Extended Duration Artemether-lumefantrine Treatment for Malaria in Children
Condition: Uncomplicated Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 4

Summary: 
      This project will determine 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 will be 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 will be
      made for the purposes of this study except for the extension of AL to 5-day dosing. This
      study will enroll 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 will use a design where children will be
      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 will be enrolled for
      each of the intensive study groups. Up to 100 (50 HIV-infected on 3-day and 50 HIV-infected
      on 5-day) and 120 (60 HIV-uninfected on 3-day and 60 HIV-uninfected on 5-day) subjects will
      be enrolled for each of the population study groups. Comparisons of AL PK exposure will be
      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 will be based on an intensive PK
      design for AL area under the concentration-time curve (AUC) estimations. Population PK study
      will be combined with intensive PK studies to allow for optimal PK-outcomes assessments.
    

Intervention name(s): Artemether-lumefantrine
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Coartem, AL
Intervention MeSH terms: Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a prospective multi-site study accomplished through a randomized design where children will be randomized to either 3-day or 5-day AL regimen and then for subsequent episodes of malaria, should they occur..
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: malaria; HIV; Children; Efavirenz; artemether; lumefantrine