HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants

NCT ID: NCT04177914

Last Updated: 2025-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

176 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-21

Study Completion Date

2027-08-31

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.

Conditions

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Hydrocephalus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ETV+CPC

Subjects randomized to this arm will undergo an ETV+CPC procedure for treatment of Hydrocephalus

Group Type ACTIVE_COMPARATOR

Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)

Intervention Type PROCEDURE

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.

Ventriculoperitoneal Shunt

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

Group Type ACTIVE_COMPARATOR

Ventriculoperitoneal Shunt

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type PROCEDURE

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.

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

1 Day

Maximum Eligible Age

104 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alabama at Birmingham

OTHER

Sponsor Role collaborator

University of British Columbia

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role collaborator

Seattle Children's Hospital

OTHER

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Hydrocephalus Association

OTHER

Sponsor Role collaborator

Penn State University

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role collaborator

Orlando Health, Inc.

OTHER

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role collaborator

Trustees of Indiana University

UNKNOWN

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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John Kestle

MD, Vice Chair of Clinical Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Kestle, MD

Role: STUDY_CHAIR

University of Utah

Abhaya Kulkarni, MD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

David Limbrick, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Richard Holubkov, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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Children's of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status NOT_YET_RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status ACTIVE_NOT_RECRUITING

Wolfson Children's Hospital

Jacksonville, Florida, United States

Site Status RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status RECRUITING

Trustees of Indiana University

Indianapolis, Indiana, United States

Site Status NOT_YET_RECRUITING

Johns Hopkins Children's Center

Baltimore, Maryland, United States

Site Status RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

The Pennsylvania State University

University Park, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status ACTIVE_NOT_RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Nichol Nunn

Role: CONTACT

801-458-6593

Jason Clawson

Role: CONTACT

Facility Contacts

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Anastasia Smith, MPH

Role: primary

205-638-5018

Bethany Norton

Role: primary

Helen Berroya

Role: primary

Susan Staulcup, 80045

Role: primary

303-724-5935

Asmaa Hatem

Role: primary

904-633-0993

Richard Guerrero

Role: primary

Mariah Shirrell

Role: primary

Sydney White

Role: primary

Diego Morales, MS

Role: primary

314-454-4688

Mary Goldschmidt

Role: backup

Jared Haught

Role: primary

Kimberly Diamond, BS, BA

Role: primary

412-692-9965

Julia Loes

Role: primary

Stephen Gannon

Role: backup

615-936-6809

Edgardo Santisbon

Role: primary

832-826-5208

Alli Ludwick

Role: primary

801-662-5352

Jessica Becerra

Role: primary

Ruksana Rashid, MBBS MPH MSc

Role: primary

403-955-5738

Annika Weirs

Role: primary

Homa Ashrafpour

Role: primary

416-813-7654 ext. 328771

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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1U01NS107486-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HCRN 012

Identifier Type: -

Identifier Source: org_study_id

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