Phase 4
Completed N=305
Extended Duration Artemether-lumefantrine Treatment for Malaria in Children
Uncomplicated Plasmodium Falciparum Malaria
Source: ClinicalTrials.gov NCT03453840 ↗
Enrolled (actual)
305
Serious AEs
0.7%
Results posted
Jan 2025
Primary outcomePrimary: AUC0-21d — 144; 205; 259; 318 hr*ug/mL
◆ Published Evidence
Emerging
12citations · ~4 / year
The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial.
Summary
This project determines the pharmacokinetic/pharmacodynamic (PK/PD) of an extended artemether-lumefantrine (AL) dosing regimen in HIV-infected children on efavirenz (EFV)-based antiretroviral therapy (ART) that is designed to improve the PK exposure and treatment efficacy of this artemisinins-based combination therapy (ACT) regimen. Our overarching goal is to inform the best treatment guidelines for young children in Africa. HIV-infected and HIV-uninfected children were enrolled for intensive PK studies, as well as additional children for population PK studies to enhance association analyses with clinical outcomes.
Linked Publications (3)
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The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial.
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Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial.
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Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY AUC0-21d |
144; 205; 259; 318 | — |
| PRIMARY Recurrent Parasitemia Following Treatment by Day 42 (Recrudescence or New Infection) |
19; 18; 80; 66 | — |
| PRIMARY AUC0-8h for Artemether |
64.0; 71.7; 95.8; 78.6 | — |
| PRIMARY AUC0-8h for Dihydroartemisinin |
109; 95.8; 241; 229 | — |
| PRIMARY Cmax for Lumefantrine |
5065; 6027; 7236; 8450 | — |
| PRIMARY Cmax for Artemether |
22.4; 23.0; 32.5; 27.3 | — |
| PRIMARY Cmax for Dihydroartemisinin |
43.8; 34.9; 89.0; 87.9 | — |
| SECONDARY Number of Participants With Serious Adverse Events |
0; 0; 2; 0 | — |
Eligibility Criteria
Inclusion Criteria
1, All participants:
- Residency within 60 km of the study clinics either at TDH or at MGH
- Agreement to come to clinic for all follow-up clinical and PK evaluations
- Provision of informed consent
- Weight ≥6 kg
- Presentation with uncomplicated falciparum malaria as indicated by positive smear for malaria parasites along with clinical evidence of infection (fever or history of fever in the past 24 hours)
- Willingness to undergo intensive PK sampling and/or population PK sampling during episode(s) of malaria.
2 HIV-infected participants:
- Confirmed HIV infection (positive rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)
- On stable EFV-based ART for at least 10 days prior to enrollment
- Age 3 years to 18 years
3 HIV-uninfected participants:
- Confirmed HIV negative test (negative rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)
- Age 6 months to 18 years
Exclusion Criteria
- History of significant comorbidities such as malignancy, active tuberculosis or other World Health Organization (WHO) stage 4 disease
- Current infection with non-P. falciparum species
- Receipt of any medications known to affect CYP450 metabolism (except ART) within 14 days of study enrollment (see 4.2.2)
- Hemoglobin < 7.0 g/dL
- For the population PK study, prior treatment for malaria within 14 days of enrollment
- For the intensive PK study, prior treatment for malaria within 28 days of enrollment
- Signs or evidence of complicated malaria, defined as unarousable coma or any two of the following symptoms: Recent febrile convulsions, altered consciousness, lethargy, unable to drink, unable to stand/sit due to weakness, severe anemia (Hb < 5.0 gm/dL), respiratory distress, jaundice (see Appendix D)
- History of toxicity to AL
The following medications are disallowed within 3 weeks prior to receiving study drug:
- Carbamazepine
- Clarithromycin
- Erythromycin (oral)
- Ketoconazole
- Phenobarbital
- Phenytoin
- Rifabutin
- Rifampin
- Halofantrine
- Any other medication known to significantly affect CYP450 metabolism.
- Grapefruit juice should be avoided during the study due to its potential effects on CYP3A4.
Data sourced from ClinicalTrials.gov (NCT03453840) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.