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Miltefosine and GM-CSF in Cutaneous Leishmaniasis

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ClinicalTrials.gov Identifier: NCT03023111
Recruitment Status : Completed
First Posted : January 18, 2017
Last Update Posted : April 7, 2020
Sponsor:
Collaborator:
Oswaldo Cruz Foundation
Information provided by (Responsible Party):
Paulo Roberto Lima Machado, 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.

Condition or disease Intervention/treatment Phase
Cutaneous Leishmaniasis Drug: Sbv Drug: Miltefosine plus placebo Drug: Miltefosine plus GM-CSF Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Miltefosine and GM-CSF in Cutaneous Leishmaniasis: a Randomized and Controlled Trial
Actual Study Start Date : June 30, 2017
Actual Primary Completion Date : August 9, 2019
Actual Study Completion Date : February 14, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leishmaniasis
Drug Information available for: Miltefosine

Arm Intervention/treatment
Active Comparator: Sbv

Meglumine antimoniate (Glucantime):

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

Drug: Sbv
Standard treatment for CL, parenteral drug used during 20 days.
Other Name: Glucantime

Experimental: 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)
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.
Other Name: Impavido plus placebo

Experimental: 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)
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.
Other Name: Impavido plus GM-CSF




Primary Outcome Measures :
  1. Final cure rate or complete cicatrization of the ulcer [ Time Frame: 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 :
  1. Initial cure rate or initial cicatrization of the ulcer [ Time Frame: 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.

  2. Healing time [ Time Frame: Up to 2 months after the end of treatment ]
    Time (in days) to achieve complete cicatrization will be recorded.

  3. Clinical and laboratory adverse events [ Time Frame: 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



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023111


Locations
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Brazil
Fundação de Medicina Tropical do Amazonas
Manaus, Amazonas, Brazil, 69.040-000
Corte de Pedra Health Post
Presidente Tancredo Neves, Bahia, Brazil, 40000
Sponsors and Collaborators
Hospital Universitário Professor Edgard Santos
Oswaldo Cruz Foundation
Investigators
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Principal Investigator: Paulo RL Machado, MD, PhD Federal University of Bahia
Study Director: Edgar M Carvalho, MD, PhD Instituto Fernandes Figueira
Study Chair: Manoel Barral Neto, MD, PhD Instituto Fernandes Figueira
Study Chair: Gerson Penna, MD, PhD Instituto Fernandes Figueira
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Paulo Roberto Lima Machado, MD, PhD, Hospital Universitário Professor Edgard Santos
ClinicalTrials.gov Identifier: NCT03023111    
Other Study ID Numbers: Mil GM CL-2017
First Posted: January 18, 2017    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Paulo Roberto Lima Machado, Hospital Universitário Professor Edgard Santos:
Cutaneous leishmaniasis
miltefosine
cytokines
treatment
Additional relevant MeSH terms:
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Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Miltefosine
Meglumine Antimoniate
Molgramostim
Sargramostim
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antifungal Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents