Better Outcomes in Babies with Bacterial meningitis: BOBBi

Research question: In babies <3 months old with suspected bacterial meningitis (BM), does administering corticosteroids (CS), compared to not administering CS, with antibiotics, improve survival without moderate or severe neurodevelopmental impairment at 24 months corrected age? Background: BM is a serious infectious disease that affects 350 babies in the UK every year; 7% will die and 23-37% will have serious long term neurodevelopmental impairments. CS are recommended as adjunctive therapy in older children with BM to improve outcomes but there is insufficient evidence to support their use in babies. Aim: To evaluate whether administering the CS dexamethasone (0.15mg/kg twice a day for 4 days), compared to not administering dexamethasone, as an adjunct to antibiotic treatment in babies <3 months of age with suspected or confirmed BM is clinically and cost-effective. Primary outcome: Survival without moderate or severe neurodevelopmental impairment across six domains (non-verbal cognition, language development, vision, hearing, seizures requiring medication, or cerebral palsy) at 24 months of age corrected for prematurity. Assessed using validated, parent-completed questionnaires with supplemental information obtained from routine follow-up and reviewed by a Blinded Endpoint Review Committee. Secondary outcomes: Individual components of the primary outcome; length of critical care and hospital stay; adverse events; behaviour/attention/social/emotional problems; quality of life, health economic outcomes. Design: A multisite, open-label, two-arm, parallel-group, pragmatic, randomised controlled trial with an integrated health economic evaluation and an 18-month internal pilot phase. Inclusion criteria: Infants from =32 corrected gestational weeks to =3 months of corrected gestational age at randomisation with suspected BM based on: seizures or bulging fontanelle or altered consciousness (coma) AND/OR Blood CRP =20 mg/L AND one or more of: raised CSF white cell count (>20/mm3 for neonates =28 days; >5/mm3 for infants 1-3 months); CSF protein =0.8g/L CSF/blood glucose ratio <0.5 AND/OR Positive CSF Gram stain or positive CSF PCR/culture for a relevant bacterium. Exclusion criteria: First dose of antibiotic >12 hours prior to planned administration of CS; <34 gestational weeks and within the first week; previous neurosurgical intervention/shunt; no realistic chance of survival; major congenital anomaly. Consent: We will use a deferred consent model. When babies meet the inclusion criteria they will be randomised, and parents will be approached within 24h for written informed consent. Sample size: 965 babies (from 60 sites) to detect survival without moderate or severe neurodevelopmental impairment at 24m of corrected age of 95.2% in CS group compared to 88.9% in the control group (risk ratio 1.07), assuming 90% power, 5% alpha, 20% loss to follow-up. Timelines for delivery (months): 1-9: set up; obtain approvals, develop study information, staff recruitment, training; 10-27: internal pilot phase; 28-63: complete trial recruitment; 90: clean/lock database, complete follow-up; 91-96: study closure, analysis, write up, dissemination. Anticipated impact and dissemination: BOBBie will allow an evidence-based recommendation to be made on the use of CS in infants <3 months of age with suspected BM and is expected to be rapidly adopted into NHS practice. We will use a wide range of routes to disseminate to professionals and parents.