Treatment of uncomplicated malaria in African children aged 6 months to =10 years Infections and Infestations
Conditions
Interventions
Treatment will be randomly assigned (block randomization) to the participants using a 1:1 ratio. Participants will receive one of the following treatments following a weight-based treatment algorithm:
Sponsors
Kwame Nkrumah University of Science and Technology
Eligibility
Sex/Gender
All
Age
6 Months to 10 Years
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 18/09/2024: 1. Children between the ages of 6 to =10 years 2. Body weight =5.0kg 3. Fever (=37.5°C axillary or 38.0°C oral, rectal or tympanic body temperature) or history of fever in the preceding 24 hours 4. Uncomplicated P. falciparum mono-infection with equal or more than 1,000 and less than 200,000 asexual P. falciparum parasites per microliter of blood. 5. Signed written informed consent from the child’s legal representative 6. Ability to comply with study procedures and follow-up schedules 7. Willing to stay in the study area during the period of follow-up 8. Ability to take oral medication Previous participant inclusion criteria: 1. Children between the ages of 6 to 59 months 2. Body weight =5.0kg 3. Fever (=37.5°C axillary or 38.0°C oral, rectal or tympanic body temperature) or history of fever in the preceding 24 hours 4. Uncomplicated P. falciparum mono-infection with equal or more than 1,000 and less than 200,000 asexual P. falciparum parasites per microliter of blood. 5. Signed written informed consent from the child’s legal representative 6. Ability to comply with study procedures and follow-up schedules 7. Willing to stay in the study area during the period of follow-up 8. Ability to take oral medication
Exclusion criteria
Exclusion criteria: 1. Presence of severe malaria following WHO definition 2. Reported intake of any antimalarial drug within the previous 28 days 3. Intake of drugs with antimalarial activity or contraindicated drugs within the previous 28 days 4. Administration of strong inducers or inhibitors of CYP3A4 such as rifampin, carbamazepine, phenytoin, millepertuis/St. John’s wort/ hypericum perforatum, grapefruit within the previous 28 days 5. Known history or evidence of clinically significant medical disorders as determined by the investigator 6. Severe malnutrition assessed by middle upper arm circumference (< 115 mm) according to WHO standard 7. Screening hemoglobin level <7 g/dL 8. Known hypersensitivity or contraindications to any AL and/or AP components 9. Known QT prolongation 10. Previous participation in a malaria vaccine study 11. Participation in the ASAAP study during the previous 42 days 12. Participation in other interventional studies within the previous 28 days 13. Patients that the investigator considers would be at particular risk if participating in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Day-28 efficacy of treatment defined as PCR-adjusted adequate clinical and parasitological response (ACPR) excluding reinfections, in the per-protocol (PP) population. 2. Day-28 efficacy of treatment defined as PCR-adjusted ACPR excluding reinfections, in the modified intention-to-treat (mITT) population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcome(s) as of 18/12/2025: 1. PCR-unadjusted day-28 ACPR by treatment arm in both the PP and the mITT population overall and in age subgroups (aged 6 to 59 months and from 60 months to =10 years) 2. PCR-adjusted and unadjusted day-42 ACPR by treatment arm in both the PP and in the mITT population overall and in age subgroups (aged 6 to 59 months and from 60 months to =10 years) 3. PCR-adjusted day-28 ACPR by treatment arm in both the PP and the mITT population in age subgroups (aged 6 to 59 months and from 60 months to =10 years); 4. Cure rate at days 14, 21, 28, 35 and 42 by treatment arm to evaluate post-treatment prophylactic efficacy in both PP and mITT populations 5. Types, proportion, severity and causality of adverse events (AEs) during treatment follow-up by the treatment arm as measures of tolerability and safety 6. Day-7 lumefantrine and desbutyl-lumefantrine plasma concentrations by treatment arm 7. Day-7 atovaquone, proguanil and its metabolite (cycloguanil) plasma concentrations when the treatment is AL +AP 8. Day 3 positivity rate by treatment arm in both PP and mITT day 3 positivity rate is defined as the proportion of patients who were still parasitaemic on day 3 after initiation of treatment 9. Concentrations of study drugs are measured in the plasma by a liquid chromatography-tandem mass spectrometry LC-MS/MS method at day-7 (168h after the first drug dosing) for all patients and at the following time points for patients involved in the pharmacokinetic studies: baseline, 5h, 48h, 72h, 120h, 168h after the first drug dosing for atovaquone, proguanil, cycloguanil, and lumefantrine ; and at baseline, 1h, 2.5h, 5h, 168h after the first drug dosing for artemether and dihydroartemisinin. 10. The basic pharmacokinetic parameters (V, CL, Q, Ka, AUC at day 7, Cmax, Tmax, t1/2) of artemether, lumefantrine, atovaquone, proguanil and their respective main metabolites are modeled by a population pharmacokinetics approach. 11. Pre and p | — |
Countries
Benin, Gabon, Ghana, Mali
Contacts
Public ContactJohn Amuasi
Outcome results
None listed