In Vivo Efficacy of Artemether-Lumefantrine and Artesunate-Amodiaquine for Uncomplicated P. Falciparum Malaria
Condition: MALARIA, FALCIPARUM
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 4

Summary: 
      This study was designed to determine the efficacy of both artemether-lumefantrine and
      artesunate-amodiaquine (but not to compare the efficacies of the two drugs) for the treatment
      of uncomplicated Plasmodium falciparum malaria at Machinga, Nkhotakota, and Karonga District
      Hospitals- Malawi.
    

Detailed description: 
      Background: Malaria is a cause of substantial morbidity and mortality in Malawi. Prompt and
      effective treatment of uncomplicated malaria remains a key strategy to reduce the public
      health burden of malaria. Due to the rising resistance to and declining efficacy of
      sulfadoxine-pyrimethamine, the first-line treatment for uncomplicated malaria from 1993 to
      2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines
      in 2007 and again in 2013. The revised treatment guidelines recommend artemether-lumefantrine
      as the first-line treatment for uncomplicated malaria and artesunate-amodiaquine as a
      second-line treatment for uncomplicated malaria. Data from Malawi suggests that these drugs
      remain efficacious. In a study conducted in 2004-2006 in Blantyre, artemether-lumefantrine
      was found to be efficacious. A more recent assessment of artemether-lumefantrine in vivo
      efficacy conducted in six sites in Malawi in 2009 also suggests that the standard formulation
      artemether-lumefantrine remains highly efficacious. In addition, both the dispersible
      formulation of artemether-lumefantrine (Coartem-D™) and artesunate-amodiaquine were extremely
      well tolerated and safe in studies conducted in Malawi as well as in other Sub-Saharan
      African countries. Given the potential for development of parasite resistance, it is
      imperative to continue to monitor the efficacy of these drugs as long as they remain the
      recommended treatment regimens.

      Objective: Determine the efficacy of artemether-lumefantrine and co-formulated
      artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria at
      Machinga, Nkhotakota, and Karonga District Hospitals- Malawi

      Methods: A randomized drug efficacy trial will be conducted in Malawi. The trial will include
      453 febrile children 6-59 months old with confirmed uncomplicated P. falciparum infection,
      seeking care at Machinga, Nkhotakota, and Karonga District Hospitals; 151 patients will be
      enrolled at each site (113 for artemether-lumefantrine and 38 for co-formulated
      artesunate-amodiaquine). Patients will be randomized to receive treatment with either the
      dispersible formulation of artemether-lumefantrine at a dose of 2/12 mg/kg body weight of
      artemether and lumefantrine, respectively, per dose, given twice a day for 3 days; or
      co-formulated artesunate-amodiaquine at a dose of 4 mg/kg/day artesunate and 10 mg/kg/day
      amodiaquine once a day for 3 days. Clinical and parasitological parameters will be monitored
      over a 28-day follow-up period to evaluate drug efficacy.
    

Intervention name(s): artemether-lumefantrine (AL); artesunate-amodiaquine (ASAQ)
Intervention type(s): Drug; Drug
Intervention description(s): Dispersible formulation of artemether-lumefantrine (Coartem-D™; 20mg artemether/120mg lumefantrine per tablet, Novartis, Switzerland) administered twice a day for 3 days according to manufacturer recommended dosing for weight; Co-formulated artesunate-amodiaquine (25mg artesunate/67.5mg amodiaquine and 50mg artesunate/135mg amodiaquine tablets) administered once a day for 3 days, according to manufacturer recommended dosing for weight
Other intervention name(s): Coartem; Coarsucam
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Amodiaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: MALARIA, FALCIPARUM; MALAWI; ARTEMETHER-LUMEFANTRINE; ARTESUNATE-AMODIAQUINE