Treatment of Mucosal Bolivian Leishmaniasis

Treatment of Bolivian Mucosal Leishmaniasis With Miltefosine, Pentavalent Antimony or Liposomal Amphotericin B

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.

Study Overview

• Status: Recruiting
• Conditions: Mucosal Leishmaniasis
• Intervention / Treatment: Drug: Group 1: Miltefosine; Drug: Group 2: Pentavalent Antimony; Drug: Group 3: Liposomal amphotericin B

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: jaime soto, MD; Phone Number: +59175648894; Email: jasm.dlb@gmail.com
• Study Contact Backup: Name: Paula Soto, MD; Phone Number: +59175648893; Email: dra.paula.dermalaser@gmail.com

Study Locations

• Bolivia
  • SC
    • Santa Cruz de la Sierra, SC, Bolivia, 00000
      • Recruiting
      • Hospital Dermatologico de Jorochito
      • Contact: jaime soto, MD; Phone Number: 75648894; Email: Jasm.dlb@gmail.com
      • Contact: Patricia Gutierrez, Lic; Phone Number: 67842725; Email: pgutierrezduenas@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Oral Miltefosine; 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; Miltefosine 50 mg pill will be administered po every 8 hours with food, during 28 days
Active Comparator: Group 2: Intravenous pentavalent antimony; 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; will be administered by IV infusion diluted in 150 ml of DWD5% over 20 minutes
Experimental: Group 3: Intravenous liposomal amphotericin B; 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; 3 amps (150 mg) will be administered by IV infusion iver 2 hours every other day for a total of 15 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and laboratory safety of these 3 drugs	The secondary purpose is to determine the tolerance of these regimens. Descriptive statistics will be used to present adverse event data. Continuous variables will be presented as number of observations (n), mean, standard deviation (SD), median, minimum and maximum values. Categorical variables will be presented as counts and percentages. Adverse effects will be compared between groups by appropriate statistics. During treatment administration clinical symptoms (nausea/vomit/abdominal pain; myalgias/arthralgias; headache/dizziness) and laboratory (AST, alkaline phosphatase, lipase, creatinine, CBC) and EKG (in patients receiving antomony) will be evaluated.	Base line to 1 month after the end of therapy

Collaborators and Investigators

• Sponsor: Fundacion Nacional de Dermatologia
• Collaborators: Hospital Dermatologico de Jorochito; Centro Nacional de Enfermedades Tropicales CENETROP; ABF Foundation for Medical Research

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

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, Cutaneous; Leishmaniasis; Leishmaniasis, Mucocutaneous; Anti-Infective Agents; Antineoplastic Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Miltefosine; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: ABF-BO-2021-100

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