Background: Vancomycin remains one of the most widely prescribed antibiotics for Gram-positive neonatal late onset sep- sis (LOS). Robust neonatal clinical outcome data comparing different vancomycin dosing regimens is lacking. NeoVanc (NCT02790996) is a European, multicentre, phase IIb, randomised controlled, non-inferiority trial comparing an optimised and standard vancomycin regimen in infants aged ≤90 days with known/suspected Gram-positive LOS.
Materials/methods: Infants with clinical sepsis (≥3 clinical/laboratory criteria) or confirmed sepsis (Gram-positive blood culture and ≥1 clinical/laboratory criterion) were included. Participants were randomised 1:1 to an optimised regimen (loading dose [25 mg/kg] followed by 5±1 days of 15 mg/kg q12h or q8h dependent on postmenstrual age [PMA] or a standard regimen [10±2 day course at 15 mg/kg q24h, q12h, or q8h dependent on PMA]). The primary endpoint was successful outcome at end of vancomycin therapy and no clinically/microbiologically significant relapse/new infection requiring treatment with anti-staphylococcal antibiotics within 10 days of stopping vancomycin.
Secondary endpoints included safety and pharmacokinetics. ‘Per protocol’ was all participants receiving/not receiving the loading dose as randomised and ≥48h of study vancomycin.
Results: 242 infants were randomised between March 2017 and July 2019 from 22 neonatal intensive care units in 5 European countries. Per-protocol population is presented (183 participants): 55% were male, with a median (IQR) postmenstrual age of 32(29–37) weeks and postnatal age at onset of LOS of 14(8–25) days. Mean weight was 1663g(924g SD) and central lines were present in 115/183(63%) participants at randomisation. 133/183(73%) received antibiotics in the 7 days before randomi- sation. 25/183(14%) had positive blood culture for Gram-positive organisms of interest at randomisation, and 179/183(98%) had ≥3 clinical/laboratory signs on randomisation. 141/183(77%) received vancomycin according to the randomised duration. There were 4 deaths and 4 withdrawals/loss to follow-up prior to TOC.
There were 40 post-randomisation exclusions.
128/179(72%) had a successful primary outcome. 2/165(1%) of all randomised infants had abnormal renal function at short- term follow-up.
Conclusions: NeoVanc is the largest LOS vancomycin trial to provide clinical efficacy and safety outcome data associated with alternative dosing strategies. Preliminary results are included (some events not yet adjudicated): final results comparing randomised groups and outcomes will be presented.