A Study Comparing Two Treatments for Infants With Hydrocephalus

International Infant Hydrocephalus Study: A Multicentre, Prospective Study

The purpose of this study is to study whether infants with triventricular hydrocephalus (TVH) have a better long-term outcome at 5 years when they are treated with a new procedure, endoscopic third ventriculostomy (ETV), than infants treated with the more traditional treatment, insertion of a cerebrospinal fluid (CSF) shunt.

Study Overview

• Status: Completed
• Conditions: Hydrocephalus
• Intervention / Treatment: Procedure: Endoscopic Third Ventriculostomy; Procedure: CSF Shunt Insertion

Detailed Description

TVH is a relatively uncommon condition in infants, in which CSF accumulates in the brain's ventricles due to a blockage in outflow at the level of cerebral aqueduct. This can cause increased intracranial pressure, with adverse effect on brain development. The causes of this include congenital aqueductal stensois or acquired aqueductal stenosis from previous brain hemorrhage or infection.

TVH is currently treated through one of the following two approaches:

• Extra-cranial CSF diversion through ventricular shunts. Extra-cranial shunting has been the standard approach over the past few decades, since functional shunts were first developed and inserted successfully.
• Intra-cranial internal CSF diversion using endoscopic techniques. The principles of internal diversion were clear from the time neurosurgeons first understood the nature of hydrocephalus. However, internal diversion was never really practical or successful on a large scale until the more recent development of neuroendoscopy. There is currently a revived interest in diversionary hydrocephalus treatment through neuroendoscopic surgical techniques, with the primary focus on endoscopic third ventriculostomy (ETV).

• Study Type: Interventional
• Enrollment (Anticipated): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Nacional de Pediatria
• Brazil
  • Nova Lima, Brazil
    • Biocor Instituto
  • Sao Paulo, Brazil
    • UNIFESP
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Germany
  • Giessen, Germany
    • University Hospital Giessen and Marburg
• Hungary
  • Debrecen, Hungary
    • University of Debrecen
• India
  • Lucknow, India
    • Sanjay Gandhi Postgraduate Institute of Medical Sciences
  • New Delhi, India
    • All India Institute of Medical Sciences
• Israel
  • Tel Aviv, Israel
    • Dana Children's hospital, Tel Aviv Medical Center
• Italy
  • Genova, Italy
    • Giannina Gaslini Hospital
  • Rome, Italy
    • Catholic University Medical School Rome
• Netherlands
  • Nijmegen, Netherlands
    • University Medical Center St Radboud
• Poland
  • Katowice, Poland
    • Medical University of Silesia
  • Lodz, Poland
    • Polish Mother's Memorial Hospital
  • Warsaw, Poland
    • Children's Memorial Health Institute
• Russian Federation
  • Moscow, Russian Federation
    • Burdenko Neurosurgical Institute
• Serbia
  • Belgrade, Serbia
    • Institute for Neurosurgery
• Spain
  • Barcelona, Spain
    • Hospital Sant Joan de Deu
• Turkey
  • Ankara, Turkey
    • Hacettepe University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Children's Hospital
  • Liverpool, United Kingdom
    • Alder Hey Children's Hospital
• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic TVH requiring treatment.
• No previous treatment for TVH
• Under 24 months of age at time of surgery
• Full-term pregnancy (>36 weeks)
• Mandatory pre-operative MRI that includes mid-sagittal T1 & T2 scans which show: Tri-ventricular pattern of hydrocephalus; proof of no flow through aqueduct; presence of CSF collection over the convexity and/or inter-hemispheric fissure is acceptable; configuration of third ventricle floor could vary; deformed tectal plate is acceptable; posterior fossa fluid collections may be included as long as: aqueduct is closed; vermis preserved (complete Dandy Walker Syndrome excluded); questionable flow in aqueduct acceptable as long as TVH exists
• History or suggestion of intra-ventricular bleed (intra-uterine or post-natal) or intracranial infection qualifies (excluding intraventricular hemorrhage of prematurity).
• Ability to participate in followup for at least 5 years

Exclusion Criteria:

• Open Spina Bifida
• Complete Dandy Walker syndrome (vermian agenesis / dysgenesis)
• Prematurity
• Perinatal asphyxia
• Severe dysmorphic anatomical features or known chromos (e.g. agenesis of corpus callosum, heterotopias, large cysts)
• intracranial tumor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ETV	Procedure: Endoscopic Third Ventriculostomy; A standard frontal burr hole will be made and an endoscopic camera used to visualize the floor of the third ventricle. A ventriculostomy will be created in the floor of the third using the surgeon's own preferred method of perforation.
Active Comparator: CSF Shunt	Procedure: CSF Shunt Insertion; The procedure involves creating a burr hole in the frontal or occipital regions and cannulating the ventricle with a silastic catheter. This is then attached to a valve mechanism and distal silastic tubing which runs subcutaneously in the peritoneal cavity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Health Status Outcome as measured by the Health Utilities Index - 2	At 5 years of age

Secondary Outcome Measures

Outcome Measure	Time Frame
Death	Duration of the Study
Neurodevelopment as measured by the Denver Developmental Screening Test	Up to 3 years of Age
Health status outcome using the Hydrocephalus Outcome Questionnaire	At 5 years of Age
In-depth Evaluation of Neurodevelopment, Functioning and Intelligence, as mesured by the Weschler Intelligence Scale for Children or Weschler Preschool and Primary Scale of Intelligence	At 5 years of Age
Number of Subsequent Hydrocephalus-Related Operations	Duration of the Study
Surgical Morbidity	Duration of the Study
Incidence of failure of initial intervention	Duration of the Study
Hospitalization Time	5 years post-operation
Need for repeat radiological scans	Duration of the Study
Complications such as CNS infection, focal neurological deficit, significant hemorrhage, seizures requiring medication	Duration of the Study
Ventricular size and the existence of flow void (ETV group)assessed through radiological evaluation	3 years of age

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: The International Study Group for Neuroendoscopy (ISGNE); The International Society for Pediatric Neurosurgery
• Investigators: Principal Investigator: Abhaya Kulkarni, MD, The Hospital for Sick Children, Toronto Canada; Principal Investigator: Shlomi Constantini, MD, Dana Children's hospital, Tel Aviv Medical Center; Principal Investigator: Spyros Sgouros, MD, Birmingham Children's Hospital

Publications and helpful links

General Publications

• Kulkarni AV, Sgouros S, Leitner Y, Constantini S; International Infant Hydrocephalus Study Investigators. International Infant Hydrocephalus Study (IIHS): 5-year health outcome results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus. Childs Nerv Syst. 2018 Dec;34(12):2391-2397. doi: 10.1007/s00381-018-3896-5. Epub 2018 Jul 9.
• Kulkarni AV, Sgouros S, Constantini S; International Infant Hydrocephalus Study Investigators. Outcome of treatment after failed endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: results from the International Infant Hydrocephalus Study (IIHS). Childs Nerv Syst. 2017 May;33(5):747-752. doi: 10.1007/s00381-017-3382-5. Epub 2017 Mar 29.
• Kulkarni AV, Sgouros S, Constantini S; IIHS Investigators. International Infant Hydrocephalus Study: initial results of a prospective, multicenter comparison of endoscopic third ventriculostomy (ETV) and shunt for infant hydrocephalus. Childs Nerv Syst. 2016 Jun;32(6):1039-48. doi: 10.1007/s00381-016-3095-1. Epub 2016 Apr 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: March 31, 2008
• First Submitted That Met QC Criteria: March 31, 2008
• First Posted (Estimate): April 3, 2008

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: September 7, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: infants; Ventriculostomy; neurosurgery; Hydrocephalus; Cerebrospinal Fluid Shunt
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus
• Other Study ID Numbers: 1000007601