Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.

BACKGROUND: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years. OBJECTIVE: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age. PARTICIPANTS: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age. INTERVENTION: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device. PRIMARY OUTCOME: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability. RESULTS: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003). CONCLUSION: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement. TRIAL REGISTRATION NUMBER: ISRCTN80286058.

Ten-year follow-up of a randomised trial of drainage, irrigation and fibrinolytic therapy (DRIFT) in infants with post-haemorrhagic ventricular dilatation.

BACKGROUND: The drainage, irrigation and fibrinolytic therapy (DRIFT) trial, conducted in 2003-6, showed a reduced rate of death or severe disability at 2 years in the DRIFT compared with the standard treatment group, among preterm infants with intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation. OBJECTIVES: To compare cognitive function, visual and sensorimotor ability, emotional well-being, use of specialist health/rehabilitative and educational services, neuroimaging, and economic costs and benefits at school age. DESIGN: Ten-year follow-up of a randomised controlled trial. SETTING: Neonatal intensive care units (Bristol, Katowice, Glasgow and Bergen). PARTICIPANTS: Fifty-two of the original 77 infants randomised. INTERVENTIONS: DRIFT or standard therapy (cerebrospinal fluid tapping). MAIN OUTCOME MEASURES: Primary - cognitive disability. Secondary - vision; sensorimotor disability; emotional/behavioural function; education; neurosurgical sequelae on magnetic resonance imaging; preference-based measures of health-related quality of life; costs of neonatal treatment and of subsequent health care in childhood; health and social care costs and impact on family at age 10 years; and a decision analysis model to estimate the cost-effectiveness of DRIFT compared with standard treatment up to the age of 18 years. RESULTS: By 10 years of age, 12 children had died and 13 were either lost to follow-up or had declined to participate. A total of 52 children were assessed at 10 years of age (DRIFT, n = 28; standard treatment, n = 24). Imbalances in gender and birthweight favoured the standard treatment group. The unadjusted mean cognitive quotient (CQ) score was 69.3 points [standard deviation (SD) 30.1 points] in the DRIFT group compared with 53.7 points (SD 35.7 points) in the standard treatment group, a difference of 15.7 points, 95% confidence interval (CI) -2.9 to 34.2 points; p = 0.096. After adjusting for the prespecified covariates (gender, birthweight and grade of IVH), this evidence strengthened: children who received DRIFT had a CQ advantage of 23.5 points (p = 0.009). The binary outcome, alive without severe cognitive disability, gave strong evidence that DRIFT improved cognition [unadjusted odds ratio (OR) 3.6 (95% CI 1.2 to 11.0; p = 0.026) and adjusted OR 10.0 (95% CI 2.1 to 46.7; p = 0.004)]; the number needed to treat was three. No significant differences were found in any secondary outcomes. There was weak evidence that DRIFT reduced special school attendance (adjusted OR 0.27, 95% CI 0.07 to 1.05; p = 0.059). The neonatal stay (unadjusted mean difference £6556, 95% CI -£11,161 to £24,273) and subsequent hospital care (£3413, 95% CI -£12,408 to £19,234) costs were higher in the DRIFT arm, but the wide CIs included zero. The decision analysis model indicated that DRIFT has the potential to be cost-effective at 18 years of age. The incremental cost-effectiveness ratio (£15,621 per quality-adjusted life-year) was below the National Institute for Health and Care Excellence threshold. The cost-effectiveness results were sensitive to adjustment for birthweight and gender. LIMITATIONS: The main limitations are the sample size of the trial and that important characteristics were unbalanced at baseline and at the 10-year follow-up. Although the analyses conducted here were prespecified in the analysis plan, they had not been prespecified in the original trial registration. CONCLUSIONS: DRIFT improves cognitive function when taking into account birthweight, grade of IVH and gender. DRIFT is probably effective and, given the reduction in the need for special education, has the potential to be cost-effective as well. A future UK multicentre trial is required to assess efficacy and safety of DRIFT when delivered across multiple sites. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80286058. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 4. See the NIHR Journals Library website for further project information. The DRIFT trial and 2-year follow-up was funded by Cerebra and the James and Grace Anderson Trust.