HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

Hydrocephalus Clinical Trial

— ESTHI  

Official title:

Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04177914
• Other study ID #: HCRN 012
• Secondary ID: 1U01NS107486-01A
• Status: Recruiting
• Phase: Phase 3
• Start date: July 21, 2020
• Est. completion date: September 30, 2027

Study information

• Verified date: May 2024
• Source: University of Utah
• Contact: Nichol Nunn
• Phone: 801-662-5344
• Email: nichol.nunn[@]hsc.utah.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 176
• Est. completion date: September 30, 2027
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 104 Weeks

Eligibility

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, de?ned 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 ?uid 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 de?ned 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 ?oor 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 ?rst-time permanent procedure for the treatment of hydrocephalus.

Related Conditions & MeSH terms

• Hydrocephalus

Intervention

Procedure:
• Endoscopic 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.

Device:
• Ventriculoperitoneal Shunt
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.

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins Children's Center	Baltimore	Maryland
United States	Children's of Alabama	Birmingham	Alabama
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Wolfson Children's Hospital	Jacksonville	Florida
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	The Pennsylvania State University	University Park	Pennsylvania

Sponsors (20)

Lead Sponsor

Collaborator

University of Utah

Baylor College of Medicine, Children's Hospital Los Angeles, Hydrocephalus Association, Johns Hopkins University, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Nationwide Children's Hospital, Orlando Health, Inc., Penn State University, Seattle Children's Hospital, The Hospital for Sick Children, University of Alabama at Birmingham, University of British Columbia, University of Calgary, University of Colorado, Denver, University of Florida, University of Pittsburgh, Vanderbilt University Medical Center, Washington University School of Medicine

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Vineland-3 Communication Domain Score	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.	12 months post randomized surgical intervention
Other	Vineland-3 Daily Living Skills Domain Score	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.	12 months post randomized surgical intervention
Other	Vineland-3 Socialization Domain Score	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.	12 months post randomized surgical intervention
Other	Vineland-3 Motor Skills Domain Score	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.	12 months post randomized surgical intervention
Other	Vineland-3 Adaptive Behavior Composite Score	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.	12 months post randomized surgical intervention
Other	The occurrence of treatment failure.	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.	Through study completion, a maximum of 7 years.
Other	Time to failure.	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.	Through study completion, a maximum of 7 years
Other	Total number of hospital admission days within 12 months after surgery	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.	12 months post randomized surgical intervention
Other	Total number of repeat surgeries within 12 months after surgery	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.	12 months post randomized surgical intervention
Other	Total number of brain imaging (CT, MRI, ultrasound) scans within 12 months after surgery	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.	12 months post randomized surgical intervention
Other	All major peri-operative and post-operative complications	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.	Through study completion, a maximum of 7 years
Other	Brain and ventricle volume on MRI performed at 12 months after surgery	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.	12 months post randomized surgical intervention
Other	dMRI corpus collosum (CC) and corticospinal tract (CST) fractional anisotropy (FA) at 12 months after surgery.	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.	12 months post randomized surgical intervention
Other	Cerebral spinal fluid myelin basic protein (MBP) levels measured at the time of ETV+CPC or shunt	Examine correlations of cerebral spinal fluid myelin basic protein (MBP) levels to post-operative Bayley-IV Cognitive Scale score.	12 months post randomized surgical intervention
Other	Cerebral spinal fluid amyloid precursor protein (APP) levels measured at the time of ETV+CPC or shunt	Examine correlations of cerebral spinal fluid amyloid precursor protein (APP) to post-operative Bayley-IV Cognitive Scale score	12 months post randomized surgical intervention
Other	Cerebral spinal fluid NCAM-1 levels measured at the time of ETV+CPC or shunt	Examine correlations of cerebral spinal fluid NCAM-1 levels to post-operative Bayley-IV Cognitive Scale score	12 months post randomized surgical intervention
Other	Cerebral spinal fluid glial fibrillary acid protein (GFAP) levels measured at the time of ETV+CPC or shunt	Examine correlations of cerebral spinal fluid glial fibrillary acid protein (GFAP) to post-operative Bayley-IV Cognitive Scale score	12 months post randomized surgical intervention
Other	Wechsler Preschool & Primary Scale of Intelligence (WPPSI) Scores	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.	At 5 years of age
Primary	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	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
Secondary	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