NCT04177914

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
176

participants targeted

Target at P25-P50 for phase_3

Timeline
16mo left

Started Jul 2020

Longer than P75 for phase_3

Geographic Reach
2 countries

21 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress82%
Jul 2020Aug 2027

First Submitted

Initial submission to the registry

October 27, 2019

Completed
1 month until next milestone

First Posted

Study publicly available on registry

November 26, 2019

Completed
8 months until next milestone

Study Start

First participant enrolled

July 21, 2020

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2027

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2027

Last Updated

June 11, 2025

Status Verified

June 1, 2025

Enrollment Period

6.9 years

First QC Date

October 27, 2019

Last Update Submit

June 5, 2025

Conditions

Keywords

HydrocephalusInfantsVentriculoperitoneal ShuntETV+CPCendoscopic third ventriculostomychoroid plexus cauterization

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Bayley Scale of Infant Development-IV (Bayley-IV) Language Scaled Score

    12 months post randomized surgical intervention

  • Bayley Scale of Infant Development-IV (Bayley-IV) Motor Scaled Score

    12 months post randomized surgical intervention

Other Outcomes (19)

  • Vineland-3 Communication Domain Score

    12 months post randomized surgical intervention

  • Vineland-3 Daily Living Skills Domain Score

    12 months post randomized surgical intervention

  • Vineland-3 Socialization Domain Score

    12 months post randomized surgical intervention

  • +16 more other outcomes

Study Arms (2)

ETV+CPC

ACTIVE COMPARATOR

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)

Ventriculoperitoneal Shunt

ACTIVE COMPARATOR

Subjects randomized to this arm will undergo a Ventriculoperitoneal Shunt procedure for treatment of Hydrocephalus

Device: Ventriculoperitoneal Shunt

Interventions

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.

ETV+CPC

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.

Ventriculoperitoneal Shunt

Eligibility Criteria

Age1 Day - 104 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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
  • +1 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

NOT YET RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

ACTIVE NOT RECRUITING

Wolfson Children's Hospital

Jacksonville, Florida, 32207, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

Trustees of Indiana University

Indianapolis, Indiana, 46202, United States

NOT YET RECRUITING

Johns Hopkins Children's Center

Baltimore, Maryland, 21287, United States

RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

The Pennsylvania State University

University Park, Pennsylvania, 16802, United States

ACTIVE NOT RECRUITING

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84118, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

ACTIVE NOT RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

MeSH Terms

Conditions

Hydrocephalus

Interventions

VentriculostomyVentriculoperitoneal Shunt

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Cerebrospinal Fluid ShuntsAnastomosis, SurgicalSurgical Procedures, OperativeNeurosurgical Procedures

Study Officials

  • John Kestle, MD

    University of Utah

    STUDY CHAIR
  • Abhaya Kulkarni, MD

    University of Toronto

    PRINCIPAL INVESTIGATOR
  • David Limbrick, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR
  • Richard Holubkov, PhD

    University of Utah

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, Vice Chair of Clinical Research

Study Record Dates

First Submitted

October 27, 2019

First Posted

November 26, 2019

Study Start

July 21, 2020

Primary Completion (Estimated)

May 30, 2027

Study Completion (Estimated)

August 31, 2027

Last Updated

June 11, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will share

After subject enrollment and 5 year follow up have been completed, we will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. We will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Within one year of primary publication or within 18 months of the last study visit of the last subject, whichever occurs first.

Locations