Treatment of Mucosal Bolivian Leishmaniasis

NCT04799236 | Recruiting Phase 3

• 1 other identifier: ABF-BO-2021-100
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this protocol is to conduct a randomized comparison of the efficacy and tolerance of miltefosine, LAMB, and pentavalent antimony for the treatment of mucosal leishmaniasis. With such controlled pharmacodynamic data, and additional considerations of administrative convenience (oral \>\>IV) and cost, we hope that it will be possible for policy makers, treatment professionals, and patients to choose the most appropriate therapy for ML.

Conditions

Mucosal Leishmaniasis

Outcome Measures

Primary Outcomes (1)

• Healing of mucosal lesions

  The primary purpose is to perform a controlled evaluation of the cure rate of miltefosine, LAMB, and Sb for L braziliensis ML in Bolivia. Using a standarized scale we'll qualify from 0 (absent) to 3 (severe) the following items: erythema, edema/swelling, infiltration, erosion/ulceration, in five different places: nasal and perinasal skin, nasal mucosa, palate and oral mucosa, pharynx and larynx. Additionally, changes in voice quality will be registered. 63 will be the maximun score and means severe and massive compromise. clinical cure: \>90% loss of presenting severity score clinical improvement: 50%-90% loss of presenting severity score no clinical change: 25% worsening to 49% improvement in presenting severity score clinically worse: \>25% worsening of presenting score or relapse after initial improvement

  Baseline to 12 month follow up

Secondary Outcomes (1)

• Clinical and laboratory safety of these 3 drugs

  Base line to 1 month after the end of therapy

Study Arms (3)

Group 1: Oral Miltefosine

ACTIVE COMPARATOR

Miltefosine will be administered per os at 150 mg/day \[50 mg tid\] for 28 days. This is the standard regimen of miltefosine for persons \>45 kg.

Drug: Group 1: Miltefosine

Group 2: Intravenous pentavalent antimony

ACTIVE COMPARATOR

IV pentavalent antimony (meglumine antimoniate) will be administrated at 20 mg x kg x d during 20 consecutive days. Antimony will be diluted in 10 times its volume in 5%Dextrose in destilled water and injected IV in 20 minutes

Drug: Group 2: Pentavalent Antimony

Group 3: Intravenous liposomal amphotericin B

EXPERIMENTAL

LAMB will be administered IV at 3 ampules \[150 mg\] on each of days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Three ampules is the individual dose suggested by Aronson et al \[2016\] and equals 2.5 mg/kg/dose for a 60 kg person. 15 doses of 3 ampules (total of 2250 mg) equals 37.5 mg/kg for a 60 kg person.

Drug: Group 3: Liposomal amphotericin B

Interventions

Group 1: Miltefosine DRUG

Miltefosine 50 mg pill will be administered po every 8 hours with food, during 28 days

Group 1: Oral Miltefosine

Group 2: Pentavalent Antimony DRUG

will be administered by IV infusion diluted in 150 ml of DWD5% over 20 minutes

Group 2: Intravenous pentavalent antimony

Group 3: Liposomal amphotericin B DRUG

3 amps (150 mg) will be administered by IV infusion iver 2 hours every other day for a total of 15 doses.

Group 3: Intravenous liposomal amphotericin B

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• weight over 45 kg
• Parasitological confirmation of the lesion will be made by visualization of Leishmania, culture of Leishmania, or molecular identification of Leishmania (PCR) from the biopsy or aspirate of the lesion.

You may not qualify if:

• Previous treatment for leishmaniasis in the last 12 months
• concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with treatment
• values of complete blood count, liver function (aspartate aminotransferase, alkaline phosphatase), renal function (creatinine), pancreatic function (lipase), or uric acid beyond 1.5 x normal range
• EKG with clinically significant abnormalities
• Women of childbearing age not agreeing with the use of secure reproductive contraception for 4 months after initiating miltefosine therapy.

Sponsors & Collaborators

• Fundacion Nacional de Dermatologia: lead
• Hospital Dermatologico de Jorochito: collaborator
• Centro Nacional de Enfermedades Tropicales CENETROP: collaborator
• ABF Foundation for Medical Research: collaborator

Study Sites (1)

Hospital Dermatologico de Jorochito

Santa Cruz de la Sierra, SC, 00000, Bolivia

RECRUITING

MeSH Terms

Conditions

Leishmaniasis, Mucocutaneous

Condition Hierarchy (Ancestors)

Leishmaniasis, Cutaneous; Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

jaime soto, MD

CONTACT

+59175648894; jasm.dlb@gmail.com

Paula Soto, MD

CONTACT

+59175648893; dra.paula.dermalaser@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Because of the disparate routes of administration, the study will not be blinded for the patients or clinical team. However, the ENT doctor who provides data to calculate the primary endpoint, the mucosal severity score, will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary purpose is to perform a controlled evaluation of the cure rate of miltefosine, LAMB, and Sb for L braziliensis ML in Bolivia. A secondary purpose is to determine the tolerance of these regimens. Patients will be randomized between: Group 1---40 patients. Oral miltefosine. Group 2---40 patients. Intravenous pentavalent antimony (Glucantime) Group 3---40 patients. Intravenous liposomal amphotericin B (Ambisome) Because of the disparate routes of administration, the study will not be blinded for the patients or clinical team. However, the ENT doctor who provides data to calculate the primary endpoint, the mucosal severity score, will be blinded. After treatment, all patients will be followed for 2, 6, 9, and 12 months after the beginning of therapy. In addition, all attempts will be made to effect follow-up at 24 months.

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 16, 2021
• Study Start: April 1, 2021
• Primary Completion: April 30, 2024
• Study Completion: November 30, 2024
• Last Updated: March 5, 2024

Record last verified: 2024-03

Locations

BO (1)