Aqueous chlorhexidine 1% versus 2% for neonatal skin antisepsis: a randomised non-inferiority trial

OBJECTIVE: To evaluate whether 1% aqueous chlorhexidine gluconate (CHG) when compared with 2% aqueous chlorhexidine gluconate is non-inferior for neonatal skin antisepsis. DESIGN: Parallel, blinded, non-inferiority randomised trial. SETTING: Level III, academic, neonatal intensive care unit. PATIENTS: Infants born at 26(0/7) to 42(6/7) weeks of gestation from June 2019 to December 2019. INTERVENTIONS: Participants were randomised to skin antisepsis by either 1% aqueous CHG or 2% aqueous CHG. MAIN OUTCOME MEASURES: The primary outcome was the proportion of negative skin swab cultures after skin antisepsis. Secondary outcomes were local skin reactions at 0, 6, 12 and 24 hours and plasma chlorhexidine levels in a subset of the study population. RESULTS: A total of 308 neonates with a median gestation age of 34 (31–37) weeks and mean birth weight of 2029 g were randomised on 685 occasions (1% CHG: n=341; 2% CHG: n=344). 93.0% of the post-antisepsis skin swabs were sterile in 1% CHG group compared with 95.6% of the swabs in the 2% CHG group (risk difference −2.7%, 95% CI −6.2% to +0.8%). The lower bound of 95% CI crossed the pre-specified absolute non-inferiority limit of 5%. Neonates developed mild dermatitis on 16 (2.3%) occasions. There was no significant difference in median plasma CHG levels in the two groups, 19.6 (12.5–36.4) and 12.6 (8.7–26.6) ng/mL, respectively. CONCLUSIONS: Application of 1% aqueous CHG was not shown to be non-inferior to 2% chlorhexidine aqueous for skin antisepsis in neonates. There were no severe skin-related adverse events in either of the two groups. TRIAL REGISTRATION NUMBER: CTRI/2019/06/019822; (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=33453&EncHid=&userName=CTRI/2019/06/019822)