Venous Stenting Evaluation in Patients With Intracranial Hypertension Under Long-term Acetazolamide (DIVEIINLATE)

Direct Intracranial Venous Stenting Evaluation in Patients With Idiopathic INtracranial Hypertension Under Long-term Treatment With AceTazolamidE With Inadequate Treatment Response

This study is aimed at patients suffering from long term intracranial hypertension (caracterized by visual loss, chronic headache and/or tinnitus), receiving acetazolamide for more than 1 year, having inadequate response to treatment (untolerable side effects or insufficient efficacy).

The goal is to evaluate if stenting of a specific vein in the brain could decrease the hypertension and improve associated symptoms. Patients will be randomly assigned in either best medical care group (recommended medication associated with weight loss) or interventional group (best medical care + stenting of the specific vein) and will undergo specific follow-up visits after 1, 3 and 12 months.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Intracranial Hypertension (IIH)
• Intervention / Treatment: Drug: Acetazolamide; Device: Stent (Tentos 4F or Precise ProRX)

Detailed Description

The DIVE-IIN-LATE trial is a multicenter randomized controlled trial designed to evaluate whether transverse sinus stenting is more effective than best medical therapy alone for patients with idiopathic intracranial hypertension (IIH) treated with acetazolamide for more than one year. The study targets patients diagnosed with IIH with bilateral transverse sinus stenosis or unilateral stenosis of the dominant transverse sinus with a hypoplastic contralateral sinus.

Idiopathic intracranial hypertension is, in most cases, associated with narrowing of the transverse sinus vein, which may be the cause of increased intracranial blood pressure, resulting in the accumulation and increase in intracranial fluid pressure. This increased pressure is thought to be responsible for papilledema, chronic headaches, and tinnitus, among other symptoms.

Restoring a normal luminal diameter of the transverse sinus using a stent could therefore allow for the rapid restoration of normal intracranial pressures and an improvement in various symptoms.

Stent implantation in the transverse sinus is now part of standard care, but no large-scale clinical trial has formally established the superiority of the technique compared to the standard of care (drug therapy combined with weight loss). This study aims to provide evidence on the potential benefits of transverse venous sinus stenting as a treatment option for patients with idiopathic intracranial hypertension, which could significantly change the current management approach of this disease.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fédérico CAGNAZZO, MD, PhD; Phone Number: +33 467 337 532; Email: f-cagnazzo@chu-montpellier.fr
• Study Contact Backup: Name: Vincent COSTALAT, MD, PhD; Phone Number: +33 467 337 532; Email: v-costalat@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Chu De Montpellier Hopital Gui De Chauliac
    • Contact: Vincent COSTALAT, MD, PhD; Phone Number: +33 467 337 532; Email: v-costalat@chu-montpellier.fr
  • Reims, France, 51092
    • Not yet recruiting
    • CHU de Reims
    • Contact: Sébastien SOIZE, MD, PhD; Phone Number: +33 326 788 764; Email: ssoize@chu-reims.fr
  • Toulouse, France, 31000
    • Not yet recruiting
    • CHU de Toulouse
    • Contact: Guillaume BELLANGER, MD, PhD; Phone Number: +33 561 772 339; Email: bellanger.g@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is ≥ 18 years old at inclusion.
2. Subject with definite diagnosis of IIH satisfying the modified Dandy criteria (A to E) ) at the time of initial diagnosis, under BMM including ACZ for more than 1 year
3. Patient with elevated intracranial pressure defined as > 25 cm H20 or 18 mmHg
4. Subject with intracranial TVS stenosis on dominant transverse sinus and hypoplastic contralateral one (or bilateral TVS stenosis) diagnosed on MRI
5. Normal MRI findings excepted intracranial TVS stenosis or IIH related abnormalities
6. Patient having received information about data collection and having signed and dated an Informed Consent Form
7. Subjects must be able to attend all scheduled visits and to comply with all trial procedures
8. Subjects must be covered by public health insurance

Exclusion Criteria:

1. Patients receiving topiramate in the previous month
2. Known contrast product, Nickel, titanium allergy
3. Exposure to an oral drug (other than ACZ), substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis (lithium, vitamin A, tetracycline and related compounds)
4. History of intracranial venous thrombosis or intracranial neoplasia
5. Fulminant decrease of visual acuity due to the IIH defined as a visual loss (of the most seriously impaired eye) of at least 3/10 (from corrected vision) within 4 weeks, in absence of any other ophthalmologic pathology and Mean Deficit of visual field superior to -10 dB
6. Optic nerve atrophy
7. Amblyopia
8. Refractive error greater ±8 sphere or more than ±3 in cylinder in either eye if there are abnormalities in funduscopy (optic disc tilt, staphyloma), previous glaucoma, other disorders causing visual loss
9. Pregnancy: if a woman is of childbearing potential a urine or serum beta HCG test is positive
10. Patient with a severe or fatal comorbidity that will likely prevent improvement or follow-up or that will render the procedure unlikely to benefit the patient.
11. Evidence of intracranial hemorrhage (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.)
12. Life expectancy under 6 months
13. Patients with renal failure (creatinine > 1.5 mg/dl and/or creatinine clearance < 60 mL/min, except if patient is already on hemodialysis)
14. History of previously implanted intra-cranial sinus stent
15. Previous gastric bypass surgery AAP-DGOS PHRC-N 22_0175 CHU DE MONTPELLIER Pr Costalat Vincent/Pr Ducros Anne Version n°2.2 date 25/03/2025 Page 28 sur 63
16. Contra-indication to general anesthesia
17. Contra-indication to aspirin, clopidogrel or other P2Y12 anti-aggregant
18. History of chronic obstructive pulmonary disease or other severe respiratory disease
19. History of deep vein thrombosis or pulmonary embolism
20. History of atrial fibrillation or other risks of stroke
21. Cerebral vascular lesions (arteriovenous malformation, arteriovenous fistula, aneurysms, significant stenosis of extra- or intra-cranial vessels other than the targeted venous sinus stenosis, intracranial artery dissection, etc.).
22. Anatomical anomaly of the venous sinus which would prevent safe catheterization and stenting
23. Subject who are in a dependency or employment with the sponsor or the investigator
24. Participation in another clinical trial or administration of an unapproved drug within the last 4 weeks before the screening date
25. Subject protected according to the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acetazolamide; Acetazolamide and recommended weight loss	Drug: Acetazolamide; Acetazolamide will be maintained and weight loss will be recommended; Other Names: Weight loss
Experimental: Experimental (stenting, neuro-radiological intervention); Stenting of the transverse sinus vein	Device: Stent (Tentos 4F or Precise ProRX); Transverse venous sinus will be stented by neuroradiological intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with normalization of intra-cranial pressure	Rate of patients with normalization of intra-cranial pressure (defined as ≤ 25 cm H20 or 18 mmHg)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly headache days	Change in monthly headache days (within the last month) reported on patients' dairy	3 and 12 months
Visual field	Change in decibel of Mean Deficit visual field assessed on automated perimetry in both eyes with Humphrey Field Analyzer SITA Standard 24-2 test pattern. Each participant will have at least 2 initial visual field examinations conducted at least 30 minutes apart. The 2 Perimetric Mean Deviation (PMD) measurements will be averaged.	3 and 12 months
Patient's autonomy	Change in quality of life assessed on EQ5D questionnaire	3 and 12 months
Discontinuation of Acetazolamide	Percentage of patients discontinuing ACZ in the stenting group without papillary edema recurrence	1 month
Discontinuation of Acetazolamide	Percentage of patients discontinuing ACZ in the stenting group without papillary edema recurrence	3 months
Headache	Change in mean HIT-6 grading scale score (patient's questionnaire containing 6 questions to evaluate the severity of headache)	3 and 12 months
Tinnitus	Change in THI (Tinnitus Handicap Inventory) score	3 and 12 months
Visual acuity	Change of visual acuity score evaluated on ETDRS (far vision) at 4 meters and reproducible lighting using the best optical correction	3 and 12 months
Visual acuity	Change of visual acuity score evaluated on Parinaud scale (near vision) using the best optical correction	3 and 12 months
Papilledema	Change of papilledema assessed on Frisen score on OCT	3 and 12 months
Papilledema	Change of papilledema assessed on RNFL on OCT	3 and 12 months
Patient's cognition	Change in Montreal Cognitive Assessment (MoCA)	3 and 12 months
Cognition	Change in Trail Making Test (TMT)	3 and 12 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Direction Générale de l'Offre de Soins
• Investigators: Study Director: Vincent COSTALAT, MD, PhD, University hospital of Montpellier, FRANCE

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): January 5, 2029
• Study Completion (Estimated): January 5, 2030

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 22, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Tinnitus; Intracranial hypertension; Chronic headache; Stenting; Papillary edema; Transverse sinus vein
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Headache Disorders; Intracranial Hypertension; Tinnitus; Pseudotumor Cerebri; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Equipment and Supplies; Thiadiazoles; Prostheses and Implants; Acetazolamide; Stents
• Other Study ID Numbers: RECHMPL 23_0410; IDRCB (Other Identifier: 2025-A01568-41)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No