The first pregnant woman infected with malaria has been recruited into a Phase 3 trial that is evaluating the efficacy and safety of antimalarial drugs during the first trimester of pregnancy.

Pregnant women are more susceptible to malaria as they have reduced immunity, and malaria poses serious risks to both mothers and babies.

Malaria in pregnancy is responsible for 20% of all stillbirths and 11% of all newborn deaths in sub‑Saharan Africa, as well as 10,000 maternal deaths globally each year. It can also cause severe maternal anaemia, miscarriage, stillbirth, preterm delivery and low birthweight. 

Some 12.4 million pregnant women in sub-Saharan Africa were exposed to malaria in in 2023, according to the World Health Organization (WHO), yet treatment options for pregnant women, particularly in the first trimester, are extremely limited.

The SAFIRE consortium aims to address this research gap through this trial, which will also be run in Burkina Faso and Kenya.

“To advance the malaria elimination agenda in a meaningful and sustainable manner, properly tolerated and effective options must be made available to everyone at risk of malaria, including pregnant women,” says Myriam El Gaaloul, SAFIRE co-principal investigator. 

‘More equitable’

“Enrolling the first patient into the SAFIRE trial is a decisive step forward that will help pave the way towards a more just and equitable future in the fight against this disease,” added El Gaaloul, who heads the Malaria in Mothers and Babies (MiMBa) strategy at Medicines for Malaria Venture (MMV).

The trial is recruiting women in the first trimester of pregnancy with a malaria who will be treated with one of the three artemisinin-based combination therapies (ACTs).

The trial aims to compare the safety and efficacy of pyronaridine-artesunate (PA) and dihydroartemisinin-piperaquine (DP), both approved for the general population but not yet in early pregnancy, to artemether-lumefantrine (AL), which is approved By the WHO for use in the first trimester.

The women will receive follow-up care throughout their pregnancy until delivery, while their newborns will be followed for up to six months after birth.

“The SAFIRE trial will, on one hand, fill the ethical gap of excluding pregnant women from clinical trials, and on the other hand, provide the necessary information to increase therapeutic options in the guidelines for the management of malaria in all stages of pregnancy, thus contributing to reducing the unacceptable burden of malaria among pregnant women,” says Prof Kassoum Kayentao of The Université des Sciences, des Techniques et des Technologies de Bamako in Mali, SAFIRE’s co-principal investigator.

Before recruiting the women, the consortium conducted formative research to ensure recruitment strategies and participant materials were culturally appropriate and reflected the realities of local communities. 

“The formative research we conducted as part of community engagement was key in understanding socio-cultural beliefs and barriers that could hinder the recruitment and retention of participants,” said Dr Innocent Valea, SAFIRE co-principal investigator from The Institut de Recherche en Sciences de la Santé Burkina Faso.

“It allows us to leverage facilitators and co-design appropriate messages targeted at pregnant women and communities. Moving forward, we remain committed to maintaining this engagement to foster trust and successful collaboration.”

Image Credits: WHO.