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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01NS107486-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Alabama at Birmingham | OTHER |
| University of British Columbia | OTHER |
| University of Pittsburgh | OTHER |
| The Hospital for Sick Children |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ETV+CPC | Active Comparator | Subjects randomized to this arm will undergo an ETV+CPC procedure for treatment of Hydrocephalus |
|
| Ventriculoperitoneal Shunt | Active Comparator | Subjects randomized to this arm will undergo a Ventriculoperitoneal Shunt procedure for treatment of Hydrocephalus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Bayley Scale of Infant Development-IV (Bayley-IV) Cognitive Scale score | The primary objective is to determine, in infants <104 weeks corrected age, with hydrocephalus requiring treatment at tertiary care pediatric neurosurgery centers in North America, if treatment with ETV+CPC compared to shunt results in non-inferior cognitive outcome at 12 months from surgery, as measured by Bayley-IV Cognitive Scale score with a non-inferiority margin of 1.5. Scaled scores range from 1-19. Higher scores indicate better outcomes. Scores will also be obtained at 3 and 5 years of age. | 12 months post randomized surgical intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Bayley Scale of Infant Development-IV (Bayley-IV) Language Scaled Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Bayley-IV Language Scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Vineland-3 Communication Domain Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Communication Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention |
| Vineland-3 Daily Living Skills Domain Score |
Inclusion Criteria:
Corrected age <104 weeks and 0 days,
AND
Child is ≥ 37 weeks post menstrual age,
AND
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:
AND
No prior history of shunt insertion or endoscopic third ventriculostomy (ETV) procedure (previous temporization devices and/or external ventricular drains permissible)
Exclusion Criteria:
Hydrocephalus due to intraventricular hemorrhage in a child born before 37 weeks gestational age; OR
Anatomy not suitable for ETV+CPC or anteriorly placed ventriculoperitoneal shunt defined as:
Underlying condition with a high chance of mortality within 12 months; OR
Hydrocephalus with loculated CSF compartments; OR
Peritoneal cavity not suitable for distal shunt placement; OR
Active CSF infection; OR
Hydranencephaly; OR
Child requires an intraventricular procedure (e.g. endoscopic biopsy) in addition to the initial first-time permanent procedure for the treatment of hydrocephalus.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nichol Nunn | Contact | 801-458-6593 | nichol.nunn@hsc.utah.edu | |
| Jason Clawson | Contact | jason.clawson@hsc.utah.edu |
| Name | Affiliation | Role |
|---|---|---|
| John Kestle, MD | University of Utah | Study Chair |
| Abhaya Kulkarni, MD | University of Toronto | Principal Investigator |
| David Limbrick, MD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's of Alabama | Recruiting | Birmingham | Alabama | 35233 | United States |
After subject enrollment and 5 year follow up have been completed, we will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. We will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document.
In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.
Within one year of primary publication or within 18 months of the last study visit of the last subject, whichever occurs first.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jun 20, 2019 | Oct 17, 2019 |
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| OTHER |
| Seattle Children's Hospital | OTHER |
| Vanderbilt University Medical Center | OTHER |
| Washington University School of Medicine | OTHER |
| Nationwide Children's Hospital | OTHER |
| Johns Hopkins University | OTHER |
| University of Calgary | OTHER |
| University of Colorado, Denver | OTHER |
| Children's Hospital Los Angeles | OTHER |
| National Institutes of Health (NIH) | NIH |
| Hydrocephalus Association | OTHER |
| Penn State University | OTHER |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
| Baylor College of Medicine | OTHER |
| University of Florida | OTHER |
| Orlando Health, Inc. | OTHER |
| Virginia Commonwealth University | OTHER |
| Trustees of Indiana University | UNKNOWN |
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| Ventriculoperitoneal Shunt | 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. |
|
| Bayley Scale of Infant Development-IV (Bayley-IV) Motor Scaled Score |
To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Bayley-IV Motor Scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. |
| 12 months post randomized surgical intervention |
To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Daily Living Skills Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. |
| 12 months post randomized surgical intervention |
| Vineland-3 Socialization Domain Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Socialization Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention |
| Vineland-3 Motor Skills Domain Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Motor Skills Domain scores. Domain scores range from 20-140. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention |
| Vineland-3 Adaptive Behavior Composite Score | To determine, in the same cohort of infants, if ETV+CPC compared to shunt results in non-inferior Vineland-3 Adaptive Behavior Composite (ABC) scores. ABC scores range from 20-140. Higher scores indicate better outcomes. | 12 months post randomized surgical intervention |
| The occurrence of treatment failure. | Treatment failure is defined as obstruction, loculated compartments, overdrainage, CSF infection, or significant intraoperative complication. The rate of occurrence of each type, for the initial procedure, will be calculated. Failure can be captured at anytime during the course of the 7 year study. Occurrence between treatment arms will be compared. | Through study completion, a maximum of 7 years. |
| Time to failure. | Time to failure is the number of days in which the intervention is functionally successful. It is calculated from date of surgery to date of failure, as described in Outcome 9. Time to failure between treatment arms will be compared. | Through study completion, a maximum of 7 years |
| Total number of hospital admission days within 12 months after surgery | Number of days subject is admitted to the hospital during the first 12 months following the initial surgical intervention. All hospital admissions included, regardless of reason for admission. Number of hospital admission days between treatment arms will be compared. | 12 months post randomized surgical intervention |
| Total number of repeat surgeries within 12 months after surgery | Number of shunt and ETV+CPC procedures during the first 12 months following the initial surgical intervention. Number of repeat surgeries between treatment arms will be compared. | 12 months post randomized surgical intervention |
| Total number of brain imaging (CT, MRI, ultrasound) scans within 12 months after surgery | Number of CT, MRI, and ultrasound brain scans during the first 12 months following the initial surgical intervention. Total imaging between treatment arms will be compared. | 12 months post randomized surgical intervention |
| All major peri-operative and post-operative complications | Number of peri-operative and post-operative complications to include those related to CSF circulation, infection, hemorrhage, seizures, and new neurological deficits. Number of complications between treatment arms will be compared. | Through study completion, a maximum of 7 years |
| Brain and ventricle volume on MRI performed at 12 months after surgery | Brain and CSF volumes will be converted to Z-scores based on previously described age- and sex-adjusted distributions and used for comparison of brain volume and growth between ETV+CPC and shunt treatment groups. | 12 months post randomized surgical intervention |
| dMRI corpus collosum (CC) and corticospinal tract (CST) fractional anisotropy (FA) at 12 months after surgery. | Develop dMRI maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Tract-based spatial statistics (TBSS) will be used for voxel-wise analyses of white matter tracts. Maps will be used to compare cerebral structural connectivity between the two treatment arms. | 12 months post randomized surgical intervention |
| Cerebral spinal fluid myelin basic protein (MBP) levels measured at the time of ETV+CPC or shunt | Examine correlations of cerebral spinal fluid myelin basic protein (MBP) levels to post-operative Bayley-IV Cognitive Scale score. | 12 months post randomized surgical intervention |
| Cerebral spinal fluid amyloid precursor protein (APP) levels measured at the time of ETV+CPC or shunt | Examine correlations of cerebral spinal fluid amyloid precursor protein (APP) to post-operative Bayley-IV Cognitive Scale score | 12 months post randomized surgical intervention |
| Cerebral spinal fluid NCAM-1 levels measured at the time of ETV+CPC or shunt | Examine correlations of cerebral spinal fluid NCAM-1 levels to post-operative Bayley-IV Cognitive Scale score | 12 months post randomized surgical intervention |
| Cerebral spinal fluid glial fibrillary acid protein (GFAP) levels measured at the time of ETV+CPC or shunt | Examine correlations of cerebral spinal fluid glial fibrillary acid protein (GFAP) to post-operative Bayley-IV Cognitive Scale score | 12 months post randomized surgical intervention |
| Wechsler Preschool & Primary Scale of Intelligence (WPPSI) Scores | To determine, in infants who reach 5 years of age before the end of the study, if ETV+CPC compared to shunt results in non-inferior WPPSI scaled scores. Scaled scores range from 1-19. Higher scores indicate better outcomes. | At 5 years of age |
| Health related quality of life (HRQoL) measurements | To compare health-related quality of life (HRQoL), as measured by vi-sual analogue scales (VAS), Health Utilities Preschool (HuPS), and the Hydrocephalus Outcome Questionnaire (HOQ), between treatment arms. | 12 months post randomized surgical intervention, and at 3 and 5 years of age |
| Washington University School of Medicine |
| Principal Investigator |
| Richard Holubkov, PhD | University of Utah | Principal Investigator |
| Phoenix Children's Hospital | Not yet recruiting | Phoenix | Arizona | 85016 | United States |
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| Children's Hospital of Los Angeles | Recruiting | Los Angeles | California | 90027 | United States |
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| Children's Hospital Colorado | Recruiting | Aurora | Colorado | 80045 | United States |
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| Yale University | Active, not recruiting | New Haven | Connecticut | 06520 | United States |
| Wolfson Children's Hospital | Recruiting | Jacksonville | Florida | 32207 | United States |
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| Arnold Palmer Hospital for Children | Recruiting | Orlando | Florida | 32806 | United States |
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| Trustees of Indiana University | Not yet recruiting | Indianapolis | Indiana | 46202 | United States |
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| Johns Hopkins Children's Center | Recruiting | Baltimore | Maryland | 21287 | United States |
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| St. Louis Children's Hospital | Recruiting | St Louis | Missouri | 63110 | United States |
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| Nationwide Children's Hospital | Recruiting | Columbus | Ohio | 43205 | United States |
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| Children's Hospital of Pittsburgh of UPMC | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
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| The Pennsylvania State University | Active, not recruiting | University Park | Pennsylvania | 16802 | United States |
| Monroe Carell Jr. Children's Hospital at Vanderbilt | Recruiting | Nashville | Tennessee | 37232 | United States |
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| Texas Children's Hospital | Recruiting | Houston | Texas | 77030 | United States |
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| Primary Children's Hospital | Recruiting | Salt Lake City | Utah | 84118 | United States |
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| Virginia Commonwealth University | Active, not recruiting | Richmond | Virginia | 23284 | United States |
| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98105 | United States |
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| Alberta Children's Hospital | Recruiting | Calgary | Alberta | T3B 6A8 | Canada |
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| British Columbia Children's Hospital | Recruiting | Vancouver | British Columbia | V6H 3V4 | Canada |
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| The Hospital for Sick Children | Recruiting | Toronto | Ontario | M5G 1X8 | Canada |
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| ICF_000.pdf |
| ID | Term |
|---|---|
| D006849 | Hydrocephalus |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D014696 | Ventriculostomy |
| D017287 | Ventriculoperitoneal Shunt |
| ID | Term |
|---|---|
| D002557 | Cerebrospinal Fluid Shunts |
| D000714 | Anastomosis, Surgical |
| D013514 | Surgical Procedures, Operative |
| D019635 | Neurosurgical Procedures |
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