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

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

    • Amazonas
      • Manaus, Amazonas, Brazil, 69.040-000
        • Fundação de Medicina Tropical do Amazonas
    • Bahia
      • 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:

  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.

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:
  • 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)
Oral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. Placebo gel cream will be used topically.
Other Names:
  • 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)
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:
  • Impavido plus GM-CSF

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.

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

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.

Clinical Trials on Cutaneous Leishmaniasis

Clinical Trials on Sbv

Subscribe