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Treatment of Mucosal Bolivian Leishmaniasis

Primary Purpose

Mucosal Leishmaniasis

Status
Recruiting
Phase
Phase 3
Locations
Bolivia
Study Type
Interventional
Intervention
Group 1: Miltefosine
Group 2: Pentavalent Antimony
Group 3: Liposomal amphotericin B
Sponsored by
Fundacion Nacional de Dermatologia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucosal Leishmaniasis

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Dermatologico de JorochitoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

Group 1: Oral Miltefosine

Group 2: Intravenous pentavalent antimony

Group 3: Intravenous liposomal amphotericin B

Arm Description

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.

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

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
March 9, 2021
Last Updated
June 14, 2022
Sponsor
Fundacion Nacional de Dermatologia
Collaborators
Hospital Dermatologico de Jorochito, Centro Nacional de Enfermedades Tropicales CENETROP, ABF Foundation for Medical Research
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1. Study Identification

Unique Protocol Identification Number
NCT04799236
Brief Title
Treatment of Mucosal Bolivian Leishmaniasis
Official Title
Treatment of Bolivian Mucosal Leishmaniasis With Miltefosine, Pentavalent Antimony or Liposomal Amphotericin B
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion Nacional de Dermatologia
Collaborators
Hospital Dermatologico de Jorochito, Centro Nacional de Enfermedades Tropicales CENETROP, ABF Foundation for Medical Research

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucosal Leishmaniasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
Investigator
Masking Description
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.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Oral Miltefosine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Group 2: Intravenous pentavalent antimony
Arm Type
Active Comparator
Arm Description
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
Arm Title
Group 3: Intravenous liposomal amphotericin B
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Group 1: Miltefosine
Intervention Description
Miltefosine 50 mg pill will be administered po every 8 hours with food, during 28 days
Intervention Type
Drug
Intervention Name(s)
Group 2: Pentavalent Antimony
Intervention Description
will be administered by IV infusion diluted in 150 ml of DWD5% over 20 minutes
Intervention Type
Drug
Intervention Name(s)
Group 3: Liposomal amphotericin B
Intervention Description
3 amps (150 mg) will be administered by IV infusion iver 2 hours every other day for a total of 15 doses.
Primary Outcome Measure Information:
Title
Healing of mucosal lesions
Description
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
Time Frame
Baseline to 12 month follow up
Secondary Outcome Measure Information:
Title
Clinical and laboratory safety of these 3 drugs
Description
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.
Time Frame
Base line to 1 month after the end of therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jaime soto, MD
Phone
+59175648894
Email
jasm.dlb@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Paula Soto, MD
Phone
+59175648893
Email
dra.paula.dermalaser@gmail.com
Facility Information:
Facility Name
Hospital Dermatologico de Jorochito
City
Santa Cruz de la Sierra
State/Province
SC
ZIP/Postal Code
00000
Country
Bolivia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jaime soto, MD
Phone
75648894
Email
jasm.dlb@gmail.com
First Name & Middle Initial & Last Name & Degree
Patricia Gutierrez, Lic
Phone
67842725
Email
pgutierrezduenas@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Treatment of Mucosal Bolivian Leishmaniasis

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