Title: ANODE: prophylactic ANtibiotics for the prevention of infection following Operative DElivery
Funder: Department of Health and Social Care

Abstract: Design: Randomised, double-blind, placebo-controlled trial Setting: Consultant-led maternity units Target population: Pregnant women undergoing delivery by forceps (any type) or ventouse (any type) at 37+0 weeks or greater gestation Health technology being assessed: A single dose of intravenous co-amoxiclav (1g amoxycillin/200mg clavulanic acid) following clamping of the cord, versus placebo (normal saline). Measurement of outcomes: The primary outcome will be confirmed or suspected maternal infection within 6 weeks of delivery, as defined by the prescription of antibiotics, endometritis or confirmed systemic infection on culture. Secondary outcome measures, evaluated at six weeks post-delivery will include severe sepsis, perineal wound infection, perineal pain, use of pain relief, hospital bed stay, hospital / GP visits, need for additional perineal care, dyspareunia, patient reported outcomes including the ability to sit comfortably to feed the baby, maternal general health, breast feeding and wound breakdown, as well as any potential side effects of antibiotic usage such as anaphylaxis. Standard measurement tools from previous studies will be used alongside specific questions. Sample size: Existing literature suggests a conservative estimate of the background rate of maternal infection following operative delivery of 4% and an estimated reduction of 50% in this rate with antibiotic prophylaxis. To conduct a study with 90% power and a two-sided 5% level of significance, with 5% loss to follow-up gives 1,712 per group, or a total of 3,424 women. Project timetable: Planned duration 38 months, recruitment over 2 years assuming a conservative 1 in 3 women will be accessed, agree to participate and provide complete outcome data, greater than observed in previous trials of antibiotic prophylaxis for caesarean section. March-August 2015: Obtain approvals and set-up the study sites; train local personnel in trial procedures. September 2015-August 2017: Recruitment in study sites. October 2017: Completion of follow-up. November 2017-April 2018: Analysis, reporting and dissemination of results. Expertise in team: The team has extensive experience of conducting clinical trials in the maternity field, as well as other studies of severe pregnancy complications, and includes members with key expertise in obstetrics, statistics, microbiology, epidemiology, public health and midwifery.

Lay abstract: Background: Maternal infection is a common problem after women have had a baby that has been delivered either by forceps or ventouse (vacuum/suction cup). We estimate that up to one in ten women will have localised infection around their birth canal, and almost one in 20 may have a more severe infection, such as infection of the lining of the womb, or an infection in the bloodstream (septiciaemia). It is fortunately very rare for women to die from infection after pregnancy, but infection is becoming more of a concern, as the number of mothers who have died from infection following pregnancy has increased in recent years. Alongside this, we are concerned that using too many antibiotics may lead to the development of “superbugs”, that is, bacteria which can no longer be killed by antibiotics. It is important that to prevent the development of superbugs we only use antibiotics when absolutely necessary. A single dose of antibiotics at the time of giving birth has been shown to be effective in preventing maternal infection after caesarean delivery, and the aim of this study is to investigate whether a single dose of preventive antibiotics is similarly effective after giving birth with the assistance of forceps or ventouse. Methods/Design: Pregnant women at full term (more than 37 weeks of pregnancy) who have their baby delivered by forceps or ventouse will be randomly allocated (i.e. by chance, like tossing a coin) to receive an injection of antibiotics into a vein (intravenous) or to an injection of salt solution without any antibiotics. We shall determine if there are fewer infections in the mother if we give antibiotics. The study will also find out if this strategy leads to better healing and less discomfort from the wounds around the birth canal (either from tears or the cut (episiotomy) used to help delivery). We will find out when the woman leaves hospital whether she has had symptoms or signs of infection, and also by a follow-up phone call from a research midwife when her baby is six weeks old. We will also ask women to complete a questionnaire, either on paper, on the internet or by telephone, when the baby is six weeks old, to describe how the mother is feeling, and any problems with pain, healing or infection she has had or continues to have.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;6.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH