Randomized Controlled Trial of Shunt vs ETV/CPC for PIH in Ugandan Infants

Neurocognitive Outcomes and Changes in Brain and Cerebral Spinal Fluid (CSF) Volume After Treatment of Post-Infectious Hydrocephalus (PIH) in Ugandan Infants by Shunting Versus ETV/CPC

Two treatment options exist for infant patients with hydrocephalus. Most patients are treated with a surgical procedure in which a shunt is inserted into the brain and abdomen. In recent years, however, another treatment has developed called Endoscopic Third Ventriculostomy (ETV) with Choroid Plexus Cauterization (ETV/CPC).This research study is being done to measure the results of these procedures in children less than six months of age who have hydrocephalus as the result of a brain infection, called post-infectious hydrocephalus, or PIH. This study will evaluate patients in more detail to measure brain growth and development.

Study Overview

• Status: Active, not recruiting
• Conditions: Hydrocephalus
• Intervention / Treatment: Device: Chhabra Shunt Placement; Procedure: ETV/CPC

Detailed Description

World over, infants with hydrocephalus are mainly treated using a shunt, which is a device made of soft plastic tubing that moves extra fluid from the brain to the abdomen. Surgery is required to insert a shunt into the brain and the abdomen. In recent years, we have developed another treatment called Endoscopic Third Ventriculostomy (ETV) with Choroid Plexus Cauterization (ETV/CPC). This research study is being done to measure the results of these procedures in children less than six months of age who have hydrocephalus as the result of a brain infection, called post-infectious hydrocephalus, or PIH. This is the most common cause of hydrocephalus in Ugandan babies. This study will evaluate patients in more detail to measure brain growth and development. Children in the study will have special testing to measure developmental progress as well as special imaging to evaluate the progress of their brain growth.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Uganda
  • Mbale, Uganda
    • CURE Children's Hospital Uganda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants less than 180 days (six months) old
• Symptomatic hydrocephalus
• Post-infectious Hydrocephalus based on clinical and CT parameters2
• Must be from the following Ugandan districts: Bugiri, Busia, Iganga, Jinja, Kampala, Kamuli, Kapchorwa, Katakwi, Kumi, Mayuge, Mbale, Mukono, Pallisa, Sironko, Soroti, and Tororo

Exclusion Criteria:

• Any patient with a scalp erosion or infection that would exclude the patient from shunt implantation
• Any patient with ventricular loculations that would normally indicate the use of ventriculoscopy as an adjunct to shunt placement
• Any patient with absence of any visible cortical mantle on the CT
• Patients must be appropriate candidates for either surgical procedure - shunt placement alone or ETV/CPC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chhabra Shunt Placement; The shunting arm will comprise a standard frontal approach ventriculoperitoneal shunt using a silastic Chhabra system.	Device: Chhabra Shunt Placement
Active Comparator: ETV/CPC; The Endoscopic Third Ventriculostomy/Choroid Plexus Cauterization (ETV/CPC) arm will comprise a standard frontal approach with flexible endoscopy.	Procedure: ETV/CPC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Age-normed Bayley Scales of Infant Development (BSID)-III scores	Neurocognition will be measured using the BSID-III Cognitive Scale. Change will be assessed at 24 months post treatment from baseline score (12 months post treatment).	12 months and 24 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Volume	Volume unit of measure is cubic millimeters. Volume is measured using CT scans.	12 months, 24 months, 5 years, and 7-10 years post treatment
CSF Volume	Volume unit of measure is cubic millimeters. Volume is measured using CT scans.	12 months, 24 months, 5 years, and 7-10 years post treatment
Vineland Adaptive Behavior Scales	The primary purpose of the VABS is to assess the social abilities of school age children.	5 years and 7-10 years post treatment

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: The Hospital for Sick Children; Penn State University; CURE Children's Hospital, Uganda
• Investigators: Principal Investigator: Benjamin C Warf, MD, Boston Children's Hospital

Publications and helpful links

General Publications

• Harper JR, Cherukuri V, O'Reilly T, Yu M, Mbabazi-Kabachelor E, Mulando R, Sheth KN, Webb AG, Warf BC, Kulkarni AV, Monga V, Schiff SJ. Assessing the utility of low resolution brain imaging: treatment of infant hydrocephalus. Neuroimage Clin. 2021;32:102896. doi: 10.1016/j.nicl.2021.102896. Epub 2021 Nov 23.
• Punchak M, Mbabazi Kabachelor E, Ogwal M, Nalule E, Nalwoga J, Ssenyonga P, Mugamba J, Rattani A, Dewan MC, Kulkarni AV, Schiff SJ, Warf B. The Incidence of Postoperative Seizures Following Treatment of Postinfectious Hydrocephalus in Ugandan Infants: A Post Hoc Comparison of Endoscopic Treatment vs Shunt Placement in a Randomized Controlled Trial. Neurosurgery. 2019 Oct 1;85(4):E714-E721. doi: 10.1093/neuros/nyz122.
• Kulkarni AV, Schiff SJ, Mbabazi-Kabachelor E, Mugamba J, Ssenyonga P, Donnelly R, Levenbach J, Monga V, Peterson M, MacDonald M, Cherukuri V, Warf BC. Endoscopic Treatment versus Shunting for Infant Hydrocephalus in Uganda. N Engl J Med. 2017 Dec 21;377(25):2456-2464. doi: 10.1056/NEJMoa1707568.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2013
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimated): September 6, 2013

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus
• Other Study ID Numbers: P00002785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with researchers outside of the study team.