Randomised Trial of 3 Artemisinin Combination Therapy for Malaria in Pregnancy
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a randomised, open label trial, comparing standard dose of
      dihydroartemisinin-piperaquine (DP) with standard fixed artesunate-mefloquine regimen (MAS3)
      and with a longer regimen of artemether-lumefantrine (ALN+) in the treatment of uncomplicated
      malaria in pregnant women. The sample size is 335 women in each arm which would be 1005 women
      in total. Pregnant patients in 2nd and 3rd trimester with acute uncomplicated malaria who
      meet eligibility criteria will be asked to participate in the study. The primary objective is
      to determine if the efficacy of DP and MAS3 are superior to ALN+ in the treatment of
      uncomplicated malaria in pregnancy. The study will also incorporate a dense pharmacokinetic
      study of mefloquine and artesunate (15 women in the MAS3 arm) and a population
      pharmacokinetic study for mefloquine, piperaquine and lumefantrine.
    

Detailed description: 
      The 3 treatment regimens are 3 days of DHA-piperaquine (DP), 3 days of artesunate-mefloquine
      (MAS3) with mefloquine given as 8,8,8 mg/kg per day and an augmented dose of 4 days (5 tabs
      BID) of artemether- lumefantrine (ALN+). This will focus on efficacy and safety. Patients
      will be randomized equally to one of three treatment groups.

      Within the trial there are two nested pharmacokinetic studies comprising dense data on 15
      women for mefloquine and artesunate and sparse data for mefloquine, lumefantrine and
      piperaquine. Pregnant women will be followed up until delivery or day 63 if later than
      delivery and their infants will be followed until the end of the first year of life The
      follow up of babies will be monthly until 1 year (summarized in the table). Visits will
      include body weight, length, head circumference, arm circumference, physical examination,
      motor milestones by observation and caregiver interview, developmental examination and
      monthly haematocrit and stool testing. The mother is free to bring her infant at any time to
      the clinic and investigations appropriate to the presenting complaint and symptoms will be
      carried out as necessary to provide care for the infant.

      Infants born to mothers who have a positive peripheral smear at delivery are at risk of
      congenital malaria and will be actively screened weekly for 2 months. In the last study one
      congenital malaria P.falciparum occurred at day 21 and the infant was very sick and was cured
      with artesunate. Infants who are positive for malaria would have a PCR spot to verify if the
      malaria was congenital.
    

Intervention name(s): dihydroartemisinin-piperaquine; Artesunate-mefloquine; arthemeter-lumefantrin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Standard 3 days regimen DHA-piperaquine: (DHA/PPQ 40 mg/320 mg) 2.4 mg/kg DHA and 20 mg/kg PPQ once daily for 3 days; Standard three day regimen of artesunate-mefloquine (12/24 mg/kg) given as artesunate 4mg/kg/day and mefloquine 8mg/kg/day on Days 0, 1 and 2.; Augmented 4 day regimen of artemether lumefantrine 2 doses per day for 4 days. Each dose consists of 5 tablets (20/120 mg of artemether/lumefantrine per tablet).
Other intervention name(s): Artekin; Coartem
Intervention MeSH terms: Artesunate; Piperaquine; Artenimol; Mefloquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: pregnancy, malaria, artemisinin, vivax, falciparum