Endoscopic Treatment vs. Shunt Surgery for Hydrocephalus

(ESTHI Trial)

Recruiting at 21 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether a newer endoscopic procedure, Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC), can treat hydrocephalus in babies as effectively as the traditional Ventriculoperitoneal Shunt surgery. Hydrocephalus, a condition where fluid accumulates in the brain, often affects infants. The trial compares the impact of each treatment on intellectual development and brain health. Babies with noticeable symptoms of hydrocephalus, such as a rapidly growing head or unexplained vomiting, might be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for hydrocephalus.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) procedure is generally well-tolerated. In one study, complications were relatively low, with about 5% of patients experiencing seizures and about 3% having cerebrospinal fluid (CSF) leaks. Another study found that ETV+CPC was successful in 48% of patients after six months, indicating a positive response in many cases.

The Ventriculoperitoneal Shunt has been the traditional treatment for hydrocephalus and has been used for a long time, suggesting its safety for widespread use. However, like any surgery, it carries risks, but healthcare providers generally manage these well.

Both treatments have their pros and cons, and the decision often depends on various factors, including the child's specific condition. It is important to consult a healthcare provider to understand the risks and benefits of each option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments for hydrocephalus in this trial because they offer new approaches compared to traditional methods like ventriculoperitoneal shunt surgery. Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC) is unique because it minimizes the need for implanting hardware in the body, potentially reducing infection risks associated with shunt surgeries. ETV+CPC also targets the root cause by creating a new pathway for cerebrospinal fluid flow and reducing fluid production, which might offer a more sustainable solution. Meanwhile, ventriculoperitoneal shunts remain the standard, but ETV+CPC could provide a less invasive and more natural alternative for managing hydrocephalus.

What evidence suggests that this trial's treatments could be effective for hydrocephalus?

Research has shown that Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization (ETV+CPC), which participants in this trial may receive, can effectively treat hydrocephalus in infants. Studies have found that ETV+CPC manages this condition well, particularly in infants over one month old with noninfectious hydrocephalus, such as aqueductal stenosis. This procedure is less invasive and may lead to fewer long-term problems compared to traditional treatments. Patients who have undergone ETV+CPC have experienced positive outcomes, suggesting it could be a promising option for managing hydrocephalus without needing a permanent shunt. Meanwhile, the Ventriculoperitoneal Shunt, another treatment option in this trial, represents a traditional approach that has been widely used for managing hydrocephalus. ^{1 3 5 6 7}

Who Is on the Research Team?

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

Principal Investigator

Washington University School of Medicine

John Kestle, MD

Principal Investigator

University of Utah

Abhaya Kulkarni, MD

Principal Investigator

University of Toronto

Richard Holubkov, PhD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Trustees of Indiana University

Collaborator

Trials

1

Recruited

1,000+

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36754024/

Endoscopic Third Ventriculostomy with Choroid Plexus ... Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) provides an opportunity for an affordable and less constraining treatment for ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33991213/

Endoscopic third ventriculostomy and choroid plexus ... Choroid plexus cauterization (CPC) in combination with endoscopic third ventriculostomy (ETV) has emerged as an effective treatment for some infants with ...

3. thejns.org thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/32/2/article-p201.xml

Endoscopic third ventriculostomy with choroid plexus ... This study examined long-term outcomes after ventriculoperitoneal shunt (VPS) placement and endoscopic third ventriculostomy (ETV)/choroid ...

4. karger.com karger.com/pne/article/58/1/38/832756/Endoscopic-Third-Ventriculostomy-with-Choroid

Endoscopic Third Ventriculostomy with Choroid Plexus ... A retrospective study analyzed the outcome of hydrocephalus children aged under 12 months old who underwent ETV/CPC between July 2013 and ...

5. journals.lww.com journals.lww.com/neur/fulltext/2021/69002/endoscopic_third_ventriculostomy_and_choroid.38.aspx

Endoscopic Third Ventriculostomy And Choroid Plexus... The likelihood of success following ETV+CPC is the highest among infants older than 1 month, those with noninfectious hydrocephalus (e.g., aqueductal stenosis ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37178026/

Endoscopic third ventriculostomy with choroid plexus ... Conclusions: ETV/CPC successfully treated hydrocephalus in most patients younger than 1 year irrespective of etiology, averting observed ...

7. thejns.org thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/21/3/article-p214.xml

Endoscopic third ventriculostomy and choroid plexus ... The 6-month success rate was 36%. The most common complications included seizures (5.1%) and CSF leak (3.4%). Important predictors of treatment ...