Renal Stent Placement for the Treatment of Renal Artery Stenosis in Patients With Resistant Hypertension

This is a prospective, single-arm, multicenter clinical trial that will take place at up to
25 US/ Outside US (OUS) sites. Primary endpoints have been determined to show the safety,
effectiveness, and clinical outcomes of the iCAST™ RX Stent System. Safety and effectiveness
will be evaluated based on the primary patency rate at 9-months on a per lesion basis
evaluated against a performance goal of published studies with bare-metal stents. The primary
clinical endpoint will assess the improvement in Systolic Blood Pressure (SBP) at 9-months as
compared to baseline Systolic Blood Pressure.

Eligible subjects will undergo a two-week Medical Documentation Screening period to confirm
resistant hypertension (SBP ≥ 155mmHg) while on maximum tolerable doses of ≥ three
anti-hypertensive medications from at least three distinct classes of drugs, one of which
must be a diuretic.

There must be documented clinical evidence to support likelihood of angiographic findings >
80% whether it is Duplex Ultrasound (DUS), Computed Tomography angiogram (CTa), Magnetic
Resonance angiogram (MRa) or other medical evidence. After meeting screening and clinical
eligibility criteria, subjects will undergo a baseline assessment for angiographic
eligibility. After angiographic documentation of a ≥ 80% renal artery stenosis or Fraction
Flow Reserve (FFR) < 0.8 is confirmed, the subject may be enrolled in the trial by placement
of the investigational device.

The 9-month visit will include a follow-up DUS of the target renal artery. If the DUS is
non-diagnostic due to an imaging problem, such as overlying bowel gas or body habitus, a
second DUS may be attempted. If the DUS is indicative of ≥ 60% stenosis as determined by the
core laboratory, or the second DUS remains non-diagnostic, a contrast angiogram will be used
to assess the degree of restenosis of the covered stent(s).

Clinical follow-up visits will be required for all enrolled subjects at 30-days, 9-months,
12-months, 24-months, and 36-months. A 6-month and 18-month visit will occur via telephone to
collect medication usage and Adverse Events (AEs) only. The 36-month clinic office visit will
be required as the final safety visit.

General Inclusion Criteria:

1. Age ≥ 18 at the time of informed consent.

2. Subject or subject's legal representative have been informed of the nature of the
trial, agrees to participate, and has signed an Institutional Review Board
(IRB)/Ethics Committee (EC) approved Informed Consent Form (ICF).

3. Subjects that have bilateral kidneys or a solitary functioning kidney with Renal
Artery Stenosis in at least one kidney and an average Systolic Blood Pressure (SBP) ≥
155mmHg.

4. Subject has a history of maximum tolerable dose of ≥ 3 anti-hypertensive medications
of different classes, one of which must be a diuretic (for at least two weeks prior to
Medical Documentation Screening period).

a. A documented history for a minimum of 3 months showing reasonable and aggressive
efforts to manage hypertension prior to consent. This must include the use of a broad
variety of medications that have been used and failed or not tolerated.

5. Subject must have documented clinical evidence to support likelihood of angiographic
findings > 80% whether it is DUS, CTa, MRa or other medical evidence.

6. New York Heart Association (NYHA) class I, II, or III the time of trial enrollment.

NOTE: When a subject has bilateral Renal Artery Stenosis both of which require stenting, it
is recommended to treat both kidneys with an iCAST™ RX Stent System during the index
procedure. In the event that a subject needs a renal stenting procedure staged for renal
protection, it is important that the Investigator treats the second renal artery with an
iCAST™ RX Stent System after 30 days of the index procedure. If subjects with bilateral
stenosis have only one lesion that meets protocol inclusion criteria that lesion should be
treated per protocol. The recommendation is to NOT treat the second non-qualifying lesion,
however if the operator feels strongly it is indicated, then they should treat per standard
of care after 30-days post index procedure in order to comply with exclusion criteria #10.

Subjects with flash pulmonary edema are allowed into the trial should they meet all other
Inclusion and Exclusion criteria.

Angiographic Anatomic Inclusion Criteria:

1. Angiographic diameter renal artery stenosis ≥ 80% involving unilateral or bilateral
renal arteries.

a. The degree of percent diameter stenosis for all lesions intended to be treated,
must be confirmed via one of the following methods: i. Manual or automated measurement
with calipers ii. Measured Flow Fraction Reserve (FFR) < 0.8 using a pressure wire
iii. Measured translesional peak pressure gradient of > 21mmHg after induced hyperemia
via dopamine or papaverine using a 4Fr or less catheter or pressure wire.

b. Subjects with 60-79% angiographic stenosis who have confirmed FFR < 0.8 may be
enrolled.

2. Renal pole-to-pole length > 8cm (per visual estimate).

3. Target lesion length ≤ 16mm per vessel (per visual estimate).

4. Renal artery vessel diameter ≥ 5.0mm and ≤ 7.0mm (per visual estimate).

5. Lesion originating ≤ 15mm of the renal ostium.

General Exclusion Criteria:

1. Subject's estimated life expectancy is < 12 months.

2. Subject has a history of transplanted kidney(s), has had another recent organ
transplant or polycystic kidney disease.

3. Subject with estimated eGFR ≤ 25mL/min/1.73m2

4. Subject has a history of bleeding diathesis or coagulopathy or refuses blood
transfusions.

5. Subject has a known contraindication to heparin, aspirin, thienopyridine, other
anti-coagulant/antithrombotic therapies, contrast media, stainless steel, and/or
polytetrafluoroethylene (PTFE).

6. Subject has had a previous renal bypass operation, a bypass is planned, or the target
lesion is located within or beyond a bypass graft.

7. Subject has received a thrombolytic agent within the past 30 days.

8. Subject has documented acute pulmonary edema or systolic heart failure with ejection
fraction < 30% and/or hospitalization requiring intubation and ventilation support for
this diagnosis within the previous 90 days or hypertensive emergencies defined as
resulting in organ damage.

9. Concurrent enrollment in any investigational trial wherein subject's participation has
not been completed.

10. Subject has had a planned or anticipated cardiovascular surgical or interventional
procedure outside of the affected renal artery (including, but not limited to, aortic,
renal, cardiac, carotid, femoro-popliteal, and below the knee) within 30 days prior to
the index procedure and prior to completion of the 30 day follow-up.

11. Subject has suffered a stroke or Transient Ischemic Attack (TIA) in the past 3 months.

12. Subject is pregnant, lactating, or is of child-bearing potential and plans to become
pregnant during the follow-up trial period.

13. Subject with significant valvular disease.

14. Subject with known significant proteinuria > 2+ or > 2.0gm/d.

15. Subject with known bilateral upper-extremity arterial stenosis that result in
spuriously low arm pressures or without the ability to gain reliable blood pressure
measurements in at least one upper extremity.

16. Subject with active sepsis.

17. Subject with serum creatinine ≥ 3.0mg/dL.

18. Subject with NYHA Class IV at the time of enrollment.

19. Subject is on hemodialysis.

20. Subject has a history of renal aneurysm.

21. Subject with cardiogenic shock.

22. Subject with cardiomyopathy.

23. Subject has an uncontrolled concurrent illness, including but not limited to ongoing
or active infection or active autoimmune disease requiring immunosuppressive therapy.

24. Any subject with clinically significant cardiovascular, respiratory, neurologic,
hepatic, endocrine, major systematic disease, making implementation or interpretation
of the protocol or protocol results difficult or who in the opinion of the
investigator would not be a good candidate for enrollment.

Angiographic Anatomic Exclusion Criteria:

1. The planned site of intervention is totally occluded or has an anatomic configuration
likely to prohibit adequate dilatation, and/or passage or implantation of the
investigational device.

2. Subject has multiple ipsilateral lesions of the target renal artery that cannot be
covered by a single stent.

3. There is a previously implanted stent in the target vessel or there is a previously
implanted stent in the contralateral vessel < one year.

4. Subject has fibromuscular dysplasia, in renal artery and/or other vascular bed.

5. The target lesion site is associated with a thrombus.

6. Target lesion treated with laser atherectomy, directional atherectomy or other
adjuncts to PTA.

7. Subject has a critical stenotic (> 70%) small accessory renal artery.

8. Subject has an abdominal aortic aneurysm > 4.0cm in diameter or a severe
atherosclerotic aorta.

9. Main renal artery length ≤ 15mm precluding the safe deployment of a covered renal
stent.

10. Any lesion that would include blocking of renal artery side branch.

11. Renal artery stenosis due to dissection of renal artery: spontaneous or traumatic.