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21/537 Neuroendoscopic lavage for preterm babies with post-haemorrhagic ventricular dilatation

Contents

Introduction

The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

In preterm infants with post-haemorrhagic ventricular dilatation (PHVD), does addition of neuroendoscopic lavage to temporary cerebrospinal fluid (CSF) drainage improve outcomes?

  1. Intervention: Neuroendoscopic lavage conducted at same time as insertion of temporary cerebrospinal fluid (CSF)-draining device (applicants to define and justify).
  2. Patient group: Premature neonates with PHVD to be defined and justified by applicants. Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  3. Setting: Paediatric neurosurgery.
  4. Control: Insertion of temporary CSF-draining device (applicants to define and justify).
  5. Study design: A randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial.
  6. Important outcomes: Neurodevelopment outcomes at two years’ corrected age; parent/carer acceptability; severe adverse events. Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise.
  7. Other outcomes: Requirement for a ventriculoperitoneal (VP) shunt (applicants should also consider whether utilisation of the UK Shunt Registry to assess longer term outcomes would be appropriate); number of children in grades 3 to 5 on the Gross Motor Function Classification System (GMFCS); need for further surgical procedures, such as additional lavage procedures and VSG shunt revision; function of VP shunt to include survival, infection and revision rate over the two-year follow up; development and treatment of loculated hydrocephalus; development of epilepsy; cost- effectiveness.
  8. Minimum duration of follow-up: 2 years. Longer-term follow up: If appropriate, researchers should consider obtaining consent to allow potential future follow-up through efficient means (such as routine data) as part of a separately funded study.

Rationale

Despite major advances in survival, bleeding in the brain, called intraventricular haemorrhage (IVH), remains one of the most serious complications of preterm birth. Infants with the most severe forms of IVH can be further complicated by progression to post-haemorrhagic ventricular dilatation (PHVD) and post-haemorrhagic hydrocephalus (PHH) which have high rates of mortality or subsequent cognitive disability, sensory problems and cerebral palsy.

While reducing neonatal brain injury remains a priority, no standardized treatment for these infants has been found, although a number of treatments designed to prevent ongoing brain injury after severe IVH and subsequent PHVD and PHH have been studied.

The drainage, irrigation, and fibrinolytic therapy (DRIFT) procedure showed promise in short and longer-term outcomes but is technically complex and as such has not yet entered widespread use. Neuroendoscopic lavage (NEL) conducted as an adjunct to temporary CSF drainage device insertion is emerging as a promising therapeutic candidate from small scale studies.

Based on the hypothesis that blood and its breakdown products persist for months and contribute to free radical injury and inflammation, NEL aims to wash away the blood contaminated cerebrospinal fluid (CSF) lying in contact with the walls of the ventricle. By washing out blood, NEL may also reduce scarring within the CSF flow pathways, improve CSF circulation and reduce the risk of requiring permanent CSF drainage with a ventriculoperitoneal VP shunt.

Although endoscopy is used routinely by paediatric neurosurgeons, its use for lavage in PHVD has only limited evidence. A high quality randomised controlled trial is needed.

Applications should be co-produced, demonstrating an equal partnership with service commissioners, providers and service users (including carers) in order to provide evidence and actionable findings of immediate utility to decision-makers and service users. Applicants may wish to consult the NIHR INVOLVE guidance on co-producing research.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.

Making an application

If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 1 December 2021. Applications will be considered by the HTA Funding Committee at its meeting in January 2022.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

Important: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May 2022.

Applications received electronically after 1300 hours on the due date will not be considered.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application eg a lead from a named charity or a unique national expert in a condition. For such exceptions (i) each application needs to state the case as to why the same person is included (ii) the shared co-applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared. 

Should you have any queries please contact us by email htacommissioning@nihr.ac.uk.