Clinical trial NCT00652470: A Study Comparing Two Treatments for Infants With Hydrocephalus
Official title: International Infant Hydrocephalus Study: A Multicentre, Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hydrocephalus
Keywords: infants
Hydrocephalus
Cerebrospinal Fluid Shunt
Ventriculostomy
neurosurgery
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: The International Study Group for Neuroendoscopy (ISGNE)
name: The International Society for Pediatric Neurosurgery
First posted: 2008-04-03
Enrollment: 182
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Health Status Outcome as measured by the Health Utilities Index - 2
timeFrame: At 5 years of age
Secondary outcomes:
measure: Death
timeFrame: Duration of the Study
measure: Neurodevelopment as measured by the Denver Developmental Screening Test
timeFrame: Up to 3 years of Age
measure: Health status outcome using the Hydrocephalus Outcome Questionnaire
timeFrame: At 5 years of Age
measure: 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
timeFrame: At 5 years of Age
measure: Number of Subsequent Hydrocephalus-Related Operations
timeFrame: Duration of the Study
measure: Surgical Morbidity
timeFrame: Duration of the Study
measure: Incidence of failure of initial intervention
timeFrame: Duration of the Study
measure: Hospitalization Time
timeFrame: 5 years post-operation
measure: Need for repeat radiological scans
timeFrame: Duration of the Study
measure: Complications such as CNS infection, focal neurological deficit, significant hemorrhage, seizures requiring medication
timeFrame: Duration of the Study
measure: Ventricular size and the existence of flow void (ETV group)assessed through radiological evaluation
timeFrame: 3 years of age
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Buenos Aires
country: Argentina
facility: Nacional de Pediatria
city: Nova Lima
country: Brazil
facility: Biocor Instituto
city: Sao Paulo
country: Brazil
facility: UNIFESP
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Giessen
country: Germany
facility: University Hospital Gießen and Marburg
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Lucknow
country: India
facility: Sanjay Gandhi Postgraduate Institute of Medical Sciences
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Tel Aviv
country: Israel
facility: Dana Children's Hospital, Tel Aviv Medical Center
city: Genova
country: Italy
facility: Giannina Gaslini Hospital
city: Rome
country: Italy
facility: Catholic University Medical School Rome
city: Nijmegen
country: Netherlands
facility: University Medical Center St Radboud
city: Katowice
country: Poland
facility: Medical University of Silesia
city: Lodz
country: Poland
facility: Polish Mother's Memorial Hospital
city: Warsaw
country: Poland
facility: Children's Memorial Health Institute
city: Moscow
country: Russian Federation
facility: Burdenko Neurosurgical Institute
city: Belgrade
country: Serbia
facility: Institute for Neurosurgery
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Ankara
country: Turkey
facility: Hacettepe University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Abhaya Kulkarni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana Children's Hospital, Tel Aviv Medical Center
name: Shlomi Constantini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Birmingham Children's Hospital
name: Spyros Sgouros, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.