Three Alternative Drug Regimens for Malaria Seasonal Preventive Treatment in Senegal
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this trial is to compare the acceptability, efficacy and safety of three
      alternative drug regimens for use for seasonal Intermittent Preventive Treatment to prevent
      malaria in children. Children aged 2 months to 5 years will be randomized to receive IPT with
      one of three regimens during the transmission season: sulfadoxine-pyrimethamine (SP) plus
      amodiaquine, show to be highly effective for IPT in a recent trial; SP plus piperaquine, used
      for malaria prophylaxis in China for many years; or Duocotexcin (a combination of piperaquine
      with an artemisinin).
    

Detailed description: 
      In areas of seasonal malaria transmission the burden of severe disease and mortality due to
      malaria is mainly among children under 5 years of age. Intermittent preventive treatment
      (IPT) with antimalarial drugs given to all children once a month during the transmission
      season is a promising new strategy for malaria prevention. Seasonal IPT with
      sulfadoxine-pyrimethamine (SP) and one dose of artesunate resulted in a 90% reduction in
      incidence of clinical malaria in a recent trial in Senegal (Cisse et al., Lancet 2006). An
      important consideration is the possible impact of seasonal IPT on the emergence and spread of
      drug resistant parasite genotypes, the choice of drug regimen is therefore critical. A second
      trial in Senegal showed that a combination of two non-artemisinin drugs with relatively long
      half lives (SP and amodiaquine (AQ) over three days) was more effective than SP with
      artesunate and more effective than AQ with artesunate, in preventing malaria; and very few
      children developed parasitaemia, so that the potential for drug resistant genotypes to emerge
      and spread was low. Although SP+AQ was more efficacious than the artemisinin-containing
      regimens tested, it was associated with a higher frequency of adverse events, especially
      vomiting, and AQ has a bitter unpleasant taste, and therefore we have concerns about the
      acceptability of AQ for widespread use for IPT. It is important to select a drug regimen that
      is not only effective but safe and acceptable to the community. Each treatment is a 3-dose
      regimen over 3 days, the first dose will be supervised and the other 2 doses given by the
      mother or carer. One month after each treatment round, children will be visited at home to
      check for malaria symptoms, children with fever or a history of fever in the last 48 hours
      will be asked to give a finger prick blood sample for malaria diagnosis. One month after the
      last treatment all children will be asked to give a finger prick blood sample for
      parasitology and haemoglobin, axillary temperature will be measured. The child's carer will
      be interviewed about compliance and adverse events. The endpoints will be the cumulative
      incidence of malaria, the proportion of children experiencing moderate and severe adverse
      events, compliance with and acceptability of the regimen, the prevalence of parasitaemia, and
      the proportion of children carrying parasite genotypes associated with resistance to
      sulfadoxine or pyrimethamine at the end of the transmission season. Since acceptability is
      difficult to assess in the formal setting of a trial, and because the method of delivery may
      affect compliance and acceptability, drug treatments will be delivered by community workers
      replicating the conditions under IPT would be delivered routinely in Senegal. Treatments will
      be administered at home by local community workers, each worker covering a circuit of
      approximately 60-80 children. The community worker circuit will be the unit of randomization,
      for simplicity in the field to minimise allocation errors, and to avoid contamination due to
      sharing of tablets within a household.
    

Intervention name(s): sulfalene-pyrimethamine plus amodiaquine; dihydroartemisinin plus piperaquine; sulfadoxine pyrimethamine plus piperaquine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Monthly treatments during the malaria transmission season; Monthly treatments during the transmission season; Monthly treatments during the malaria transmission season
Other intervention name(s): Dualkin; Duo cotexcin; sulfadoxine pyrimethamine; piperaquine phosphate
Intervention MeSH terms: Pyrimethamine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine; Artenimol; Sulfalene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria; IPT; preventive treatment