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:

• Age ≥ 18 at the time of informed consent.
• 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).
• 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.
• 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.

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

• 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 > 21 mmHg after induced hyperemia via dopamine or papaverine using a 4 Fr or less catheter or pressure wire.

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

• Renal pole-to-pole length > 8cm (per visual estimate).
• Target lesion length ≤ 16mm per vessel (per visual estimate).
• Renal artery vessel diameter ≥ 5.0mm and ≤ 7.0mm (per visual estimate).
• Lesion originating ≤ 15mm of the renal ostium.

General Exclusion Criteria:

• Subject's estimated life expectancy is < 12 months.
• Subject has a history of transplanted kidney(s), has had another recent organ transplant or polycystic kidney disease.
• Subject with estimated glomerular filtration rate (eGFR) ≤ 25 mL/min/1.73 m2
• Subject has a history of bleeding diathesis or coagulopathy or refuses blood transfusions.
• Subject has a known contraindication to heparin, aspirin, thienopyridine, other anti-coagulant/antithrombotic therapies, contrast media, stainless steel, and/or polytetrafluoroethylene (PTFE).
• Subject has had a previous renal bypass operation, a bypass is planned, or the target lesion is located within or beyond a bypass graft.
• Subject has received a thrombolytic agent within the past 30 days.
• 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.
• Concurrent enrollment in any investigational trial wherein subject's participation has not been completed.
• 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.
• Subject has suffered a stroke or Transient Ischemic Attack (TIA) in the past 3 months.
• Subject is pregnant, lactating, or is of child-bearing potential and plans to become pregnant during the follow-up trial period.
• Subject with significant valvular disease.
• Subject with known significant proteinuria > 2+ or > 2.0gm/d.
• 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.
• Subject with active sepsis.
• Subject with serum creatinine ≥ 3.0mg/dL.
• Subject with NYHA Class IV at the time of enrollment.
• Subject is on hemodialysis.
• Subject has a history of renal aneurysm.
• Subject with cardiogenic shock.
• Subject with cardiomyopathy.
• Subject has an uncontrolled concurrent illness, including but not limited to ongoing or active infection or active autoimmune disease requiring immunosuppressive therapy.
• 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:

• 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.
• Subject has multiple ipsilateral lesions of the target renal artery that cannot be covered by a single stent.
• There is a previously implanted stent in the target vessel or there is a previously implanted stent in the contralateral vessel < one year.
• Subject has fibromuscular dysplasia, in renal artery and/or other vascular bed.
• The target lesion site is associated with a thrombus.
• Target lesion treated with laser atherectomy, directional atherectomy or other adjuncts to percutaneous balloon angioplasty (PTA).
• Subject has a critical stenotic (> 70%) small accessory renal artery.
• Subject has an abdominal aortic aneurysm > 4.0cm in diameter or a severe atherosclerotic aorta.
• Main renal artery length ≤ 15mm precluding the safe deployment of a covered renal stent.
• Any lesion that would include blocking of renal artery side branch.
• Renal artery stenosis due to dissection of renal artery: spontaneous or traumatic.