HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

Study Overview
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Brief Summary
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Hydrocephalus is a potentially debilitating neurological condition that primarily affects babies under a year of age and has traditionally been treated by inserting a shunt between the brain and the abdomen. A newer endoscopic procedure offers hope of shunt- free treatment that may reduce complications over a child's life, but it is not clear if the endoscopic procedure results in similar intellectual outcome as shunt. Therefore, the investigators propose a randomized trial to compare intellectual outcome and brain structural integrity between these two treatments, to help families make the best treatment decision for their baby.

Detailed Description
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The ESTHI Trial is a multi-center randomized controlled trial (RCT) comparing endoscopic third ventriculostomy with choroid plexus cauterization (ETV+CPC) and shunt in infants with hydrocephalus. The study will leverage the infrastructure of the Hydrocephalus Clinical Research Network (HCRN), a committed group of 14 leading North American pediatric neurosurgical centers with a long track-record of successful collaborative clinical research and RCTs in hydrocephalus. Optimal cognitive outcome is the primary concern of families and will, therefore, be the primary outcome. Assessment of dMRI, a validated, non-invasive method of measuring white matter microstructural integrity and structural connectivity in the developing brain, will provide further insight into the developmental consequences of these two treatments. The results of the RCT will help families determine the optimal treatment of hydrocephalus for their child.

Official Title
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Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

Conditions
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Hydrocephalus

Intervention / Treatment
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* Procedure: Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)
* Device: Ventriculoperitoneal Shunt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Corrected age <104 weeks and 0 days, AND Child is ≥ 37 weeks post menstrual age, AND Child must have symptomatic hydrocephalus, deﬁned as: Ventriculomegaly on MRI (frontal-occipital horn ratio (FOR) >0.45, which approximates moderate ventriculomegaly), and at least one of the following: Head circumference >98th percentile for corrected age with either bulging fontanelle or splayed sutures Upgaze paresis/palsy (sundowning) CSF leak Papilledema Tense pseudomeningocele or tense ﬂuid along a track Vomiting or irritability, with no other attributable cause Bradycardias or apneas, with no other attributable cause Intracranial pressure (ICP) monitoring showing persistent elevation of pressure with or without plateau waves AND No prior history of shunt insertion or endoscopic third ventriculostomy (ETV) procedure (previous temporization devices and/or external ventricular drains permissible) Exclusion Criteria: Hydrocephalus due to intraventricular hemorrhage in a child born before 37 weeks gestational age; OR Anatomy not suitable for ETV+CPC or anteriorly placed ventriculoperitoneal shunt deﬁned as: Moderate to severe prepontine adhesions on steady state free precession (SSFP) or T2 weighted fast (turbo) spin echo (FSE/TSE) MRI, which includes the following sequences: FIESTA, FIESTA-C, TrueFISP, CISS, Balanced FFE (bFFE), CUBE, SPACE, VISTA, IsoFSE, and 3D MVOX Closure of one or both foramina of Monro Thick ﬂoor of third ventricle (≥ 3mm) Narrow third ventricle (<5mm) Presence of scalp, bone, or ventricular lesions that make placement of an anterior shunt impracticable; OR Underlying condition with a high chance of mortality within 12 months; OR Hydrocephalus with loculated CSF compartments; OR Peritoneal cavity not suitable for distal shunt placement; OR Active CSF infection; OR Hydranencephaly; OR Child requires an intraventricular procedure (e.g. endoscopic biopsy) in addition to the initial ﬁrst-time permanent procedure for the treatment of hydrocephalus.

Ages Eligible for Study
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Maximum Age: 104 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ETV+CPC<br>Subjects randomized to this arm will undergo an ETV+CPC procedure for treatment of Hydrocephalus | Procedure: Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)<br>* Since the early 1990s, ETV has become the main alternative to shunting for hydrocephalus. This procedure involves placing an endoscopic camera into the ventricles of the brain and creating a hole in the floor of the third ventricle to act as an internal bypass for obstructed CSF. The cauterization of choroid plexus (CPC) involves the use of a device to burn or cauterize tissue from the choroid plexus. The choroid plexus of the brain exists in the lateral ventricles, the third ventricle, and the fourth ventricle. Its main role is the production of CSF. The success of ETV alone is poor in infants, but when combined with CPC, improved results have been observed and ETV+CPC has become a safe viable option for these children.<br>|
| Active Comparator: Ventriculoperitoneal Shunt<br>Subjects randomized to this arm will undergo a Ventriculoperitoneal Shunt procedure for treatment of Hydrocephalus | Device: Ventriculoperitoneal Shunt<br>* The most common treatment for hydrocephalus has been the insertion of a ventriculoperitoneal shunt, which has been in popular use for over 50 years. This consists of silastic tubing attached to a valve mechanism that runs subcutaneously from the head to the abdomen. It is one of the most common procedures performed by pediatric neurosurgeons.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bayley Scale of Infant Development-IV (Bayley-IV) Cognitive Scale score | The primary objective is to determine, in infants <104 weeks corrected age, with hydrocephalus requiring treatment at tertiary care pediatric neurosurgery centers in North America, if treatment with ETV+CPC compared to shunt results in non-inferior cognitive outcome at 12 months from surgery, as measured by Bayley-IV Cognitive Scale score with a non-inferiority margin of 1.5. Scaled scores range from 1-19. Higher scores indicate better outcomes. Scores will also be obtained at 3 and 5 years of age. | 12 months post randomized surgical intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bayley Scale of Infant Development-IV (Bayley-IV) Language Scaled Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Bayley-IV Language Scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention | 
| Bayley Scale of Infant Development-IV (Bayley-IV) Motor Scaled Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Bayley-IV Motor Scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydrocephalus, Infants, Ventriculoperitoneal Shunt, ETV+CPC, endoscopic third ventriculostomy, choroid plexus cauterization