Venous Sinus Stenting With the River Stent in IIH

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.

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 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 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.