Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana
Condition: Pregnancy Complicated by Malaria as Antepartum Condition
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

Summary: 
      Malaria in pregnancy poses enormous public health challenges, contributing to significant
      maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low
      birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility
      to malaria and mediate these adverse outcomes.

      The World Health Organization recommends treatment with artemisinin-combination therapy.
      Ghana uses quinine for malaria in first trimester pregnancies while artesunate-amodiaquine
      (AS-AQ) and quinine again are used in later trimesters. Recent amendments added
      artesunate-lumefantrine and dihydroartemisinin-piperaquine (DHA-PPQ) to the antimalarials
      used in the country. A high degree of safety and efficacy of DHA-PPQ is documented in several
      studies. DHA-PPQ, though not specified for use in pregnancy as of now, is accessible and
      available following its inclusion in the national malaria guidelines and may inadvertently be
      used to treat malaria in pregnancy. Paucity of data on DHA-PPQ use in pregnancy makes it
      pertinent to study its safety, tolerability and efficacy in pregnancy.

      We propose an open label, randomized controlled non-inferiority comparison of DHA-PPQ and
      AS-AQ for treatment of uncomplicated malaria in pregnancy in second and third trimesters to
      assess safety, tolerability and efficacy of DHA-PPQ. Outcomes of interest include
      PCR-corrected cure rates at days 28 and 42, maternal haemoglobin levels at days 14 and 42,
      prevalence of congenital abnormalities and pregnancy wastage. Proportions and percentages
      will be described at 95% Confidence Intervals and compared using chi-square tests. Parametric
      and non-parametric tests of significance will be applied as appropriate to determine
      significance of differences in outcomes between the treatment groups.
    

Detailed description: 
      Pregnant women of all ages, gravidity and with gestational ages 16-30 weeks, living within 15
      km of the study center and presenting for antenatal care or diagnosed with uncomplicated
      malaria will be screened with P.falciparum rapid diagnostic test kits after obtaining
      consent. Those testing positive will have blood film microscopy done and only those with
      positive blood film microscopy will be recruited to participate in the study. Participants
      will be randomized to receive either dihydroartemisinin-piperaquine at an estimated total
      dosing of 6.75mg/kg of dihydroartemisinin and 55mg/kg of piperaquine for 3 days rounded to
      the nearest half tablet) or artesunate-amodiaquine(artesunate 4mg/kg and amodiaquine 10mg/kg
      in two twelve hourly doses daily for 3 days) after giving informed consent and a physical
      examination. This will be followed by home visits on days 1, 3, 7, 14, 28 and 42
      post-treatment to assess occurrence of adverse events and to obtain blood samples for
      microscopy, filter paper blots for PCR analysis and haematology. The mentioned laboratory
      investigations will also be conducted at recruitment.

      Participants will be followed up to delivery and 6 weeks post-partum to gather data on
      maternal peripheral and placental parasitaemia, cord parasitaemia, maternal haemoglobin
      levels, low birth weights, stillbirths, preterm deliveries, neonatal jaundice, birth defects
      and infant deaths.
    

Intervention name(s): artesunate-amodiaquine; Dihydroartemisinin-piperaquine
Intervention type(s): Drug; Drug
Intervention description(s): The 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days; a fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days
Other intervention name(s): camosunate; artekin
Intervention MeSH terms: Artesunate; Piperaquine; Amodiaquine; Artenimol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: malaria,; pregnancy,; dihydroartemisinin-piperaquine,; efficacy,; safety,; Ghana