Efficacy of Artemether-lumefantrine, Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Malawi
Condition: Malaria, Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional

Summary: 
      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 falling efficacy of
      sulfadoxine-pyrimethamine, the first-line treatment of uncomplicated malaria from 1993 to
      2007, the National Malaria Control Program (NMCP) revised the national treatment guidelines
      in 2007. 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. The change in policy was based primarily on efficacy data from other
      countries in sub-Saharan Africa. However, although both artemether-lumefantrine and
      artesunate-amodiaquine have been in use in Malawi since 2007, there are relatively few
      studies assessing their efficacy. In a study conducted in 2004-2006 in Blantyre,
      artemether-lumefantrine was found to be efficacious.1 In addition, 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
      (Kamija Phiri, personal communication).

      Although, some Malawi-specific data on the in vivo efficacy of the standard formulation of
      artemether-lumefantrine exists, there are additional data that is needed to support the
      current policy and inform future policy decisions. In 2010 the NMCP has introduced the
      dispersible formulation of artemether-lumefantrine (Coartem-D™) for use as a first-line
      antimalarial in Malawi, due to the global unavailability of the standard formulation of
      artemether-lumefantrine from Novartis, the key supplier of the standard formulation of
      artemether-lumefantrine (Coartem™) in Malawi. In light of these developments, an assessment
      of the efficacy, safety and tolerability of the dispersible formulation of
      artemether-lumefantrine is warranted. In addition, the efficacy, safety and tolerability of
      co-formulated artesunate-amodiaquine, the current secondline treatment for uncomplicated
      malaria, has never been assessed in Malawi and should be evaluated. Lastly,
      dihydroartemisinin-piperaquine has recently been added to the new World Health Organization
      (WHO) guidelines for the treatment of uncomplicated malaria. This promising new antimalarial
      might have a role as a first-line or second-line antimalarial for the treatment of
      uncomplicated malaria, but there are no efficacy and safety data from Malawi. This knowledge
      gap needs to be addressed to help inform policy makers about the potential role of
      dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria in Malawi.

      Objective: Efficacy and safety of the dispersible formulation of artemether-lumefantrine,
      co-formulated artesunate-amodiaquine and co-formulated dihydroartemisinin-piperaquine for the
      treatment of uncomplicated Plasmodium falciparum malaria at Machinga District Hospital-
      Malawi

      Methods: An antimalarial drug efficacy trial will be conducted in Malawi. The participants
      will be febrile people 6-59 months old with confirmed uncomplicated P. falciparum infection.
      Patients will be sequentially allocated 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; or co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day
      dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days. Clinical and
      parasitological parameters will be monitored over a 42-day follow-up period to evaluate drug
      effi¬cacy. The study will be conducted from January to December, 2011. The results of this
      study will be used to assist the Ministry of Health in Malawi in assessing the current
      national treatment guidelines for uncomplicated P. falciparum malaria.
    


Intervention name(s): Artemether-lumefantrine combination; Artesunate-amodiaquine combination; Dihydroartemisinin-piperaquine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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; 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; Co-formulated dihydroartemisinin-piperaquine at a dose of 4 mg/kg/day dihydroartemisinin and 18 mg/kg/day piperaquine once a day for 3 days
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Piperaquine; Artemether, Lumefantrine Drug Combination; Amodiaquine; Artenimol; Amodiaquine, artesunate drug combination
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment