NCT03453840

Extended Duration Artemether-lumefantrine Treatment for Malaria in Children

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 305 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 6 Months – 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a prospective multi-site study to evaluate the PK/PD of extended duration AL in HIV-infected children on EFV-based ART and HIV-uninfected children not on ART. AL is the first-line treatment for malaria in Uganda. No change in standard of care treatment was made for the purposes of this study except for the extension of AL to 5-day dosing. This study enrolled a) HIV-infected children, and b) HIV-uninfected children. All participants may be enrolled through Tororo District Hospital (TDH) or Masafu General Hospital (MGH) in Busia, or other referral centers the area. we used a design where children were randomized to either 3-day or 5-day AL and then for subsequent episodes of malaria, should they occur. Conservatively, assuming each enrolled child participates for only a single episode of malaria, up to 60 (30 HIV-infected on 3-day and 30 HIV-infected on 5-day) and 100 (50 HIV-uninfected on 3-day and 50 HIV-uninfected on 5-day) subjects were enrolled for each of the intensive study groups. 16 (9 HIV-infected on 3-day and 7 HIV-infected on 5-day) and 120 (60 HIV-uninfected on 3-day and 60 HIV-uninfected on 5-day) subjects were enrolled for each of the population study groups. Enrollment of HIV-infected subjects for population PK study groups was not halted due to the lack of HIV-infected children in the study area. Comparisons of AL PK exposure were made among and between a) HIV-infected children with malaria receiving EFV-based ART and b) HIV-uninfected children who are not on ART. Comparisons were based on an intensive PK design for AL area under the concentration-time curve (AUC) estimations.

Conditions

• Uncomplicated Plasmodium Falciparum Malaria

Interventions

Type	Name	Description
DRUG	Artemether-lumefantrine	Children will receive the dispersible formulation of AL which contains 20 mg artemether, 120 mg of lumefantrine (Coartem® Dispersible). Weight-based dosing will be as below: \<15kg, 1tablet; 15-25kg, 2 tablets; 25-35kg, 3 tablets; \>=35kg, 4 tablets.

Timeline

• Start date: 2018-02-21
• Primary completion: 2021-08-31
• Completion: 2021-08-31
• First posted: 2018-03-05
• Last updated: 2025-04-15
• Results posted: 2025-01-03

Locations

2 sites across 1 country: Uganda