Novel clinical trial to improve treatment for newborns with sepsis launches

22 May 2023

NeoSep1, an international clinical trial to evaluate much-needed new antibiotic combinations for newborn babies with sepsis, has started in three hospitals in South Africa and Kenya. The trial will be expanded to other countries and regions next year, with a target of recruiting up to 3,000 newborns overall. 

Neonatal sepsis, a life-threatening infection, affects up to 3 million babies per year globally. It has become increasingly hard to treat, as about 40% of infections are resistant to standard antibiotic treatments. More than 214,000 newborn babies die of drug-resistant neonatal sepsis every year, mostly in low- and middle-income countries.   

The NeoSep1 trial will first assess best doses of three new combinations of older antibiotics (fosfomycin-amikacin, flomoxef-amikacin and flomoxef-fosfomycin). Researchers will do this by measuring the levels of drugs in the babies’ blood. This is called a pharmacokinetic (PK) study. 

These results will inform the second part of the trial, which will rank how well these and other antibiotic regimens prevent babies dying from neonatal sepsis. 

A key goal is to find out whether some antibiotic treatments perform better than others in low and middle-income countries where highly resistant bacteria are common. The trial will also consider how these combination treatments can best be used in hospital settings with varying levels of antibiotic resistance. 

NeoSep1 will use a new methodology called the Personalised Randomised Controlled Trial (PRACTical) design. This design was specifically developed by the MRC Clinical Trials Unit at UCL to address challenges such as the lack of a universal, effective standard of care for neonatal sepsis and different patterns of antibiotic resistance in different parts of the world. 

NeoSep1 builds on findings from a global observational study of sepsis in newborn babies, NeoOBS, which found a worryingly wide variation in treatment, frequent use of last-line antibiotics, and frequent switching of antibiotics because of high resistance to treatments. 

The NeoSep1 trial aims to generate relevant and reliable evidence of the most effective antibiotic combinations and dosages for newborns with neonatal sepsis. This will help doctors choose treatments that are likely to work well for newborns in their setting, especially in hospitals where there are high levels of antimicrobial resistance. 

The trial is sponsored by the Global Antibiotic Research and Development Partnership (GARDP) in collaboration with the MRC CTU at UCL; St George’s, University of London; and Penta. 

The MRC CTU at UCL has also released an episode of the Trial Talk podcast focusing on the NeoOBS study and the global challenge of neonatal sepsis. This will be followed next month by a second episode, looking at the design of the NeoSep1 trial. 


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