Clinical trial NCT04177914: HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
Official title: Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hydrocephalus
Keywords: Hydrocephalus
Infants
Ventriculoperitoneal Shunt
ETV+CPC
endoscopic third ventriculostomy
choroid plexus cauterization
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: University of Alabama at Birmingham
name: University of British Columbia
name: University of Pittsburgh
name: The Hospital for Sick Children
name: Seattle Children's Hospital
name: Vanderbilt University Medical Center
name: Washington University School of Medicine
name: Nationwide Children's Hospital
name: Johns Hopkins University
name: University of Calgary
name: University of Colorado, Denver
name: Children's Hospital Los Angeles
name: National Institutes of Health (NIH)
name: Hydrocephalus Association
name: Penn State University
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Baylor College of Medicine
name: University of Florida
name: Orlando Health, Inc.
name: Virginia Commonwealth University
name: Trustees of Indiana University
First posted: 2019-11-26
Enrollment: 176
Sex: ALL
Minimum age (years): 1
Maximum age (years): 104
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bayley Scale of Infant Development-IV (Bayley-IV) Cognitive Scale score
timeFrame: 12 months post randomized surgical intervention
Secondary outcomes:
measure: Bayley Scale of Infant Development-IV (Bayley-IV) Language Scaled Score
timeFrame: 12 months post randomized surgical intervention
measure: Bayley Scale of Infant Development-IV (Bayley-IV) Motor Scaled Score
timeFrame: 12 months post randomized surgical intervention
Other outcomes:
measure: Vineland-3 Communication Domain Score
timeFrame: 12 months post randomized surgical intervention
measure: Vineland-3 Daily Living Skills Domain Score
timeFrame: 12 months post randomized surgical intervention
measure: Vineland-3 Socialization Domain Score
timeFrame: 12 months post randomized surgical intervention
measure: Vineland-3 Motor Skills Domain Score
timeFrame: 12 months post randomized surgical intervention
measure: Vineland-3 Adaptive Behavior Composite Score
timeFrame: 12 months post randomized surgical intervention
measure: The occurrence of treatment failure.
timeFrame: Through study completion, a maximum of 7 years.
measure: Time to failure.
timeFrame: Through study completion, a maximum of 7 years
measure: Total number of hospital admission days within 12 months after surgery
timeFrame: 12 months post randomized surgical intervention
measure: Total number of repeat surgeries within 12 months after surgery
timeFrame: 12 months post randomized surgical intervention
measure: Total number of brain imaging (CT, MRI, ultrasound) scans within 12 months after surgery
timeFrame: 12 months post randomized surgical intervention
measure: All major peri-operative and post-operative complications
timeFrame: Through study completion, a maximum of 7 years
measure: Brain and ventricle volume on MRI performed at 12 months after surgery
timeFrame: 12 months post randomized surgical intervention
measure: dMRI corpus collosum (CC) and corticospinal tract (CST) fractional anisotropy (FA) at 12 months after surgery.
timeFrame: 12 months post randomized surgical intervention
measure: Cerebral spinal fluid myelin basic protein (MBP) levels measured at the time of ETV+CPC or shunt
timeFrame: 12 months post randomized surgical intervention
measure: Cerebral spinal fluid amyloid precursor protein (APP) levels measured at the time of ETV+CPC or shunt
timeFrame: 12 months post randomized surgical intervention
measure: Cerebral spinal fluid NCAM-1 levels measured at the time of ETV+CPC or shunt
timeFrame: 12 months post randomized surgical intervention
measure: Cerebral spinal fluid glial fibrillary acid protein (GFAP) levels measured at the time of ETV+CPC or shunt
timeFrame: 12 months post randomized surgical intervention
measure: Wechsler Preschool & Primary Scale of Intelligence (WPPSI) Scores
timeFrame: At 5 years of age
measure: Health related quality of life (HRQoL) measurements
timeFrame: 12 months post randomized surgical intervention, and at 3 and 5 years of age
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Wolfson Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Indianapolis
country: United States
facility: Trustees of Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: University Park
country: United States
facility: The Pennsylvania State University
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: University of Utah
name: John Kestle, MD
role: STUDY_CHAIR
affiliation: University of Toronto
name: Abhaya Kulkarni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: David Limbrick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Richard Holubkov, PhD
role: PRINCIPAL_INVESTIGATOR
References: