Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants
Condition: Malaria
MeSH terms: Malaria
Intervention: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy; Monthly dihydroartemisinin-piperaquine (DP) for infants; 3-monthly dihydroartemisinin-piperaquine (DP) for infants
Intervention MeSH terms: Pyrimethamine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Artenimol; Artemisinins
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 300.0
Sex: Female
Minimum age: 16 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Chemoprevention; Malaria; Uganda; Sulfadoxine-pyrimethamine; Dihydroartemisinin-piperaquine

Summary:

      This will be a double-blinded randomized controlled phase III trial of 300 HIV uninfected
      pregnant women and the children born to them. The study interventions will be divided into
      two phases. In the first phase, HIV uninfected women at 12-20 weeks gestation will be
      randomized in equal proportions to one of three intermittent preventive therapy in pregnancy
      (IPTp) treatment arms: 1) 3 doses of sulfadoxine-pyrimethamine (SP), 2) 3 doses of
      dihydroartemisinin-piperaquine (DP), or 3) monthly DP. All three interventions arms will have
      either SP or DP placebo to ensure adequate blinding is achieved. Follow-up for the pregnant
      women will end approximately 6 weeks after giving birth. In the second phase of the study,
      all children born to mothers enrolled in the study will be followed from birth until they
      reach 36 months of age. Children born to mothers randomized to receive 3 doses of SP during
      pregnancy will receive DP every 3 months between 2-24 months of age. Children born to mothers
      randomized to receive 3 doses of DP or monthly DP during pregnancy will receive either DP
      every 3 months or monthly DP between 2-24 months of age. To ensure adequate blinding,
      children who will receive DP every 3 months will be given DP placebo during the months they
      will not be taking DP. Children will then be followed an additional year between 24-36 months
      of age following the interventions. We will test the hypothesis that IPT with DP will
      significantly reduce the burden of malaria in pregnancy and infancy and improve the
      development of naturally acquired antimalarial immunity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pregnancy confirmed by positive urine pregnancy test or intrauterine pregnancy by
             ultrasound

          2. Estimated gestational age between 12-20 weeks

          3. Confirmed to be HIV uninfected by rapid test

          4. 16 years of age or older

          5. Residency within 30km of the study clinic

          6. Provision of informed consent by the pregnant woman for herself and her unborn child

          7. Agreement to come to the study clinic for any febrile episode or other illness and
             avoid medications given outside the study protocol

          8. Plan to deliver in the hospital

        Exclusion Criteria:

          1. History of serious adverse event to SP or DP

          2. Active medical problem requiring inpatient evaluation at the time of screening

          3. Intention of moving more than 30km from the study clinic

          4. Chronic medical condition requiring frequent medical attention

          5. Prior SP preventive therapy or any other antimalarial therapy during this pregnancy

          6. Early or active labor (documented by cervical change with uterine contractions)