Cutaneous LeishmaniasisPhase 3NCT03023111

Miltefosine and GM-CSF in Cutaneous Leishmaniasis

A Phase 3 study testing Sbv and Miltefosine plus GM-CSF in people with Cutaneous Leishmaniasis, run by Hospital Universitário Professor Edgard Santos at 2 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Cutaneous Leishmaniasis
What is being tested?: Sbv and Miltefosine plus GM-CSF
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 300 participants
Where: 2 sitesBrazil
Study dates: 30 Jun 2017to 14 Feb 2020
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

Brazil2 sites

Fundação de Medicina Tropical do Amazonas
Manaus, Amazonas, 69.040-000
Corte de Pedra Health Post
Presidente Tancredo Neves, Estado de Bahia, 40000

Other trials in Brazil

About this study

Official title: 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.

Conditions: Cutaneous Leishmaniasis
Being tested: Sbv, Miltefosine plus placebo, Miltefosine plus GM-CSF
Keywords: Cutaneous leishmaniasis, miltefosine, cytokines, treatment
Medical subject headings: Leishmaniasis, Cutaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SbvDrug
Also called Glucantime
Standard treatment for CL, parenteral drug used during 20 days.
Miltefosine plus placeboDrug
Also called Impavido plus placebo
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-CSFDrug
Also called Impavido 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.

Study groups in NCT03023111
Study group	Role	What they receive
Sbv	Active comparator	Meglumine antimoniate (Glucantime): Dosage: 20 mg / kg / day, intravenously, during 20 days. Receives: Drug: Sbv
Miltefosine plus placebo	Experimental	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) Receives: Drug: Miltefosine plus placebo
Miltefosine plus GM-CSF	Experimental	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) Receives: Drug: Miltefosine plus GM-CSF

What is being measured

The primary outcome is the main question the study is designed to answer.

Final cure rate or complete cicatrization of the ulcer
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.
Measured: 6 months after the end of treatment

Secondary outcomes (3)

Initial cure rate or initial cicatrization of the ulcer
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.
Measured: 2 months after the end of treatment
Healing time
Time (in days) to achieve complete cicatrization will be recorded.
Measured: Up to 2 months after the end of treatment
Clinical and laboratory adverse events
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
Measured: During treatment and through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jun 201714 Feb 2020

First posted18 Jan 2017 (estimated)
Study start30 Jun 2017
Primary completion9 Aug 2019
Study completion14 Feb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Cutaneous LeishmaniasisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 300 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03023111
Sponsor's protocol ID: Mil GM CL-2017
Status last verified: Apr 2020
First submitted: 27 Dec 2016
Last updated: 7 Apr 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 33253864
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.
PubMed 32894278

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cutaneous Leishmaniasis trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Miltefosine and GM-CSF in Cutaneous Leishmaniasis: a Randomized and Controlled Trial
ClinicalTrials.gov ID: NCT03023111
Acronym / sponsor ID: Mil GM CL-2017
Conditions: Cutaneous Leishmaniasis
Keywords: Cutaneous leishmaniasis, miltefosine, cytokines, treatment
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 300 participants (actual)
Lead sponsor: Hospital Universitário Professor Edgard SantosUniversity, hospital or other
Collaborators: Oswaldo Cruz Foundation
Study start: 30 Jun 2017 (actual)
Primary completion: 9 Aug 2019 (actual)
Study completion: 14 Feb 2020 (actual)
First posted: 18 Jan 2017 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Sbv	Active comparator	Drug: SbvMeglumine antimoniate (Glucantime): Dosage: 20 mg / kg / day, intravenously, during 20 days.
Miltefosine plus placebo	Experimental	Drug: Miltefosine plus placeboMiltefosine (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)
Miltefosine plus GM-CSF	Experimental	Drug: Miltefosine plus GM-CSFMiltefosine (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)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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;

Key exclusion criteria (8 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SbvAlso: GlucantimeStandard treatment for CL, parenteral drug used during 20 days.	Drug	Sbv
Miltefosine plus placeboAlso: Impavido plus placeboOral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. Placebo gel cream will be used topically.	Drug	Miltefosine plus placebo
Miltefosine plus GM-CSFAlso: Impavido plus GM-CSFOral treatment for CL, capsules with 50mg used 3 times a day, during 28 days. GM-CSF gel cream will be used topically.	Drug	Miltefosine plus GM-CSF

Primary outcome

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.

3 secondary outcomes

Initial cure rate or initial cicatrization of the ulcer
Time frame: 2 months after the end of treatment
Healing time
Time frame: 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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
Derived from this study: PubMed 33253864Mendes 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.
Derived from this study: PubMed 32894278Machado 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.
Individual participant dataSharing planned: No

Related trials for Cutaneous Leishmaniasis

RecruitingObservational study
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Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paulo RL Machado, MD, PhD principal investigator

Federal University of Bahia

Edgar M Carvalho, MD, PhD study director

Instituto Fernandes Figueira

Manoel Barral Neto, MD, PhD study chair

Instituto Fernandes Figueira

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sbv and Miltefosine plus GM-CSF in people with Cutaneous Leishmaniasis, run by Hospital Universitário Professor Edgard Santos at 2 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Final cure rate or complete cicatrization of the ulcer (time frame: 6 months after the end of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03023111, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2020.