Abstract
BackgroundAsymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring. Unfortunately, there is insufficient information on the safety and efficacy of most antimalarials in pregnancy. Indeed, clinical trials assessing antimalarial treatments systematically exclude pregnancy for fear of teratogenicity and embryotoxicity. The little available information originates from South East Asia while in sub-Saharan Africa such information is still limited and needs to be provided.DesignA Phase 3, non-inferiority, multicentre, randomized, open-label clinical trial on safety and efficacy of 4 ACT when administered during pregnancy was carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This is a four arm trial using a balanced incomplete block design. Pregnant women diagnosed with malaria are randomised to receive either amodiaquine-artesunate (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL), or mefloquine-artesunate (MQAS). They are actively followed up until day 63 post-treatment and then monthly until 4–6 weeks post-delivery. The offspring is visited at the time of the first birthday. The primary endpoint is treatment failure (PCR adjusted) at day 63 and safety profiles. Secondary endpoints included PCR unadjusted treatment failure up to day 63, gametocyte carriage, Hb changes, placenta malaria, mean birth weight and low birth weight. The primary statistical analysis will use the combined data from all 4 centres, with adjustment for any centre effects, using an additive model for the response rates. This will allow the assessment of all 6 possible pair-wise treatment comparisons using all available data.DiscussionThe strength of this trial is the involvement of several African countries, increasing the generalisability of the results. In addition, it assesses most ACTs currently available, determining their relative ‘-value-’ compared to others. The balanced incomplete block design was chosen because using all 4-arms in each site would have increased complexity in terms of implementation. Excluding HIV-positive pregnant women on antiretroviral drugs may be seen as a limitation because of the possible interactions between antiretroviral and antimalarial treatments. Nevertheless, the results of this trial will provide the evidence base for the formulation of malaria treatment policy for pregnant women in sub-Saharan Africa.Trial registrationNCT00852423
Highlights
Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring
Excluding Human immunodeficiency virus (HIV)-positive pregnant women on antiretroviral drugs may be seen as a limitation because of the possible interactions between antiretroviral and antimalarial treatments
Pregnant women are one of the high risk groups affected by the malaria burden and few antimalarials are available to treat them
Summary
Pregnant women are one of the high risk groups affected by the malaria burden and few antimalarials are available to treat them. Considering that most pregnant women recruited in the study will have an infection with a relatively low parasite density and that they will be treated with an ACT, it is expected that the number of treatment failures in this specific sub-group would be extremely low They will have to be treated in any case as the consequences of the malaria infection on the woman’s health and that of her offspring are well known. DHA-PQ is the first line treatment in Papua Indonesia, where it is used to treat pregnant women with malaria; an observational study reported significant benefits of DHA-PQ over quinine-based regimens in reducing recurrent malaria and poor foetal outcome in pregnant women in the second or third trimester [26] This trial will increase significantly the knowledge on the use of DHA-PQ in African pregnant women.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.