EPIC SELF-EXPANDING NITINOL STENT SYSTEM
Device Facts
| Record ID | P110035 |
|---|---|
| Device Name | EPIC SELF-EXPANDING NITINOL STENT SYSTEM |
| Applicant | Boston Scientific Corp |
| Product Code | NIO · Cardiovascular |
| Decision Date | Apr 13, 2012 |
| Decision | APPR |
| Device Class | Class 3 |
| Attributes | Therapeutic |
Intended Use
The Epic Vascular Self-Expanding Stent System is indicated for the improvement of luminal diameter in patients with de novo or restenotic symptomatic atherosclerotic lesions up to 120 mm in length in the common and/or external iliac arteries, with a reference vessel diameter between 5 and 11 mm.
Device Story
The Epic Stent System is a self-expanding, laser-cut Nitinol stent with tantalum radiopaque markers, delivered via a 6F coaxial Over-The-Wire system. Used in clinical settings by physicians, the device is deployed by retracting an exterior shaft, allowing the stent to expand at body temperature to appose the vessel wall. The system is compatible with 0.035" guidewires. By improving luminal diameter in iliac arteries, the device treats symptomatic atherosclerotic lesions, potentially reducing claudication and improving blood flow. Clinical output is monitored via angiography and duplex ultrasound to assess patency and restenosis. The device is intended for permanent implantation.
Clinical Evidence
Evidence includes the prospective, single-arm ORION trial (N=125) and supplemental data from the SUMMIT registry. Primary endpoint (9-month MAE rate) was 3.4% (95% CI: 0.9%, 8.5%), significantly below the 17% performance goal (p<0.0001). Secondary endpoints at 9 months included 95.9% primary patency and 89.9% clinical success (Rutherford improvement ≥1 class). No device-related deaths or amputations occurred through 9 months. Bench testing confirmed biocompatibility, 10-year fatigue durability, and MRI compatibility.
Technological Characteristics
Stent: Laser-cut Nitinol (ASTM F2063-00) with tantalum (ASTM F560-04) radiopaque markers. Delivery system: 6F coaxial, Over-The-Wire, compatible with 0.035" guidewires. Sterilization: Ethylene oxide (EO) per ISO 11135:2007. MR Conditional. Shelf life: 3 years.
Indications for Use
Indicated for patients ≥18 years with symptomatic atherosclerotic iliac artery disease (Rutherford/Becker categories 1-4) requiring improvement of luminal diameter in de novo or restenotic lesions ≤120 mm in length, with reference vessel diameters 5-11 mm. Contraindications include known hypersensitivity to Nitinol, intolerance to antiplatelet/anticoagulant/thrombolytic medications, or target lesions with in-stent restenosis.
Regulatory Classification
Identification
Stent, Iliac -- a metal scaffold placed via a delivery catheter into the iliac artery to maintain the lumen
Reference Devices
- Boston Scientific Wallstent® Endoprosthesis
Related Devices
- P090006 — COMPLETE SE VASCULAR STENT SYSTEM · Medtronic Vascular · Mar 17, 2010
- P110028 — ABSOLUTE PRO VASCULAR SELF-EXPANDING STENT SYSTEM · Abbott Vascular, Inc. · Feb 22, 2012
- P140030 — ASTRON PERIPHERAL SELF-EXPANDING NITINOL STENT SYSTEM · Biotronik, Inc. · Dec 17, 2015
- P090003 — EXPRESS LD ILIAC PREMOUNTED STENT SYSTEM · Boston Scientific Corporation · Mar 5, 2010
- P080007 — BARD E-LUMINEXX VASCULAR STENT · Bard Peripheral Vascular, Inc. · Dec 4, 2008
Submission Summary (Full Text)
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# Summary of Safety and Effectiveness Data (SSED)
## I. GENERAL INFORMATION
| Device Generic Name: | Stent, Iliac (NIO) |
| --- | --- |
| Device Trade Name: | Epic™ Vascular Self-Expanding Stent System (Epic Stent System) |
| Applicant's Name and Address: | Boston Scientific Corporation
One Scimed Place
Maple Grove, MN 55311 |
| Date(s) of Panel Recommendation | None |
| Premarket Approval Application (PMA) Number: | P110035 |
| Date of FDA Notice of Approval: | April 13, 2012 |
| Expedited: | Not Applicable |
## II. INDICATIONS FOR USE
The Epic Vascular Self-Expanding Stent System is indicated for the improvement of luminal diameter in patients with de novo or restenotic symptomatic atherosclerotic lesions up to 120 mm in length in the common and/or external iliac arteries, with a reference vessel diameter between 5 and 11 mm.
## III. CONTRAINDICATIONS
There are no known contraindications.
## IV. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the Epic Vascular Self-Expanding Stent System Directions for Use (DFU).
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# V. DEVICE DESCRIPTION
The Epic Stent System is comprised of two components: the implantable endoprosthesis and the stent delivery system. The stent is a laser cut self-expanding stent composed of a nickel titanium alloy (Nitinol). On both the proximal and distal ends of the stent, radiopaque markers made of tantalum increase visibility of the stent to aid in placement. The stent is constrained within a 6F (2.1 mm maximum Outside Diameter) delivery system. The delivery system is a coaxial design with an exterior shaft to protect and constrain the stent prior to deployment.
When ready to be implanted, the stent is deployed by retracting the exterior shaft of the delivery system. A radiopaque marker at the distal end of the delivery system aids in visibility during deployment. As the stent is exposed to body temperature, it expands to appose the vessel wall.
The Epic Stent System is available in stent diameters ranging from 6 – 12 mm and lengths ranging from 20 – 120 mm. The delivery system is an Over-The-Wire system compatible with 0.035" (0.89 mm) guidewires and 6F (2.1 mm) introducer or guide sheaths. The delivery system is offered in two shaft lengths (75 cm and 120 cm).
The Epic Stent System is illustrated in Figure 1.
Figure 1: Epic Stent System
The commercial matrix is shown in Table 1 below:
Table 1: Epic Stent System Product Description
| Target Stent Length | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Stent Diameter | Model | (mm) | 20 | 30 | 40 | 50 | 60 | 70 | 80 | 100 | 120 |
| | SD | 6 | X | X | X | X | X | X | X | X | X |
| | | 7 | X | X | X | X | X | X | X | X | X |
| | LD | 8 | X | X | X | X | X | X | X | X | X |
| | | 9 | X | X | X | X | X | X | X | X | |
| | | 10 | X | X | X | X | X | X | X | X | |
| | XLD | 12 | | X | X | X | X | | | | |
*Actual labeled stent lengths for each stent diameter may vary slightly.
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# VI. ALTERNATIVE PRACTICES AND PROCEDURES
Alternative procedures to treat occlusive disease of the iliac arteries include Percutaneous Transluminal angioplasty (PTA), PTA accompanied by stenting, stenting with another stent for which there is an approved indication, thrombolytic therapy, conservative medical management, exercise therapy, and/or surgical procedures. Atherosclerotic risk factors may be reduced through lifestyle modifications such as cessation of smoking, weight reduction, lipid, control, blood pressure control, and diabetes management.
# VII. MARKETING HISTORY
The Epic Stent System has been marketed for a peripheral vascular use in the European Union and other countries since January 2008. There was one recall in April, 2008 due to catheter tip withdrawal issues, and the tip was redesigned. Since January 2009, the new device has been marketed for peripheral vascular use in the European Union and other countries with no market withdrawals. The list of countries where the Epic Stent System is commercially available follows.
Table 2: Countries where the Epic Stent System is Marketed
| Albania | Djibouti | Kenya | Philippines |
| --- | --- | --- | --- |
| Algeria | Dominican Republic | Kuwait | Poland |
| Andorra | Dutch Antilles | Latvia | Portugal |
| Antigua/Barbuda | El Salvador | Lebanon | Qatar |
| Argentina | Estonia | Libya | Romania |
| Armenia | Finland | Liechtenstein | Saudi Arabia |
| Aruba | France | Lithuania | Serbia |
| Australia | Georgia | Luxembourg | Singapore |
| Austria | Germany | Macedonia | Slovakia |
| Bahamas | Great Britain | Malaysia | Slovenia |
| Bahrain | Greece | Malta | South Africa |
| Bangladesh | Guatemala | Martinique | Spain |
| Barbados | Guyana | Mauritania | Sri Lanka |
| Belgium | Haiti | Moldavia | Surinam |
| Belize | Honduras | Nepal | Sweden |
| Bermuda | Hong Kong | Netherlands | Switzerland |
| Brazil | Hungary | New Zealand | Trinidad & Tobago |
| Bulgaria | Iceland | Nicaragua | Tunisia |
| Canada* | India | Norway | Turkey |
| Chile | Ireland | Oman | United Arab Emirates |
| Colombia | Israel | Pakistan | Uruguay |
| Cyprus | Italy and San Marino | Palestinian Territory | Yemen |
| Czechoslovakia | Jamaica | Panama | |
| Denmark | Japan* | Paraguay | |
*The Epic Stent System is marketed for biliary use in Canada and Japan.
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# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
Potential adverse events that may occur following intravascular stent implantation include, but are not limited to:
- Abscess
- Allergic reaction (to drug, contrast, device or other)
- Amputation
- Aneurysm
- Angina/coronary ischemia
- Arrhythmia
- Arteriovenous fistula
- Death
- Drug reactions
- Embolization (air, plaque, thrombus, device, or other)
- Entanglement of delivery system in deployed stent
- Fever
- GI bleeding
- Hemorrhage/hematoma
- Hypotension/hypertension
- Myocardial Infarction (MI)
- Need for urgent intervention or surgery
- Pseudoaneurysm
- Renal insufficiency or failure
- Restenosis of stented artery
- Sepsis/infection
- Stent fracture
- Stent migration
- Stent misplacement/jumping
- Stent thrombosis with possible neurological injury
- Stroke
- Thrombosis/thrombus
- Tissue ischemia/necrosis
- Vasospasm
- Vessel injury, examples include perforation, dissection, intimal tear, rupture
- Vessel occlusion
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# IX. SUMMARY OF PRECLINICAL STUDIES
A series of non-clinical laboratory studies were performed to evaluate the device.
## A. Biocompatibility Studies
A series of Good Laboratory Practice (GLP) biocompatibility tests were conducted to demonstrate that the components of the Epic Stent System are biocompatible.
All biocompatibility testing was conducted in accordance with:
- Guidance for Industry and FDA Staff: Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems Guidance, April 2010
- Good Laboratory Practices Regulations (§21 CFR Part 58)
- EN ISO 10993-1, Biological Evaluation of Medical Devices
The tests summarized in Table 3 have been conducted in support of the Epic stent component as recommended for a permanent implantable device contacting circulating blood for > 30 days.
Table 3: Biological Evaluation Tests Performed on Stent
| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Cytotoxicity MEM Elution / Part 5 | To determine the potential for cytotoxicity | The test article meets test requirements if none of the cultures treated with the test article show greater than Mild reactivity (Grade 2). | Pass |
| Sensitization Guinea Pig Max / Part 10 | To evaluate the allergenic potential or sensitizing capacity of a test article. | Skin reaction scores received by the test group must be equal or less than the scores received by the negative control group. | Pass |
| Irritation Intracutaneous Reactivity / Part 10 | To screen test article extracts for potential irritation effects. | The requirements of the test are met if the difference between the test article and the control mean score is 1.0 or less (negligible or slight). | Pass |
| Acute Systemic Toxicity / Part 11 | To screen test article extracts for potential systemic toxic effects. | Test is considered negative if none of the animals injected with the test article show a significantly greater biological reaction than the animals treated with the vehicle control. | Pass |
| Material-Mediated Rabbit Pyrogenicity / Part 11 | To determine the presence of chemical pyrogens in extracts of a test article causing a febrile response in rabbits. | If no rabbit shows an individual rise in temperature of 0.5°C or more above baseline, the test article meets the requirements of the test. | Pass |
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| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Hemolysis Direct Contact / Part 4 | To assess the hemolytic activity of the test article when in direct contact with blood. | Results are considered "pass" if the hemolytic index of test article is 5% or less. | Pass |
| Hemolysis Indirect Contact / Part 4 | To assess the hemolytic activity of a test article extract in contact with blood. | Results are considered "pass" if the hemolytic index of test article extract is 5% or less. | Pass |
| Complement Activation / Part 4 | Measurement of complement activation indicates whether a test article is capable of inducing a complement-induced inflammatory immune response in humans. | The concentration of C3a and SC5b-9 in serum exposed to the positive control should be significantly greater than those in the corresponding untreated serum. The test article will be considered positive or negative based upon a statistical comparison to the positive control. | Pass |
| In Vitro Hemocompatibility Assay / Part 4 | To determine if the test article would adversely affect the various cellular and non-cellular components of the blood. | Test article results should be comparable to the results of the negative blood control or the reference material controls. | Pass |
| Partial Thromboplastin Time / Part 4 | To determine the time citrated plasma exposed to a test material takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride. | Results are considered "pass" if the average clotting time of the test article is at least 50% compared to that of the negative control. | Pass |
| Genotoxicity Ames Assay / Part 3 | To evaluate the mutagenic potential of leachables from the test article. | The test article is considered negative if it does not cause increase in 2-fold the mean revertant in all test strains of bacteria. | Pass |
| Genotoxicity Mouse Lymphoma / Part 3 | To evaluate mutagenicity of the test agents. | The test article is considered negative if the test article-dosed cultures have a mutation frequency (MF) of less than 1.8 fold higher than that of the concurrent negative control plates. | Pass |
| Sub-chronic Toxicity, Implantation/ Part 6 & 11 | To evaluate the potential for local and systemic toxicity of a test article implanted subcutaneously in rats for 13 weeks. | Test is considered negative if the test article did not induce a significantly greater biological reaction than the control article. | Pass |
| Implantation - In Vivo Thrombogenicity / Part 4 & 6 | This test is to confirm there is no abnormal thrombosis related to the stent. | No significant differences in vascular response between test article and control stents in stent-related mortality or luminal thrombus. | Pass |
| Implantation / Part 6 | To evaluate the potential for a local irritant or toxic response to material(s) implanted in direct contact with subcutaneous tissue of the rabbit. | Test is considered negative if the test article did not induce a significantly greater biological reaction than the control article. | Pass |
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| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| USP Physicochemical Test for Plastics / Part 18 | To determine the physical and chemical properties of an extract of a test material. | Non-volatile residue <15mg, residue on ignition <5mg (only performed when Non-volatile residue is > 15 mg), heavy metals <1ppm and buffering capacity <10ml. | Pass |
The tests summarized in Table 4 have been performed in support of the Epic delivery system catheter as recommended for externally communicating device contacting the circulating blood with limited exposure of < 24 hours.
Table 4: Biological Evaluation Tests Performed on Epic Delivery System Catheter
| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Cytotoxicity MEM Elution / Part 5 | To determine the potential for cytotoxicity | The test article meets test requirements if none of the cultures treated with the test article show greater than Mild reactivity (Grade 2). | Pass |
| Sensitization Guinea Pig Maximization / Part 10 | To evaluate the allergenic potential or sensitizing capacity of a test article. | Skin reaction scores received by the test group must be equal or less than the scores received by the negative control group. | Pass |
| Irritation Intracutaneous Reactivity / Part 10 | To screen test article extracts for potential irritation effects. | The requirements of the test are met if the difference between the test article and the control mean score is 1.0 or less (negligible or slight). | Pass |
| Acute Systemic Toxicity / Part 11 | To screen test article extracts for potential systemic toxic effects. | Test is considered negative if none of the animals injected with the test article show a significantly greater biological reaction than the animals treated with the vehicle control. | Pass |
| Material-Mediated Rabbit Pyrogenicity / Part 11 | To determine the presence of chemical pyrogens in extracts of a test article causing a febrile response in rabbits. | If no rabbit shows an individual rise in temperature of 0.5°C or more above baseline, the test article meets the requirements of the test. | Pass |
| Hemolysis Direct Contact / Part 4 | To assess the hemolytic activity of the test article when in direct contact with blood. | Results are considered “pass” if the hemolytic index of test article is 5% or less. | Pass |
| Hemolysis Indirect Contact / Part 4 | To assess the hemolytic activity of a test article extract in contact with blood. | Results are considered “pass” if the hemolytic index of test article extract is 5% or less. | Pass |
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| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Complement Activation / Part 4 | Measurement of complement activation indicates whether a test article is capable of inducing a complement-induced inflammatory immune response in humans. | The concentration of C3a and SC5b-9 in serum exposed to the positive control should be significantly greater than those in the corresponding untreated serum. The test article will be considered positive or negative based upon a statistical comparison to the positive control. | Pass |
| In Vitro Hemocompatibility Assay / Part 4 | To determine if the test article would adversely affect the various cellular and non-cellular components of the blood. | Test article results should be comparable to the results of the negative blood control or the reference material controls. | Pass |
| Partial Thromboplastin Time / Part 4 | To determine the time citrated plasma exposed to a test material takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride. | Results are considered "pass" if the average clotting time of the test article is at least 50% compared to that of the negative control. | Pass |
| USP Physicochemical Test for Plastics <661> / Part 18 | To determine the physical and chemical properties of an extract of a test material. | Non-volatile residue <15mg, residue on ignition <5mg (only performed when Non-volatile residue is > 15 mg), heavy metals <1ppm and buffering capacity <10ml. | Pass |
## B. In Vitro Engineering Testing
In vitro engineering testing on the Epic Stent System was conducted, as applicable, in accordance with:
- FDA Guidance for Industry and Staff: Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, April 18, 2010
- FDA Guidance for Industry and Staff: Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment, August 2008
The in vitro engineering studies are summarized in Table 5. "Pass" denotes that the test results met product specifications and/or the recommendation in the above-referenced guidance documents.
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Table 5: Stent and Delivery Catheter Engineering Testing
| Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Material Composition | To verify the composition of nitinol and tantalum stent materials and to measure the composition and thickness of the surface passivation layer | The stent material must conform to ASTM F2063-00 for the nitinol material and to ASTM F560-04 for the tantalum material. The Epic stent exhibited surface composition and passive layer depth consistent with published literature for nitinol surfaces. | Pass |
| Shape Memory and Superelasticity of Intravascular Stents | To determine the Austenite finish transition temperature (Af) of the stent. | The Epic stent must have an Af temperature ≤ 30°C. | Pass
The stent demonstrated an Af temperature between 17.5 °C and 27.2°C when tested per ASTM F2082. |
| Stent Corrosion Resistance - Post 10-year Pulsatile Fatigue Cycling | To document the potential for fretting, pitting and crevice corrosion of the Epic stent. | Both fretting corrosion and crevice and pitting corrosion are evaluated on stents after 10-year pulsatile fatigue cycling (400 million cycles). The stents must have no fretting corrosion greater than 75% of any cross section. Pitting and crevice corrosion was characterized and found no evidence of pitting or material loss when tested per ASTM F2129. | Pass |
| Stent Corrosion Resistance - Galvanic Corrosion | To document the potential for galvanic corrosion when coupled with stents of dissimilar materials. | The resistance to galvanic corrosion was characterized when the Epic stent was coupled separately with the Boston Scientific's Elgiloy Wallstent and tantalum material in an electrolyte solution. No significant stent mass loss was detected indicating that testing did not cause the Epic stents to lose material | Pass |
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| Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Stent Dimensional Verification | To characterize the unconstrained diameter of the Epic stent. | The unconstrained expanded diameter must be within -0.5 mm/+1 mm of its labeled diameter. | Pass |
| Percent Surface Area | To characterize the metal to lumen ratio of the stent. | The metal to lumen must be ≤ 30% for all stent sizes. | Pass |
| Foreshortening | To determine the foreshortening of the stent from the catheter constrained diameter to use diameter. | The Epic stent percent change in length must be < 10% for stent diameters 6-10mm and < 21% for the 12mm stent diameter. | Pass |
| Stent Integrity (Stent Over Expansion) | To verify the stent has no clinically significant defects or flaws after deployment | The stent must exhibited no structural damage or factures after deployment and over expansion. In addition overlapping Epic stents were inspected post 10-year pulsatile fatigue at 200x magnification and exhibited no cracks. | Pass |
| Radial Stiffness and Radial Strength | To characterize ability of the stent to resist collapse when subject to an external load. | The Epic stent must have a compression resistance > 8.5 g/mm for the 6-10 mm stent diameters and > 5.3 g/mm for the 12 mm stent diameter. | Pass |
| Radial Outward Force | To characterize the minimum and maximum outward radial force of the stent within use range. | The outward radial force of each stent diameter must meet the specifications shown below.
Outward Radial Force Specifications | Pass |
| Stent Size (mm) | Min Force (g/mm) | Max Force (g/mm) |
| 6 | ≥ 1.9 | ≤ 17.8 |
| 7 | ≥ 1.9 | ≤ 16.5 |
| 8 | ≥ 1.9 | ≤ 15.2 |
| 9 | ≥ 1.9 | ≤ 13.9 |
| 10 | ≥ 1.9 | ≤ 12.6 |
| 12 | ≥ 1.5 | ≤ 11.4 |
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| Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Mechanical Properties - Pre processing | To evaluate nitinol material prior to processing. | The mechanical properties of the nitinol material must meet the following specifications.
• Loading Plateau > 60ksi
• Unloading Plateau > 17ksi
• Ultimate Tensile Strength > 150ksi
• Strain at Peak Load > 10%
• Unrecovered Strain (permanent set after 8% strain) < 0.5% | Pass |
| Mechanical Properties - Post Processing | To verify the permanent set of the nitinol material post-thermal processing. | The permanent set of the nitinol material post-thermal processing must be <1.5%. | Pass |
| Stress/Strain Analysis/Fatigue Analysis (Finite Element Analysis) | To evaluate the durability and integrity of the Epic stent using Finite Element Analysis (FEA). The FEA analysis simulated the concentric expansion and compression of the Epic stent in vivo | The FEA analysis must demonstrate that the Epic stent maintains acceptable fatigue safety using the Goodman fatigue analysis. | Pass |
| Accelerated Durability Testing | To characterize the accelerated durability of overlapping Epic stents after 10-year pulsatile fatigue cycling. | No stent shall have type II or greater fracture occurrence after 400 million cycles (10 year simulation). No stent fractures were observed in any of the stent pairs after fatigue testing. | Pass |
| Magnetic Resonance Imaging (MRI) Safety and Compatibility | To evaluate the Epic stent for magnetically induced forced, magnetically induced torque, image artifact, and radio frequency (RF) induced heating when placed in field strengths of 1.5 and 3.0 Tesla. | The stent must meet the requirements of Guidance for Industry and FDA Staff: Establishing Safety and Compatibility of Passive Implants in the MR (Magnetic Resonance) Environment, ASTM F2052, ASTM F2213, ASTM F2182, and ASTM 2119 standards for MR Conditional. The conditions under which the device can be safety scanned are reflected in the Directions for Use (DFU). | Pass |
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| Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Radiopacity | To assess the radiopacity of the stent. | The radiopacity of the Epic stent while loaded in the delivery system and post stent deployment must be clinically acceptable when assessed During animal testing. | Pass |
| Crush Resistance | To verify the ability of the stent to recover to its size and shape after applying an external load. | The unconstrained expanded diameter of the Epic stent must be +1mm to -0.5mm of the labeled diameter post-crush. | Pass |
| Kink Resistance | To characterize the smallest radius of curvature the stent can withstand without kinking. | All stents tested recovered to the original shape and size; neither permanent deformation nor full collapse occurred during testing of the Epic stent. | Pass |
| Stent Marker Securement | To characterize the force required to dislodge a tantalum marker from the stent. | The force to dislodge the marker from the stent must be ≥0.7lbs. | Pass |
| Delivery System Dimensional Verification | To document dimensional characteristics of the Epic delivery system. | The catheter effective length must be within ± 1.0cm of the labeled catheter length. The delivery system working length profile must be 6F. The delivery system minimum inner diameter (ID) must allow a 0.036" mandrel or equivalent to pass through the lumen. | Pass |
| Delivery, Deployment and Retraction | To assess the ability of the delivery system to deliver the stent to the intended location and deploy the stent. | The force required to advance and withdraw the delivery system in a simulated clinical model must be < 690g (1.52lbs.). The Epic device must fully deploy the stent and the delivery system must remain fully intact. | Pass |
| Catheter Bond Strength | To evaluate the tensile strength of the delivery system bonds. | The tensile strength of the Epic delivery system bonds must meet product specifications (specification ranged from ≥ 1.57 lbs to ≥ 7.65 lbs depending on bond being tested). | Pass |
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| Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Delivery System Flexibility and Kink Test | To determine the susceptibility of the delivery system to kink. | The Epic delivery system must not kink and must maintain guidewire movement when placed on minimum radius of curvature of 1.5" (38.1 cm). | Pass |
| Torque Strength | To assess the ability of the delivery system to withstand torsional forces. | The delivery system must be able to be subjected to 2 handle rotations without catheter failure. | Pass |
| Delivery System Radiopacity | To assess the radiopacity of the stent. | The Epic delivery system markers must exhibited clinically acceptable radiopacity. | Pass |
## C. Packaging Testing
Packaging verification testing was performed to demonstrate that the design of the Epic Stent System packaging can withstand the hazards of the distribution environment and that the sterility of the device is maintained throughout the labeled shelf life.
## D. Shelf Life Testing
Performance testing was conducted following 3 years of aging to demonstrate that the device and packaging performs within product specifications for a labeled shelf life of 3 years.
## E. Sterilization
The Epic Stent System is sterilized using ethylene oxide (EO) gas and has been validated per AAMI / ANSI / ISO 11135:2007, Sterilization of health care products - Ethylene oxide - Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices. Results from the sterilization studies show that the product satisfies a minimum Sterility Assurance Level (SAL) of $10^{-6}$ and residual levels were within acceptable ranges in accordance with EN ISO 10993-7:2008, Biological Evaluation of Medical Devices - Part 7: Ethylene Oxide Sterilization Residuals.
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# F. Animal Studies
The objective of the nonclinical study program for the Epic Stent System was to evaluate the safety, vascular compatibility, stent integrity, and device and delivery system performance of the Epic stent as compared to the commercially available Boston Scientific Wallstent® Endoprosthesis (Wallstent).
Preclinical evaluations of the Epic stent using the overlapping porcine external iliac artery stent model supported safety and vascular compatibility, with comparable results to Wallstent in key safety parameters including early and late in-stent healing. Epic stent and delivery system acute performance as assessed in the same porcine model demonstrated acceptable clinical performance. Studies were conducted in accordance with §21 CFR 58 (Good Laboratory Practices).
The results support the conclusion that the Epic Stent System is safe based on comparison to a commercially approved product, and is appropriate for commercial release. Summaries of the study designs and results are included in Table 6.
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Table 6: Summary of Epic GLP Animal Studies
| Device | Evaluation Time Points | Target # Stents/Animal & # of Animals | Vessel Location/ Approach | Testing Objective | Results |
| --- | --- | --- | --- | --- | --- |
| Porcine Safety Study 1 | | | | | |
| Epic | 30, 90, 180 days | 2 overlap pair/animal
45 animals | Ilio-femoral artery/carotid approach | Compare vascular response of Epic to Wallstent Control in support of safety using mortality, adverse events, morphology, morphometry parameters | Results support safety and vascular compatibility for Epic and Wallstent:
No device related mortality or adverse events.
No stent thrombosis, no luminal thrombi observed.
Complete endothelialization and tissue strut coverage at all time points.
Inflammation, para-strut fibrin, and medial smooth muscle cell loss-graded predominantly absent or mild.
Neointimal area, medial area, and vascular wall stable over time. |
| Wallstent | | | | | |
| Porcine Safety Study 2 | | | | | |
| Epic | Acute, 30, 180 days | 2 overlap pair/animal
13 animals | Iliac artery/carotid approach | Compare vascular response of Epic to Wallstent Control in support of safety using mortality, adverse events, morphology, morphometry parameters
Evaluate device and delivery system handling characteristics | Results support safety and vascular compatibility for Epic and Wallstent:
No device related mortality or adverse events.
No stent thrombosis, no luminal thrombi observed.
Complete endothelialization and tissue strut coverage at all time points.
Para-strut fibrin and inflammation graded absent or mild.
Neointimal area, medial area, and vascular wall stable over time.
Acceptable acute device performance for all parameters. |
| Wallstent | 30, 180 days | 2 overlap pair/animal
8 animals | | | |
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| Device | Evaluation Time Points | Target # Stents/Animal & # of Animals | Vessel Location/ Approach | Testing Objective | Results |
| --- | --- | --- | --- | --- | --- |
| Porcine Acute Performance Study | | | | | |
| Epic | Acute | 2 non-overlapping stents/animal
6 animals | Iliac and femoral artery/
contralateral femoral approach | Evaluate device and delivery system
handling characteristics
using a contralateral approach model | Acceptable acute device performance for all parameters. |
# X. SUMMARY OF PRIMARY CLINICAL STUDY
The applicant collected clinical data through the ORION clinical trial to establish a reasonable assurance of safety and effectiveness of iliac stenting with the Epic Stent System for the treatment of atherosclerotic lesions found in iliac arteries. The trial was evaluated under IDE G080045. Data from this clinical trial were the basis for the PMA approval decision. A summary of the clinical trial is presented below. Additional data from a clinical study (SUMMIT) conducted in Germany was used to support a reasonable assurance of safety and effectiveness of iliac artery stenting using the 6.0 mm diameter and 120 mm length Epic Stent System for the treatment of subjects with atherosclerotic de novo and restenotic iliac artery disease (Section E – Additional Clinical Data).
# A. STUDY DESIGN
The ORION clinical study was a prospective, single-arm, non-randomized clinical trial which was designed to determine whether the Epic Stent System showed acceptable performance at 9 months for primary stenting of iliac atherosclerotic lesions. The primary endpoint was the 9-month device- and/or procedure-related major adverse event (MAE) rate, adjudicated by an independent Clinical Events Committee (CEC). MAE was defined as death within 30 days, myocardial infarction (MI) that occurs during index hospitalization, target vessel revascularization (TVR) through 9 months, and/or amputation of index limb through 9 months. For the primary endpoint of 9-month MAE, an exact, one-sided 95% upper confidence bound was calculated and compared to the prespecified performance goal. The expected 9-month MAE rate of 8.0% for the Epic Stent System and for iliac artery stenting with self-expanding stents was based on published literature. The performance goal (17.0%) included this expected rate of 8.0% plus a margin of 9.0%.
There were 125 subjects enrolled at 28 investigational centers in the US. Subjects were enrolled from May 14, 2009, to December 14, 2010. The study was considered complete with regard to the primary endpoint when subjects completed 9-month follow-up evaluations. Additional follow-up is ongoing to 3 years.
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Subjects were enrolled after they signed the written informed consent form, their eligibility had been established and the Epic Stent System had entered the body. All MAEs were adjudicated by an independent CEC.
Core laboratories were utilized to review angiographic (CardioVascular Institute at Beth Israel Deaconess Medical Center) and ultrasound data (VasCore). An independent, multidisciplinary CEC was utilized to adjudicate clinical events according to the study protocol.
## 1. Clinical Inclusion and Exclusion Criteria
Enrollment in the ORION study was limited to patients who met the following inclusion criteria:
### General:
- Signed informed consent
- At least 18 years old
- Documented chronic, symptomatic iliac artery atherosclerotic disease (Rutherford/Becker category 1, 2, 3 or 4)
- Lifestyle-limiting claudication or rest pain
### Angiographic:
- De novo or restenotic lesions in the common and/or external iliac artery (applies to all target lesions if multiple)
- Subjects with bilateral disease may have only one target lesion treated per side
- Two target lesions may be treated with a maximum of two stents (if two target lesions are treated, each lesion must be covered with a maximum of one stent)
- Length of diseased segment(s) ≤ 13 cm and treatment is planned with no more than 2 overlapped Epic stents
- Baseline diameter stenosis ≥ 50% (operator visual assessment)
- Reference vessel diameter ≥ 5 mm and ≤ 11 mm
- At least one sufficient ipsilateral infrapopliteal run-off vessel
- Origin of profunda femoris artery is patent
Patients were not permitted to enroll in the ORION study if they met any of the following exclusion criteria:
### General:
- Target vessel with in-stent restenosis
- Acute critical limb ischemia
- Tissue loss (Rutherford/Becker category 5 or 6)
- Any major amputations to the target limb
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- Any minor amputation of the target limb in the last 12 months. If a minor amputation occurred greater than 12 months, stump needs to be completely healed.
- Life expectancy less than 24 months due to other medical co-morbid condition(s) that could limit the subject’s ability to participate in the trial, limit the subject’s compliance with the follow-up requirements, or impact the scientific integrity of the trial
- Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated.
- Intolerance to antiplatelet, anticoagulant, or thrombolytic medications
- Platelet count < 150,000 mm³ or > 600,000 mm³
- Serum creatinine > 2.0 mg/dL
- Dialysis-dependent end stage renal disease
- Pregnancy
- Current participation in another drug or device trial that has not completed the primary endpoint or that may potentially confound the results of this trial
- Known allergy to Nitinol
**Angiographic:**
- Presence of arterial lesions (with the exception of renal, carotid or short, focal SFA lesions) requiring intervention within 30 days of the index procedure
- Superficial femoral artery occlusion in the limb supplied by target vessel
- Heavily calcified and/or excessively tortuous lesions in the target vessel as determined by angiography
- Target lesion is within or near an aneurysm
- Persistent, intraluminal thrombus of the proposed target lesion post-thrombolytic therapy
- Perforated vessel as evidenced by extravasation of contrast media
- Vascular graft, aneurysm or postsurgical stenosis of the target vessel
- Multiple lesions in the same target vessel unable to be treated with a maximum of two stents
## 2. Follow-up Schedule
The schedule of visits and assessments were required for the study is presented in Table 7. Office follow-up examinations were required at 30 days, 9 months and 1 year post index procedure, with additional phone follow-up at 2 and 3 years post index procedure.
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Table 7: Examination Schedule
| | Baseline | | Index Procedure | Postprocedure/Pre-Hospital Discharge | 1-Month (30 days) ± 7 days | 9-month (270 days) ± 30 days | 1-year (365 days) ± 30 days | 2-year (730 days) ± 30 days | 3-year (1,095 days) ± 30 days |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | ≤ 7 days Before Index Procedure | ≤ 24 hours Before Index Procedure | | | | | | | |
| Informed Consent | X | | | | | | | | |
| Inclusion/Exclusion | X | X | X | | | | | | |
| Demographics and Medical History | X | | | | | | | | |
| Physical Examination^{1} | X | | | | | | | | |
| Rutherford Categorization | X | | | X | X | X | X | | |
| ABI | X | | | X | X | X | X | | |
| TASC Classification | | | X | | | | | | |
| Pregnancy Test^{2} | | X | | | | | | | |
| Serum Creatinine | X | | | | | | | | |
| Platelets | X | | | | | | | | |
| Recommended Anti-Coagulant Therapy^{3} Assessment | X | | | | | | | | |
| Required Anti-Platelet Therapy^{4} Assessment | | X | X | X | X | X | X | X | X |
| Walking Impairment Questionnaire (WIQ) | X | | | | | X | X | | |
| Duplex Ultrasound (DUS) | | | | | X | X | X | | |
| Angiography | | | X | | | | | | |
| AE Assessment^{4} | | | X | X | X | X | X | X | X |
1. Physical examination includes gross assessment of standard organ systems (e.g., cardiac, pulmonary, etc).
2. Pregnancy test (via urine or blood) required only for females of childbearing potential.
3. Anti-platelet therapy preprocedure and required to be continued throughout participation in the trial, and procedural anti-coagulant medication consistent with current clinical practice.
4. AE assessment and reporting includes AEs, SAEs and MAEs.
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# 3. Clinical Endpoints
Adverse events were collected throughout the study with a prespecified subset of events adjudicated by an independent Clinical Events Committee.
The Primary Endpoint was the 9-month device- and/or procedure-related major adverse event (MAE) rate (subject-based), adjudicated by an independent CEC. MAE was defined as death within 30 days, myocardial infarction (MI) that occurs during index hospitalization, target vessel revascularization (TVR) through 9 months, and/or amputation of index limb through 9 months.
Secondary Endpoints through 30 days included:
- Technical success (residual stenosis ≤30% based on visual assessment immediately post-procedure)
- Procedural success (technical success and no in-hospital major adverse events)
- Early clinical success at hospital discharge and 30 days post-procedure: improvement in Rutherford classification by ≥1 class as compared to baseline
- Early hemodynamic success at hospital discharge and 30 days post-procedure: improvement in Ankle-Brachial Index (ABI) by ≥0.1 as compared to baseline
- Frequency distribution of Rutherford classification preprocedure and at 30 days postprocedure
- Target vessel revascularization (TVR)
- Target lesion revascularization (TLR)
- Amputation of index limb
- Myocardial infarction (MI) that occurs during index hospitalization
- Death
- Stent thrombosis
Secondary Endpoints through 9 months included:
- Late clinical success at 9 months post-procedure: improvement in Rutherford classification by ≥1 class as compared to baseline
- Frequency distribution of Rutherford classification at 9 months
- Primary, primary-assisted, and secondary patencies at 9 months as assessed by duplex ultrasound
- Restenosis at 9 months as assessed by duplex ultrasound
- Late hemodynamic success at 9 months postprocedure: improvement in ABI by ≥0.1 as compared to baseline
- Change in Walking Impairment Questionnaire scores at 9 months postprocedure
- Target vessel revascularization (TVR)
- Target lesion revascularization (TLR)
- Amputation of index limb
- Death
- Stent thrombosis
- Incidence of unanticipated adverse device effects
- Incidence of all serious adverse events (SAE) reported within the trial
- Incidence of all non-serious adverse events reported within the trial
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# B. Accountability of PMA Cohort
Of the 125 patients enrolled, 91.1% (113/124) completed 9-month follow-up evaluations. Details of 1-month and 9-month follow-up compliance are provided in Table 8.
Table 8: Subject Disposition, Clinical Follow-up Compliance Intent-to-Treat, All Subjects (N=125)
| | Total (Subject) | Total (Lesion) |
| --- | --- | --- |
| Intent to Treat (All Enrolled Subjects) | 125 | 166 |
| Per Protocol (Received Study Stent) | 125 | 166 |
| Not Eligible for 1-Month Clinical Follow-up | 0 | 0 |
| Death ≤ 37 Days with no 1-Month Clinical Follow-up Performed | 0 | 0 |
| Eligible for 1-Month Clinical Follow-up | 125 | 166 |
| No 1-Month Clinical Follow-up | 5 | 6 |
| Missed Follow-up | 1 | 1 |
| Alive, Unable to Contact | 1 | 1 |
| Terminated | 4 | 5 |
| Died | 0 | 0 |
| Withdrawal | 1 | 1 |
| Loss to Follow-up | 3 | 4 |
| 1-Month Visit Clinical Follow-up Performed | 120 | 160 |
| 1-Month Visit Clinical Follow-up Compliance¹ | 96.0% (120/125) | 96.4% (160/166) |
| Not Eligible for 9-Month Clinical Follow-up | 1 | 1 |
| Death ≤ 300 Days with no 9-Month Clinical Follow-up Performed | 1 | 1 |
| Eligible for 9-Month Clinical Follow-up | 124 | 165 |
| No 9-Month Clinical Follow-up | 11 | 14 |
| Missed Follow-up | 4 | 5 |
| Alive, Unable to Contact | 1 | 1 |
| Alive, Refused to Return for Visit | 3 | 4 |
| Terminated | 7 | 9 |
| Died | 0 | 0 |
| Withdrawal | 3 | 4 |
| Loss to Follow-up | 4 | 5 |
| 9-Month Visit Clinical Follow-up Performed | 113 | 151 |
| 9-Month Visit Clinical Follow-up Compliance¹ | 91.1% (113/124) | 91.5% (151/165) |
¹ Death prior to the 9-Month (1-Month) window does not contribute to the denominators and numerators of the compliance rates.
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# C. Study Population and Baseline Parameters
Table 9 presents baseline demographic and clinical characteristics. The ORION population was predominantly male (64.8%) with a history of smoking (96.0%), claudication (92.8%), hyperlipidemia (78.4%), and hypertension (76.0%). Table 10 summarizes baseline lesion characteristics. Among the 160 evaluable baseline lesions, mean RVD was 7.69±1.79 mm, mean lesion length was 31.04±22.13 mm, and mean percent diameter stenosis was 71.51±16.27%.
Table 9: Baseline Demographics and Clinical Characteristics All Subjects (N=125)
| Variable | (N=125 Subjects) |
| --- | --- |
| Demographics | |
| Age, Mean±SD (N), (min,max) | 61.09±9.25 (125)
(39.00, 83.00) |
| Male Gender | 64.8% (81/125) |
| Race/Ethnicity | |
| Hispanic or Latino | 2.4% (3/125) |
| Caucasian | 89.6% (112/125) |
| Asian | 0.0% (0/125) |
| Black, or African heritage | 6.4% (8/125) |
| Native Hawaiian or other Pacific Islander | 0.0% (0/125) |
| American Indian or Alaska Native | 0.8% (1/125) |
| Other | 0.8% (1/125) |
| General Medical History | |
| History of Smoking | 96.0% (120/125) |
| Current Diabetes Mellitus | 36.8% (46/125) |
| History of Hyperlipidemia | 78.4% (98/125) |
| History of Hypertension | 76.0% (95/125) |
| History of COPD | 24.8% (31/125) |
| Cardiac History | |
| History of CAD | 58.4% (73/125) |
| History of MI | 28.0% (35/125) |
| History of PCI | 36.8% (46/125) |
| History of CABG | 17.6% (22/125) |
| Neurologic/Renal History | |
| History of Transient Ischemic Attacks | 4.0% (5/125) |
| History of Cerebrovascular Accident | 5.6% (7/125) |
| History of Renal Insufficiency | 7.2% (9/125) |
| Peripheral Vascular History | |
| History of Peripheral Vascular Surgery | 8.0% (10/125) |
| History of Other Peripheral Endovascular Interventions | 20.0% (25/125) |
| History of Claudication | 92.8% (116/125) |
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Table 10: Baseline Lesion Characteristics – Core Lab All Lesions (N=166)
| Lesion Characteristic | (N=166 Lesions) |
| --- | --- |
| Iliac Artery Segment | |
| Left Common Iliac Artery | 36.3% (58/160) |
| Left External Iliac Artery | 10.0% (16/160) |
| Right Common Iliac Artery | 36.3% (58/160) |
| Right External Iliac Artery | 17.5% (28/160) |
| Reference Vessel Diameter (RVD, mm) | 7.69±1.79 (160)
(4.61, 12.79) |
| Stent Size to RVD Ratio | 1.19±0.25 (160)
(0.68, 1.87) |
| Minimum Lumen Diameter (MLD, mm) | 2.20±1.34 (160)
(0.00, 5.44) |
| Percent Diameter Stenosis (% DS) | 71.51±16.27 (160)
(39.78, 100.00) |
| Lesion Length (mm) | 31.04±22.13 (160)
(4.08, 130.10) |
| Calcification | |
| None/Mild | 23.1% (37/160) |
| Moderate | 28.1% (45/160) |
| Severe | 48.8% (78/160) |
## D. Safety and Effectiveness Results
### 1. Safety Results
For the primary endpoint of 9-month MAE, an exact, one-sided 95% upper confidence bound was calculated and compared to the prespecified performance goal. The expected 9-month MAE rate of 8.0% for the Epic Stent System and for iliac artery stenting with self-expanding stents was based on published literature. The performance goal (17.0%) included this expected rate of 8.0% plus a margin of 9.0%. All enrolled subjects were assessed for adverse events at the 9-month follow-up visit. Assuming a maximum of 15% attrition due to non-compliance with follow-up or other reasons, a minimum of 104 subjects was required to be evaluable for the primary endpoint.
Mathematical representations of the null and alternative hypotheses for the primary endpoint are:
$$
H_0: \theta_{\text{Test}} \geq PG \text{ (Unacceptable Performance)}
$$
$$
H_1: \theta_{\text{Test}} < PG \text{ (Acceptable Performance)}
$$
where $\theta_{\text{Test}}$ is the expected 9-month MAE rate for Epic™ and PG is the prespecified Performance Goal (17%).
The primary endpoint of the ORION Clinical Study is detailed in Table 11. The 9-month MAE rate (primary endpoint) was 3.4% (4/117) with a one-sided upper confidence bound of 7.7%, significantly less than the performance goal of 17.0% (P < 0.0001). The individual components of the composite MAE experienced are presented in Table 12. There were 4 subjects with TVR
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through 9 months, no deaths within 30 days, no index hospitalization MI and no amputations of the index limb through 9 months.
Table 11: Primary Endpoint- Performance Goal Assessment, All Subjects (N=125)
| Measure | (N=125 Subjects) | One-sided 95% Upper Confidence Bound | Performance Goal | p-Value* |
| --- | --- | --- | --- | --- |
| 9-Month MAE | 3.4% (4/117) | 7.7% | 17.0 | <0.0001 |
*P-value is from the one-sided exact-test
Table 12: Primary Safety Results All Subjects (N=125)
| | (N=125 Subjects) | [95% CI] |
| --- | --- | --- |
| 9-Month MAE (per subject) | 3.4% (4/117) | [0.9%, 8.5%] |
| Device- or index procedure-related Death within 30 days | 0.0% (0/117) | [0.0%, 3.1%] |
| Myocardial Infarction (MI) during index hospitalization | 0.0% (0/117) | [0.0%, 3.1%] |
| Target Vessel Revascularization (TVR) through 9 months | 3.4% (4/117) | [0.9%, 8.5%] |
| Amputation of index limb through 9 months | 0.0% (0/117) | [0.0%, 3.1%] |
The Kaplan-Meier curve for all evaluable subjects is presented in Figure 2. The MAE rate is acceptable through the 9-month follow-up time point (270 days).
Figure 2: Freedom from 9 month MAE Event-Free Survival ± 1.96 SE, All Subjects (N=125)
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# 2. Effectiveness Results
Secondary endpoints were summarized at the specified time points using the descriptive statistics, individually or in comparison to their values at baseline.
Primary and secondary effectiveness results are summarized in Table 13 and 14.
Table 13: Primary and Secondary Effectiveness Results, (N=125 Subjects; N=162 Limbs; N=166 Vessels; N=166 Lesions)
| Parameter | Epic^{a} |
| --- | --- |
| 9-Month Clinical Outcomes | |
| Subject based | |
| Late clinical success^{a} | 89.9% (98/109) |
| Lesion based | |
| Primary patency | 95.9% (117/122) |
| Primary-assisted patency | 98.4% (120/122) |
| Secondary patency | 100% (120/120) |
| Restenosis | 2.5% (3/122) |
| Target lesion revascularization (TLR) | 3.2% (5/156) |
| Limb based | |
| Early hemodynamic success^{b} | |
| Hospital discharge | 61.2% (93/152) |
| 30 days | 66.2% (100/151) |
| Late hemodynamic success^{c} | 66.7% (94/141) |
| Vessel based | |
| TVR | 3.2% (5/156) |
| Peri-procedural Endpoints | |
| Technical success (per lesion)^{d} | 100% (166/166) |
| Procedure success (per subject)^{e} | 99.2% (124/125) |
Numbers are % (counts/sample size) or mean±SD (n); outcomes are based on protocol definitions.
a Improvement in Rutherford classification at 9 months by ≥ 1 class as compared to baseline
b: Improvement in ankle-brachial index at hospital discharge and 30 days by ≥ 0.1 as compared to baseline
c: Improvement in ankle-brachial index at 9 months by ≥ 0.1 as compared to baseline
d: Residual stenosis ≤ 30% based on visual assessment immediately post-procedure
e: Residual stenosis ≤ 30% based on visual assessment immediately post-procedure and no in-hospital MAE
Table 14: Summary of Patency and Restenosis Results at 9 Months due to Alternate Analysis, (All Lesions (N=166) in all Subjects (N=125))
| | Epic^{a} |
| --- | --- |
| Lesion Based | |
| Primary-assisted patency | 96.7% (118/122) |
| Secondary patency | 98.3% (118/120) |
| Restenosis | 4.1% (5/122) |
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*Two cases of restenosis and TLR occurred in subject (Left Common and Right Common Iliac Arteries) at the most proximal part of the stents (located at the ostium of both iliac arteries). In this case, conventional method of deriving Systolic Velocity Ratio (SVR) is invalid and the Proximal PSV (Peak Systolic Velocity) was analyzed to assess restenosis at 9 months. These are the results after the alternate analysis has been applied.
The rates of center-reported serious adverse events (SAEs) are summarized by MedDRA System / Organ Class and MedDRA Preferred Term in Tables 15. The rates include all reported serious events, regardless of study device or procedure relatedness.
Table 15. Rates of Center-Reported Serious Adverse Events to 300 Days Intent-to-Treat, All Subjects (N=125)
| Serious Adverse Event | | (N=125 Subjects) | |
| --- | --- | --- | --- |
| MedDRA System/Organ Class | MedDRA Preferred Term | Events | Rate of Subjects with Event |
| Total | Total | 88 | 32.0% (40/125) |
| Not Coded | Not Coded | 1 | 0.8% (1/125) |
| Blood And Lymphatic System Disorders | Total | 4 | 1.6% (2/125) |
| | Anaemia | 2 | 0.8% (1/125) |
| | Febrile Neutropenia | 1 | 0.8% (1/125) |
| | Haemorrhagic Anaemia | 1 | 0.8% (1/125) |
| Cardiac Disorders | Total | 23 | 12.8% (16/125) |
| | Acute Coronary Syndrome | 1 | 0.8% (1/125) |
| | Angina Pectoris | 3 | 2.4% (3/125) |
| | Angina Unstable | 1 | 0.8% (1/125) |
| | Atrial Fibrillation | 7 | 3.2% (4/125) |
| | Cardiac Arrest | 1 | 0.8% (1/125) |
| | Coronary Artery Disease | 4 | 2.4% (3/125) |
| | Coronary Artery Stenosis | 1 | 0.8% (1/125) |
| | Ischaemic Cardiomyopathy | 2 | 1.6% (2/125) |
| | Mitral Valve Stenosis | 1 | 0.8% (1/125) |
| | Myocardial Infarction | 2 | 1.6% (2/125) |
| Eye Disorders | Total | 1 | 0.8% (1/125) |
| | Blindness | 1 | 0.8% (1/125) |
| Gastrointestinal Disorders | Total | 6 | 2.4% (3/125) |
| | Abdominal Pain | 2 | 0.8% (1/125) |
| | Constipation | 1 | 0.8% (1/125) |
| | Gastrointestinal Haemorrhage | 1 | 0.8% (1/125) |
| | Ileus | 1 | 0.8% (1/125) |
| | Upper Gastrointestinal Haemorrhage | 1 | 0.8% (1/125) |
| General Disorders And Administration Site Conditions | Total | 5 | 4.0% (5/125) |
| | Catheter Site Haematoma | 1 | 0.8% (1/125) |
| | Catheter Site Haemorrhage | 1 | 0.8% (1/125) |
| | Chest Discomfort | 1 | 0.8% (1/125) |
| | Non-cardiac Chest Pain | 1 | 0.8% (1/125) |
| | Oedema Peripheral | 1 | 0.8% (1/125) |
| Hepatobiliary Disorders | Total | 3 | 1.6% (2/125) |
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| Serious Adverse Event | | (N=125 Subjects) | |
| --- | --- | --- | --- |
| MedDRA System/Organ Class | MedDRA Preferred Term | Events | Rate of Subjects with Event |
| Hepatobiliary Disorders | Bile Duct Stenosis | 1 | 0.8% (1/125) |
| | Cholecystitis Acute | 1 | 0.8% (1/125) |
| | Cholecystitis Chronic | 1 | 0.8% (1/125) |
| Infections And Infestations | Total | 8 | 4.0% (5/125) |
| | Abdominal Abscess | 1 | 0.8% (1/125) |
| | Clostridial Infection | 1 | 0.8% (1/125) |
| | Diverticulitis | 2 | 0.8% (1/125) |
| | Pneumonia | 3 | 2.4% (3/125) |
| | Wound Infection | 1 | 0.8% (1/125) |
| Injury, Poisoning And Procedural Complications | Total | 6 | 4.0% (5/125) |
| | Drug Toxicity | 1 | 0.8% (1/125) |
| | Stent-graft Malfunction | 2 | 1.6% (2/125) |
| | Vascular Pseudoaneurysm | 2 | 1.6% (2/125) |
| | Wound Dehiscence | 1 | 0.8% (1/125) |
| Investigations | Total | 1 | 0.8% (1/125) |
| | Blood Creatinine Increased | 1 | 0.8% (1/125) |
| Musculoskeletal And Connective Tissue Disorders | Total | 2 | 1.6% (2/125) |
| | Lumbar Spinal Stenosis | 1 | 0.8% (1/125) |
| | Pain In Extremity | 1 | 0.8% (1/125) |
| Neoplasms Benign, Malignant And Unspecified (incl Cysts And Polyps) | Total | 3 | 2.4% (3/125) |
| | Breast Cancer | 1 | 0.8% (1/125) |
| | Lung Neoplasm Malignant | 1 | 0.8% (1/125) |
| | Recurrent Cancer | 1 | 0.8% (1/125) |
| Nervous System Disorders | Total | 4 | 3.2% (4/125) |
| | Carotid Artery Stenosis | 1 | 0.8% (1/125) |
| | Diplegia | 1 | 0.8% (1/125) |
| | Headache | 1 | 0.8% (1/125) |
| | Hypoaesthesia | 1 | 0.8% (1/125) |
| Psychiatric Disorders | Total | 1 | 0.8% (1/125) |
| | Mental Status Changes | 1 | 0.8% (1/125) |
| Respiratory, Thoracic And Mediastinal Disorders | Total | 7 | 3.2% (4/125) |
| | Acute Pulmonary Oedema | 1 | 0.8% (1/125) |
| | Acute Respiratory Failure | 1 | 0.8% (1/125) |
| | Chronic Obstructive Pulmonary Disease | 4 | 1.6% (2/125) |
| | Pneumonia Aspiration | 1 | 0.8% (1/125) |
| Vascular Disorders | Total | 13 | 8.8% (11/125) |
| | Angiodysplasia | 1 | 0.8% (1/125) |
| | Arterial Stenosis | 1 | 0.8% (1/125) |
| | Iliac Artery Thrombosis | 1 | 0.8% (1/125) |
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| Serious Adverse Event | | (N=125 Subjects) | |
| --- | --- | --- | --- |
| MedDRA System/Organ Class | MedDRA Preferred Term | Events | Rate of Subjects with Event |
| Vascular Disorders | Intermittent Claudication | 2 | 1.6% (2/125) |
| | Peripheral Artery Dissection | 3 | 2.4% (3/125) |
| | Peripheral Ischaemia | 1 | 0.8% (1/125) |
| | Peripheral Vascular Disorder | 1 | 0.8% (1/125) |
| | Thrombosis | 1 | 0.8% (1/125) |
| | Vascular Occlusion | 1 | 0.8% (1/125) |
| | Vessel Perforation | 1 | 0.8% (1/125) |
Conclusions: The ORION trial demonstrated the Epic Stent System to be safe and effective in the treatment of atherosclerotic iliac artery disease.
## 3. Subgroup Analysis
## ORION Study Results by Gender/Sex
The ORION clinical study enrolled a total of 81 (64.8%) male subject and 44 (35.2%) female subjects. As shown in Table 16, there were 3 TVR events among the female subjects and 1 TVR among the male subjects. Lesion based primary patency was reported as 98.7% (75/76) and 91.3% (42/46) for the male and female subgroups respectively. These data support similar safety and efficacy outcomes for males and females.
Table 16: Primary Effectiveness and Safety Endpoints by Gender All Lesions (N=166) in (N=125) Subjects
| Measures | Male Event Rate | Female Event Rate |
| --- | --- | --- |
| 9-Month MAE (per subject) | 1.3% (1/76) | 7.3% (3/41) |
| Device- or index procedure-related Death within 30 days | 0.0% (0/76) | 0.0% (0/41) |
| Myocardial Infarction (MI) during index hospitalization | 0.0% (0/76) | 0.0% (0/41) |
| Target Vessel Revascularization (TVR) through 9 months | 1.3% (1/76) | 7.3% (3/41) |
| Amputation of index limb through 9 months | 0.0% (0/76) | 0.0% (0/41) |
| Lesion Based | | |
| 9-Month Primary patency | 98.7% (75/76) | 91.3% (42/46) |
| 9-Month Primary-assisted patency | 98.7% (75/76) | 97.8% (45/46) |
| 9-Month Secondary patency | 100.0% (75/75) | 100.0% (45/45) |
| Subject Based | | |
| 9-Month Primary patency | 98.4% (62/63) | 90.6% (29/32) |
| 9-Month Primary-assisted patency | 98.4% (62/63) | 96.9% (31/32) |
| 9-Month Secondary patency | 100.0% (63/63) | 100.0% (31/31) |
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# Applicability to Pediatric Population
Peripheral artery disease is not typically found in pediatric populations. The Epic Stent System is not indicated for use in pediatric patients. The BSC ORION clinical study did not evaluate safety and effectiveness in the pediatric population.
# XI. SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION
## 1. Study Design
The SUMMIT Registry is an investigator-sponsored, multicenter study in Germany designed to assess the performance of the Epic stent system in symptomatic subjects with superficial femoral artery (SFA)/popliteal artery disease. The study includes follow-up visits at 6 months and 12 months. One hundred subjects were enrolled in the study. To date, baseline data for all subjects and interim clinical and Duplex Ultrasound (DUS) data from the first 35 subjects have been analyzed.
## 2. Study Endpoints
The primary effectiveness endpoint of the study is duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) comparing data within the treated segment to the proximal normal arterial segment at 6 months and 12 months. A PSVR > 2.5 suggests >50% restenosis.
The primary safety endpoint of the study is a composite outcome measure defined as freedom from all cause death, index limb amputation and target lesion revascularization through 30 days.
Key secondary endpoints include technical success, ankle-brachial index assessments, and rate of clinically driven target lesion revascularization.
## 3. Conclusion
Of the 35 patients evaluated in this interim analysis of the SUMMIT Registry, there were 16 patients treated with 6 mm-diameter Epic stents and 13 patients treated with the 120 mm-length Epic stents that support the safety and effectiveness of the Epic Stent System in treatment of iliac artery lesions. All lesions were treated successfully. All subjects assessed by DUS at discharge had a PSVR below 2.5. Of the 35 subjects assessed at 6 months, there was one target lesion revascularization at 6 months in a 6 x 120 mm stent. There were 4 subjects (11.4%) that experienced binary restenosis (PSVR ≥2.5). One subject underwent a pre-determined amputation of the 5th toe on the target limb; this subject was classified as Rutherford 5 at baseline. There were no stent-related serious adverse events and no stent thromboses among these 35 subjects.
While the ORION study provided sufficient data to demonstrate safety and effectiveness in vessel diameters 5 - 11 mm and lesion lengths up to 120 mm, there were only a few patients who received the 6 mm diameter stent or the 120 mm stent length. Therefore, the sponsor submitted supplemental clinical data from the SUMMIT study to support the safety and effectiveness
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of the 6 mm diameter and 120 mm length stent sizes. Given that SFA disease is typically more difficult to treat than iliac disease, and that the ORION study already demonstrated safety and effectiveness in the appropriate iliac vessel diameters and lesion lengths the SUMMIT data were considered appropriate to be used to supplement the safety and effectiveness data from the ORION study.
## XII. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION
In accordance with the 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 System Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.
## XIII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES
### A. Safety and Effectiveness Conclusions
The biocompatibility and in vivo animal testing demonstrated that the acute and chronic in vivo performance characteristics of the Epic Stent System provide reasonable assurance of safety and acceptability for clinical use.
The in vitro engineering testing conducted on the stent and delivery system demonstrated that the performance characteristics met the product specifications.
The test results obtained from the sterilization testing demonstrated that the product can be adequately sterilized and is acceptable for clinical use.
The shelf life testing has established acceptable performance for a labeled shelf life up to 3 years.
The ORION clinical study evaluated the safety and efficacy of the Epic Stent System in the treatment of iliac artery stenosis in de novo or restenotic (from prior PTA) lesions ≤ 13 cm in length in arteries with diameter ≥ 5 mm to ≤ 11 mm. The primary endpoint was met as the rate of 9-month MAE with the intent-to-treat analysis set was 3.4% (4/117) with a one-sided upper confidence bound of 7.7%, significantly less (P < 0.0001) than the prespecified performance goal of 17.0%. Target vessel revascularization was 3.4% (4/117) and accounted for the observed MAE rate. There were 3 stent thrombosis events in the first 30 days, possibly related to placement technique and/or patient comorbidities, resulting in revascularization of the target lesions, and one additional subject with a revascularization at 9 months. There were no device- and/or procedure-related deaths or amputations through 9 months. All lesions were patent at 9 months (also accounting for those which were revascularized).
In summary, the results of the ORION study met the prespecified performance criterion for MAE and demonstrated safety and effectiveness measures that compare favorably with those of other iliac stents.
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## B. Overall Conclusions
The clinical testing conducted demonstrated that the Epic Stent System provides a reasonable assurance of safety and effectiveness when used as indicated in accordance with the Directions for Use.
## XIV. CDRH DECISION
CDRH issued an approval order on April 13, 2012. The final conditions of approval cited in the approval order are described below.
The applicant’s manufacturing facilities were inspected and found to be in compliance with the device Quality System (QS) regulation (§21 CFR 820).
## XV. APPROVAL SPECIFICATIONS
Directions for use: See device labeling.
Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling.
Post-approval Requirements and Restrictions: See approval order.
