Endoscopic lavage after intraventricular haemorrhage in neonates in the UK: a national randomised controlled trial on the efficacy of neuro-endoscopic lavage

ISRCTN	ISRCTN14018410
DOI	https://doi.org/10.1186/ISRCTN14018410
IRAS number	322127
Secondary identifying numbers	CPMS 56647, NIHR151288, IRAS 322127

Submission date: 15/11/2023
Registration date: 21/12/2023
Last edited: 10/06/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Around one in thirteen infants 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 with severe Intraventricular Haemorrhage (IVH) and Post-haemorrhagic Ventricular Dilatation (PHVD) 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. This study 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 years of age

Who can participate?
Premature infants born before 37 weeks of gestational age with severe IVH and PHVD

What does the study involve?
Eligible participants will be randomly allocated into one of two groups:
1. Intervention group: neuroendoscopic lavage, or washout, and temporary drainage device.
2. Control group: continue with usual care.
After the operation all participants will be cared for in the usual way. Participants from both groups will undergo follow ups which will include regular neurosurgical and paediatric check-ups over a 2-year period. During study visits the participant’s parent/guardian(s) will be asked to complete questionnaires to collect information about their views of the participant’s development. They will also be asked about the participants’ and their own quality of life. At about 2 years of age, participants will also be required to attend an additional visit where they will undergo specific assessments to see how well the participant is developing. This assessment will be done by a qualified healthcare professional with experience at performing developmental assessments for children and who does not know which group the participant is in.

What are the possible benefits and risks of participating?
The information from the trial will help to improve treatment for future patients with IVH.
All medical procedures involve the risk of harm, but this is usually low. The risks of taking part in the study are mostly associated with the side effects of the washout procedure and the temporary device insertion. These are listed below:
Risk of infection
Risk of causing further bleeding into the brain
Drainage tube blockage or dysfunction – If this occurs the participant’s doctor will assess if they may need to have another operation to correct this or to insert a permanent VP shunt.
Seizure (seizures are caused by a sudden burst of electrical activity that temporarily affects how it works).
Leakage of fluid surrounding the brain
Electrolyte disturbance
Stroke (less than 1 %): Any procedure carried out on the brain carries a small risk of stroke.
For participants randomised to receive neuroendoscopic lavage (or washout) (Intervention Group), this is a more invasive procedure. It therefore increases the anaesthetic time by about 30 minutes, but this is not thought to be a significant risk. General anaesthetics have some risks and side effects, and the participant’s anaesthetist will discuss these with the parent/guardian(s) before surgery.
Risks associated with the neuroendoscopic lavage (or washout) are listed here:
Risk of brain injury (less than 1%): The procedure involves the insertion of a small camera (neuroendoscope) into the fluid spaces of the brain to wash out as much of the blood as possible before inserting the temporary drainage tube. Because the camera (neuroendoscope) has a slightly larger diameter than the catheter used to inset the drainage device, there is the potential to cause damage to the brain at the point where the camera enters the fluid space.
Risk of further bleeding (less than 1 in 10): Washing the blood clot out from the ventricular system may also carry a risk of causing a further bleed within the brain. In a small pilot study the rate of rebleeding was found to be very low, but adding the washout procedure to the normal standard treatment may increase the risk.
Electrolyte disturbance: The use of a washout fluid may cause fluctuations in salt levels in the blood. This also increases the risk of seizure in babies that receive the washout.
Study doctors will be monitoring all participants in the study very carefully. Continuing to assess any risk related to this procedure is an important part of the study.

Where is the study run from?
UCL Comprehensive Clinical Trials Unit (CCTU) (UK)

When is the study starting and how long is it expected to run for?
March 2023 to February 2029

Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).

Who is the main contact?
1. Chief Scientific Investigator: Kristian Aquilina: kristian.aquilina@gosh.nhs.uk
2. Trial Manager: Sue Massingham: cctu.enlivenuk@ucl.ac.uk

Contact information

Mr Kristian Aquilina
Scientific, Principal Investigator

Consultant paediatric neurosurgeon
Great Ormond Street Hospital
Department of Neurosurgery
Level 10 Old Nurses Home
Great Ormond Street
London
WC1N 3JH
United Kingdom

Phone	+44 (0)7791613155
Email	kristian.aquilina@gosh.nhs.uk

Ms Sue Massingham
Public

Comprehensive Clinical Trials Unit at UCL
Floor 2, 90 High Holborn
London
WC1V 6LJ
United Kingdom

Phone	+44 (0)20 7679 9351
Email	cctu.enlivenuk@ucl.ac.uk

Study information

Study design	Phase III multi-centre assessor-blinded randomized controlled interventional trial, including an internal pilot study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment, Efficacy
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	Endoscopic lavage after intraventricular haemorrhage in neonates in the UK: a national randomised controlled trial on the efficacy of neuro-endoscopic lavage
Study acronym	ENLIVEN-UK
Study objectives	It is hypothesised that the addition of Neuroendoscopic Lavage (NEL) will be safe and will improve neurodevelopmental outcomes at 2 years in children with severe Intraventricular Haemorrhage (IVH) and Post-haemorrhagic Ventricular Dilatation (PHVD).
Ethics approval(s)	Approved 14/12/2023, South West - Central Bristol (2 Redman Place, London, E20 1JQ, United Kingdom; 0207 104 8197; centralbristol.rec@hra.nhs.uk), ref: 23/SW/0137
Health condition(s) or problem(s) studied	Intraventricular Haemorrhage (IVH) and Post-haemorrhagic Ventricular Dilatation (PHVD) in premature infants born before 37 weeks of gestational age
Intervention	This 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). Arm A (Intervention): NEL with the temporising device. NEL will be carried out within the same operative procedure as the insertion of a clinically indicated temporising device. NEL involves the irrigation of the blood and its breakdown products within the ventricular system and is carried out in a controlled procedure, within approximately 30 minutes, under direct vision. Arm B (Control/Usual Care) - temporising device alone. Infants will undergo the standard surgical procedure to insert either a Ventricular access device (VAD) or Ventriculosubgaleal shunt (VSGS), at the discretion of the treating surgeon, in line with their standard current practice. Both the intervention (Arm A) and control arm (Arm B) procedures will be performed by paediatric neurosurgeons who have experience in infant neuro-endoscopy. All infants in Arms A and B will be followed up until they reach 2 years corrected age (+/-2 months). A computer-generated randomisation sequence, using the SealedEnvelope.com system, will be used to assign the participants to one of the two treatment arms using a 1:1 ratio.
Intervention type	Procedure/Surgery
Primary outcome measure	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 outcome measures	1. Developmental measures: 1.1. Motor quotient (MQ): Age equivalent motor score of the Bayley IV divided by corrected age at assessment, measured at 2 years’ corrected age 1.2. 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: 2.1. Presence of seizures during the first 2 years and use of anticonvulsant medication at 2 years 2.2. Presence of cerebral palsy (+ accompanying Gross Motor Function Classification System (GMFCS) grade and deficit distribution map using the Classification of SCPE 2.3. Assessment of hearing and vision (British Association of Perinatal Medicine classification) at 2 years’ corrected age 2.4. Parent report at 2 years’ corrected age: 2.4.1. Brief Infant Toddler Social Emotional Assessment (BITSEA) 2.4.2. Quantitative Checklist for Autism in Toddlers (Q-CHAT) 3. Mortality up to 2 years corrected age 4. NEL and VP shunt related outcomes: 4.1. Safety of NEL, measured by the number of Adverse Events reported until 2 years’ corrected age 4.2. Number and type of further surgical procedures required until 2 years’ corrected age 4.3. Requirement for permanent VP shunt insertion at 6 months’ corrected age 5. Quality of life and health economic assessments: 5.1. Health-related quality of life (HRQoL) in children measured using the TNO-AZL Preschool Children’s Quality of Life (TAPQOL) at 12 months and 2 years’ corrected age 5.2. HRQoL in primary caregiver measured using the EuroQoL EQ-5D-5L at baseline, 6 months, 12 months and 2 years’ corrected age 5.3. Healthcare resource use costs (CSRI (adapted) children version) at 3, 6, 12, 18 months and 2 years’ corrected age 5.4. Subsequent cost-effectiveness analysis and cost-benefit analysis of impact on carers based on responses to the EQ-5D-5L
Overall study start date	01/03/2023
Completion date	28/02/2029

Eligibility

Participant type(s)	Patient
Age group	Neonate
Lower age limit	22 Weeks
Upper age limit	36.85 Weeks
Sex	Both
Target number of participants	Planned Sample Size: 100; UK Sample Size: 100
Key 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.
Key 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.
Date of first enrolment	09/05/2024
Date of final enrolment	31/08/2026

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Great Ormond Street Hospital for Children

Great Ormond Street
London
WC1N 3JH
United Kingdom

Alder Hey Children's Hospital

Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom

Sponsor information

University College London
University/education

Comprehensive Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
90 High Holborn
London
WC1V 6LJ
England
United Kingdom

Phone	+44 (0)20 7679 9351
Email	cctu.enlivenuk@ucl.ac.uk
Website	http://www.ucl.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Government

National Institute for Health and Care Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	01/01/2030
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	The results of the trial will be disseminated regardless of the magnitude and interpretation of any effect of the intervention. The publication of the results will comply with the UCL CCTU Publication Policies. A lay summary of the results will also be produced to be disseminated to those participants who took part who express an interest in the findings. A summary of results will be submitted to the REC via the HRA and published through an open-access mechanism in a peer-reviewed journal within 12 months of the trial closure.
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Editorial Notes

10/06/2025: The following changes were made:
1. The public contact was updated.
2. The recruitment end date was changed from 28/02/2027 to 31/08/2026.
21/05/2024: The recruitment start date was changed from 01/01/2024 to 09/05/2024.
02/01/2024: Contact details updated.
15/11/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).