- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03023111
Miltefosine and GM-CSF in Cutaneous Leishmaniasis
April 3, 2020 updated by: Paulo Roberto Lima Machado, Hospital Universitário Professor Edgard Santos
Miltefosine and GM-CSF in Cutaneous Leishmaniasis: a Randomized and Controlled Trial
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
300
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Amazonas
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Manaus, Amazonas, Brazil, 69.040-000
- Fundação de Medicina Tropical do Amazonas
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Bahia
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Presidente Tancredo Neves, Bahia, Brazil, 40000
- Corte de Pedra Health Post
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- Age: 18 to 65 years;
- Sex: male and female patients;
- Presence of at least 1 ulcerated lesion at any location;
- Presence of a maximum of 3 ulcerated lesions;
- Diameter of lesions varying between 1 and 5 cm;
- Clinical evolution of the disease of not less than 1 month and not more than 3 months.
Exclusion Criteria:
- Evidence of severe underlying disease (cardiac, renal, hepatic, pulmonary) or malignant disease;
- Patients with immunodeficiency or HIV carriers;
- Serious protein and / or caloric malnutrition;
- Active and uncontrolled infectious-contagious disease such as tuberculosis, leprosy, systemic fungal disease (histoplasmosis, paracoccidioidomycosis) or any other similar condition;
- Women who are pregnant or breastfeeding;
- Allergy to Sbv or miltefosine;
- Previous treatment for leishmaniasis;
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Sbv
Meglumine antimoniate (Glucantime): Dosage: 20 mg / kg / day, intravenously, during 20 days. |
Standard treatment for CL, parenteral drug used during 20 days.
Other Names:
|
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)
|
Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days.
Placebo gel cream will be used topically.
Other Names:
|
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)
|
Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days.
GM-CSF gel cream will be used topically.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
6 months after the end of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 months after the end of treatment
|
Healing time
Time Frame: Up to 2 months after the end of treatment
|
Time (in days) to achieve complete cicatrization will be recorded.
|
Up to 2 months after the end of treatment
|
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
|
During treatment and through study completion, an average of 1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- 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 and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
June 30, 2017
Primary Completion (ACTUAL)
August 9, 2019
Study Completion (ACTUAL)
February 14, 2020
Study Registration Dates
First Submitted
December 27, 2016
First Submitted That Met QC Criteria
January 17, 2017
First Posted (ESTIMATE)
January 18, 2017
Study Record Updates
Last Update Posted (ACTUAL)
April 7, 2020
Last Update Submitted That Met QC Criteria
April 3, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Skin Diseases, Parasitic
- Skin Diseases, Infectious
- Euglenozoa Infections
- Leishmaniasis
- Leishmaniasis, Cutaneous
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunologic Factors
- Antifungal Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Miltefosine
- Sargramostim
- Molgramostim
- Meglumine Antimoniate
Other Study ID Numbers
- Mil GM CL-2017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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