OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
- Registration Number
- NCT06514560
- Lead Sponsor
- Institute of Tropical Medicine, Belgium
- Brief Summary
While there are indications that 28 days of miltefosine is not sufficient for treating CL by L. aethiopica, a better understanding of what happens in terms of parasite clearance and drug dosing is lacking. In this study, longitudinal measurements of parasite and drug concentrations during treatment are done to monitor parasite kinetics as well as pharmacokinetics. This data will be crucial to provide more information on duration and dosing of miltefosine in CL patients globally, and in Ethiopia and pediatric patients in particular.
- Detailed Description
In this project, parasite dynamics and miltefosine pharmacokinetics in the skin and blood during routine durations of miltefosine treatment (4-8 weeks) are studied with the aim to provide evidence to optimize miltefosine dosing for treatment of CL. By also studying these factors in children who get allometric miltefosine dosing, data which can be used to adapt the current allometric dosing scheme specifically to children with CL will be produced. Exploratory objectives will look into searching for more objective outcome assessment measures, resistance, helminth infection and nutritional status as potential factors affecting treatment response.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- Clinical or parasitological (microscopy or PCR) confirmation of leishmaniasis
- Age >2
- Clinical decision to start miltefosine treatment as systemic treatment
- In case of females of child-bearing age: willing to take contraceptive for 6 months (parenteral or IUD or implant)
- Willing and able to provide informed consent
- Willing to be hospitalized for the duration of treatment
- Currently on treatment or having received modern treatment for leishmaniasis in the last 3 months
- Pregnant (pregnancy test at D0) or breastfeeding
- Unlikely to come for follow-up visits
- Abnormal lab values Hemoglobin <5.0g/100mL Platelets <50 x 10^9/L White blood count <1 x 10^9/L ASAT/ALAT >3x upper normal range Creatinine above the normal limit
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Non-allometric dosing Miltefosine 40 patients who will not use allometric dosing will be included miltefosine will be given based on weight: 30-45 kg: 100mg miltefosine per day \>45 kg: 150mg miltefosine per day allometric dosing (weight below 30 kg) Miltefosine 40 patients who weigh less than 30kg and therefore get allometric dosing will be recruited. Dosing is given based on weight, height, and sex, according to Dorlo et al 2012
- Primary Outcome Measures
Name Time Method MIltefosine plasma concentrations - Time of maximum concentration (Tmax) Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180 Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Miltefosine plasma concentrations - Maximum plasma concentration (Cmax) Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180 Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC) Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180 Determined by LC-MS/MS, miltefosine pharmacokinetics are assessed through calculation of the area under the plasma concentration-time curve from start of treatment until end of treatment (AUC0-EoT), stratified by whether patients received allometric dosing or not.
- Secondary Outcome Measures
Name Time Method Adapted allometric dosing scheme specifically for children with CL Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180 Population PK and PK-PD analysis of the relationship between miltefosine exposure and parasite kinetics will be done at UU, based on results from miltefosine plasma concentrations. Structural pharmacokinetic modelling will be used to develop and simulate alternative dosing schemes for children with CL, using Monte Carlo simulations.
Parasite kinetics in blood and skin Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180 To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR
Treatment outcomes of patients on miltefosine treatment Day 28, day 90 and day 180 Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling
Assess safety of miltefosine Day 28 Side-effects: number and proportion of patients with adverse events
Trial Locations
- Locations (1)
Africa Leprosy, Tuberculosis, Rehabilitation and Training (ALERT) Hospital
🇪🇹Addis Abeba, Ethiopia