SAFIRE

The challenge

Women are particularly vulnerable to malaria during pregnancy. Malaria infections can affect both their health and that of their fetus, increasing the risk of stillbirth and other adverse pregnancy outcomes. 

Early pregnancy is a particularly vulnerable time. More than seven million women are exposed to malaria during the first trimester every year, leading to half a million infections. Preventive antimalarial treatments cannot be used at this time because of concerns about their impact on the developing fetus. Generally, insecticide-impregnated bed nets are provided at a second antenatal visit, during the second trimester. 

As pregnant women are typically excluded from clinical trials, data on the safety and efficacy of antimalarial treatments are often lacking, leading to long delays before women begin to benefit from new drugs. Although artemisinin combination therapies (ACTs) have long been known to be effective treatments for malaria, they were first recommended by the WHO for use in pregnancy only in 2022, as data from observational studies confirmed their safety. 

Even now, due to a lack of data, only one ACT is recommended for use in the first trimester of pregnancy (artemether–lumefantrine, AL), even though the WHO recommends using a range of treatments to limit the risk of drug resistance. 

The project

Pregnant women could potentially benefit from multiple ACTs, including treatments that are of greater efficacy and longer acting, providing better protection against reinfection. Relying on pregnancy registries to collect safety data would lead to long delays in access. Data could be generated more rapidly through a clinical trial.

The SAFIRE project has been designed to deliver high-quality safety and efficacy data on newer ACTs in women in the first trimester of pregnancy. It has adopted an innovative adaptive platform design, which will allow multiple treatments to be compared with AL. Initial work will focus on a comparison with pyronaridine–artesunate (PA, Pyramax), which appears to provide longer-lasting protection and is increasingly being introduced in Africa. Additional studies will be integrated when funding is available. For example, the Medicines for Malaria Venture (MMV) has expressed an interest in assessing dihydroartemisinin–piperaquine (DHP) in this population.

The project is adopting a highly participatory approach, engaging with global and national stakeholders on trial design, to ensure that the evidence generated is sufficient to inform decision-making. It is also engaging with communities and pregnant women to discuss the potentially sensitive issue of research in early pregnancy, ensuring support for the trial and informing its design.

Impact

The SAFIRE project will provide key evidence on the safety, efficacy and acceptability of pyronaridine–artesunate (PA, Pyramax) and potentially other ACTs in women in early pregnancy. It will:

• Establish whether such women can benefit from new, highly effective ACTs.
• Provide countries with more options for the treatment of malaria in this group.
• Generate communication materials to support the introduction of new treatments.
• Create a platform for the evaluation of additional treatments in pregnant women.
• Build capacity in adaptive trial designs and clinical trials in early pregnancy.

Ultimately, the project will ensure that women in early pregnancy benefit more rapidly from newly developed antimalarials, reducing the number of women and babies harmed by malaria infections during pregnancy.