Safety and efficacy of antiseptic cleansing to reduce vertical transmission of multi-drug resistant pathogens to neonates (NeoVT-AMR). An open-label, single centre, factorial randomised clinical trial

ImportanceNeonatal sepsis causes significant mortality. Antiseptic application to the perineum and vagina of labouring women or to neonatal skin could reduce neonatal pathogenic bacterial colonisation, lowering sepsis risk. ObjectiveThis study aimed to identify a safe, efficacious antiseptic regimen for a future effectiveness trial. DesignRandomised controlled trial conducted between March 2022-March 2023. Laboratory staff (who assessed the primary outcome), were blinded to allocation. SettingThe trial was conducted at Zomba Central Hospital, Malawi on the antenatal and labour wards (maternal stratum) and the neonatal and postnatal wards (neonatal stratum). Participants149 women in labour and 147 neonates participated. InterventionsParticipants were individually randomised in an unblinded factorial design to antiseptic (chlorhexidine 1% [CHG1%], chlorhexidine 2% [CHG2%], octenidine 0.1%/phenoxyethanol 2% [OCT]) once or multiple times (maternal: [&le;]6 four-hourly applications; neonatal: [&le;]3 24- hourly applications postnatally) or to standard of care (SOC). Main Outcomes and MeasuresThe primary outcome was change in total vaginal or neonatal skin bacterial load. Secondary outcomes in both strata assessed safety by skin condition score, serious adverse events and temperature (neonatal strata only). Additionally, bacterial load of the neonates born to women in the maternal stratum was assessed. ResultsMean baseline maternal vaginal bacterial load was 6.3 log10CFU (log10 colony forming units (log10CFU), SD=2.0), decreasing to 1.5 (SD=2.0) for CHG1% at 4hrs and 5.7 (SD=1.8) for SOC. CHG1% was more efficacious than OCT (absolute effect size=1.7 log10CFU, 95%CI[0.9,2.5], p<0.001) and SOC (effect size 3.5, 95%CI [2.4,4.5], p<0.001). There was no difference in efficacy between CHG1% and CHG2% or between application frequencies. Mean baseline neonatal bacterial load was 4.3 log10CFU (SD=2.9), rising to 5.5 (SD=2.7) for CHG1% and 7.4 (SD=2.4) for SOC at 24 hours. CHG1% showed greater efficacy than SOC (effect size=1.2, 95%CI [0.2,2.3], p=0.023), with no difference between antiseptics. Multiple applications showed increasing benefits over time. No safety concerns were observed. Conclusion and RelevanceCHG1% was efficacious in both strata, with effect sizes higher in the maternal stratum. This suggests chlorhexidine cleanses could be incorporated into future multimodal infection prevention intervention trials. Trial registrationNeoVT-AMR is registered on the ISRCTN registry (ISRCTN78026255), registration date 26th May 2022. Protocol and statistical analysis plan available at: https://doi.org/10.1186/ISRCTN78026255. Key pointsQuestion: is antiseptic application in labouring women and neonates safe and efficacious at reducing bacterial load? Findings: this randomised clinical trial included 149 women in labour and 147 neonates. 1% chlorhexidine was efficacious in reducing bacterial load in both strata, with effect sizes higher in the maternal stratum. No safety concerns were observed. Meaning: chlorhexidine cleanses could be incorporated into multimodal infection prevention intervention trials in neonates and labouring women.