HydrocephalusPhase 2NCT00652470
A Study Comparing Two Treatments for Infants With Hydrocephalus
A Phase 2 study testing Endoscopic Third Ventriculostomy and CSF Shunt Insertion in people with Hydrocephalus, run by The Hospital for Sick Children at 22 sites in 16 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 1 day to 24 months
- Conditions the study is for
- Hydrocephalus
- What is being tested?
- Endoscopic Third Ventriculostomy and CSF Shunt Insertion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 22 sitesin 16 countries
- Study dates
- Sep 2005to 1 May 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
22 sites in 16 countries.
22 sites in 16 countries
Poland3 sites
Medical University of Silesia
Katowice
Polish Mother's Memorial Hospital
Lodz
Children's Memorial Health Institute
Warsaw
India2 sites
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow
All India Institute of Medical Sciences
New Delhi
Italy2 sites
Giannina Gaslini Hospital
Genova
Catholic University Medical School Rome
Rome
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham
Alder Hey Children's Hospital
Liverpool
United States1 site
Children's Medical Center of Dallas
Dallas, Texas, 75235
About this study
Official title: 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.
Read the 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).
- Conditions
- Hydrocephalus
- Being tested
- Endoscopic Third Ventriculostomy, CSF Shunt Insertion
- Keywords
- infants, Hydrocephalus, Cerebrospinal Fluid Shunt, Ventriculostomy, neurosurgery
- Medical subject headings
- Hydrocephalus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endoscopic Third VentriculostomyProcedure or surgery
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.
CSF Shunt InsertionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| ETV | Active comparator | Not described Receives: Procedure: Endoscopic Third Ventriculostomy |
| CSF Shunt | Active comparator | Not described Receives: Procedure: CSF Shunt Insertion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health Status Outcome as measured by the Health Utilities Index - 2
Measured: At 5 years of age
Secondary outcomes (11)
Death
Measured: Duration of the Study
Neurodevelopment as measured by the Denver Developmental Screening Test
Measured: Up to 3 years of Age
Health status outcome using the Hydrocephalus Outcome Questionnaire
Measured: 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
Measured: At 5 years of Age
Number of Subsequent Hydrocephalus-Related Operations
Measured: Duration of the Study
Surgical Morbidity
Measured: Duration of the Study
Incidence of failure of initial intervention
Measured: Duration of the Study
Hospitalization Time
Measured: 5 years post-operation
Need for repeat radiological scans
Measured: Duration of the Study
Complications such as CNS infection, focal neurological deficit, significant hemorrhage, seizures requiring medication
Measured: Duration of the Study
Ventricular size and the existence of flow void (ETV group)assessed through radiological evaluation
Measured: 3 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2008 (estimated)
- Study startSep 2005
- Primary completion1 May 2018
- Study completion1 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HydrocephalusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- The International Study Group for Neuroendoscopy (ISGNE), The International Society for Pediatric Neurosurgery
- Responsible party
- Principal investigator, Abhaya Kulkarni, The Hospital for Sick Children
- Investigators
- Abhaya Kulkarni, MD, Principal investigator, The Hospital for Sick Children, Toronto CanadaShlomi Constantini, MD, Principal investigator, Dana Children's Hospital, Tel Aviv Medical CenterSpyros Sgouros, MD, Principal investigator, Birmingham Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00652470
- Sponsor's protocol ID
- 1000007601
- Status last verified
- Sep 2018
- First submitted
- 31 Mar 2008
- Last updated
- 10 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 29987375Kulkarni 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.
PubMed 28357554Kulkarni 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.
PubMed 27107887
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Infant Hydrocephalus Study: A Multicentre, Prospective Study
- ClinicalTrials.gov ID
- NCT00652470
- Acronym / sponsor ID
- 1000007601
- Conditions
- Hydrocephalus
- Keywords
- infants, Hydrocephalus, Cerebrospinal Fluid Shunt, Ventriculostomy, neurosurgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 182 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- The International Study Group for Neuroendoscopy (ISGNE), The International Society for Pediatric Neurosurgery
- Study start
- Sep 2005
- Primary completion
- 1 May 2018 (actual)
- Study completion
- 1 May 2018 (actual)
- First posted
- 3 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ETV | Active comparator | Procedure: Endoscopic Third Ventriculostomy |
| CSF Shunt | Active comparator | Procedure: CSF Shunt Insertion |
Who may qualify
- Ages
- 1 day to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endoscopic Third VentriculostomyA 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. | Procedure or surgery | ETV |
| CSF Shunt InsertionThe 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. | Procedure or surgery | CSF Shunt |
Primary outcome
Health Status Outcome as measured by the Health Utilities Index - 2
Time frame: At 5 years of age
11 secondary outcomes
Death
Time frame: Duration of the Study
Neurodevelopment as measured by the Denver Developmental Screening Test
Time frame: Up to 3 years of Age
Health status outcome using the Hydrocephalus Outcome Questionnaire
Time frame: 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
Time frame: At 5 years of Age
Number of Subsequent Hydrocephalus-Related Operations
Time frame: Duration of the Study
Surgical Morbidity
Time frame: Duration of the Study
Incidence of failure of initial intervention
Time frame: Duration of the Study
Hospitalization Time
Time frame: 5 years post-operation
Need for repeat radiological scans
Time frame: Duration of the Study
Complications such as CNS infection, focal neurological deficit, significant hemorrhage, seizures requiring medication
Time frame: Duration of the Study
Ventricular size and the existence of flow void (ETV group)assessed through radiological evaluation
Time frame: 3 years of age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Derived from this study: PubMed 29987375Kulkarni 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.
- Derived from this study: PubMed 28357554Kulkarni 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.
- Derived from this study: PubMed 27107887Kulkarni 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abhaya Kulkarni, MD principal investigator
The Hospital for Sick Children, Toronto Canada
Shlomi Constantini, MD principal investigator
Dana Children's Hospital, Tel Aviv Medical Center
Spyros Sgouros, MD principal investigator
Birmingham Children's Hospital
22 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Endoscopic Third Ventriculostomy and CSF Shunt Insertion in people with Hydrocephalus, run by The Hospital for Sick Children at 22 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Poland, Brazil, India, Italy, United Kingdom and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health Status Outcome as measured by the Health Utilities Index - 2 (time frame: At 5 years of age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00652470, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.