An open-label randomised controlled trial comparing novel combination and currently used antibiotic regimens for the empiric treatment of neonatal sepsis with a run-in confirmatory pharmacokinetic phase
What are safe doses of antibiotics used in 3 new treatment regimens used to treat neonatal sepsis, and how effective are these new regimens and existing regimens in treating neonatal sepsis?
What is this study about?
Globally, there is an increase in antimicrobial resistance (AMR), which means that infections can be more difficult to treat using existing antibiotics. We need to find new ways of treating these infections, including neonatal sepsis. Using combinations of existing antibiotics is one possibility. Fosfomycin, flomoxef, and amikacin are three antibiotics that could be combined into different two-drug combinations for the treatment of neonatal sepsis.
The NeoSep1 study will be divided into two parts.
Part 1 will test how well giving fosfomycin and amikacin, or flomoxef and amikacin, or fosfomycin and flomoxef works to treat babies with severe sepsis. We will do this by measuring the levels of the drugs in the baby’s blood; this is called a pharmacokinetic study (PK) study. The information collected in this part of the study will confirm how much fosfomycin and/or flomoxef we should use in the next part of the study.
In Part 2 of the study, we will test how well these three combinations, as well as other antibiotics that are used routinely to treat sepsis in newborn babies, treat bacterial infections and stop babies from dying.
Listen to our collaborator Mike Sharland from the Centre for Neonatal and Paediatric Infection at St George's University of London on the One Health Trust podcast, discussing drug-resistant infections and the need for better antibiotics in neonates.
Type of study
Who is funding the study?
The trial is funded by the Global Antibiotic Research and Development Partnership (GARDP); the MRC CTU at UCL is supported by core funding by the Medical Research Council, via UK Research and Innovation (UKRI).
When is it taking place?
The first baby was enrolled into the trial on 7th March 2023, and recruitment is still ongoing. It is expected to run until the end of December 2026
Where is it taking place?
Part 1 is taking place in Kenya and South Africa. Part 2 will take place in multiple international sites still to be confirmed. Criteria for selection of these sites include a high prevalence of neonatal sepsis, types of antibiotics prescribed, and bacterial resistance patterns.
Who is included?
60 babies and 3000 babies will be enrolled into Part 1 and Part 2, respectively. These babies will be hospitalised, aged 28 days or less with a clinical diagnosis of sepsis to be treated with antibiotics.
‘25 at 25’: The PRACTical trial design
15 Feb 2024