Octenidine or Sterile Water Cleansing and Late-Onset Sepsis in Neonates in the NICU: A Randomized Clinical Trial.

Importance: While skin cleansing with octenidine has shown promise in preventing health care infections, its effectiveness for preventing late-onset sepsis in neonates is unproven. Objective: To compare the incidence rates of late-onset sepsis (LOS) in neonates admitted to the neonatal intensive care unit (NICU) who were cleansed daily with octenidine wipes vs those cleansed with sterile water. Design, Setting, and Participants: This single-center, open-label, parallel-group randomized clinical trial was conducted in the level II and level III NICUs of a tertiary care hospital in India between September 1, 2023, and August 31, 2025. All neonates admitted to the NICU within 48 hours of birth without early-onset sepsis or preexisting skin lesions and not discharged from the NICU before 72 hours were included. Intervention: Neonates were assessed and randomly assigned to receive once-daily full-body cleansing with either 0.1% octenidine dihydrochloride antimicrobial wipes or sterile water applied with sterile gauze until discharge, transfer to another facility, or death. Separate wipes or gauze were used for the upper and lower body, with genital cleansing performed last. No rinsing was performed after application to allow residual antimicrobial activity. Skin condition was assessed daily using the Neonatal Skin Condition Score. Main Outcomes and Measures: The primary outcome was LOS rates (occurring >72 hours after birth through 28 days of life) among neonates cleansed with octenidine wipes vs with sterile water until discharge or transfer to the maternal bedside, assessed using relative risk (RR). Time to LOS was compared using the hazard ratio (HR). All cases were independently adjudicated by 2 blinded neonatologists. Secondary outcomes included LOS at 7 and 14 days, all-cause mortality, length of NICU stay, and adverse skin reactions. Results: Of 530 neonates eligible for intention-to-treat analysis (299 males [56.4%]; median gestational age, 35.0 weeks [IQR, 32.0-37.0 weeks]), LOS occurred in 39 of 266 (14.7%) in the octenidine group and 34 of 264 (12.9%) in the sterile water group (RR, 1.10; 95% CI, 0.75-1.70; P = .60). Time to LOS was similar between groups (HR, 1.11; 95% CI, 0.71-1.78; P = .63). Secondary outcomes for the octenidine vs sterile water interventions were similar, including LOS by 7 days (24 neonates [9.0%] vs 23 [8.7%]) and 14 days (15 [5.6%] vs 11 [4.2%]), all-cause mortality (12 [4.5%] vs 5 [1.9%]), and length of NICU stay in days (median, 11.0 [IQR, 6.0-21.0] vs 10.0 [IQR, 6.0-19.0]). Adverse skin reactions occurred in 15 neonates (5.6%) in the octenidine group and 16 (6.1%) in the sterile water group (RR, 1.10; 95% CI, 0.55-2.10). Conclusions and Relevance: In this randomized clinical trial, daily skin cleansing with octenidine wipes showed no evidence of reducing the incidence of LOS in NICU neonates compared with sterile water, suggesting that infection prevention strategies should focus on multimodal interventions rather than relying solely on skin cleansing. Trial Registration: CTRI Identifier: CTRI/2023/08/056562.