Extended Duration Artemether-lumefantrine Treatment for Malaria in Children — EXALT  

Uncomplicated Plasmodium Falciparum Malaria Clinical Trial

Official title: Extended Duration Artemether-lumefantrine Treatment for Malaria in Children

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Uncomplicated Plasmodium Falciparum Malaria

• NCT number: NCT03453840
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Completed
• Phase: Phase 4
• Start date: February 19, 2018
• Completion date: August 31, 2021