Treatment of Bolivian Mucosal Leishmaniasis With Miltefosine, Pentavalent Antimony or Liposomal Amphotericin B
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Healing of mucosal lesions
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (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.
Eligibility Criteria
- Ages
- 12 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Group 1: Miltefosine (Drug)
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
Intervention: Group 2: Pentavalent Antimony (Drug)
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.
Intervention: Group 3: Liposomal amphotericin B (Drug)
Outcomes
Primary Outcomes
Healing of mucosal lesions
Time Frame: Baseline to 12 month follow up
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 Outcomes
- Clinical and laboratory safety of these 3 drugs(Base line to 1 month after the end of therapy)