Endoscopic Treatment vs. Shunt Surgery for Hydrocephalus

(ESTHI Trial)

Recruiting at 18 trial locations

Overseen By Jason Clawson

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Utah

Disqualifiers: Intraventricular hemorrhage, High mortality, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: Immediate post-surgical period

176 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) for hydrocephalus?

Research shows that ETV+CPC can increase the chances of avoiding shunt-related complications in infants with hydrocephalus compared to using ETV alone. Studies have found that this combined approach can be effective in reducing the need for permanent shunt systems, which are often associated with risks. ^{1 2 3 4 5}

Is endoscopic treatment for hydrocephalus safe?

Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) is generally considered safe for treating hydrocephalus in infants, with studies reporting on its safety and complication rates. It is designed to avoid the risks associated with permanent shunt hardware, such as infections, and has been studied in various populations, including North America. ^{1 2 3 4 6}

How does the treatment for hydrocephalus differ from other treatments?

Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) is unique because it involves creating a new pathway for cerebrospinal fluid to flow within the brain, reducing the need for a permanent implant like a shunt. This approach can be less invasive and avoids the complications associated with shunt systems, which are more common in traditional treatments for hydrocephalus. ^{7 8 9 10 11}

Research Team

David Limbrick, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Richard Holubkov, PhD

Principal Investigator

University of Utah

John Kestle, MD

Principal Investigator

University of Utah

Abhaya Kulkarni, MD

Principal Investigator

University of Toronto

Eligibility Criteria

This trial is for babies under 2 years old with symptomatic hydrocephalus, a condition where fluid builds up in the brain. They should have no prior shunt or endoscopic procedures and meet specific criteria on MRI scans and symptoms like head size, eye movement issues, or irritability without other causes.

Inclusion Criteria

I have never had a shunt insertion or ETV procedure.

My child is less than 2 years old.

My child is at least 37 weeks post menstrual age.

Exclusion Criteria

My child was born prematurely and has hydrocephalus from bleeding in the brain.

My condition or anatomy makes certain brain surgeries or shunt placements not suitable for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either a Ventriculoperitoneal Shunt procedure or an ETV+CPC procedure for treatment of Hydrocephalus

Immediate post-surgical period

Follow-up

Participants are monitored for safety, effectiveness, and cognitive outcomes after treatment

12 months

Regular follow-up visits at 12 months, 3 years, and 5 years

Long-term Follow-up

Participants are monitored for long-term outcomes including treatment failure and cognitive development

Up to 7 years

Treatment Details

Interventions

• Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC)
• Ventriculoperitoneal Shunt

Trial Overview The study compares two treatments for infant hydrocephalus: a traditional shunt insertion versus an endoscopic procedure that might avoid the need for a shunt. The goal is to see which treatment leads to better intellectual development and brain structure.

Participant Groups

Group I: Ventriculoperitoneal Shunt Active Control 1 Intervention

Subjects randomized to this arm will undergo a Ventriculoperitoneal Shunt procedure for treatment of Hydrocephalus

Group II: ETV+CPC Active Control 1 Intervention

Subjects randomized to this arm will undergo an ETV+CPC procedure for treatment of Hydrocephalus

Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) is already approved in European Union, United States, Switzerland for the following indications:

Approved in European Union as Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization for:

• Obstructive hydrocephalus
• Non-communicating hydrocephalus

Approved in United States as ETV+CPC for:

• Hydrocephalus in infants
• Postinfectious hydrocephalus
• Posthemorrhagic hydrocephalus

Approved in Switzerland as Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization for:

• Early childhood hydrocephalus
• Infantile hydrocephalus

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Penn State University

Collaborator

Trials

380

Recruited

131,000+

Findings from Research

In a North American study of 91 infants with hydrocephalus, combined endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) resulted in 57% of patients requiring no further treatment for hydrocephalus after one year, demonstrating its effectiveness.

The procedure was found to be safe, with only minor complications reported and no deaths, suggesting that ETV/CPC could be a durable alternative to traditional shunt placement for treating hydrocephalus in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment for infant hydrocephalus: a prospective North American series. Stone, SS., Warf, BC.[2022]

The failure rate of endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) for treating infant hydrocephalus is approximately 44%, with lower-middle-income countries showing a significantly lower failure rate (32%) compared to high-income countries (53%).

The study also reports very low rates of perioperative mortality (0.1%), intraoperative abandonment (4%), and cerebrospinal fluid infections (0.04%), indicating that ETV+CPC is a relatively safe procedure, although the overall evidence quality is low, suggesting a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis. Ben-Israel, D., Mann, JA., Yang, MMH., et al.[2022]

Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) effectively treated hydrocephalus in most infants under 1 year old, with 59% achieving long-term shunt freedom, especially in those older than 2.5 months.

Younger infants (under 2.5 months) with prior cerebrospinal fluid diversion and severe ventriculomegaly had a high likelihood of needing a shunt after ETV/CPC, suggesting that surgery may be better delayed for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy with choroid plexus cauterization: predictors of long-term success and comparison with shunt placement for primary treatment of infant hydrocephalus. Warf, BC., Weber, DS., Day, EL., et al.[2023]

ETV revision after initial ETV+CPC failure had a significantly lower 1-year success rate of 29.5% compared to the initial ETV+CPC success rate of 45%, indicating that revising the procedure is less effective.

When compared to shunt placement after ETV+CPC failure, ETV revision also showed a lower success rate (29.5% vs 77.8%), although complication rates were similar across all surgical options, suggesting that while ETV revision is an option, shunting may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy revision after failure of initial endoscopic third ventriculostomy and choroid plexus cauterization. Arynchyna-Smith, A., Rozzelle, CJ., Jensen, H., et al.[2023]

In a study of 710 children with hydrocephalus, the combination of endoscopic third ventriculostomy (ETV) and bilateral choroid plexus cauterization (CPC) showed a significantly higher success rate (66%) compared to ETV alone (47%) in infants younger than 1 year.

The combined ETV-CPC procedure was particularly effective for infants with myelomeningocele (76% success) and nonpostinfectious hydrocephalus (70% success), suggesting it may be a safer and more effective treatment option in regions where shunt dependence poses risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. Warf, BC.[2022]

Endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) shows reasonable safety in infants with hydrocephalus, with no major complications reported in a study of 36 patients, although there were some postoperative infections and unrelated deaths.

The success rate of ETV + CPC was 52% at 12 months, which is lower compared to shunt procedures, and achieving near-complete CPC (≥ 90%) significantly improved outcomes, indicating that surgical technique and experience may play a crucial role in the procedure's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy and choroid plexus cauterization in infants with hydrocephalus: a retrospective Hydrocephalus Clinical Research Network study. Kulkarni, AV., Riva-Cambrin, J., Browd, SR., et al.[2022]

Bilateral pallidotomy (PVP) in patients with severe Parkinson's disease led to severe adverse effects, including depression and worsened motor functions, resulting in the discontinuation of the trial for this procedure.

In contrast, the combination of unilateral pallidotomy and contralateral pallidal stimulation (PVP+PVS) resulted in significant motor improvements without the severe side effects seen in the bilateral procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral pallidotomy for treatment of Parkinson's disease induced corticobulbar syndrome and psychic akinesia avoidable by globus pallidus lesion combined with contralateral stimulation. Merello, M., Starkstein, S., Nouzeilles, MI., et al.[2019]

Surgery for Parkinson's disease, particularly deep brain stimulation, has seen a resurgence due to limitations of current medications and advances in understanding the brain's movement control systems, leading to new insights into the disease's mechanisms.

Emerging surgical techniques like gene therapy, neural transplantation, and nanotechnology show great potential not only for treating Parkinson's disease but also for enhancing our understanding of its underlying causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical insights into Parkinson's disease. Pereira, EA., Aziz, TZ.[2022]

Neurosurgery for movement disorders like Parkinson's disease, essential tremor, and dystonia has proven effective and safe, with traditional methods involving lesion-based surgeries such as thalamotomy and pallidotomy.

High-frequency deep brain stimulation is now preferred over ablative surgery because it achieves similar therapeutic effects without creating permanent brain lesions, preserving brain anatomy and potentially reducing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical treatment of movement disorders. Espay, AJ., Mandybur, GT., Revilla, FJ.[2006]

For patients with advanced Parkinson's disease who no longer respond to levodopa, deep brain stimulation is emerging as the most effective and safe treatment option.

Cell transplantation has not yet proven to be a successful alternative for these patients, highlighting the need for effective neurosurgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurosurgical intervention for Parkinson's disease: an update. Kolchinsky, A.[2019]

Thalamotomy and posteroventral pallidotomy (PVP) are effective surgical procedures for alleviating motor symptoms in Parkinson's disease, with thalamotomy showing greater improvement in tremor compared to PVP.

Both procedures significantly reduce rigidity and dopa-induced dyskinesia, and PVP also has implications for improving psychological symptoms, bradyphrenia, and emotional changes in patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic surgery and Parkinson's disease. Narabayashi, H.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment for infant hydrocephalus: a prospective North American series. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy with choroid plexus cauterization: predictors of long-term success and comparison with shunt placement for primary treatment of infant hydrocephalus. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy revision after failure of initial endoscopic third ventriculostomy and choroid plexus cauterization. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Endoscopic third ventriculostomy and choroid plexus cauterization in infants with hydrocephalus: a retrospective Hydrocephalus Clinical Research Network study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Bilateral pallidotomy for treatment of Parkinson's disease induced corticobulbar syndrome and psychic akinesia avoidable by globus pallidus lesion combined with contralateral stimulation. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Surgical insights into Parkinson's disease. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Surgical treatment of movement disorders. [2006]

10. United States pubmed.ncbi.nlm.nih.gov

Neurosurgical intervention for Parkinson's disease: an update. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic surgery and Parkinson's disease. [2018]