HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

Phase 3

Recruiting

• Conditions: Hydrocephalus
• Interventions: Procedure: Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC); Device: Ventriculoperitoneal Shunt

• Registration Number: NCT04177914
• Lead Sponsor: University of Utah

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.

Study Timeline

• Study First Submitted: 2019-10-27
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-26
• Study Start: 2020-07-21
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-20
• Last Update Posted: 2024-06-25
• Primary Completion: 2027-05-30
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 176

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ETV+CPC	Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)	Subjects randomized to this arm will undergo an ETV+CPC procedure for treatment of Hydrocephalus
Ventriculoperitoneal Shunt	Ventriculoperitoneal Shunt	Subjects randomized to this arm will undergo a Ventriculoperitoneal Shunt procedure for treatment of Hydrocephalus

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (19)

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

Wolfson Children's Hospital; 🇺🇸 Jacksonville, Florida, United States

Johns Hopkins Children's Center; 🇺🇸 Baltimore, Maryland, United States

St. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

The Pennsylvania State University; 🇺🇸 University Park, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Children's of Alabama; 🇺🇸 Birmingham, Alabama, United States

Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Arnold Palmer Hospital for Children; 🇺🇸 Orlando, Florida, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States