Africa-Europe Partnership Launches First-Ever Clinical Trial for Malaria Treatment in Early Pregnancy
Key Insights
The SAFIRE project has initiated a first-of-its-kind Phase III adaptive platform trial testing two artemisinin-based combination treatments in first-trimester pregnant women across Mali, Burkina Faso, and Kenya.
Currently, only one ACT (artemether-lumefantrine) is recommended for first-trimester use; the trial compares pyronaridine-artesunate (search) and dihydroartemisinin-piperaquine against the standard of care.
Over 12 million pregnant women in sub-Saharan Africa are exposed to malaria (search) annually, yet just 4% of clinical trials over the past decade allowed inclusion of pregnant women.
A landmark Africa-Europe research collaboration has enrolled the first participants in what is being described as the first clinical trial specifically designed to investigate antimalarial drugs in women during the first trimester of pregnancy. The Phase III adaptive platform trial, part of the SAFIRE project and funded by the Global Health EDCTP3, aims to expand the extremely limited treatment arsenal available for one of the most vulnerable patient populations in malaria (search)-endemic regions.
The trial (NCT06962319) has already enrolled 13 women in Mali, 31 in Burkina Faso, and eight in Kenya, and is comparing the efficacy and safety of two artemisinin-based combination treatments (ACTs) — pyronaridine-artesunate (search) and dihydroartemisinin-piperaquine — against the current standard of care. At present, only one ACT, artemether-lumefantrine, is recommended by the World Health Organization (WHO) for use during the first trimester.
"This first-of-its-kind trial addresses an important need for the treatment of malaria (search) during the first trimester of pregnancy, being able to treat the infection with safe and effective drugs. The SAFIRE project will provide an evidence base to make additional drugs available for malaria treatment in the first trimester and also contribute to addressing the lack of equity in enrolling pregnant women in clinical trials," said Dr Henk Schallig, SAFIRE coordinator at Amsterdam University Medical Center (search) (UMC).
The scale of the unmet need
Every year, over 12 million pregnant women in sub-Saharan Africa are exposed to malaria (search), resulting in roughly half a million infections in the first trimester alone. The WHO African Region continues to face the most acute crisis, accounting for 94% of all malaria cases and 95% of malaria deaths globally. The consortium's study aims to inform national and international treatment guidelines to prevent maternal anaemia, stillbirth, and neonatal mortality, while also reducing the burden of malaria in pregnant women.
Pregnant women have historically been excluded from clinical research due to safety concerns — a situation the WHO has been calling to change. Analysis led by the Global Observatory on Health Research and Development of all clinical trials in the International Clinical Trials Registry Platform (ICTRP) reveals that just 4% of clinical trials over the past decade allowed the inclusion of pregnant women. As a result, many pregnant and breastfeeding women are left without treatment options or take prescription medicines off-label, without adequate data to inform safe use.
Consortium leadership and structure
The consortium is led by Amsterdam UMC and features the involvement of the University of Sciences, Techniques and Technologies of Bamako (USTTB) and the Kenya Medical Research Institute (KEMRI). The adaptive platform design allows for flexibility in evaluating multiple interventions, potentially accelerating the generation of evidence needed to update treatment guidelines.
Parallel advances: malaria (search) prevention in pregnant women with HIV (search)
In a related development, KEMRI has also published encouraging results from a separate study investigating malaria (search) prevention in pregnant women living with HIV (search). Published in The Lancet in early January, the study found that adding the antimalarial drug dihydroartemisinin-piperaquine to the standard daily co-trimoxazole (search) treatment significantly reduced malaria infections by 68%.
The WHO estimates that one million pregnant women living with HIV (search) in sub-Saharan Africa contract malaria (search) each year. Currently, the WHO advocates daily administration of co-trimoxazole (search), an antibiotic, to prevent malaria in pregnant women living with HIV in regions with high malaria transmission. However, experts highlight the compromised efficacy of co-trimoxazole due to escalating resistance of malaria parasites to the drug.
The trial involved 904 randomly assigned participants and compared the efficacy of adding monthly dihydroartemisinin-piperaquine to daily co-trimoxazole (search) against a control group receiving a monthly placebo alongside daily co-trimoxazole.
"Not only did we find that adding dihydroartemisinin-piperaquine to co-trimoxazole (search) was safe and prevented two out of every three malaria (search) infections during pregnancy, but it was also well tolerated by pregnant women, which is important when a drug is given for prevention," said Dr Hellen Barsosio, clinical research scientist at KEMRI's Centre for Global Health Research and lead author of the study.
KEMRI CEO Elijah Songok celebrated the findings, emphasizing their potential impact on a disease that risks about 70% of the population. Malaria (search) in pregnancy can lead to serious health complications including miscarriage, stillbirth, preterm delivery, and growth restriction in newborn babies, and co-infection with HIV (search) doubles these risks.
Simon Kariuki, head of the Malaria (search) Programme at KEMRI-CGHR, expressed hope that the study's outcomes, coupled with a parallel trial underway in Gabon and Mozambique, will contribute valuable insights to shape malaria prevention guidelines issued by the WHO and influence the development of national health policies. Dr Barsosio similarly expressed optimism that the findings could lead to a much-needed policy change to improve maternal and newborn health in Africa.