Pregnancy Complicated by Malaria as Antepartum Condition Clinical Trial
Official title:
Efficacy, Safety and Tolerability of Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Falciparum Malaria in Pregnancy: an Open-label, Randomised Controlled, Non-inferiority Trial
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment