Title: The efficacy and safety of two topical antiseptic solutions for skin disinfection prior to percutaneous central venous catheter insertion in preterm neonates: a feasibility study
Funder: Department of Health and Social Care

Abstract: 1. Background Percutaneous central venous catheters (PCVCs) are inserted daily in neonatal intensive care for intravenous feeding of sick premature neonates. Their presence is a significant risk factor for catheter-related sepsis (CRS), a dangerous healthcare complication associated with considerable morbidity and mortality. Adequate skin antisepsis at catheter insertion is an important component of catheter-care bundles to prevent CRS. Despite many advances in neonatal care in the past few decades we still do not know the best antiseptic to use for preterm babies. There are very few studies in neonates and their vulnerability to skin damage is greater. Consequently there is no national recommendation regarding the preferred antiseptic for neonates and a wide variety are currently used. Alcohol-based antiseptics are considered superior in adults, but there are no controlled studies of alcohol-based antiseptics for PCVC insertion in neonates. Topical alcohol use increases the risk of neonatal skin damage and systemic chemical absorption[2,3], yet still there is no evidence in babies that alcohol is an essential component of antiseptics for preventing CRS. Antibiotic/antiseptic-impregnated PCVCs are recommended in older children and adults only after failure of comprehensive measures to reduce CRS that include a >0.5% chlorhexidine preparation with alcohol .[4] Clearly optimising skin antisepsis in babies must be prioritised. Studies are needed to find out whether alcohol-based antiseptics are indicated for PCVC insertion. 2. Aims This study aims to obtain information essential for the design of a large future multi-centre, randomised controlled non-inferiority trial that will compare the efficacy and safety of two topical antiseptics for skin disinfection prior to neonatal PCVC insertion. This feasibility study will test study procedures and, in particular, will estimate the prevalence of catheter colonisation at the time of catheter removal to allow accurate estimation of the requisite sample size for the large-scale study. 3. Plan of investigation This feasibility study will be a multi-centre, randomised controlled trial of two antiseptics for neonatal skin disinfection. We aim to recruit 93 preterm infants undergoing planned insertion of a PCVC in two centres over an 18-month period. Infants will be randomised to either aqueous-based 2% chlorhexidine gluconate (2%CHG) or 70% isopropyl alcohol-based 2% chlorhexidine gluconate (70%IPA/2%CHG) for skin disinfection prior to PCVC insertion. Both these antiseptics are commonly used in neonates in the UK, Europe, and United States[5-7]. Neonatal skin burns have been reported with alcohol-based antiseptics[3,8-12], but we have identified only a single report with 2% CHG aqueous[13]. Thus there is good reason to prefer the CHG solution, should it provide at least equivalent efficacy against infection as the alcohol-based solution. The 2%CHG aqueous solution will allow direct comparison of neonatal skin sterilisation versus the alcohol containing preparation. Two PCVC segments and an insertion-site skin swab will be collected for microbiological culture at catheter removal. Isolates from culture-positive skin swabs, catheter segments, and blood will undergo molecular typing to verify that skin-colonising and blood-cultured organisms match catheter-colonising organisms to a species level. Neonatal skin morbidity will be assessed using a validated neonatal contact dermatitis scoring system. 4. Potential impact This feasibility study will directly inform the design of a large-scale trial. The large trial will test whether 2% CHG aqueous is not significantly inferior in antiseptic efficacy to 70%IPA/2%CHG for skin disinfection prior to PCVC insertion in preterm neonates. This will provide sound evidence for preferred antiseptic in neonates. If both antiseptics are found to be equally effective, then use of aqueous rather than alcohol-based chlorhexidine can be widely promoted for use in neonates. This would remove risks and costs of morbidity from neonatal skin damage and the potential harm of systemic absorption from alcoholic chlorhexidine use.

Lay abstract: During intensive care, many premature babies need to have a special catheter (line) put into one of their larger (central) veins to give special liquid nutrition safely to help them grow. These catheters are vital, but can sometimes become infected. Catheter infection is a dangerous complication. Cleaning a baby s skin with antiseptic before inserting a catheter is important to prevent infection. Some antiseptics may be better at preventing catheter infection as well as safer to use on the thin vulnerable skin of premature babies. Doctors don t yet know which antiseptics are safest and best to use in premature babies. We need to find out which antiseptics are best for premature babies. In the future we will do a large study to compare two antiseptics commonly used to clean the skin in premature babies: we will test if chlorhexidine on its own is just as good at cleaning a baby s skin as chlorhexidine mixed with alcohol. The findings will guide doctors in deciding which antiseptic to choose for skin preparation in premature babies. First however we must do a small feasibility study in order to gather vital information for designing the large study properly. Parents of babies needing a catheter for routine clinical care will be asked if they would like to include their babies in the study. Babies in the study will have their skin cleaned with one or other of the two antiseptics before the catheter is inserted. We will test the skin and also the catheters to see if they end up coated with (colonised by) bacteria by the time of catheter removal, because catheter colonisation is a major risk factor for infection. At the end of this study, we will know how to design the large trial and how many babies will be needed for it.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH