Title: PREPS - Vaginal Preparation at caesarean section to Reduce Endometritis and Prevent Sepsis – a feasibility study of Chlorhexidine Gluconate
Funder: Department of Health and Social Care

Abstract: Background: Worldwide caesarean section (CS) is the commonest major operation, UK data demonstrates 26.2% women birth via CS (elective 13.2% v emergency 13%). Sepsis/infection constitute significant maternal mortality and morbidity with impact on postnatal recovery/maternal wellbeing. Following vaginal delivery 4% will have postnatal endometritis, after elective CS 8% and emergency CS 16%. Literature review: A Cochrane review has investigated iodine for vaginal cleansing demonstrating reduced infection rates but this has not been adopted due to concerns regarding fetal iodine absorption. There are no studies using chlorhexidine gluconate at CS. Aims The aim of this research is to determine whether vaginal cleansing at CS can reduce infectious mortality and morbidity after CS; this funding proposal is for a feasibility study that addresses uncertain parameters within design and outcome measures detailed in the objectives. Question to be addressed in feasibility What are the appropriate recruitment and randomisation processes? Can we blind women to intervention? What is the precise estimate of sample size to determine effectiveness and to develop women centered outcome measures and testing the proposed method to collect these to inform a multi-centre RCT that will determine whether vaginal cleansing at CS reduces infectious morbidity and mortality. Plan of investigation Design: Feasibility randomised controlled trial (telephone randomisation) with qualitative arm for development of women centered outcomes Setting: Three maternity units in West Midlands, UK. Participants: Women undergoing elective or emergency CS and able to give informed consent. We will follow women up until 6 weeks post natal and evaluate if infection/sepsis develops. Intervention Chlorhexidine gluconate 4% vaginal cleansing before CS. This is an antiseptic solution that is routinely applied to the abdominal skin to reduce surgical site infection; this solution can also be applied inside the vagina (safety profile established in other obstetric and gynaecological procedures). Standard treatment No vaginal cleansing. Feasibility outcomes The success of the feasibility study will be judged by criteria related to the feasibility measurements and help us ascertain if a larger study is feasible in its current format, needs modification or is not workable. Specifically we would aim for 50% of women screened and 50% acceptance of the trial by women. Although the rate of screening can be lower in the larger trial, with a larger number of sites needed to reach target. We would need more than 30% of screened women to be randomised to be sufficiently acceptable by women to sustain a larger study. We would also expect at least a 90% follow-up rate at 6 weeks and if the rate was lower than this we would need to tailor the precise sample size calculation to accommodate this lower follow up rate. Sample size: 125 women in each arm plus non-randomised audit of women with infectious outcome to develop women centered outcomes. Recruitment timetable: Commence June 2017 for 15 months. Qualitative arm and women centered outcome development until month 5. Intervention arm commencing recruitment in month 5 with outcome data collection continuing for 8 weeks post the close of recruitment. Remaining 12 weeks analysis and reporting. Summary of the potential to the NHS Reduction of infection/sepsis is a key priority for the NHS. Decreasing the morbidity and hence mortality of CS is an important public health objective. The recent Chief Medical Officer s focus on both the health of women and antibiotic resistance highlights the global importance of evaluating interventions that reduce infection/sepsis and improve outcomes following CS. If effective, benefits would include cost-savings, improved maternal health and well-being, thus impacting maternal-baby bonding and thus continuation of breast feeding.

Lay abstract: One in four women has a caesarean section. Most women recover quickly and without complications. However, some women develop an infection; this may be inside the womb, in the scar on the skin or a severe infection that is present in the blood stream. Developing an infection makes the women's recovery following caesarean more difficult and complicated. We are designing a research study aiming to reduce the number of women that develop infection after a caesarean section. The antiseptic solution that is applied to the abdomen to clean the skin and reduce the risk of infection before a caesarean section can also be applied inside the vagina. The antiseptic solution is routinely used for some surgical procedures in pregnancy and is safe. The research study being developed would ask women to randomly have either the cleansing of the vagina with the antiseptic solution or no cleansing (standard practice), if they have a caesarean section. Women will then be asked to receive a follow up telephone interview at 4-6 weeks postdelivery to review if any infection has developed. We will also review their medical notes. Before we start this proposed study, we need to complete a smaller test study. This is designed to evaluate if it is possible to carry out the necessary procedures to fully answer if vaginal cleansing is beneficial. For example, we would like to test if women would be happy to take part in the study and if we can reliably collect all the information needed to find out if this treatment works. We will also be asking women to help us determine what are the best measures of infection and wellbeing post caesarean section

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;INFECTION;INFLAMMATORY AND IMMUNE SYSTEM