Endoscopic Lavage after Intraventricular Haemorrhage in Neonates in the UK: A national randomised controlled trial on the efficacy of neuro-endoscopic lavage (ENLIVEN-UK)

Research Question Does the addition of neuroendoscopic lavage (NEL) to the standard procedure of inserting a temporary cerebrospinal fluid (CSF) drainage device improve neurodevelopmental outcome at two years' corrected age in infants with post-haemorrhagic ventricular dilatation (PHVD)? Background In England almost 500 preterm infants develop intraventricular haemorrhage (IVH) annually. Over 50% progress to PHVD, with ventricular enlargement, pressure on the developing brain and neural toxicity from the blood and its breakdown products. IVH and PHVD are the commonest causes and strongest predictors of cognitive disability. Standard treatment drains CSF reducing pressure but does not address the toxicity from the blood. DRIFT was a randomised controlled trial evaluating the efficacy of CSF washout for 5 days in preterms with PHVD, in neonatal intensive care units. This complex procedure is only carried out in one UK centre, it is thus difficult to disseminate through the NHS but is the only intervention leading to improvement in cognitive scores, maintained through 10 years of age. Our work with parents tells us they regard improvement in cognition as the most important outcome of treatment. Recent experience demonstrates the safety and efficacy of NEL in washing out blood from the ventricles in PHVD. NEL is a 30-minute adjunct to inserting a temporary CSF diversion device, and most paediatric neurosurgeons already have the skills to perform it. There is weak evidence that NEL may improve cognition at 2y. Aims and objectives The primary objective is to determine whether the addition of NEL to standard treatment improves the Bayley III cognitive quotient at 2y by 20 points. Secondary objectives include other neurodevelopmental measures, mortality, safety of NEL, need for permanent CSF diversion, quality of life and health economic outcomes. Methods Single-blinded randomised controlled trial of NEL with temporising device (study arm) vs temporising device alone (control arm) in preterm infants with PHVD, including an in-folded pilot study. We will recruit 100 infants over 3 years in 12 neurosurgical units throughout the country. Infants born 4mm over the 97th centile for gestation despite 2 lumbar punctures are eligible. Infants receive joint care by neurosurgeons and neonatal teams, as standard practice. NEL will be carried out by paediatric neurosurgeons with experience in infant neuro-endoscopy. A collaborative consensus statement to standardise the procedure has been produced with all participants. Haemorrhage evacuation will be evaluated on postoperative ultrasound. Outcome at 2y age corrected for prematurity will be assessed by an experienced assessor masked to allocation. Interim outcomes will be collected through 2y. Timelines for delivery Recruitment commences in Sept 2023 with a 12 month in-folded pilot with clear progression criteria. If successful, substantive recruitment ends in Aug 2026, follow-up in Aug 2028. Data analysis and dissemination will be completed by Feb 2029. Anticipated impact and dissemination As most of the paediatric neurosurgical units in the country are involved in the study, adoption throughout the NHS will be rapid, benefitting over 200 children per year in the UK. Dissemination will be via peer review journals and academic meetings, and patient organisations in the UK, particularly through our partner organisations, Shine and BANNFU.