Effectiveness and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine for the Treatment of Malaria in Yaounde
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 4

Summary: 
      Artesunate-amodiaquine and artemether-lumfantrine are currently being used for the treatment
      of uncomplicated Plasmodium falciparum in Cameroon. Globally, many studies have reported high
      efficacy and safety of artemisinin-based combination therapies (ACTs) mostly under strict
      supervision of drug intake and limited to children less than 5 years of age. Patients over 5
      years of age are usually not involved in such studies. The main objective of this study is to
      assess the genetic markers of antimalarial drug resistance and drug metabolism subsequent to
      the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine during a 28-day
      follow-up period in children with acute uncomplicated P. falciparum malaria in Yaounde,
      Cameroon. A randomized, open-labelled, controlled clinical trial comparing
      artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) will be carried out from 9th
      May 2019 to 30th November 2020 at two secondary health centres (Cité Verte and Minkoameyos)
      in Yaounde. The study participants shall include febrile patients aged 6 months to 10 years,
      with confirmed uncomplicated P. falciparum infection. Eligible children for whom
      parent/guardian informed consents are obtained will be randomized to receive either
      artesunate-amodiaquine (group A) or artemether-lumefantrine (group B) in the ratio 1:1. A
      minimum sample of 76 patients will be required for the study. With a 20 % increase to allow
      loss to follow-up and withdrawals during the 28-day follow-up period, 92 patients will be
      enrolled for each of the two study arms. The study will recruit a total of 184 patients. Drug
      intake will be partially supervised only for the first dose and subsequent doses administered
      unsupervised as pertains in routine practice in the field. Patients or their
      parents/guardians will be advised on the time and mode of administration for the 3 days (D0,
      D1 and D2) treatment unobserved at home. Follow-up visits will be performed on days 3, 7, 14,
      21, and 28 to evaluate clinical and parasitological resolution of their malaria episode as
      well as adverse events. Polymerase chain reaction (PCR) genotyping of merozoite surface
      proteins 1 and 2 (msp-1, msp-2) as well as glutamate rich protein (GLURP) will be used to
      differentiate between recrudescence and new infection.
    

Detailed description: 
      Background: Artesunate-amodiaquine and artemether-lumfantrine are currently being used for
      the treatment of uncomplicated Plasmodium falciparum in Cameroon. Globally, many studies have
      reported high efficacy and safety of artemisinin-based combination therapies (ACTs) mostly
      under strict supervision of drug intake and limited to children less than 5 years of age.
      Patients over 5 years of age are usually not involved in such studies.

      Objective: To assess the genetic markers of antimalarial drug resistance and drug metabolism
      subsequent to the efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine
      during a 28-day follow-up period in children with acute uncomplicated P. falciparum malaria
      in Yaounde, Cameroon.

      Study sites: District Hospital Cité Verte and District Medical Centre Minkoa Meyos in
      Yaounde, Cameroon. The two drugs, artesunate-amodiaquine and artemether-lumefantrine will be
      tested in each site.

      Study period: 9th May 2019 to 30th November 2020.

      Study design: This surveillance study is a two-arm, open-label, randomized controlled
      clinical trial.

      Patient population: Febrile patients aged 6 months to 10 years, with confirmed uncomplicated
      P. falciparum infection. Eligible children for whom parent/guardian informed consents are
      obtained will be randomized to receive either artesunate-amodiaquine (group A) or
      artemether-lumefantrine (group B) in the ratio 1:1.

      Sample size: A minimum sample of 76 patients will be required for the study. With a 20 %
      increase to allow loss to follow-up and withdrawals during the 28-day follow-up period, 92
      patients will be enrolled for each of the two study arms. The study will recruit a total of
      184 patients.

      Treatment (s) and follow-up: Drug intake will be partially supervised only for the first dose
      and subsequent doses administered unsupervised as pertains in routine practice in the field.
      Patients or their parents/guardians will be advised on the time and mode of administration
      for the 3 days (D0, D1 and D2) treatment unobserved at home. Follow-up visits will be
      performed on days 3, 7, 14, 21, and 28 to evaluate clinical and parasitological resolution of
      their malaria episode as well as adverse events. Polymerase chain reaction (PCR) genotyping
      of merozoite surface proteins 1 and 2 (msp-1, msp-2) as well as glutamate rich protein
      (GLURP) will be used to differentiate between recrudescence and new infection.

      Classification of treatment outcomes Classification of treatment outcomes will be done based
      on the WHO 2009 guidelines: treatment failure (Early Treatment Failure-ETF, Late Clinical
      failure-LCF and Late Parasitological Failure-LPF) and treatment success (Adequate Clinical
      and Parasitological Response-ACPR).
    

Intervention name(s): Artesunate-amodiaquine combination; Artemether, Lumefantrine Drug Combination
Intervention type(s): Drug; Drug
Intervention description(s): Artesunate-amodiaquine (Coarsucam®: Sanofi-Aventis, France) is co-packaged as artesunate 50 mg and amodiaquine hydrochloride USP equivalent to amodiaquine base of 153.1 mg. Each child shall be given one, two or three tablets depending on the weight.; Artemether-lumefantrine (Coartem®: Novartis, Switzerland) is formulated as tablets and will be provided in blister packs. Each tablet contains 20 mg artemether and 120 mg lumefantrine. Every pack has a picture showing how the drug should be given and contains two blisters for each day with one, two or three tablets depending on the weight of the child
Other intervention name(s): Coarsucam; Coartem®
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Amodiaquine; Artemether, Lumefantrine Drug Combination; Amodiaquine, artesunate drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible children for whom parent/guardian informed consent are obtained will be randomized to receive either artesunate-amodiaquine (group A) or artemether-lumefantrine (group B) in the ratio 1:1.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Malaria; Plasmodium falciparum; Artesunate-amodiaquine; Artemether-lumefantrine; Effectiveness; Safety