Clinical trial NCT03556085: Venous Sinus Stenting With the River Stent in IIH
Official title: Clinical Evaluation of the Serenity River Stent System to Treat Idiopathic Intracranial Hypertension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Idiopathic Intracranial Hypertension
Keywords: idiopathic intracranial hypertension
venous sinus stenting
Lead sponsor: Serenity Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-14
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, multicenter, single arm, open label clinical study
Primary purpose: TREATMENT

Brief summary: The objective of the study is to show that stenting the transverse-sigmoid sinus with the River stent is safe and has probable benefit to relieve clinical symptoms in subjects with idiopathic intracranial hypertension (IIH).

The study will enroll 39 IIH subjects with moderate to severe visual field loss or severe headaches that have failed medical therapy.

The primary safety endpoint is the rate of major adverse event at 12 months The primary probable benefit endpoint is a composite at 12 months of absence of significant sinus stenosis and clinically relevant improvement.

Detailed description: Study objective: The objective of the study is to show that stenting the transverse-sigmoid sinus with the River stent is safe and has probable benefit to relieve clinical symptoms in subjects with idiopathic intracranial hypertension (IIH)

Investigational product: Serenity River Stent System

Study design: prospective, multicenter, single arm, open label clinical trial

Subject population: IIH subjects with significant (\>50%) stenosis of the transverse-sigmoid sinuses and moderate to severe visual field loss or severe headaches that have failed medical therapy. In the absence of this trial, subjects would have been offered a surgical treatment of IIH such as sinus stenting with an off-label device, cerebrospinal fluid shunting, or optic nerve sheath fenestration by the treating physician.

* For subjects with visual field loss: if moderate to severe visual field loss (mean deviation between -6db and -30 db) for at least 2 weeks despite escalation of acetazolamide to 1000 mg twice a day or if the visual field deteriorates by more than 2 db during treatment, or treatment intolerance.
* For subjects with headaches: if they have severe headaches (HIT \> 59) for at least 4 weeks despite treatment with topiramate 100 mg twice a day or other headache medication, or treatment intolerance.

Enrollment size and sites: 39 subjects will be enrolled in up to 10 US sites.

Primary safety endpoint: Major Adverse Event at 12 months. The MAE is a composite of the following: moderate or severe stroke (NIHSS \> 3), neurological death, perforation or thrombosis of sinus or cerebral vein, device distal embolization, need for target lesion revascularization or need for alternate IIH surgical procedure such as cerebrospinal fluid shunting or optic nerve sheath fenestration.

Primary probable benefit endpoint: a composite at 12 months of:

* Absence of significant (\>50%) stenosis of the stented sinus on retrograde catheter venography and
* Trans-stent pressure gradient \< 8 mm Hg and
* Clinically relevant improvement in the main clinical outcome per specific inclusion criteria and stabilization or better of the other:

  * Headaches: if the specific inclusion criteria was headaches, improvement in the HIT- 6 scale by \> 4 points and improvement or stabilization of visual field.
  * Ophthalmic: if the specific inclusion criteria was visual field loss, improvement of visual field by \> 29% of the baseline value in the study eye, stabilization or improvement in the fellow eye, and improvement or stabilization of headaches.

Study duration and follow-up: The subjects will be followed at 2 weeks, 3 months, 6 months and 12 months. At 12 months, clinical examination, lumbar puncture and retrograde catheter venography with manometry will be performed to evaluate the patency of the treated sinus and the absence of trans-stent pressure gradient. Subjects will be consented to be clinically followed annually for up to 5 years.

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for participation in the study:

1. Subject is \> 18 year-old and has given informed consent.
2. Diagnosis of IIH per Modified Dandy Criteria.
3. CSF opening pressure is \> 25 cm H2O.
4. Radiological examination (magnetic resonance venography (MRV) or computed tomographic venography (CTV)) shows bilateral transverse-sigmoid venous sinus stenosis (\> 50%) or unilateral stenosis of the dominant sinus with contralateral hypoplastic sinus.
5. Presence of IIH clinical symptoms (6. OR 7.)
6. Headaches: Score \> 59 (severe impact) on the HIT-6 scale, refractory to medical therapy (e.g. acetazolamide 1000 mg twice daily, topiramate 100 mg twice daily, or other headache medication) for ≥ 4 weeks, or treatment intolerance OR
7. Visual field loss: defined by perimetric mean deviation (PMD) between -6 dB and -30 dB in one or both eyes (with papilledema Grade \>1) despite at least 2 weeks of medical therapy with acetazolamide 1000 mg twice daily, or if the visual field deteriorates by more than 2 dB during treatment, or treatment intolerance.
8. In the absence of this study, the subject would have been offered a surgical intervention by Optic Nerve Sheath Fenestration (ONSF), Cerebro Spinal Fluid (CSF) shunting procedure, or venous sinus stenting with an off-label device.
9. Catheter manometry shows a pressure gradient \> 8 mm Hg across the transverse sigmoid sinus stenosis.
10. Venographic evidence of sinus stenosis (\> 50%)

Exclusion Criteria:

Subject must be excluded from participation in this study if any of the following criteria are met

1. Subjects presenting with de novo papilledema and severe visual field(VF) deficit (VF loss \> -15db) that requires immediate surgical treatment without prior attempt of medical therapy.
2. Currently has or plans to have an implanted CSF shunt.
3. History of previously implanted intra-cranial sinus stent.
4. Transverse-sigmoid sinus vessel size \<5 mm or \>10 mm.
5. Creatinine \> 1.5 mg/dl and/or creatinine clearance \< 60 mL/min (except if patients is already on hemodialysis).
6. Allergic to imaging contrast media (iodine or gadolinium) despite premedication.
7. Allergic to nitinol or nickel.
8. Contra-indication to general anesthesia.
9. Contra-indication to aspirin, clopidogrel or other anticoagulant.
10. Hypercoagulable state (Factor V Leiden, Protein C or S deficiency, Anticardiolipin antibodies, Lupus anticoagulant, B2-glycoprotein-1 antibodies, or Hyperhomocysteinemia).
11. Currently requiring full anti-coagulation for other medical reasons, such as atrial fibrillation (AF), artificial valves, deep vein thrombosis pulmonary embolism, etc.
12. History of stroke or transient ischemic attack (TIA).
13. History of AF or other risks of stroke.
14. History of deep vein thrombosis or pulmonary embolism.
15. History of severe chronic obstructive pulmonary disease or other severe respiratory disease.
16. History of severe carotid atherosclerotic disease.
17. History of heart failure, dilated cardiomyopathy, or congenital heart conditions, etc. that are at high thrombogenic risk.
18. History of uncontrolled diabetes.
19. Use (oral) of tetracycline derivative, retinoid or vitamin A during the last 3 months.
20. Cerebral vascular lesions (arteriovenous malformation (AVM), arteriovenous fistula, aneurysms, significant stenosis of extra- or intra-cranial vessels other than the targeted venous sinus stenosis,intracranial artery dissection, etc.).
21. Patient has visions loss due to other disease (e.g. cataract, macular degeneration, glaucoma, etc.).
22. Inability to provide reliable and reproducible visual field examinations (\>15% false positive errors and/or failure to maintain fixation for eye monitoring).
23. For female subject of child bearing potential, pregnant or not willing to use contraception for 12 months.
24. Presence of a physical, mental or social condition that could prevent adequate one-year follow-up (homelessness, drug dependency, anticipation of moving far away, life threatening disease, terminal illness).
25. Anatomical anomaly of the venous sinus which would prevent safe catheterization and stenting (e.g multi-channel sinus)
26. Currently enrolled in a premarket investigational study. Enrollment in a post market study that does not impact the River™ Stent procedure or device is allowed.

Primary outcomes:
measure: Major Adverse Event (MAE)
timeFrame: 12 months
measure: Clinical improvement with no restenosis of the venous sinus
timeFrame: 12 months
Secondary outcomes:
measure: Individual components of MAE.
timeFrame: 12 months
measure: Cerebrospinal fluid (CSF) opening pressure at 12 months
timeFrame: 12 months
measure: Stent patency at 12 months
timeFrame: 12 months
measure: Medications
timeFrame: 12 months
measure: Headaches
timeFrame: 12 months
measure: Papilledema
timeFrame: 12 months
measure: Visual acuity
timeFrame: 12 months
measure: Retinal Nerve Fiber Layer Thickness
timeFrame: 12 months
measure: Tinnitus
timeFrame: 12 months
measure: Quality of Life SF-12
timeFrame: 12 months
measure: Quality of Life NEI-VFQ-25
timeFrame: 12 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Baptist Health
state: Florida
city: Buffalo
country: United States
facility: UB Neurosurgery
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Northwell Health
name: Athos Patsalides, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Albuquerque FC, Gross BA, Levitt MR. Time to re-assess the treatment of idiopathic intracranial hypertension. J Neurointerv Surg. 2016 Jun;8(6):549-50. doi: 10.1136/neurintsurg-2016-012460. No abstract available.
citation: Abubaker K, Ali Z, Raza K, Bolger C, Rawluk D, O'Brien D. Idiopathic intracranial hypertension: lumboperitoneal shunts versus ventriculoperitoneal shunts--case series and literature review. Br J Neurosurg. 2011 Feb;25(1):94-9. doi: 10.3109/02688697.2010.544781.
citation: Aguilar-Perez M, Martinez-Moreno R, Kurre W, Wendl C, Bazner H, Ganslandt O, Unsold R, Henkes H. Endovascular treatment of idiopathic intracranial hypertension: retrospective analysis of immediate and long-term results in 51 patients. Neuroradiology. 2017 Mar;59(3):277-287. doi: 10.1007/s00234-017-1783-5. Epub 2017 Mar 2.
citation: Ahmed RM, Wilkinson M, Parker GD, Thurtell MJ, Macdonald J, McCluskey PJ, Allan R, Dunne V, Hanlon M, Owler BK, Halmagyi GM. Transverse sinus stenting for idiopathic intracranial hypertension: a review of 52 patients and of model predictions. AJNR Am J Neuroradiol. 2011 Sep;32(8):1408-14. doi: 10.3174/ajnr.A2575. Epub 2011 Jul 28.
citation: Dinkin MJ, Patsalides A. Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial. J Neuroophthalmol. 2017 Jun;37(2):113-121. doi: 10.1097/WNO.0000000000000426.
citation: Kanagalingam S, Subramanian PS. Cerebral venous sinus stenting for pseudotumor cerebri: A review. Saudi J Ophthalmol. 2015 Jan-Mar;29(1):3-8. doi: 10.1016/j.sjopt.2014.09.007. Epub 2014 Sep 27.
citation: Dinkin MJ, Patsalides A. Venous Sinus Stenting for Idiopathic Intracranial Hypertension: Where Are We Now? Neurol Clin. 2017 Feb;35(1):59-81. doi: 10.1016/j.ncl.2016.08.006.