Hydrocephalus
Conditions
Keywords
Hydrocephalus, Infants, Ventriculoperitoneal Shunt, ETV+CPC, endoscopic third ventriculostomy, choroid plexus cauterization
Brief summary
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
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.
Interventions
PROCEDUREEndoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)
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.
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.
Sponsors
University of Utah
University of Alabama at Birmingham
University of British Columbia
University of Pittsburgh
The Hospital for Sick Children
Seattle Children's Hospital
Vanderbilt University Medical Center
Washington University School of Medicine
Nationwide Children's Hospital
Johns Hopkins University
University of Calgary
University of Colorado, Denver
Children's Hospital Los Angeles
National Institutes of Health (NIH)
Hydrocephalus Association
Penn State University
National Institute of Neurological Disorders and Stroke (NINDS)
Baylor College of Medicine
University of Florida
Orlando Health, Inc.
Virginia Commonwealth University
Trustees of Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 104 Weeks
Healthy volunteers
No
Inclusion criteria
1. Corrected age \<104 weeks and 0 days, AND 2. Child is ≥ 37 weeks post menstrual age, AND 3. 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 4. No prior history of shunt insertion or endoscopic third ventriculostomy (ETV) procedure (previous temporization devices and/or external ventricular drains permissible)
Exclusion criteria
1. Hydrocephalus due to intraventricular hemorrhage in a child born before 37 weeks gestational age; OR 2. 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 3. Underlying condition with a high chance of mortality within 12 months; OR 4. Hydrocephalus with loculated CSF compartments; OR 5. Peritoneal cavity not suitable for distal shunt placement; OR 6. Active CSF infection; OR 7. Hydranencephaly; OR 8. Child requires an intraventricular procedure (e.g. endoscopic biopsy) in addition to the initial first-time permanent procedure for the treatment of hydrocephalus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bayley Scale of Infant Development-IV (Bayley-IV) Cognitive Scale score | 12 months post randomized surgical intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bayley Scale of Infant Development-IV (Bayley-IV) Language Scaled Score | 12 months post randomized surgical intervention | 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. |
| Bayley Scale of Infant Development-IV (Bayley-IV) Motor Scaled Score | 12 months post randomized surgical intervention | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Vineland-3 Motor Skills Domain Score | 12 months post randomized surgical intervention | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Motor Skills Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. |
| Vineland-3 Adaptive Behavior Composite Score | 12 months post randomized surgical intervention | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Adaptive Behavior Composite (ABC) scores. ABC scores range from 20-140. Higher scores indicate better outcomes. |
| The occurrence of treatment failure. | Through study completion, a maximum of 7 years. | Treatment failure is defined as obstruction, loculated compartments, overdrainage, CSF infection, or significant intraoperative complication. The rate of occurrence of each type, for the initial procedure, will be calculated. Failure can be captured at anytime during the course of the 7 year study. Occurrence between treatment arms will be compared. |
| Time to failure. | Through study completion, a maximum of 7 years | Time to failure is the number of days in which the intervention is functionally successful. It is calculated from date of surgery to date of failure, as described in Outcome 9. Time to failure between treatment arms will be compared. |
| Total number of hospital admission days within 12 months after surgery | 12 months post randomized surgical intervention | Number of days subject is admitted to the hospital during the first 12 months following the initial surgical intervention. All hospital admissions included, regardless of reason for admission. Number of hospital admission days between treatment arms will be compared. |
| Total number of repeat surgeries within 12 months after surgery | 12 months post randomized surgical intervention | Number of shunt and ETV+CPC procedures during the first 12 months following the initial surgical intervention. Number of repeat surgeries between treatment arms will be compared. |
| Total number of brain imaging (CT, MRI, ultrasound) scans within 12 months after surgery | 12 months post randomized surgical intervention | Number of CT, MRI, and ultrasound brain scans during the first 12 months following the initial surgical intervention. Total imaging between treatment arms will be compared. |
| All major peri-operative and post-operative complications | Through study completion, a maximum of 7 years | Number of peri-operative and post-operative complications to include those related to CSF circulation, infection, hemorrhage, seizures, and new neurological deficits. Number of complications between treatment arms will be compared. |
| Vineland-3 Communication Domain Score | 12 months post randomized surgical intervention | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Communication Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. |
| dMRI corpus collosum (CC) and corticospinal tract (CST) fractional anisotropy (FA) at 12 months after surgery. | 12 months post randomized surgical intervention | Develop dMRI maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Tract-based spatial statistics (TBSS) will be used for voxel-wise analyses of white matter tracts. Maps will be used to compare cerebral structural connectivity between the two treatment arms. |
| Cerebral spinal fluid myelin basic protein (MBP) levels measured at the time of ETV+CPC or shunt | 12 months post randomized surgical intervention | Examine correlations of cerebral spinal fluid myelin basic protein (MBP) levels to post-operative Bayley-IV Cognitive Scale score. |
| Cerebral spinal fluid amyloid precursor protein (APP) levels measured at the time of ETV+CPC or shunt | 12 months post randomized surgical intervention | Examine correlations of cerebral spinal fluid amyloid precursor protein (APP) to post-operative Bayley-IV Cognitive Scale score |
| Cerebral spinal fluid NCAM-1 levels measured at the time of ETV+CPC or shunt | 12 months post randomized surgical intervention | Examine correlations of cerebral spinal fluid NCAM-1 levels to post-operative Bayley-IV Cognitive Scale score |
| Cerebral spinal fluid glial fibrillary acid protein (GFAP) levels measured at the time of ETV+CPC or shunt | 12 months post randomized surgical intervention | Examine correlations of cerebral spinal fluid glial fibrillary acid protein (GFAP) to post-operative Bayley-IV Cognitive Scale score |
| Wechsler Preschool & Primary Scale of Intelligence (WPPSI) Scores | At 5 years of age | To determine, in infants who reach 5 years of age before the end of the study, if ETV+CPC compared to shunt results in non-inferior WPPSI scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. |
| Health related quality of life (HRQoL) measurements | 12 months post randomized surgical intervention, and at 3 and 5 years of age | To compare health-related quality of life (HRQoL), as measured by vi-sual analogue scales (VAS), Health Utilities Preschool (HuPS), and the Hydrocephalus Outcome Questionnaire (HOQ), between treatment arms. |
| Brain and ventricle volume on MRI performed at 12 months after surgery | 12 months post randomized surgical intervention | Brain and CSF volumes will be converted to Z-scores based on previously described age- and sex-adjusted distributions and used for comparison of brain volume and growth between ETV+CPC and shunt treatment groups. |
| Vineland-3 Daily Living Skills Domain Score | 12 months post randomized surgical intervention | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Daily Living Skills Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. |
| Vineland-3 Socialization Domain Score | 12 months post randomized surgical intervention | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Socialization Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. |
Countries
Canada, United States
Contacts
Primary ContactNichol Nunn
Backup ContactJason Clawson
Outcome results
None listed