Title: Surgical drainage irrigation and fibrinolytic therapy (drIFT) in premature infants with post-haemorrhagic ventricular dilatation: Brain function and structure at school age
Funder: Department of Health (England)

Abstract: Severe intraventricular haemorrhage (IVH) with post-haemorrhagic ventricular dilatation (PHVD) is a serious neurological complication seen in preterm infants with significant neurodisability in survivors. 40% of children with PHVD will develop cerebral palsy and approximately 25% will have multiple disabilities. No medical intervention has been proven to reduce neurodevelopmental disability in infants with PHVD.Design:Long-term follow-up of a multicentre randomised controlled trial. Setting: The drIFT trial was set in Tertiary level Neonatal Intensive Care Units with a specialist Paediatric Neurosurgical Service. Units were based in Bristol UK and Katowice Poland.Literature review: A full PubMed literature review was conducted to assess all possible interventions for the treatment of Post Haemorrhagic Ventricular Dilatation (PHVD) in preterm infants.Target population: Children now aged 8-11 years randomised to the drIFT trial as preterm infants in Bristol and Poland between 2003 and 2006. All participants had suffered a severe degree of Post Haemorrhagic Ventricular Dilatation (PHVD).Health technology being assessed: drainage irrigation and fibrinolytic therapy (drIFT) was developed as a novel neurosurgical method of irrigating the ventricles to clear the effects of haemorrhage. Preterm infants were randomised to either drIFT or standard therapy which consisted of cerebrospinal fluid (CSF) tapping to control PHVD. At 2 years post term severe disability or death was significantly reduced in the drIFT group. There was an important decrease in severe cognitive disability (Bayley mental development index 3 Standard Deviations below mean) from 59% to 31% (adjusted odds ratio: 0.17 [95% CI 0.05-0.57]) and the difference in median cognitive score was more than 18 points. However as cognitive and visual assessments at 2 years have limited validity definitive assessment needs to be performed at school age to reach a valid conclusion about the sustained efficacy of drIFT.An estimated 200 infants per year develop PHVD in the UK. If the reduction in severe disability seen at 2 years of age with the drIFT intervention is sustained through childhood a potential health and social services cost saving of £600000 per year could be predicted for the UK. The economic relief on family carers and educational services would also be significant.Measurement of outcomes:The primary outcome is severe cognitive (learning) disability at school age. The secondary outcomes are: cerebral visual function sensorimotor disability functional status (degree of independence with activities of daily living) emotional/behavioural function and surgical complications seen on brain MRI. Economic outcomes are: costs of health and social care and the broader impact on families through informal care and time off work and three generic preference based measures of health relatedquality of life (HUI3 and CHU9D and EQ-5D-5L).Sample size: In total 74 children (54 from Bristol and 20 from Poland) were randomised to the drIFT trial of which 66 survived. 16 children are available for assessment in Poland and 50 in Bristol. Based on a similar effect size documented with severe cognitive disability at 2 years of age a two group continuity corrected chi-square test with a 5% two-sided significance level will have 80% power to detect the difference in severe cognitive disability between a control group proportion of 59% and odds ratio of 0.17 (i.e. an intervention proportion of 19.7%) when the sample size in each group is 28. With 60 infants (30 in each group) we will have 97% power (with an alpha of 5%) to detect a mean cognitive difference of 1 standard deviation (commonly 15 points) between the drIFT and control groups.Project timetable:5 months preceding start of study: Pre-Startup period (REC and NHS approvals producing study forms staff recruitment set-up website).Month 1 – Month 18: Recruitment assessment of Children data collection. Month 19 – Month 21: Final analysis write-up dissemination (showcase day for participant families and workshop for 4 potential drIFT site Tertiary Neonatal Units to discuss NHS implementation of the drIFT national service).Expertise in Team:The research team collaborated on the drIFT project (from inception to delivery of the RCT) and brings together additional considerable expertise in neurosurgery neonatology neurodevelopment child psychology visual development perinatal epidemiology health economics and statistics. In addition the research team will be supported by a very experienced Clinical Trial Unit the Bristol Randomised Trials Collaboration (BRTC) with additional expertise in trial project and database management. The service user guiding the team has previous experience of this role from the original drIFT trial. The NHS clinicians (neurosurgeons and neonatologists) have experience of implementation of new neonatal interventions in the NHS (therapeutic hypothermia) and are closely involved with national level commissioning of new paediatric neurosurgical services.


Research activity codes: 6.4 SURGERY
Health categories: MENTAL HEALTH;NEUROLOGICAL;REPRODUCTIVE HEALTH AND CHILDBIRTH