OPTImizing MIltefosine Treatment for Cutaneous LEISHmaniasis Patients
ConditionCutaneous Leishmaniases
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2+
SponsorInstitute of Tropical Medicine, Belgium
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial population
A total of 40 children on allometric dosing and 40 other patients will be enrolled in the study
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Miltefosine
DrugMiltefosine will be prescribed by the treating physician for a minimum of 4 weeks. If treatment response is not sufficient, treatment extension could be decided by the treating physician up to 8 weeks
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Non-allometric dosing1 intervention
Group B: allometric dosing (weight below 30 kg)1 intervention
Trial outcomes
Primary outcomes
1
Miltefosine plasma concentrations - Area under the plasma concentration versus time curve (AUC)
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.
Time frame
Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 1802
Miltefosine plasma concentrations - Maximum plasma concentration (Cmax)
Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Time frame
Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 1803
MIltefosine plasma concentrations - Time of maximum concentration (Tmax)
Determined by LC-MS/MS, stratified by whether patients received allometric dosing or not.
Time frame
Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 180Secondary outcomes
1
Parasite kinetics in blood and skin
To determine parasite kinetics in terms of Ct-values in blood and skin (microbiopsy sample) measured by quantitative PCR
Time frame
Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 1802
Adapted allometric dosing scheme specifically for children with CL
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.
Time frame
Day 0, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42/Day 56, Day 90, Day 1803
Treatment outcomes of patients on miltefosine treatment
Clinical cure rate determined by complete flattening, complete reepithelization and absence of erythema, crustation, and swelling
Time frame
Day 28, day 90 and day 1804
Assess safety of miltefosine
Side-effects: number and proportion of patients with adverse events
Time frame
Day 28Other outcomes
1
To explore optimization of outcome assessment using a 3D scanner
Machine learning models will be built to explore accuracy (% correctly predicted) of 3D scanning models to predict clinical outcomes.
Time frame
Day 28, Day 90, Day 1802
To explore whether nutritional status in CL patients is related to treatment outcomes
Logistic regression models will be made with clinical cure/no cure as outcome, and nutritional status measured through Z-scores as predictor.
Time frame
Nutritional status at Day 0, outcome at Day 90/Day 1803
To explore whether helminth infection in CL patients is related to treatment outcomes
Logistic regression models will be made with clinical cure/no cure as outcome, and helminth infection (determined as present/not present by wet mount stool exam) as predictor.
Time frame
Helminth infection at Day 0, outcome at Day 90/Day 1804
To explore sequencing to detect intrinsic and acquired resistance markers for miltefosine
Whole genome sequencing will be done at AHRI to check for intrinsic (before treatment samples) and acquired resistance (relapse and end of treatment samples).
Time frame
Day 0, Day 28/Day 42/Day 56, unscheduled visitSponsors and contacts
Click on the lead sponsor to view all of their trials.
Institute of Tropical Medicine, Belgium
Lead sponsor
Alert Hospital, Ethiopia
Collaborator
Armauer Hansen Research Institute, Ethiopia
Collaborator
Uppsala University
Collaborator
The Netherlands Cancer Institute
Collaborator
Source ClinicalTrials.gov