COLLABORATORS

Dear Collaborators, on this page you will find the key facts of the ENDOVEST trial for quick reference, together with the most important study documents for download. If you are considering joining ENDOVEST as a site, please do not hesitate to contact us.

BACKGROUND

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition of older age, characterised by the clinical triad of gait and balance disturbance, cognitive decline and urinary dysfunction. It is frequently underdiagnosed, yet it is often described as the only potentially reversible cause of dementia.

The current standard of care is the ventriculoperitoneal shunt (VPS). While effective, it relies on permanently implanted hardware and carries a substantial rate of complications and revision surgery. Endoscopic third ventriculostomy (ETV) offers an alternative that creates an additional cerebrospinal fluid outflow pathway without implanted hardware. Existing evidence suggests comparable clinical efficacy with markedly lower surgical morbidity, but high-quality randomised data are lacking. ENDOVEST is designed to close this gap.

DESIGN

ENDOVEST is a national, multicentre, two-arm, open-label randomised controlled trial with 1:1 allocation. A total of 150 patients (75 per arm) will be enrolled over a study period of approximately four years.

CROSS-OVER

Patients in the ETV arm may cross over to a VPS if the treating physician judges that no clinical and/or radiological treatment success has been achieved. The decision and its reason are documented at follow-up. Following the intention-to-treat principle, these patients remain part of the ETV arm in the primary analysis.

OBJECTIVES AND OUTCOMES

The trial has two co-primary objectives, both assessed at 12 months:

to demonstrate the superiority of ETV over VPS with respect to the complication rate;
to demonstrate the non-inferiority of ETV compared with VPS with respect to clinical improvement, measured by the Japanese iNPH grading scale.

A two-point change on the iNPH grading scale is considered clinically relevant; the non-inferiority margin is set at 1.5 points (tested one-sided at 5%).

Secondary endpoints include:

Functional and clinical outcome: Hellström score, MoCA, Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS)
Gait and balance: Timed-Up-and-Go, tandem walk, 10-metre walk and balance testing (as part of the Hellström test)
Neuropsychological testing: full battery (see below)
Radiological variables: iNPH-Radscale, ventricle volumetry, CSF flow and perfusion measures, and the presence of a flow-void at the third ventricular floor (in the case of ETV)
Patient-reported outcomes: 15D and Beck Depression Inventory (BDI)
Rate of revision surgery and mortality

ELIGIBILITY

Inclusion criteria

Age > 40 years
Gait and/or balance disturbance, plus cognitive impairment and/or urinary dysfunction
Ventricular enlargement (Evans index > 0.3), not attributable to cerebral atrophy or congenital enlargement
Clinical improvement in at least one main symptom after spinal tap test (20–40 ml CSF withdrawal)
Written informed consent

Exclusion criteria

Age ≤ 40 years
Antecedent head trauma, intracranial haemorrhage, meningitis, or other cause of secondary hydrocephalus
Macroscopic obstruction to CSF flow
Other neurologic, psychiatric or general medical conditions sufficient to explain the presenting symptoms
Prior procedures involving the ventricular system
Other associated dementia syndromes
Incapacity to walk
Pregnancy or breastfeeding

PARTICIPATING AS A STUDY CENTRE

ENDOVEST is open to any neurosurgical department that routinely performs both ETV and VPS. A dedicated gait laboratory is not required: sites without instrumented gait analysis perform the simpler Hellström-based battery (Timed-Up-and-Go, tandem walk, 10-metre walk and balance).

PARTICIPATING CENTRES

Switzerlang: Basel: Universitätsspital Basel (coordinating centre)

Chur: Kantonsspital Graubünden
Lausanne: Centre hospitalier universitaire vaudois

Lucerne: Kantonsspital Luzern

Aarau: Kantonsspital Aarau

Bern: Inselspital Bern

International centres that have agreed to participate but are not yet recruiting:

Denmark: Copenhagen

Germany: Freiburg

VISIT SCHEDULE

ENDOVEST comprises seven study visits, from screening and baseline through surgery, hospitalisation and follow-up at 2, 6 and 12 months. The full schedule of assessments is shown below.

NEURPSYCHOLOGICAL ASSESSMENT BATTERY

Administered by a neuropsychologist at baseline and 12-month follow-up:

Attention: Test of Attentional Performance (TAP) — Alertness and Divided Attention subtests; Digit Span forward; Corsi Block-Tapping forward
Processing speed: Trail Making Test A; Stroop test (trial 1)
Executive function: Digit Span backward; Corsi Block-Tapping backward; Trail Making Test B; semantic fluency; phonemic fluency; Stroop test (trial 3); figural fluency; TAP — Flexibility subtest
Verbal memory: Verbal Learning and Memory Test (VLMT)
Visual memory: Rey–Osterrieth Complex Figure — recall
Language: Boston Naming Test
Visuoconstruction: Rey–Osterrieth Complex Figure — copy

DOWNLOADS

EMINENT Protocol V4.0.pdf

SOP EMINENT-ICH RCT 001_informing-and-consenting_3.0.2

SOP EMINENT-ICH RCT 002_reporting-of-serious-adverse-events_2.3.0

SOP EMINENT-ICH RCT 003_blood-sample-handling-and-storage_1.0.0

SOP EMINENT-ICH RCT 004_sop-minimal-invasive-image-guided-endoscopic-surgery

SOP EMINENT-ICH 005_sop-eminent-ich-005-outcome-assessment-via-telephone-interv

SAE Poster EMINENT

ELECTRONIC DATA CAPTURE

Data are captured electronically in REDCap.

VIDEO

Dr. Florian Ebel and Fabian Häfliger explaining the trial in greater detail:

MONITORING AND REGISTRATION

The required model is:Monitoring is performed by the CRO (Department of Clinical Research, DKF, University Hospital Basel). The trial is registered on ClinicalTrials.gov (NCT06488248).

CONTACT

Clinical Neurosurgical Research Network (CNRN), Department of Neurosurgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
Email: cnrn@usb.ch
Phone: +41 61 265 71 24.