUDY_CHAIR

Instituto Fernandes Figueira

Gerson Penna, MD, PhD

Role: STUDY_CHAIR

Instituto Fernandes Figueira

Locations

Fundação de Medicina Tropical do Amazonas

Manaus, Amazonas, Brazil

Corte de Pedra Health Post

Presidente Tancredo Neves, Estado de Bahia, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 33253864 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32894278 (View on PubMed)

Other Identifiers

Mil GM CL-2017

Identifier Type: -

Identifier Source: org_study_id