27 Nov, 2021
NeoVanc, a European trial featured in The Lancet Child & Adolescent Health, has published the findings of the largest neonatal vancomycin efficacy trial ever conducted. NeoVanc was a European, multicentre research study coordinated by Penta and funded by the European Commission’s 7th Framework Programme. It compared the efficacy, safety and pharmacokinetics of an optimised dosing regimen with a standard dosing regimen of vancomycin in infants with late onset sepsis. The NeoVanc programme* took place between March 2017 and July 2019 and involved 242 infants with serious infections from 22 neonatal intensive care units in Italy, Greece, Estonia, Spain and the UK. The aim of the study was to compare recovery from sepsis as well as relapses or new infections requiring further treatment between the two groups.
Dr Louise Hill, Lecturer in Paediatric Infectious Diseases at St George’s, University of London said, “Neonatal sepsis is a global health priority with around 3 million cases per year worldwide. Premature babies and infants in the first 3 months of life represent a particularly vulnerable group because their immune systems are not yet fully developed. In Europe, coagulase-negative staphylococci (CoNS) are the most frequently identified bacteria in neonatal late onset sepsis and vancomycin is the antibiotic most commonly used to treat them. However, despite being used for over 50 years, there are very few studies comparing different dosing regimens of vancomycin.”
To bridge this gap, the NeoVanc set out to compare the efficacy of administering an optimised regimen with a first (loading) dose of 25 mg/kg of vancomycin followed by lower doses of 15 mg/kg (at intervals determined by postmenstrual age (PMA)) over a shorter 5-day course with a standard 10-day course with lower daily dosing of 15 mg/kg of the drug throughout.
According to the Chief Investigator, Professor Mike Sharland of the Paediatric Infectious Diseases Research Group at St George’s, University of London, “the results of the study show that there is no clear advantage for adopting a shorter 5-day course, with a loading dose, over the standard 10-day course in infants under 3 months of age with severe sepsis.”
What emerged from the study was that babies in the shorter 5-day course group were more commonly assessed as not fully recovered by the end of treatment as compared with babies in the longer course group. Furthermore, twice as many babies (30%) in the short course group failed routine hearing testing compared to the longer course (15%), making further research in this area a priority.
In light of this finding, Professor Sharland added: “A NeoVanc follow-up study is currently underway to collect long-term hearing data on those infants who were affected by hearing dysfunction, particularly in relation to the use of the shorter treatment course.”
Read the paper on The Lancet Child Adolescent Health
About the article
The article is: Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-inferiority trial
Louise F Hill*, Michelle N Clements*, Mark A Turner, Daniele Donà, Irja Lutsar, Evelyne Jacqz-Aigrain, Paul T Heath, Emmanuel Roilides, Louise Rawcliffe, Clara Alonso-Diaz, Eugenio Baraldi, Andrea Dotta, Mari-Liis Ilmoja, Ajit Mahaveer, Tuuli Metsvaht, George Mitsiakos, Vassiliki Papaevangelou, Kosmas Sarafidis, A Sarah Walker, Michael Sharland, on behalf of the NeoVanc Consortium†
The Lancet Child & Adolescent Health 2021, published online Nov 26 https://doi.org/10.1016/S2352-4642(21)00305-9
The NeoVanc project set out to analyse the adaptability of an off-label medicine, vancomycin, to the specific needs of neonates and infants, by developing an optimal dosing regimen. Coordinated by Penta and funded by the European Commission’s 7th Framework Programme, NeoVanc has successfully recruited almost 250 participants, and involved more than 20 sites in 5 European countries. This randomised, open label, phase IIb study compares the efficacy, safety and pharmacokinetics of an optimised dosing regimen with a standard dosing regimen of vancomycin in neonates and infants with late onset bacterial sepsis. The study team is currently developing publications to present the results to the wider public.