In Vivo Efficacy of Artemether-lumefantrine and Amodiaquine-artesunate in Mozambican Children (MEFI_III)
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a classical in vivo clinical trial, following World Health organization's
      recommendations, ran as a multisite study within Mozambique trying to assess the efficacy and
      safety in 4 sites of the two oral ACTS artemether-lumefantrine (AL) and
      Amodiaquine-Artesunate (AQ-AS), first line treatment for malaria in mozambique, for the
      treatment of uncomplicated malaria in children aged<5 years.
    

Detailed description: 
      This study followed WHO recommendations for in vivo antimalarial efficacy trials.

      The study population comprised children aged 6 to 59 months with microscopically confirmed
      acute uncomplicated malaria. Other inclusion criteria included body weight ≥5kg, the presence
      of fever (≥37.5°C axillary) or a history of fever in the preceding 24 hours, P. falciparum
      malaria mono infection with an asexual blood density ≥2,000/µL and <200,000/µL, and the
      absence of severe signs of complicated malaria as defined by WHO. Key exclusion criteria
      included mixed malarial infections, haemoglobin <5g/dL, severe malnutrition, intake of
      anti-malarials within the preceding seven days, ongoing prophylaxis in HIV positive patients
      with cotrimoxazole or the intake of any other drug with anti-malarial activity, and any
      serious underlying disease. Patients satisfying the inclusion criteria were enrolled if the
      parent/guardian signed a detailed written informed consent.

      Eligible patients were consecutively assigned to the cohort and treated with AL (cohort 1) or
      AQ-AS (cohort 2). AL (Coartem™) was administered twice daily for three days (six doses in
      total) with dosage determined according to body weight: one tablet (20mg artemether and 120mg
      lumefantrine) for children 5 to <15kg, two tablets per dose for those 15 to <25kg, and three
      tablets per dose for those 25 to <35kg. AQ-AS (Winthrop™) was administered once daily
      according to body weight: one 25mg artesunate and 67.5mg amodiaquine tablet in children <9kg,
      one 50mg artesunate and 135mg amodiaquine tablet in children 9-17.9kg; and one 100mg
      artesunate and 270mg amodiaquine tablet in children >18-35kg. All treatments were directly
      observed for a minimum of 30 minutes. Vomiting occurring within the first 30 minutes implied
      the repetition of the full dose of treatment. For those patients living far away from the
      health facilities, and for which direct observation of the evening doses of AL was
      challenging, admission was offered for the first three days of the study.

      Antipyretics, such as paracetamol, were used to control fever>=38ºC. In the event of severe
      malaria or danger signs, the patient was hospitalized and received intravenous quinine,
      according to the national malaria treatment policy. Rescue therapy according to national
      malaria treatment guidelines was also administered in cases of early or late treatment
      failure

      Follow-up visits took place on days 1, 2, 3, 7, 14, and 28 after enrolment or at any time
      point whenever the child was sick. Patients who prematurely discontinued either study drug or
      the study were excluded from the study. Vital signs and body temperature were assessed during
      each follow-up visit. Adverse events were recorded and assessed for severity and association
      with study medication.

      Thick and thin Giemsa-stained blood slides were prepared before each dose was administered
      and at every follow-up visit of days 2, 3, 7, 14, 21 and 28. Slides were examined by two
      independent microscopists and considered negative if no parasites were seen after examination
      of 200 oil-immersion fields in a thick blood film. Species determination (and thus
      conformation of monoinfection) was made based on assessment of thin films. Blood samples for
      PCR analysis were collected from every patient at baseline and at days 7, 14 and 28, day of
      treatment failure or at any other unscheduled visit. PCR was performed centrally for all
      cases of recurrent parasitaemia from day 7 onwards to distinguish recrudescence from
      reinfection according to the standardized WHO method. The Molecular markers associated with
      suboptimal response to ACTs will be investigated.
    

Intervention name(s): Coartem™ (Artemether-lumefantrine combination); Winthrop™ (Amodiaquine-artesunate combination)
Intervention type(s): Drug; Drug
Intervention description(s): AL (Coartem™) was administered twice daily for three days (six doses in total) with dosage determined according to body weight: one tablet (20mg artemether and 120mg lumefantrine) for children 5 to <15kg, two tablets per dose for those 15 to <25kg, and three tablets per dose for those 25 to <35kg.; AQ-AS (Coarsucam™) was administered once daily according to body weight: one 25mg artesunate and 67.5mg amodiaquine tablet in children <9kg, one 50mg artesunate and 135mg amodiaquine tablet in children 9-17.9kg; and one 100mg artesunate and 270mg amodiaquine tablet in children >18-35kg.
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Amodiaquine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Treatment; Artemisine-based combinations; children