Title: Accuracy of a rapid intrapartum test for maternal group B streptococcal colonisation and its potential to reduce antibiotic usage in mothers with risk factors (GBS2)
Funder: Department of Health and Social Care

Abstract: The aim of the GBS2 study is to establish whether rapid testing technology for maternal Group B streptococcus (GBS) colonisation can be used amongst women with recognised risk factors for early-onset GBS (EOGBS) infection developing in their babies to direct the appropriate and timely administration of intrapartum antibiotic prophylaxis (IAP) for preventing EOGBS disease. Design: Prospective test accuracy study, a cluster randomised controlled trial (CRT), and economic evaluation. Setting A minimum of 16 NHS Hospital maternity units Target population Women admitted to the labour wards of all participating centres in established labour will be screened for GBS risk factors. Those <16 years or < 24 weeks gestation or requiring elective Caesarean section will be excluded. Health technologies assessed Rapid, point-of-care test (Cepheid GeneXpert System with Xpert GBS test), will be compared against a reference standard of selective enriched culture medium for test accuracy. A policy of rapid test directed IAP will be compared to the usual screening strategy based on risk factors alone. Key outcomes For the test accuracy study: determination of GeneXpert test accuracy (sensitivity, specificity, predictive values and likelihood ratios) compared to reference standard. For the CRT rates of maternal IAP use will be primary outcome. Secondary outcomes will include: neonatal antibiotic rates, duration of maternal antibiotic exposure, neonatal GBS colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and relative cost-effectiveness of the two IAP strategies. Sample size Data from at least 1340 women and their babies will be required. The sample size has been chosen primarily to give enough power to evaluate the accuracy of GeneXpert rapid testing in a real life setting but to also make sure we have enough power to detect a reduction of at least 12% (eg from 75% to 63%) in maternal IAP used in women with GBS risk factors between the two strategies in the CRT. Projected timetable The overall project will take 30 months. Months 1-4 following ethics approval will focus on identifying the total number of maternity units capable of participating and understanding their maternity information systems, and trial database development. A staggered 12 week period of collection of baseline IAP rates over 4 weeks will precede the main CRT phases. In each wave, equal numbers of experimental and control units will collect data over 4-6 weeks, to capture 83 women with risk factors. Each phase will be preceded by 4 weeks of rapid test training in the experimental units and followed by 8 weeks of data retrieval. The analysis of rapid test accuracy, the CRT and economic evaluation will take place in the final 12 months. Relevant expertise Our multi-disciplinary research team has an outstanding track record in conducting randomised trials, including numerous NIHR funded studies in intrapartum care (e.g., GBS1 and SALVO) and in neonatalogy (PulseOx, PIPS). The trial will be co-ordinated by an accredited and mature Clinical Trials Unit (BCTU). The team comprises of (a) Microbiologists with a special interest in GBS (JG, MW), (b) Obstetricians(KSK, KI, ST),(c) Neonatologists (SH, SK, MM)(d) Clinical Trialists (JPD, JJD, KSK),(e) Patient Representative (JP),(f) Health Economist (TR), (g) Trial Management (JPD, JD, KSK) and (h) Statistics (JJD, KH). JP is the Chief Executive of Group B Strep Support

Lay abstract: Group B streptococcus (GBS) is the leading cause of serious infection in newborn babies in developed countries. It is transmitted to babies around birth from mothers who carry the bacterium (bug) in their vagina without any symptoms. Antibiotics given to the mother from the start of labour reduces the risk of GBS disease in the newborn baby, by reduction of the chance of transmission and by giving the baby protective antibiotics before birth, providing it is given for long enough before delivery. Medical bodies recommend that preventative antibiotics should only be given in labour to mothers with risk factors for transmitting the infection to their baby. The babies of these mothers may then be investigated and some may be treated with antibiotics for GBS infection, particularly where more than one risk factor is present. The vast majority of these babies do not have GBS infection and are unnecessarily exposed to antibiotics, separated from their mothers for investigations and kept in hospital. Unnecessary use of antibiotics can also promote the evolution of antibiotic resistant strains of bacteria, so called “superbugs”. The aim of the GBS2 study is to establish whether rapid testing technology for establish whether the mother is carrying GBS can be used amongst women with known risk factors to direct the appropriate and timely administration of preventative antibiotics. The GBS2 study will build on the experience of our first GBS study, which recruited 1400 women during 2005-2007 and involves most of the original team. We propose to identify around 1340 mothers in labour who have risk factors for GBS infection in their newborn babies in at least 16 hospitals in the West Midlands and London during a 4-6 week study period. In half of the hospitals, all higher-risk women will be cared for as per current guidance, which would be with antibiotics. In the other hospitals, all women with GBS risk factors will have a swab taken from their vagina and rectum, to be used in the rapid test. In these hospitals, antibiotics will only be given in labour if the rapid test result is positive. If the rapid test result fails to deliver a result within 55 minutes, women will be given antibiotics as per national GBS guidelines. We consider this study design will give a reliable answer as to which strategy is best, more so than if individual women had the strategy determined at random. In another aspect of the study, we will assess the accuracy of the rapid testing, namely does it always give a positive result for women carrying GBS and negative results for those who are not. We will also determine whether the test is practical to use on a busy labour ward and give results in time for antibiotics to be given to those who need them. We will compare whether using giving antibiotics in labour based on the rapid test result, rather than giving antibiotics to all those with risk factors, results in a reduction in antibiotic usage. The impact of the two antibiotic strategies will be evaluated by measuring how many babies are found to be carrying GBS at birth and the rates of GBS infection in the first six days of the babies’ lives. We will determine which strategy offers the best value for money by calculating the costs and benefits of each. Finally, we will grow any GBS bacteria collected from mothers and their babies in laboratory and test whether any antibiotic resistant strains are found.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH