Intracranial Venous Stenting Evaluation in Patients With Idiopathic Intracranial Hypertension in the Early Phase

Official title

Direct Intracranial Venous Stenting Evaluation in Patients With Idiopathic INtracranial Hypertension in the Early Phase

Overview

This study is aimed at patients suffering from recently discovered intracranial hypertension, caracterized by visual loss, chronic headache and/or tinnitus. 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 car + stenting of the specific vein) and will undergo specific follow-up visits after 1, 3 and 12 months.

Detailed description

The DIVE-IIN-EARLY trial is a multicenter randomized controlled trial designed to evaluate whether transverse venous sinus stenting is more effective than best medical therapy alone as first-line treatment for patients with idiopathic intracranial hypertension (IIH). The study targets patients with a new diagnosis of 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 gain). 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 to this disease.

Usual medication for this condition is acetazolamide, but it's efficacy as well as it's tolerance is mostly poor. By proposing stenting in the early phase of the disease, one could avoid long term symptoms such as loss of vision and chronic headache.

Interventions

• Drug Best medical care
  Acetazolamide will be introduced at the time of papilledema discovery. Weight loss will be recommended.
• Device Intervention (stenting)
  Transverse venous sinus will be stented by neuro-radiological intervention

Primary outcome measures

• Rate of patients with resolved papilledema and normalization of intra-cranial pressure [Time frame: 3 months]

Secondary outcome measures (9)

• HIT-6 grading scale score [Time frame: 3 and 12 months]
• Monthly headache days [Time frame: 3 and 12 months]
• THI score [Time frame: 3 and 12 months]
• Visual field [Time frame: 3 and 12 months]
• Visual acuity [Time frame: 3 and 12 months]
• Papilledema [Time frame: 3 and 12 months]
• Patient's autonomy [Time frame: 3 and 12 months]
• Patient's cognition [Time frame: 12 months]
• Cognition [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Subject is ≥ 18 years old at inclusion.
• Subject with definite new diagnosis (˂ 3 months) of IIH satisfying the modified Dandy criteria (A to E)
• Subject with intracranial TVS stenosis on dominant transverse sinus and hypoplastic contralateral one (or bilateral TVS stenosis) diagnosed on MRI
• Normal MRI findings excepted intracranial TVS stenosis or IIH related abnormalities
• Subject with ophthalmologic IIH symptoms and signs (RNFL ≥ 130 µm, Frisen score ≥ 2, and absence of differential diagnostic)
• Subject without macular ganglion cells atrophy seen on OCT
• Patient having received information about data collection and having signed and dated an Informed Consent Form
• Subjects must be able to attend all scheduled visits and to comply with all trial procedures
• Subjects must be covered by public health insurance

Exclusion criteria

• Subject previously treated with acetazolamide for IIH
• Known contrast product, Nickel, titanium allergy
• Exposure to an oral drug, substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis (lithium, vitamin A, tetracycline and related compounds)
• History of intracranial venous thrombosis or intracranial neoplasia
• 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
• Macular ganglion cells atrophy seen on OCT
• Optic nerve atrophy
• Amblyopia
• 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
• Pregnancy: if a woman is of childbearing potential a urine or serum beta HCG test is positive
• 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.
• Evidence of intracranial hemorrhage (subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), etc.)
• Life expectancy under 6 months
• Chronic IIH
• Patients with renal failure (creatinine > 1.5 mg/dl and/or creatinine clearance < 60 mL/min, except if patient is already on hemodialysis)
• History of previously implanted intra-cranial sinus stent
• Previous gastric bypass surgery
• Contra-indication to general anesthesia
• Contra-indication to aspirin, clopidogrel or other P2Y12 anti-aggregant
• History of chronic obstructive pulmonary disease or other severe respiratory disease
• History of deep vein thrombosis or pulmonary embolism
• History of atrial fibrillation or other risks of stroke
• 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.).
• Anatomical anomaly of the venous sinus which would prevent safe catheterization and stenting
• Subject who are in a dependency or employment with the sponsor or the investigator
• Participation in another clinical trial or administration of an unapproved drug within the last 4 weeks before the screening date
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 3 centers

• CHU de Montpellier Hôpital Gui de Chauliac — Montpellier
• CHU de REIMS — Reims
• CHU de Toulouse — Toulouse

Identifiers

NCT: NCT06919744 · RECHMPL 23_0430 · 2024-A02444-43

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗