Dihydroartemisinin (DHA)-Piperaquine for IPT to Prevent Malaria in Children in Burkina Faso
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of the study is to determine whether piperaquine plus dihydroartemisinin (DHA-PQ) is
      as effective, and better tolerated, than sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ),
      when used for seasonal Intermittent Preventive Treatment (IPT) to prevent malaria in children
      aged 3 to 59 months in Bobo-Dioulasso, Burkina Faso and to determine the pharmacokinetics of
      piperaquine in children.
    

Detailed description: 
      There is evidence from several studies that in areas where the transmission of malaria is
      seasonal, the use of IPT can reduce substantially the incidence of clinical malaria in
      children under the age of five years, by as much as 90% (Greenwood et al, Trends in
      Parasitology 24(11):485-6, 2008). The most effective regimen is SP+AQ but alternative
      regimens are needed because amodiaquine can be poorly tolerated (Sokhna et al PlosOne
      3:e1471, 2008) and resistance to SP is increasing. In recent trials in Senegal and The
      Gambia, PQ combined with DHA or SP was as effective against malaria, and better tolerated,
      than SP+AQ. Of these regimens, only DHA+PQ is licensed for use as an antimalarial in African
      countries. However there are no data on pharmacokinetics of PQ when used for IPT in children,
      and the impact of DHA+PQ in preventing spread of resistance is not known. This trial aims to
      provide this information in order to evaluate the suitability of DHA+PQ for use for seasonal
      IPT in children and to determine the optimum dose regimen for piperaquine.

      Malaria (caused primarily by Plasmodium falciparum) is endemic in the southern third of
      Burkina Faso, occurring seasonally between June to November, with most cases occurring
      between August and October. In Burkina Faso there has been no evidence of a recent decline in
      malaria incidence as seen in some other African countries. Although the policy is to treat
      uncomplicated malaria with artemisin combinations, in practice chloroquine remains the
      treatment used in most health facilities. Several studies have shown that seasonal IPT in
      children (IPTc) can provide a high degree of protection against clinical malaria. SP+AQ is
      the most effective regimen but amodiaquine is not well tolerated and resistance to SP is
      increasing n many areas. Alternative regimens are required. Piperaquine (PQ), a long acting
      antimalarial used for prophylaxis in China, is suitable for use for IPT. In studies in
      Senegal and The Gambia piperaquine plus SP or dihydroartemisinin (DHA) was as effective and
      better tolerated than SP+AQ. The purpose of this study is to determine whether DHA-PQ is more
      effective than SP+AQ in preventing spread of drug resistant parasite genotypes and to
      determine the pharmacokinetics of piperaquine in children who receive this drug for IPT.
      Little was known about the pharmacokinetics of piperaquine until recently, and there is
      currently only limited information about the pharmacokinetics of piperaquine in children. The
      pharmacokinetic data from this study will allow us to estimate the optimum dose regimen for
      piperaquine; the current recommended regimen for DHA-PQ is three doses over three days. For
      IPT, a single dose regimen is highly desirable as it would be easier to deliver and better
      accepted by communities.

      1500 children aged 3 to 59 months will be enrolled and randomized to receive 3 monthly
      administrations of DHA-PQ or SP-AQ, in August, September and October. From August to November
      children will be visited twice weekly to check for malaria symptoms.

      A subset of 45 children in each treatment group will be asked to provide a venous blood
      sample on days 0 and 7 for analysis of biochemical and haematological parameters.

      In the DHA-PQ group only, a subset of 210 children will be asked to provide finger prick
      blood samples for PK analysis on day 0, between day 0 and day 6, on day 7, and between day 8
      and day 30. To calibrate measurements of drug concentration in peripheral blood against
      existing PK models, each month 17 of these children will be asked to also provide a venous
      sample (up to 2ml taken into a vacutainer) on three occasions (one between day 0 and 6, one
      on day 7, and one between day 8 and 30). In addition, a separate group of 750 children aged 3
      to 59 months will be recruited to be surveyed at the end of the transmission season to
      determine the prevalence of malaria parasitaemia and of drug-resistance parasite genotypes in
      the study area.
    

Intervention name(s): DHA-PQ; SP-AQ
Intervention type(s): Drug; Drug
Intervention description(s): Three monthly administrations of Duocotexcin (DHA-PQ):
dihydroartemisinin 2.1mg/kg and piperaquine phosphate 16.8 mg/kg once daily for three days; Three monthly administrations of sulfadoxine-pyrimethamine plus amodiaquine:
One dose of Sulfadoxine 25mg/kg and pyrimethamine 1.25mg/kg Three daily doses of amodiaquine phosphate 10mg/kg
Other intervention name(s): Seasonal IPTc with Duocotexcin (Holley); Seasonal IPTc with Fansidar plus amodiaquine (Flavoquine)
Intervention MeSH terms: Amodiaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria; Intermittent Preventive Treatment; IPTc; sIPTc; Burkina Faso