← Product Code NIN · P060006

# BOSTON SCIENTIFIC EXPRESS SD RENAL MONORAIL PREMOUNTED STENT SYSTEM (P060006)

_Boston Scientific Corp · NIN · Dec 11, 2008 · Cardiovascular · APPR_

**Canonical URL:** https://fda.innolitics.com/device/P060006

## Device Facts

- **Applicant:** Boston Scientific Corp
- **Product Code:** NIN
- **Decision Date:** Dec 11, 2008
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Cardiovascular
- **Attributes:** Therapeutic

## Indications for Use

The Express™ SD Monorail® Premounted Stent System (Express SD) is indicated for use as an adjunct to percutaneous transluminal renal angioplasty (PTRA) of a single de novo or restenotic atherosclerotic lesion (≤ 15 mm in length) of the renal artery, located within 5 mm of the opacified aortic lumen, with a reference vessel diameter of 4.0-7.0 mm to assist in the maintenance of vessel patency.

## Device Story

The Express SD is a balloon-expandable, 316L stainless steel stent premounted on a Monorail delivery system. Used in renal artery stenting procedures, the device is deployed via a balloon dilation catheter to maintain vessel patency in atherosclerotic renal arteries. Operated by physicians in clinical settings, the device is guided fluoroscopically to the target lesion. The stent provides structural scaffolding to the ostium of the renal artery. Clinical benefits include reduced restenosis rates compared to PTRA alone, improved renal hemodynamic parameters (RAR, PSV), and potential blood pressure control. The device is supplied sterile and is intended for single use.

## Clinical Evidence

Prospective, multi-center, single-arm RENAISSANCE trial (N=100 subjects, 117 lesions). Primary endpoint: 9-month binary in-stent restenosis rate (21.3%) compared to a 40% performance goal. Secondary endpoints included technical success (99.1%), procedural success (99.0%), and major adverse events (10.5% at 9 months). No device-related deaths or stent thrombosis reported. Significant improvements observed in systolic blood pressure and hemodynamic markers (RAR, PSV).

## Technological Characteristics

Stent: 316L surgical stainless steel, laser-cut sinusoidal bands. Delivery system: Monorail, dual-lumen coaxial catheter, DynaLEAP balloon material. Nominal burst pressure 10 atm, rated burst pressure 14 atm. Radiopaque marker bands. Sterilization: Ethylene oxide (ISO 11135). Biocompatibility: ISO 10993-1 compliant.

## Regulatory Identification

Stent, Renal -- a metal scaffold placed via a delivery catheter into the renal artery to maintain the lumen

## Reference Devices

- Express² Balloon Expandable Coronary Stent System ([P020009](/device/P020009.md))
- Liberté Stent ([P040016](/device/P040016.md))

## Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

## 1. General Information

Device Generic Name: Renal Stent with Delivery System

Device Trade Name: Express™ SD Renal Monorail® Premounted Stent System

Applicant’s Name and Address: Boston Scientific Corporation
One Boston Scientific Place
Natick, MA 01760

Premarket Approval (PMA) Application Number: P060006

Date of Panel Recommendation: None

Date of Notice of Approval to Applicant: August 8, 2008

## 2. Indications for Use

The Express™ SD Monorail® Premounted Stent System (Express SD) is indicated for use as an adjunct to percutaneous transluminal renal angioplasty (PTRA) of a single de novo or restenotic atherosclerotic lesion ($\leq 15$ mm in length) of the renal artery, located within 5 mm of the opacified aortic lumen, with a reference vessel diameter of 4.0-7.0 mm to assist in the maintenance of vessel patency.

## 3. Contraindications

Generally, contraindications for Percutaneous Transluminal Renal Angioplasty (PTRA) are also contraindications for stent placement. Contraindications associated with the use of the Express SD Renal Monorail Premounted Stent System include:

- Patients with uncorrected bleeding disorders or patients who cannot receive anticoagulation or antiplatelet aggregation therapy
- Persons with known allergies to stainless steel or its components (for example nickel)
- A lesion that is within or adjacent to the proximal or distal segments of an aneurysm
- Patients with a target lesion with a large amount of adjacent acute or subacute thrombus
- Patients with excessive vessel tortuosity
- Patients with perforated vessels evidenced by extravasation of contrast media
- Patients with a lesion that cannot be crossed with a wire and/or a balloon catheter

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# 4. Warnings and Precautions

The warnings and precautions can be found in the Express® SD Renal Monorail® Premounted Stent System labeling.

# 5. Device Description

The Express™ SD Renal Monorail® Premounted Stent System (Express SD) consists of a 316L stainless steel, balloon expandable stent premounted on a Monorail balloon delivery system. The device is designed for use in patients with atherosclerotic disease of the renal arteries. A diagram of the stent and stent delivery system is included in Figure 1.

The permanently implanted, balloon expandable Express SD renal stent is constructed entirely out of 316L surgical stainless steel. The seamless tubing is initially extruded to a cylindrical shape, and is then drawn down to the final tubing dimension. The stent is formed by laser cutting a geometric pattern from the tube, followed by cleaning and electropolishing to obtain a smooth rounded stent surface. The stent geometry consists of large and small sinusoidal bands (also referred to as thin and thick struts, respectively) that are interconnected by longitudinally oriented struts. Additional connecting struts are provided to reinforce the three rows of struts of the proximal stent end, resulting in additional scaffolding designed to support the ostium of the renal artery. The stent is radiopaque under high-resolution fluoroscopy.

![img-0.jpeg](img-0.jpeg)
Figure 1: Express® SD Renal Stent

The Express SD renal stent is supplied pre-mounted on a balloon dilation catheter. The Express SD stent delivery system (SDS) is a Monorail catheter and has a dual lumen, coaxial design, with a distally inflatable balloon and a proximal injection port. The second lumen accommodates guidewires up to 0.018". The lengths and diameters of the inflatable balloons range in size (depending on the size of the mounted stent), but all have a nominal burst pressure of 10 atm and a rated burst pressure of 14 atm.

The balloons are constructed of DynaLEAP™, which is the identical material used for other Boston Scientific commercially available balloon catheters and stent delivery systems (e.g. Express² Balloon Expandable Coronary Stent System, P020009 approved September 11, 2002). The delivery catheter is available in working lengths of either 90 or 150cm. The stent is

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centered between radiopaque marker bands attached at the proximal and distal ends of the balloon, to aid in fluoroscopic visualization.

The model numbers of the Express SD included within the scope of this PMA are included in Table 1, below.

Table 1: Express SD Renal Product Matrix Table

|  Device Model Number | Stent Diameter (mm) | Stent Length (mm) | Sheath Compatibility (Fr) | Guide Compatibility (Fr) | Catheter Length (cm)  |
| --- | --- | --- | --- | --- | --- |
|  H74937911-415900 | 4 | 15 | 5 | 6 | 90  |
|  H74937912-419900 | 4 | 19 | 5 | 6 | 90  |
|  H74937911-515900 | 5 | 15 | 5 | 6 | 90  |
|  H74937912-519900 | 5 | 19 | 5 | 6 | 90  |
|  H74937911-614900 | 6 | 14 | 5 | 6 | 90  |
|  H74937912-618900 | 6 | 18 | 5 | 6 | 90  |
|  H74937911-715900 | 7 | 15 | 6 | 7 | 90  |
|  H74937912-719900 | 7 | 19 | 6 | 7 | 90  |
|  H74937911-415150 | 4 | 15 | 5 | 6 | 150  |
|  H74937912-419150 | 4 | 19 | 5 | 6 | 150  |
|  H74937911-515150 | 5 | 15 | 5 | 6 | 150  |
|  H74937912-519150 | 5 | 19 | 5 | 6 | 150  |
|  H74937911-614150 | 6 | 14 | 5 | 6 | 150  |
|  H74937912-618150 | 6 | 18 | 5 | 6 | 150  |
|  H74937911-715150 | 7 | 15 | 6 | 7 | 150  |
|  H74937912-719150 | 7 | 19 | 6 | 7 | 150  |

## 6. Alternative Practices and Procedures

Alternative procedures for the care and treatment of renal artery disease include surgical re-vascularization, or medical therapy.

## 7. Marketing History

The Express SD has been commercially available as a biliary stent in the United States since April 2004. The vascular indicated device has been available in the European Union (EU) and in other countries around the world since April of 2003.

The device has not been withdrawn from marketing in any country for any reason related to safety and effectiveness.

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10

# 8. Potential Adverse Effects of the Device on Health

## 8.1. Observed Adverse Events

The following summary details the adverse events observed with the Express SD when studied in a prospective clinical trial. A summary of observed device malfunctions is also provided. A total of 100 patients were enrolled in the RENAISSANCE Clinical study, a prospective, single arm, multi-center study designed to assess the safety and effectiveness of the Express SD Renal Monorail Premounted Stent System as compared to a pre-specified performance goal. The performance goal was constructed from currently available literature on percutaneous transluminal renal angioplasty (PTRA), for atherosclerotic lesions in the aortorenal ostium. The primary objective of the study was to demonstrate a 9-month binary restenosis rate for the Express SD Stent System that met the performance goal.

Tables 2 and 3 provide the observed adverse event experience reported in RENAISSANCE Clinical Trial.

Table 2: Major Adverse Events* – In-Hospital vs. Out-of-Hospital Intent-to-Treat, All Subjects (N=100)

|  Event | (N=100 Subjects) | [95% CI**]  |
| --- | --- | --- |
|  In-Hospital (Post-procedure to Discharge) |  |   |
|  Device Related Death | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Index-procedure Related Death | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Target Lesion Revascularization (TLR) | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Significant Embolic Event | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Out-of-Hospital through 9 months |  |   |
|  Device Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  Index-procedure Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  Target Lesion Revascularization (TLR) | 8.4% (8/95) | [3.7%, 15.9%]  |
|  Significant Embolic Event | 2.1% (2/95) | [0.3%, 7.4%]  |
|  Total |  |   |
|  Device Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  Index-procedure Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  Target Lesion Revascularization (TLR) | 8.4% (8/95) | [3.7%, 15.9%]  |
|  Significant Embolic Event | 2.1% (2/95) | [0.3%, 7.4%]  |

*As adjudicated by the clinical events committee.
** CI = Confidence Interval

For each event type, rates are based on the number of subjects with at least one event. Subjects count only once in the combined in- and out-of-hospital rates.

Subjects discharged from the hospital who had any Major Adverse Event (MAE) within 300 days or with the last follow-up at least 240 days post-procedure contribute to the out-of-hospital through 9 months and Total (in- and out-of-hospital) rates. Events occurring after 300 days are excluded from this analysis.

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Table 3: Principal Effectiveness and Safety Results
Intent-to-Treat, All Lesions (N=117) in All Subjects (N=100)

|  Safety Measures | (N=100 Subjects) (N=117 Lesions) | [95% CI]  |
| --- | --- | --- |
|  9-Month TLR* (per lesion) | 8.1% (9/111) | [3.8%, 14.8%]  |
|  9-Month TVR* (per lesion) | 14.4% (16/111) | [8.5%, 22.4%]  |
|  9-Month MAE* (per subject) | 10.5% (10/95) | [5.2%, 18.5%]  |
|  Device-Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  Index Procedure-Related Death | 0.0% (0/95) | [0.0%, 3.8%]  |
|  TLR (per subject) | 8.4% (8/95) | [3.7%, 15.9%]  |
|  Significant Embolic Events | 2.1% (2/95) | [0.3%, 7.4%]  |
|  Stent Thrombosis (per subject) | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Acute Stent Thrombosis (≤24 hours) | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Sub-acute Stent Thrombosis (>24 hours to ≤ 30 days) | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Late Stent Thrombosis (>30 days to ≤ 90 days) | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Major Hemorrhagic/Vascular Complication through 30 Days (per subject) | 2.0% (2/100) | [0.2%, 7.0%]  |
|  Intracranial Hemorrhage | 0.0% (0/100) | [0.0%, 3.6%]  |
|  GI Bleeding | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Bleeding at the access site | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Other Bleeding^{1} | 2.0% (2/100) | [0.2%, 7.0%]  |
|  Minor Hemorrhagic/Vascular Complication^{2} (per subject) | 4.0% (4/100) | [1.1%, 9.9%]  |

* TLR = target Lesion Revascularization, TVR = Target Lesion Revascularization, MAE = Major Adverse Event
1 Other Bleeding: pseudoaneurysm, arteriovenous (AV) fistula, hematoma >6 cm, and/or retroperitoneal bleeding) that requires transfusion (>1 unit packed red blood cells) and/or vascular repair (surgical repair, percutaneous transluminal angioplasty (PTA), ultrasound- (US)-guided compression or other percutaneous intervention) through 30 days post-index procedure.
2 Any bleeding which does not require vascular repair or >1 unit packed red blood cells (e.g. oozing from access site, drop in hemoglobin (Hgb)/hemoatocrit (Hct)).

## 8.2. Potential Adverse Events

Based on the literature and on clinical and commercial experience with implantation of a stent in the renal artery the following alphabetic list includes possible adverse events associated with the use of these devices.

- Abscess
- Acute or subacute thrombosis
- Acute myocardial infarction
- Allergic reaction to stent material
- Aneurysm
- Arrhythmias, including ventricular fibrillation (VF) and ventricular tachycardia (VT)
- Artery injury, including perforation and dissection
- AV fistula
- Bowel infarct
- Death
- Drug reaction, allergic reaction to contrast media
- Drug reaction to antiplatelet agents
- Embolization of air or artherosclerotic thrombotic materials

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- Emergency surgery to correct vascular complications
- Extremity ischemia / amputation
- Fever
- Gastrointestinal symptoms from anticoagulation / antiplatelet medication
- Hemorrhage / hematoma
- Hypotension or hypertension
- Incision site pain or infection
- Intimal tear
- Kidney infarct
- Nephrectomy
- Peripheral neuropathy
- Pseudoaneurysm formation
- Renal failure or insufficiency
- Restenosis of the stented artery
- Rupture of retro-peritoneum or of neighboring organ
- Rupture, overstretching of vessel
- Sepsis/infection
- Stent embolization
- Stent migration
- Stent misplacement
- Stroke or other cerebrovascular accidents
- Thromboembolic event
- Tissue necrosis or ulceration
- Total occlusion
- Vessel spasm

## 9. Summary of Pre-Clinical Studies

Pre-clinical studies related to the Express® SD Renal Monorail® Premounted Stent System are presented in Sections 9.1 through 9.4 for *in vitro* product testing and *in vivo* product testing, biocompatibility, sterilization, packaging and shelf life testing.

## 9.1. *In Vitro* Product Testing

A brief summary of the *in vitro* (physical) testing and analytical modeling performed is provided in Table 4 (stent component) and Table 5 (delivery systems). This testing was performed according to the recommendations provided by the FDA guidance document “Guidance for Industry and FDA Staff: Non-Clinical Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems” January 13, 2005. The tables include the device component tested, name of the test, the functional requirement of the test, and a summary of test results. All testing was performed on fully processed and sterilized devices, with the exception of the stent recoil, radial stiffness, and over-expansion testing.

Table 4: In Vitro Summary For The Express® SD Renal Stent

|  In vitro Test | Objective | Summary of Method and Results  |
| --- | --- | --- |
|  Material Composition Analysis | Ensure that the stent material properties are sufficiently well-characterized. | Chemical composition of 316L Stainless steel tubing meets chemical composition requirements of American Society for Testing and Materials (ASTM) F138-00^{1}.  |
|  Surface Contamination | Detect any evidence of foreign material on surface of stent | Stent examination confirmed surface of stents met particulate contamination requirements.  |
|  Ultimate Tensile Strength and Percent Elongation | Demonstrate raw material integrity | Percent elongation and tensile strength were measured for all tubing diameters. Percent elongation and tensile strength were within specification for all samples tested.  |
|  Corrosion Resistance | • Establish compatibility of stent material with vascular environment.
• Determine extent of stent corrosion, which can result in premature stent failure or generation of toxic by-products. | All stents tested met requirements for corrosion resistance per ASTM F2129-01^{2}. Stent samples were subjected to accelerated corrosion conditions intended to simulate ten years of exposure to the in vivo environment. Stents were then inspected for signs of pitting corrosion using light and scanning electron microscopy. There were no signs of stent corrosion, indicating that the stent is sufficiently resistant to corrosion.  |
|  Dimensional Verification: Strut Width, Wall Thickness, Stent Length | • Ensure that finished devices meet established specifications.
• Ensure that the stent dimensions do not vary along the length or circumference of the stent. | Each diameter/length combination was measured for strut width, wall thickness, and stent length at various places along the length and circumference of the stent. All values fell within specifications, indicating that the stents can consistently be manufactured within specifications.  |
|  Metal to Artery Ratio | Determine the amount of vessel area in contact with the stent, as this property may affect tissue ingrowth or prolapse. | The metal to artery ratio for each stent length and each labeled stent diameter was calculated. The stented area ranged from 14.75% to 18.79%, which does not raise any concerns.  |
|  Stent Foreshortening | Determine the decrease in stent length when the stent is deployed and expanded | Measurements of the stent length were taken both pre- and post-expansion to the labeled diameter. The average percent of foreshortening ranged from 1.1% to 6.4%, which is acceptable.  |
|  Stent Recoil | Determine the decrease in expanded stent outer diameter after the balloon is removed | Stent diameter measurements were taken with the fully expanded delivery system and after delivery system removal. The average percent recoil ranged from 0.8% to 2.7%, which is considered minimal.  |
|  Stent Radial Stiffness | Characterize the ability of the stent to resist collapse under an external load following expansion to the labeled diameter | Force was uniformly applied along the length of the stent and the outward force applied by the stent to the inside of the cylindrical opening was measured. Radial compression resistance per unit length was analyzed and it was found that radial stiffness increases with outer diameter. The results demonstrate that the stent offers sufficient resistance to radial force.  |
|  Stent Compression Resistance | Determine whether the expanded stent contains sufficient force to maintain structural integrity and the patency of the renal artery | Each deployed stent was placed in a U-block compression device, and the force required to reduce the stent by a pre-determined diameter was measured. The results demonstrate that the stent offers sufficient compression resistance for the target area.  |
|  Stent Integrity / Stent Over-expansion | Ensure that the radial strength is adequate to provide structural integrity of the stent when expanded beyond its labeled outer diameter | Stents were expanded to 1.5mm larger than their outer diameters, and structural deformities were looked for using 20X magnification. No strut fractures or cracks were observed following testing indicating that the stents maintain integrity beyond their labeled diameter.  |

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Table 5: In Vitro Summary For The Express® SD Renal Monorail® Premounted Stent System

|  In vitro Test | Objective | Summary of Method and Results  |
| --- | --- | --- |
|  Balloon distension and compliance labeling | Determine the outer diameter of the renal stent at various balloon inflation pressures | Values for balloon compliance were determined and included in the product labeling.  |
|  Stent inner diameter | Ensure that the inner diameter of the stent after deployment at the nominal pressure of 10 Atm is within specifications | Balloon expansion to nominal pressures resulted in stents expanding to within 0.5mm of labeled diameter, indicating that the devices perform as expected.  |
|  Stent / balloon crossing profile | Ensure that the maximum stent system diameter is sufficient to permit lesion crossing without complication. | Measurements of the proximal and distal ends of the crimped stent were taken and all stents measured below maximum allowable profile specifications when mounted on delivery system. These results demonstrate that the stent / balloon should be able to be inserted across the target area safely.  |

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16

|  In vitro Test | Objective | Summary of Method and Results  |
| --- | --- | --- |
|  Catheter Shaft Profile | Ensure that the maximum catheter diameter is sufficient to permit access to the target vessel. | The profile was measured at distal and proximal shaft locations to verify conformance with pre-determined profile specifications for each delivery catheter. French size. These results demonstrate that the device should be able to be delivered to the target area safely.  |
|  Catheter and balloon withdrawal forces | - Verify that the balloon can be safely withdrawn from the stent following deployment
- Verify that stent delivery system (SDS) can be safely withdrawn back into the recommended sized guide catheter following stent deployment | - The delivery system and guide wire were placed into the specified guide catheter. The stents were deployed, after which the balloon was deflated and withdrawn from the stent and into the guide catheter. The peak forces were measured and recorded. They demonstrated that the balloon can be withdrawn without excessive force.
- For the catheter withdrawal test, the maximum force recorded beyond the first 3cm represents the force required to pull the delivery system back into the guide catheter. All forces were found to be under the maximum specification indicating that the SDS can be safely withdrawn following stent placement.  |
|  Stent securement force | Determine the force required to displace the crimped stent from the SDS | Each stent was placed in a testing apparatus with a pass-through hole that was designed to catch on the stent edges but not impede the movement of the delivery balloon. The force was recorded when the stent moved. Both forward and reverse motion was tested. All stent models remained in place on the delivery systems at forces greater than the specified minimum force specified for each model, indicating that the stents should not prematurely leave the delivery system under expected clinical conditions.  |
|  Delivery system tensile strength | Determine force at which the catheter bonds would fail due to tensile force | Three catheter bonds were tested to failure and all bonds tested exceeded minimum requirements of tensile strength. These results indicate the integrity of the delivery system under greater than clinically expected forces.  |
|  Stent deployment pressure and deployment accuracy | - Determine minimum pressures required for stent deployment
- Assess ability to place stent accurately in intended location | The delivery balloons were pressurized in 5 psi increments until the stent was successfully deployed. All test units for all stent models deployed at pressures below the maximum allowable deployment pressure (8 Atm) with all stents being deployed accurately in position relative to the delivery catheter marketbands. These results confirm the ability to deliver the device under labeled conditions.  |
|  Rated Burst Pressure and balloon burst within a stent | - Determine minimum balloon burst pressure
- Ensure integrity of the stent in the event a balloon burst occurs | - All catheter models were inflated to failure and the resulting burst pressure data has been provided in product labeling.
- All stents remained integral following balloon burst within the stent.  |
|  Balloon inflation and deflation time | Determine the average length of time required to inflate and deflate the balloons to their rated burst pressure (RBP) | All models tested inflated to the RBP and deflated at rates below the 60 second specification, which is reasonable.  |
|  Repeat balloon inflation within a stent | Balloon is capable of inflation within stent multiple times without failure | All balloon models tested met required number of inflate / deflate cycles (10) while positioned within the stent and without causing functional damage to the catheter.  |

# 9.2. Animal Testing

The Express SD has been evaluated in two *in vivo* animal studies. One study was conducted to evaluate the 30-day and 180-day vascular response to the stent, and to assess the safety of the stent via clinical, physiologic, and gross tissue observations in a healthy porcine model under Good Laboratory Practices (GLP) per 21 CFR Part 58. A second, non-GLP animal study was also conducted to evaluate the acute performance of the Express SD Delivery System in a healthy porcine model. A summary of these studies is provided in Table 6.

The porcine model is a well documented animal model for conducting vascular evaluations as the size of the arterial vasculature is comparable to humans and permits the use of standard clinical devices. Additionally, the relative size of the model permits accurate visualization with standard angiographic equipment. The adolescent and young adult size domestic swine model presents some confounders due to ongoing growth of the vascular system.

Table 6: *In Vivo* Summary For The Express® SD Renal Monorail® Stent System

|  Study Objectives | Number of Animals Timepoints Devices Tested | Relevant Findings  |
| --- | --- | --- |
|  GLP Study to Assess the Safety ad Vascular Response of Express SD Stents in Renal Arteries of Domestic Swine  |   |   |
|  • Evaluate vascular response to stents in renal arteries
• Assess safety of device via clinical (blood pressure changes, kidney function), physiologic (thrombus) and gross tissue observations | • 9 animals
• 30 and 180 days
• 18 devices (6.0 mm x 14 mm or 5.0 mm x 15 mm) | • No device-related mortality (0/9, 0%)
• Percent stenosis low (<15%) and stable over time
• No luminal thrombi observed at any time point
• Vessels were widely patent with consistent luminal areas at all time points
• >90% endothelialization at all time points
• Absence of pathologically significant inflammation
• No aneurysmal dilatation
• Clinical chemistry, hematology, hormonal, and urinalysis values remained within normal limits
• Stents did not affect renal function tests, electrolyte balance, or cause stimulation of the renin-angiotensin system
• Abnormal histopathologic findings were occasionally noted and judged to be unrelated to the stent
• Gross evaluation of kidneys showed mostly normal findings. Abnormal findings were occasional cystic lesions which are commonly found in domestic swine and were considered present prior to stent implantation.  |
|  Study Evaluating the Accessibility of the Express SD System in Peripheral Vascular System in the Acute Swine Model  |   |   |
|  Evaluate device deliverability and performance. | • 1 animal
• Acute (1 day)
• 4 devices (6 mm x 18 mm and 5 mm X 19 mm) | • Express SD was considered acceptable or above average for evaluated variables including: insertion, trackability, deployment characteristics, guidewire movement, balloon deflation time, withdrawal into/from a sheath
• Overall performance of the Express SD in the renal vasculature met the defined specification  |

These animal studies have demonstrated that the Express SD stent can be delivered as specified in the labeling and does not cause any abnormal systemic responses when placed in non-injured renal arteries of growing domestic swine. The abnormalities noted in the histopathology reports included proteinaceous debris in Bowman’s capsule and collecting ducts, hypercellular glomeruli, glomeruli touching Bowman’s capsule, thickened hyalinized Bowman’s capsule, and interstitial aggregates of lymphocytes and macrophages. In the absence of observable clinical syndromes, or abnormal serum indices, combined with normal growth and development, these findings were

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judged to be likely from processing artifacts or migration due to chronically-developing stent undersizing that can be seen in large domestic swine models. It should also be noted that animal food has not routinely been tested for unexpected feed additives that may induce renal dysfunction. As a result, it is not known whether diet could be a contributing factor to the renal artifacts seen in these studies.

## 9.3. Biocompatibility

Biocompatibility of the materials used in the construction of the Express® SD Renal Monorail® Premounted Stent System was determined by the results of testing conducted on the stent component and the finished device (delivery system with pre-mounted stent). The testing performed consisted of those tests recommended in the FDA Blue Book Memorandum #G95-1 modified matrix of International Standard ISO 10993-1, “Biological Evaluation of Medical Devices Part 1: Evaluation and Testing.” The stent is considered an implant with permanent blood contact (&gt;30 days). The delivery system is categorized as an external communicating device that contacts circulating blood for less than 24 hours (limited exposure). The biocompatibility test regimen is outlined in Table 7.

Table 7: Biocompatibility Test Regimen for the Express® SD Renal Monorail® Stent System

|  Name of Assay or Test | Test Build* | Test Results  |
| --- | --- | --- |
|  In Vitro Mouse Lymphoma Assay | Express Stent, P020009 | Pass  |
|  Ames Mutagenicity Assay | Liberté Stent, P040016 | Pass  |
|  Hemolysis Test Autian Method-Rabbit Blood Extract Method | Express SD System | Pass  |
|  In Vitro Hemocompatibility Assay | Express SD System | Pass  |
|  Partial Thromboplastin Time | Express SD System | Pass  |
|  Complement Activation | Express SD System | Pass  |
|  MEM Elution Cytotoxicity | Express SD System | Pass  |
|  Short Term Intramuscular Implantation (14 days) | Express Stent, P020009 | Pass  |
|  Intramuscular Implantation (30 days) | Express Stent, P020009 | Pass  |
|  Intracutaneous Reactivity | Express SD System | Pass  |
|  Guinea Pig Maximization Sensitization | Express SD System | Pass  |
|  Acute Systemic Injection | Express SD System | Pass  |
|  Materials Mediated Rabbit Pyrogen (Saline/ 37°C, 72 hours) | Express SD System | Pass  |
|  Materials Mediated Rabbit Pyrogen (Saline/ 70°C, 24 hours) | Express SD System | Pass  |
|  Subacute Intravenous Toxicity | Express Stent, P020009 | Pass  |

*This testing was performed on devices that were evaluated under previous premarket applications, as noted. Since they are composed of the same materials as the Express® SD Renal Monorail® Stent System, repeat testing on the subject system for the purposes of addressing biocompatibility was not necessary.

Tests for carcinogenicity, in vivo thrombogenicity, and chronic toxicity testing were not performed due to the extensive clinical history of the device materials and their well-characterized long-term safety profile. Implantation testing was performed in a porcine model as part of the animal studies conducted for the device.

The test results demonstrate that both the stent and delivery system are biocompatible and non-pyrogenic.

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## 9.4. Sterility and Shelf Life Testing

### Sterility

The Express® SD Monorail® Premounted Stent System is ethylene oxide sterilized per the requirements of American National Standards Institute (ANSI)/Association for the Advancement of Medical Instrumentation (AAMI)/International Organization for Standardization (ISO) 11135:1994, “Medical devices—Validation and routine control of ethylene oxide sterilization.” The validation results demonstrated that the sterilization process achieves a minimum sterility assurance level of $10^{-6}$, and that residual levels were within the acceptable ranges for an implant according to ISO 10993-7, “Biological evaluation of medical devices -- Part 7: Ethylene oxide sterilization residuals.”

### Shelf Life Tests

A three-year shelf life has been substantiated for Express® SD Monorail® Premounted Stent System. Product specifications, quality, functionality, and safety requirements were demonstrated after sterilization and accelerated aging.

Packaging verification testing was performed to demonstrate that the design of the device packaging will withstand the hazards of the distribution environment and that the sterility of the device will be maintained throughout the labeled shelf life of the product per ASTM F-88, “Standard Test Method for Seal Strength of Flexible Barrier Materials” (package peel strength) and ASTM F-1929, “Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration” (packaging seal integrity).

## 10. Summary of Clinical Studies

The Boston Scientific Corporation: A prospective, multi-center, single arm study evaluating the Express™ Renal Premounted Stent System in the treatment of atherosclerotic lesions in the aortorenal ostium (RENAISSANCE) trial was a prospective, non-randomized, multi-center, single-arm clinical trial. The trial was performed to demonstrate the safety and efficacy of the Express® SD Renal Monorail® Premounted Stent System compared to a performance goal developed from recent literature of PTRA for atherosclerotic lesions in the aortorenal ostium. The information shown in Table 8 was used in the development of this performance goal. The demonstration of safety and effectiveness was achieved by demonstrating a 9-month binary restenosis rate, defined as the proportion of target lesions with $\geq 50\%$ diameter stenosis based on Angiographic Core Lab assessment, for the Express SD Stent System that met the performance goal. A total of 100 patients were enrolled at 14 clinical sites in the United States. Of these 100, seventeen underwent stenting in both renal arteries. For these subjects, both lesions were enrolled into the RENAISSANCE trial, bringing the total lesion count to 117.

Table 8. Performance goal study information

|  Author | Lesion type & Location | # Pts. | # Arteries | Restenosis Definition | Evaluation Method | Follow-up Time | Restenosis  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Symonides, et.al. | Atherosclerotic | 27 | 27 | > 50% | Ultrasound renal/aortic ratio > 3.5 Angiographic confirm | 6 months | 29.6% (8/27)  |
|  Van de Ven, et.al. | Atherosclerotic, ostial | 42 | 51 | ≥ 50% | Angiographic | 6 months | 48% (11/24)  |
|  Weibull, et.al. | Atherosclerotic, ostial | 65 | 71 | Significant | Worsening blood pressure/renal function, Angio | 12 months | 47.5% (29/61)  |
|  Weibull et.al. | Atherosclerotic, ostial | 29 | 29 | ≥ 50% | Angiographic | 12 months | 21% (5/24)  |
|  Hoffman, et.al. | Atherosclerotic, ostial | 50 | 52 | ≥ 50% | Angiographic | 11 months (mean) | 27% (7/26)  |
|  Van Jaarsveld, et.al. | Atherosclerotic, ostial | 56 | 56 | > 50% | Angiographic | 12 months | 48% (23/48)  |
|  Weighted average |  |  |  |  |  | 9.83 months | 40% (83/210)  |

Core laboratories provided independent assessments of angiographic and ultrasound data. Monitors reviewed all data to ensure appropriate reporting of adverse events and adherence to the study protocol. A Clinical Events Committee (CEC) consisting of non-investigators adjudicated adverse event reports for study subjects. A Data Safety Monitoring Board (DSMB) monitored study progress and adverse events to ensure patient safety.

An overview of the RENAISSANCE Trial is presented in Table 9:

Table 9: Overview of RENAISSANCE Trial

|  Product Evaluated | Express® SD Renal Monorail® Premounted Stent System  |
| --- | --- |
|  Study Design | Non-randomized, multi-center, single-arm, prospective clinical trials  |
|  Patients Enrolled | 100  |
|  Number of Sites | 15 centers (14 investigative sites)  |
|  Primary Endpoint | Binary in-stent restenosis rate at 9 months, defined as the proportion of target lesions with ≥50% diameter stenosis based on Angiographic Core Lab assessment. The primary analysis was a lesion-based analysis. Subjects were required to have a 9-month renal duplex ultrasound to assess for evidence of significant stenosis. Ultrasound and angiographic core labs were utilized  |

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|  Secondary Endpoints | • Technical Success <30% residual stenosis immediately after stent deployment, including post-dilatation, as visually assessed by the investigator.
• Procedural Success <30% residual diameter stenosis as visually assessed by the investigator without the occurrence of in-hospital major adverse events (MAE).
• Target Lesion Revascularization (TLR) Clinically-driven reintervention of the target lesion through 9 months. Calculated on a per-lesion basis (as a stand-alone outcome) and on a per-subject basis (as a component of MAE).
• Target Vessel Revascularization (TVR) Clinically-driven reintervention of the target vessel through 9 months. Calculated per-lesion.
• Change (improvement) in renal function Change in serum creatinine and change in glomerular filtration rate (GFR) as estimated by Cockcroft-Gault formula, from pre-procedure to the post-procedure, 30-day and 9-month follow-up
• Change in Renal-to-Aortic Ratio, Resistive Index, and Peak Systolic Velocity (using Ultrasound Core Lab values) from pre-procedure to post-procedure and 9 months post-procedure. These values were provided by the Ultrasound Core Laboratory.
• Change (improvement) in hypertension control Change in arterial systolic and diastolic blood pressure from pre-procedure to post-procedure, 30-day and 9-month follow-ups  |
| --- | --- |
|  Study Hypothesis | Subjects treated with the Express® Renal Stent will have a lower rate of 9-month binary in-stent restenosis as compared to a performance goal of 40% (based on the expected restenosis rate for technically successful PTRA)  |
|  Patient Follow-up | 1 month post-procedure, in-clinic (adverse event assessment, clinical status, blood pressure, medication usage, and lab tests including serum creatinine, complete blood count (CBC) / platelets, and serum electrolytes)
4 months post-procedure, telephone (adverse event assessment, medication usage)
9 months post-procedure, in-clinic (adverse event assessment, clinical status, blood pressure, medication usage, duplex ultrasound to assess evidence of significant stenosis, and lab tests including serum creatinine, CBC / platelets, and serum electrolytes)  |

All subjects were to receive the hospital’s standard anti-coagulation regimen for renal artery stent implantation. After the index-procedure, subjects were to receive aspirin indefinitely and clopidogrel or ticlopidine for 30 days. Follow-up includes a 30-day office visit, 4-month telephone follow-up, 9 month office visit (primary endpoint), with additional follow-ups at 12 months, then annually for a total follow-up period of 5 years post-index procedure. All subjects were required to have ultrasound follow-up at 9-months.

## Statistical Methods

The statistical analysis of the RENAISSANCE trial was designed to show that the Boston Scientific Corporation Express® SD Renal Monorail® Premounted Stent System primary endpoint is significantly less than a performance goal of 40%. The performance goal was constructed from currently available literature on balloon angioplasty in the renal arteries.

The hypothesis used is shown below:

$$
\mathrm{H}_0: \pi_{\mathrm{e}} \geq 0.40
$$

$$
\mathrm{H}_1: \pi_{\mathrm{e}} &lt; 0.40
$$

Where $\pi_{\mathrm{e}}$ is the 9-month binary in-stent restenosis rate of subjects treated with the Express™ Renal Stent based on Core Lab assessment.

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The null hypothesis tested used a one-sided, one-sample z-test statistic at the significance level 0.025, which is:

$$
Z ^ {*} = \frac {p _ {e} - \pi_ {0}}{S E}, S E = \sqrt {\frac {\pi_ {0} (1 - \pi_ {0})}{n}}
$$

where

$\pi_0 =$ pre-specified goal of $40\%$ for PTRA

$p_e =$ observed 9-month binary in-stent restenosis rate

$n =$ number of observations

If $Z^{*} &lt; -Z_{0.025} = -1.96$ (the coefficient used to calculate a $95\%$ confidence interval), then the null hypothesis was rejected and the conclusion drawn that the restenosis rate for the Express™ Renal Stent meets the performance goal.

For binary and categorical endpoints, event counts, rates and their confidence intervals were analyzed. Continuous endpoints were evaluated by assessing the mean, standard deviation, minimum and maximum values, and $95\%$ confidence intervals. Kaplan-Meier methodology was used to estimate the distributions of time-to-event endpoints.

## Eligibility Criteria Summary

Male and female patients who were eligible for percutaneous transluminal renal angioplasty (PTRA) with a single, de novo, or restenotic (from prior PTRA) atherosclerotic lesion in the ostium of the renal artery within $5\mathrm{mm}$ of the opacified aortic lumen were considered for enrollment. To be included, the patients were required to be at least 18 years old and could have unilateral or bilateral disease or a solitary functioning kidney.

## Description of Patients Evaluated

This study population had slightly more females (52%), than males (48%). A significant number of subjects presented with clinical characteristics of coronary artery disease (73%), a history of hyperlipidemia (77%), hypertension requiring medication (99%) and 69% are current or previous smokers. The mean age was 71 years and 26% of those enrolled had medically treated diabetes. The patient demographics are shown in Table 10, below.

Table 10: Baseline Demographics and Clinical Characteristics Intent-to-Treat, All Subjects (N=100)

|  Variable | (N=100 Subjects) | [95% CI]  |
| --- | --- | --- |
|  Age (Years) | 71.4±9.0 (100) | [69.6, 73.1]  |
|   | (41.0, 85.0) |   |
|  Male | 48.0% (48/100) | [37.9%, 58.2%]  |
|  Race |  |   |
|  White | 97.0% (97/100) | [91.5%, 99.4%]  |
|  Black, of African Heritage | 3.0% (3/100) | [0.6%, 8.5%]  |
|  Asian | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Native Hawaiian or Other Pacific Islander | 0.0% (0/100) | [0.0%, 3.6%]  |
|  American Indian or Alaska Native | 0.0% (0/100) | [0.0%, 3.6%]  |
|  Medical History^{1} |  |   |

|  Variable | (N=100 Subjects) | [95% CI]  |
| --- | --- | --- |
|  Known Prior Percutaneous Coronary Intervention (PCI) | 37.1% (36/97) | [27.5%, 47.5%]  |
|  Known Prior Coronary Artery Bypass Graft (CABG) | 37.0% (37/100) | [27.6%, 47.2%]  |
|  Known Previous Myocardial Infarction (MI) | 20.6% (20/97) | [13.1%, 30.0%]  |
|  Known Congestive Heart Failure (CHF) | 17.8% (16/90) | [10.5%, 27.3%]  |
|  Known Unstable Angina | 3.1% (3/98) | [0.6%, 8.7%]  |
|  Known Coronary Artery Disease | 73.1% (68/93) | [62.9%, 81.8%]  |
|  Known Peripheral Vascular Surgery | 9.2% (9/98) | [4.3%, 16.7%]  |
|  Prior Renal Percutaneous Intervention | 4.0% (4/99) | [1.1%, 10.0%]  |
|  PTRA | 1.0% (1/96) | [0.0%, 5.7%]  |
|  Stenting | 4.0% (4/99) | [1.1%, 10.0%]  |
|  Other Peripheral Endovascular Interventions | 5.1% (5/99) | [1.7%, 11.4%]  |
|  Known Cerebrovascular Accident (CVA) | 4.0% (4/99) | [1.1%, 10.0%]  |
|  Known Transient Ischemic Attack (TIA) | 4.2% (4/95) | [1.2%, 10.4%]  |
|  Risk Factors^{1} |  |   |
|  Current or Previous Smoker^{2} | 68.7% (68/99) | [58.6%, 77.6%]  |
|  Known Medically Treated Diabetes | 26.0% (26/100) | [17.7%, 35.7%]  |
|  Insulin Requiring | 7.0% (7/100) | [2.9%, 13.9%]  |
|  Non-Insulin Requiring | 19.0% (19/100) | [11.8%, 28.1%]  |
|  Known Hyperlipidemia | 76.5% (75/98) | [66.9%, 84.5%]  |
|  Known Hypertension Requiring Treatment | 99.0% (99/100) | [94.6%, 100.0%]  |
|  Current Hypertension | 98.0% (98/100) | [93.0%, 99.8%]  |
|  Previous Hypertension | 1.0% (1/100) | [0.0%, 5.4%]  |

1 Responses of “Unknown” to the questions included in the Medical History and Risk Factors are not presented in this exhibit.
2 Defined as Current Smoker (within past 6 months) or Previous Smoker (&gt; 6 months ago).

With respect to a comparison of the RENAISSANCE trial demographics to the performance goal population demographics, the mean age in the study was 71±9 years compared to the weighted average performance goal age of 62 years. The mean systolic and diastolic blood pressures were lower in this study than in the literature. There were fewer diabetics in the performance goal population (7%) compared to the RENAISSANCE population (26%). There were similar numbers of smokers in both populations.

Baseline lesion characteristics included average reference vessel diameter (RVD) of 5.1 mm, average minimum lumen diameter (MLD) of 1.6 mm, average percent diameter stenosis (%DS) of 68.4% and average lesion length of 8.6 mm.

## Clinical Results Summary

The results of the RENAISSANCE clinical study are summarized in Table 11 and Table 12.

Table 11: Principal Effectiveness and Safety Results, Intent-to-Treat, All Lesions (N=117) in All Subjects (N=100)

|  Effectiveness Measures | (N=100 Subjects) (N=117 Lesions) | [95% CI]  |
| --- | --- | --- |
|  Technical Success (per lesion) | 99.1% (116/117) | [95.3%, 100.0%]  |
|  Procedural Success (per subject) | 99.0% (99/100) | [94.6%, 100.0%]  |
|  9-Month Binary In-Stent Restenosis (per lesion) | 21.3% (23/108) | [14.0%, 30.2%]  |

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Table 12: Secondary Effectiveness Results with Matched Data - Change from Baseline to 9-month, Intent-to-Treat, All Lesions (N=117) in All Subjects (N=100)

|  Secondary Effectiveness Measures (Change from Baseline to 9-month) * | Mean Change from Baseline*** | 95% CI for Change | Improved | No Change | Worsened  |
| --- | --- | --- | --- | --- | --- |
|  Renal function |  |  |  |  |   |
|  Serum Creatinine (mg/dl per subject)¹ | 0.07±0.48 (81)
(-1.10, 2.50) | [-0.03, 0.18] | 33.3%
(27) | 29.3%
(24) | 37.0%
(30)  |
|  GFR** Difference (calculated GFR per subject)² | -0.81±13.76 (79)
(-54.99, 24.89) | [-3.89, 2.27] | 31.7%
(25) | 31.7%
(25) | 36.7%
(29)  |
|  Renal-to-Aortic Ratio Difference (per lesion)³ | -1.96±1.80 (71)
(-7.50, 3.70) | [-2.39, -1.53] | 70.4%
(50) | 15.5%
(11) | 14.1%
(10)  |
|  Resistive Index Difference (per lesion)⁴ | 0.01±0.09 (62)
(-0.17, 0.18) | [-0.01, 0.03] | 35.5%
(22) | 24.2%
(15) | 40.3%
(25)  |
|  Renal PSV** Difference (cm/sec per lesion)⁵ | -156.75±158.37 (81)
(-615.00, 379.00) | [-191.8, -121.7] | 65.4%
(53) | 25.9%
(21) | 8.6%
(7)  |
|  Hypertension Control |  |  |  |  |   |
|  Systolic BP** Difference (mmHg per subject)⁶ | -8.60±25.65 (88)
(-101.67, 46.50) | [-14.03, -3.17] | 61.4%
(54) | 11.4%
(10) | 27.3%
(24)  |
|  Diastolic BP** Difference (mmHg per subject)⁷ | -0.82±12.54 (88)
(-26.80, 35.75) | [-3.47, 1.84] | 42.1%
(37) | 29.6%
(26) | 28.4%
(25)  |
|  Number of Anti-Hypertensive Medications (per subject)⁸ | 0.03±1.15 (97)
(-3.00, 5.00) | [-0.20, 0.26] |  |  |   |

*Changes from baseline to 9-months calculated as 9-month results minus baseline results
** GFR = Glomerular Filtration Rate, PSV = Peak Systolic Velocity, BP = Blood Pressure
***Presented as Mean±SD (N) (Min, Max) for the changes of paired data (9 month – baseline)
¹ Serum creatinine; improvement = decrease greater than 0.1 mg/dL, worsened = increase greater than 0.1 mg/dL
² GFR; improvement = increase greater than 5 mL/min, worsened = decrease greater than 5 mL/min
³ Renal-toAortic Ratio; improvement = decrease greater than 1, worsened = increase greater than 0
⁴ Resistive Index; improvement = decrease greater than 0.03, worsened = increase greater than 0.03
⁵ Renal PSV; improvement = decrease greater than 100 cm/sec, worsened = increase greater than 0 cm/sec
⁶ Systolic BP; improvement = decrease greater than 5 mmHg, worsened = increase greater than 5 mmHg
⁷ Diastolic BP; improvement = decrease greater than 5 mmHg, worsened = increase greater than 5 mmHg

The Kaplan-Meier curve through 300 days for all pivotal patients is presented in Figure 2 (data in Table 13). As can be seen, major adverse events occur within the 60 to 180 days with acceptable adverse event rates within the time period.

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![img-1.jpeg](img-1.jpeg)
Figure 2: Freedom from MAE to 9 month Follow-up, Intent-to-Treat, Event-Free Survival ± 1.96 SE, All Subjects (N=100)

Table 13: Freedom from MAE to 9 month Follow-up, Intent-to-Treat, Event-Free Survival ± 1.96 SE, All Subjects (N=100)

|  100 Subjects | 0 | 7 | 14 | 30 | 60 | 120 | 180 | 270 | 300  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Entered | 100 | 100 | 100 | 100 | 100 | 99 | 94 | 89 | 87  |
|  Censored | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 1 | 1  |
|  At Risk | 100 | 100 | 100 | 100 | 100 | 98 | 92.5 | 88.5 | 86.5  |
|  Events | 0 | 0 | 0 | 0 | 1 | 3 | 2 | 1 | 3  |
|  Events/Month | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 1.5 | 1.0 | 0.3 | 3.0  |
|  Event Free | 100% | 100% | 100% | 100% | 99.0% | 96.0% | 93.9% | 92.8% | 89.6%  |
|  Std Error - Greenwood | 0.0% | 0.0% | 0.0% | 0.0% | 1.0% | 2.0% | 2.4% | 2.6% | 3.1%  |
|  Std Error - Peto | 0.0% | 0.0% | 0.0% | 0.0% | 1.0% | 2.0% | 2.5% | 2.7% | 3.2%  |
|  Peto's Lower Limit | 100.0% | 100.0% | 100.0% | 100.0% | 97.4% | 92.7% | 89.9% | 88.4% | 84.4%  |

Intervals are end inclusive, e.g. interval 180 is defined as 121-180 days, inclusive.
Event-free and standard error estimates are for interval end. Standard errors by Greenwood formula.
Bars at selected time point show 95% confidence interval (event-free survival ± 1.96 SE (by Greenwood formula)).
Peto's standard error estimates and lower limit are also presented.

## Conclusions:

The 9-month binary restenosis primary endpoint for the Express™ SD Renal Monorail Premounted Stent was met with 21.3% compared to the predefined performance goal of 40%. This almost 50% reduction in the binary restenosis rate is associated with high technical and procedural success (99%), low TLR (8.1%) and TVR (14.4%).

There was a statistically significant improvement in systolic blood pressure with no change in diastolic blood pressure or in the number of anti-hypertensive medications used.

By duplex ultrasound, the hemodynamic endpoints specific to the treatment of renal artery stenosis showed an improvement over baseline: Renal-to-Aortic Ratio (RAR) and Renal Peak

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Systolic Velocity (PSV). Resistive Index (RI) and the surrogate measure of renal function (serum creatinine and GFR) showed no change from baseline.

The study had an acceptable safety profile with no device or procedure-related deaths, no stent thrombosis, a 2% rate of Significant Embolic Events and a 9-month MAE rate of 10.5%.

Overall the RENAISSANCE trial demonstrated the Express™ SD Renal Monorail® Premounted Stent System to be safe and effective for the treatment of renal artery stenosis as an adjunct to PTRA.

## 11. Conclusions Drawn from the Studies

Data from pre-clinical studies performed on the Express® SD Monorail® Premounted Stent System meet or exceed the established safety and effectiveness specifications. Results from the RENAISSANCE multi-center Clinical Trial demonstrate that the Express® SD Renal Monorail® Premounted Stent System is a safe and effective treatment for renal artery disease in the population studied, as an adjunct to PTRA. The combined preclinical and clinical results provide valid scientific evidence and reasonable assurance that the Express® SD Monorail® Premounted Stent System is safe and effective when used in accordance with its approved labeling.

Approval of this PMA application was predicated on the development of a new indication for use as compared to previous renal stent applications. With the concurrence of FDA, the clinical trial protocol was originally approved in 2003 and the indications for use was changed to a provisional indication after enrollment had been completed with a primary stenting study population; as a result, the study design did not meet our current expectations for a primary stenting indication, yet the patient population did not represent the provisional indication of stenting following failed / suboptimal angioplasty. Therefore, no quantitative statistical inferences or conclusions could be reached using either of FDA’s two traditional indications for use. FDA’s understanding of the clinical environment for devices of this type has advanced since this clinical study protocol was approved in 2003, and FDA’s expectation for future approvals is that marketing applications for similar devices will be accompanied by clinical data from which quantitative statistical inferences can be drawn to demonstrate success for either a primary or provisional (following failed or suboptimal PTRA) indication.

## 12. Panel Recommendation

In accordance with provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Circulatory Systems Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.

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## 13. CDRH Decision

FDA issued an approval order on August 08, 2008. The conditions of approval require a follow-up of the existing cohort of patients from the RENAISSANCE trial for a total of five years. The 1-year and 2-year visits are required to be office visits. The 3-year, 4-year and 5-year visits can be either office visits or phone calls. The 2-year office visit will include a duplex ultrasound to assess evidence of significant stenosis. All subsequent visits will document an assessment of all adverse events and medication usage. The results of these studies will be evaluated to determine whether any changes should be made to the device labeling to ensure that the information available to physicians is complete, appropriate, and up-to-date.

The applicant's manufacturing facility was inspected and was found to be in compliance with the Quality System Regulation (21 CFR 820).

## 14. Approval Specifications

Instructions for Use: See labeling

Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the labeling.

Postapproval Requirements and Restrictions: See approval order.

---

**Source:** [https://fda.innolitics.com/device/P060006](https://fda.innolitics.com/device/P060006)

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