Safety of Antimalarials in the FIRst trimEster

The SAFIRE study aims to find effective treatments with acceptable safety for malaria in early pregnancy, a particularly sensitive time for the adverse consequences of malaria in pregnancy for both mother and baby. Currently, WHO recommends the antimalarial drug artemether-lumefantrine (AL) for the treatment of uncomplicated malaria in the first trimester of pregnancy. Other promising treatments are being rolled out in malaria-endemic countries for use in adults and children and data on current exposures in the first trimester are limited and insufficient to support a recommendation. This is due to the fact that pregnant women are often excluded from clinical trials to protect fetuses, unintentionally depriving them of newer, potentially better treatments. Instead, they often received older, less effective drugs. The International Council for Harmonisation (ICH E21) and stringent regulatory authorities (e.g. EMA, FDA and MHRA) now encourage pregnant women to be included in well-designed studies to ensure they can safely benefit from medical advances. This study will compare AL with the newer antimalarial drugs that have shown no significant safety concerns in laboratory studies, accidental use during early pregnancy, or trials in later pregnancy stages. The main goal is to see if these new drugs work as well as AL in treating malaria and are safe for the mother, her pregnancy and the developing baby. The newer antimalarials being tested also offer additional benefits to pregnant women, such as preventing new malaria infections for longer after treatment than the current standard treatment (AL). Also, they can be taken just once a day instead of twice daily, like AL. A simpler dosing schedule could improve adherence to the study medication, meaning women are more likely to take the full course of treatment as prescribed. This, in turn, enhances its effectiveness in real-world settings. Future antimalarials to be tested will include those with improved resistance pro