Illustrative picture of surgery being performed

ENLIVEN-UK

Endoscopic Lavage after Intraventricular Haemorrhage in Neonates in the UK

A national randomised controlled trial on the efficacy of neuro-endoscopic lavage

Key aspects of the Trial

  • Phase III, multi-centre, assessor-blinded, randomised controlled interventional trial
  • In preterm infants with post-haemorrhagic Ventricular Dilatation (PHVD)
  • Intervention: Neuroendoscopic lavage (NEL) with temporising device
  • Control: Temporising device alone
  • Aiming to recruit 100 infants
  • Recruiting for approximately 3 years
  • Design includes an internal pilot study assessing recruitment feasibility, barriers to recruitment and protocol adherence
  • Protocol paper published in Child's Nervous System journal
  • Previous called DOLPHIN-UK

Information for parents and guardians

Around one in thirteen babies is born preterm in the United Kingdom. Despite major advances in survival, intraventricular haemorrhage (IVH) remains one of the most serious complications of preterm birth. Intraventricular haemorrhage (IVH) is bleeding into the fluid spaces of the brain and is common in babies who are born premature. This results in a build-up of brain fluid, that may increase the pressure in the brain. Bleeding in the brain can cause a risk to life and also cause problems with vision, hearing, cognition (understanding) and motor function (movement).

The current best treatment available involves implanting a temporary drainage device in a short operation. There is a new treatment called neuroendoscopic lavage (NEL), which involves the insertion of a small camera into the fluid spaces (ventricles) of the brain to wash out as much of the blood as possible before inserting the temporary drainage tube.

ENLIVEN-UK will investigate whether the addition of NEL to the standard procedure of inserting a temporary cerebrospinal fluid (CSF) drainage device will improve children's development at 2 year's of age.

The trial aims to recruit 100 babies from paediatric neurosurgical units across the UK. ENLIVEN-UK is taking place between March 2023 and February 2029. Recruitment will start in March 2024. The ENLIVEN-UK trial was designed by NHS clinicians and has been reviewed and authorised by an independent Research Ethics Committee. University College London is the Sponsor for the trial and the trial is managed by the Comprehensive Clinical Trials Unit at UCL. The Chief Investigators are Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon, Great Ormond Street Hospital) and Mr Conor Mallucci (Consultant Paediatric Neurosurgeon, Alder Hey Children’s Hospital).

Please watch this short video if you are interested in finding out more about the trial:

Patient Information Sheet

You can read more about the trial in the Patient Information Sheet:
ENLIVEN-UK PIS v2.0 08December2023 -non-localised

Team and Collaborators

A picture of the Chief Investigator, Mr Kristian Aquilina, facing the camera

Chief Investigator

Mr Kristian Aquilina FRCS(SN) MD has been surgical lead for neuro-oncology at GOSH since 2012, and is an honorary senior lecturer at the UCL Institute of Child Health. Kristian graduated from the University of Malta in 1995 and completed his neurosurgical training in Bristol in 2009. He completed a one-year clinical fellowship in paediatric neurosurgery, and particularly in paediatric neuro-oncology, at St Jude Children's Research Hospital in Memphis, Tennessee. Kristian was appointed Consultant Neurosurgeon in Bristol in 2010, and Consultant Paediatric Neurosurgeon at GOSH in June 2012.
Kristian's principal research interests include brain tumours in children, particularly in relation to clinical outcomes and imaging, intraventricular haemorrhage in preterm babies, hydrocephalus, and the outcomes of selective dorsal rhizotomy for spasticity in children with cerebral palsy.
Contact using: kristian.aquilina@gosh.nhs.uk

A picture of the Co-Chief Investigator, Mr Conor Mallucci, facing the camera

Co-Chief Investigator

Mr Conor Mallucci Senior Paediatric Neurosurgery Consultant, Alder Hey Children's NHS foundation trust, Liverpool, since 1998. Conor Mallucci qualified in London at University College in 1989. He underwent neurosurgery training in Birmingham, Nottingham and then Paris.
He is committed to improving outcomes in children with brain tumours and hydrocephalus. He has been chairman of the British Paediatric Neurosurgery Group and chaired their research group for over 10 years. He was deputy editor of the British Journal of Neurosurgery for over 10 years.
He has published extensively on brain tumours, hydrocephalus and neuroendoscopy. He has 178 publications in international peer reviewed journals, edited an international textbook on CSF disorders and written over 18 book chapters. He has over £10 million of NIHR/Grant funding awards with a particular interest in multi-centre randomised controlled trials and evidence-based medicine.

Collaborators

Dr Hakim-Moulay Dehbi, Senior Statistician, University College London
Mr Aswin Chari, Clinical Lecturer in Neurosurgery, GOSH - UCL
Ms Monica Panca, Senior Health Economist, University College London
Dr Cristine Sortica da Costa, Consultant Neonatologist, GOSH – UCL
Professor Andrew Whitelaw, Emeritus Professor of neonatology, University of Bristol
Mr Greg James, Consultant Paediatric Neurosurgeon, GOSH
Dr Cheryl Battersby, Clinical Senior Lecturer and Honorary Consultant Neonatologist, Imperial College London
Dr Sally Jary, Honorary Researcher, University of Bristol
Professor Neil Marlow, Emeritus Professor of Neonatal Medicine, University College London
Mr William Dawes, Consultant Neurosurgeon, Royal London Hospital
Laurence Galland, Patient group representative

List of Site Contacts

If you have questions about the study please contact your baby's study team at:

Great Ormond Street Hospital, London

Mr Kristian Aquilina: kristian.aquilina@gosh.nhs.uk

Alder Hey Children's Hospital, Liverpool

Ms Benedetta Pettorini: benedetta.pettorini@alderhey.nhs.uk

Bristol Royal Hospital for Children

Contact details available on request

Recruitment

Sites open to recruitment: 3
Participants recruited: 3
(Last updated 03-Sep-2024)

Contact us

ENLIVEN-UK Management Office:
Comprehensive Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
90 High Holborn, London, WC1V 6LJ
cctu.enlivenuk@ucl.ac.uk
Tel: 020 7679 9351

Trial Information

REC Reference: 322127
Clinical Trials Unit: Comprehensive Clinical Trials Unit at UCL
Sponsor: University College London
Funder: NIHR Health Technology Assessment
Recruitment Target: 100
Duration of Study: March 2023 – February 2029

Information for Healthcare Professionals

This section is for healthcare professionals involved in the ENLIVEN-UK trial. Please always refer to the current protocol.

Trial Design

The ENLIVEN-UK trial is a phase III, multi-centre, randomised, assessor-blinded, controlled trial of NEL with temporising device (intervention Arm A) vs temporising device alone (standard treatment/Control Arm B). The aim of this trial is to investigate whether the addition of NEL to the standard procedure of inserting a temporary cerebrospinal fluid (CSF) drainage device will improve children's development at 2 years of age.

A computer-generated randomisation sequence, will be used to assign the participants to one of the two treatment arms using a 1:1 ratio.

All infants in Arms A and B will be followed-up until they reach 2 years corrected age (+/-2 months). At this time, they will undergo a developmental assessment performed by qualified and validated independent clinical development specialist, blinded to the treatment arm.

Inclusion Criteria

  1. Premature infants born before 37 weeks of gestational age
  2. IVH: Papile Grades II-IV on cranial ultrasound scan
  3. PHVD: Ventricular index at or beyond the threshold point of the 97th centile for gestational age plus 4 mm on the Levene chart despite 2 attempted lumbar or ventricular punctures.

Exclusion Criteria

  1. Infants with coagulopathy (INR >1.6) or platelet disorders (platelet count under 80,000/mL) that persist on attempted correction. Clinical judgement will be made by the Investigator.
  2. Infants deemed too unstable for neurosurgical intervention. This is a clinical judgement made by the responsible neurosurgeon, neonatologist and anaesthetic team.
  3. Parents or carers unwilling to provide informed consent.

Primary Outcomes

Cognitive Quotient (CQ) measured by the Bayley Scales of Infant and Toddler Development Fourth Edition (Bayley IV) at 2 years' corrected age (+/- 2 months).

Secondary Outcomes

  1. Developmental Measures:
    1. Motor quotient (MQ): Age equivalent motor score of the Bayley IV divided by corrected age at assessment, measured at 2 years' corrected age
    2. Language quotient (LQ): Age equivalent language score of the Bayley IV divided by corrected age at assessment, measured at 2 years' corrected age
  2. Other neurological and functional assessments conducted during the 2-year follow-up visit:
    1. Presence of seizures during the first 2 years and use of anticonvulsant medication at 2 years.
    2. Presence of cerebral palsy (+ accompanying Gross Motor Function Classification System (GMFCS) grade and deficit distribution map using the Classification of SCPE
    3. Assessment of hearing and vision (British Association of Perinatal Medicine classification)
    4. Parent report:
      1. Brief Infant Toddler Social Emotional Assessment (BITSEA)
      2. Quantitative Checklist for Autism in Toddlers (Q-CHAT)
  3. Mortality up to 2 years corrected age.
  4. NEL & VP shunt related outcomes:
    1. Safety of NEL, measured by the number of Adverse Events reported
    2. Number and type of further surgical procedures required until two years' corrected age.
    3. Requirement for permanent VP shunt insertion at 6 months' corrected age.
  5. Quality of life and health economic assessments:
    1. Health-Related Quality of Life (HRQoL) in children using the TNO-AZL Preschool Children's Quality of Life (TAPQOL) to be assessed at 12-months and 2 years' corrected age
    2. HRQoL in primary caregiver using the EuroQoL EQ-5D-5L to be assessed at baseline, 6 months, 12 months- and 2 years' corrected age
    3. Healthcare resource use costs (CSRI (adapted) children version) at 3-6-,12-, 18- months and 2 years' corrected age.
    4. Subsequent cost-effectiveness analysis & cost-benefit analysis of impact on carers based on responses to the EQ-5D-5L.

Study visit summary

Participant visit flow diagram