ZENITH FENESTRATED AAA ENDOVASCULAR GRAFT

{0} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-1 # Summary of Safety and Effectiveness Data # I. GENERAL INFORMATION | Device Generic Name: | Fenestrated Endovascular Graft and Fenestration Stent | | --- | --- | | Device Trade Name: | Zenith® Fenestrated AAA Endovascular Graft and Zenith® Alignment Stent | | Applicant's Name and Address: | Cook Incorporated 750 Daniels Way P.O. Box 489 Bloomington, IN 47402-0489 USA | | Premarket Approval Application (PMA) Number: | P020018/S040 | | Date of Panel Recommendation: | None | | Date of Notice of Approval to the Applicant: | April 4, 2012 | Expedited: Granted expedited review status on November 22, 2011 because abdominal aortic aneurysms may be serious or life-threatening, or present a risk of serious morbidity. It is believed that the fenestrated endovascular graft configuration will provide an endovascular treatment option for some patients with abdominal aortic aneurysms who are not suitable for treatment with a currently-approved endovascular graft. This may offer a viable alternative to open surgical repair for these patients. Because no legally marketed endovascular device is available for the treatment of abdominal aortic aneurysms in these patients, the FDA decided to grant expedited review. The original PMA (P020018) was for the Zenith AAA Endovascular Graft, which was approved on May 23, 2003 and is indicated for the endovascular treatment of patients with abdominal aortic or aorto-iliac aneurysms having morphology suitable for endovascular repair, including a non-aneurysmal infrarenal aortic 4 April 2012 8 {1} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-2 segment (neck) proximal to the aneurysm with a length of at least 15 mm. The SSED to support the indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the Zenith AAA Endovascular Graft product line to include the Zenith Fenestrated AAA Endovascular Graft (with the Zenith Alignment Stent), which is indicated for the endovascular treatment of patients with abdominal aortic or aorto-iliac aneurysms that have an infrarenal aortic neck at least 4 mm in length. # II. INDICATIONS FOR USE # A. Zenith Fenestrated AAA Endovascular Graft The Zenith Fenestrated AAA Endovascular Graft is indicated for the endovascular treatment of patients with abdominal aortic or aortoiliac aneurysms having morphology suitable for endovascular repair, including: - Adequate iliac/femoral access compatible with required introduction systems Nonaneurysmal infrarenal aortic segment (neck) proximal to the aneurysms with: Length \(\geq 4\) mm and unsuitable for a non-fenestrated graft Diameter \(\leq 31\) mm and \(\geq 19\) mm Angle \(< 45\) degrees relative to long axis of aneurysm Angle \(< 45\) degrees relative to axis of suprarenal aorta - Ipsilateral iliac artery fixation site \(>30 \mathrm{~mm}\) in length and between 9 - 21 mm in diameter - Contralateral iliac artery distal fixation site \(>30 \mathrm{~mm}\) in length and between 7 - 21 mm in diameter # B. Zenith Alignment Stent The Zenith Alignment Stent is indicated for use as an adjunct to the Zenith Fenestrated AAA Endovascular Graft to secure positive alignment of fenestrations or scallops with the orifice of aortic branch vessels having diameters ranging from 3 to 8 mm. 4 April 2012 9 {2} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-3 ### III. CONTRAINDICATIONS The Zenith® Fenestrated AAA Endovascular Graft and Zenith® Alignment Stent are contraindicated in: - Patients with known sensitivities or allergies to stainless steel, polyester, nitinol, solder (tin, silver), polypropylene or gold - Patients with systemic or local infection that may increase the risk of endovascular graft infection ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Zenith Fenestrated AAA Endovascular Graft and Zenith Alignment Stent labeling (Instructions for Use). ### V. DEVICE DESCRIPTION #### 1. General Description – Fenestrated Endovascular Graft The Zenith Fenestrated AAA Endovascular Graft is a modular system consisting of three components, a proximal body graft, a distal bifurcated body graft and one iliac leg (Figure 1). The graft modules are constructed of full-thickness woven polyester fabric sewn to self-expanding stainless steel Cook-Z® stents with braided polyester and monofilament polypropylene suture. These materials are identical to the materials used to construct the standard Zenith® AAA Endovascular Graft, with the Zenith Fenestrated AAA Endovascular Graft also having a nitinol wire ring around the graft fenestrations. Ancillary devices that are currently available for the standard Zenith® AAA Endovascular Graft such as main body extensions, iliac leg extensions, converters, and iliac plugs may also be required. 4 April 2012 b {3} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-4  Figure 1. Zenith Fenestrated AAA Endovascular Graft main components. Each component comes in a range of lengths and diameters which allows the physician to tailor the device to individual patient anatomies and select the best proximal and distal fixation sites. Unlike the standard Zenith AAA Endovascular Graft, the Zenith Fenestrated AAA Endovascular Graft has fenestrations or scallops in the graft material, which allow the proximal edge of graft material to be placed above the renal arteries while still permitting blood flow to vessels accommodated by the fenestrations or scallops. In order to account for anatomical variation, each proximal body graft is made to order for a specific patient. ### A. Proximal Body Graft The proximal body graft is the first component of the Zenith Fenestrated AAA Endovascular Graft to be deployed during the procedure. The bare supararenal stent at the proximal end of the proximal body graft contains barbs. This graft contains up to three precisely located holes (fenestration(s)), and cut-outs from the proximal margin (scallop(s)) of the graft material (Figure 1). The fenestrations may be a combination of small fenestrations (Figure 2a), large fenestrations (Figure 2b), and scallop fenestrations (Figure 2c), and allow the proximal margin of the device to sit more cranially in the aorta than a standard 4 April 2012 11 {4} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-5 AAA endograft, including the Zenith Flex AAA Endovascular Graft, which are intended for placement of the proximal graft margin inferior to the lowest renal artery. This design permits uninterrupted blood flow to branch vessels of the aorta such as the renal and superior mesenteric arteries after device deployment. The choice and placement of the fenestrations and/or scallops is dependent on individual patient anatomy. Small fenestrations are generally used to accommodate renal arteries. Large fenestrations and scallops can be used to accommodate renal or superior mesenteric arteries. Also illustrated by Figure 2 are the gold markers used to identify the margins of each fenestration. The small and large fenestrations each contain 4 gold markers that are positioned around the perimeter at the graft material margin. The scallop fenestration is identified by 3 gold markers: 1 each at the left and right proximal most margins of the scallop, and 1 centered at the distal most margin of the scallop.  Figure 2a. Small fenestration  Figure 2b. Large fenestration  Figure 2c. Scallop fenestration Additionally, gold radiopaque markers are positioned on the proximal component as follows to aid in fluoroscopic visualization; one at the distal end of the graft and four in a circumferential orientation at the proximal end of the graft (Figure 3).  Figure 3. Gold markers at graft margin of proximal component 4 April 2012 12 {5} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-6 The proximal component also contains vertically-aligned gold markers located on the anterior aspect of the graft and horizontally-aligned gold markers located on the posterior aspect of the graft. These markers help with orientation of the proximal component by forming a cross (+) under fluoroscopy when the device is aligned as intended (Figure 4). Additional gold markers are positioned anteriorly in the shape of a tick or check marker.   Figure 4. Vertically-aligned gold markers on the anterior aspect and horizontally-aligned gold markers on the posterior aspect of the proximal component The proximal body graft is available in a number of diameters and lengths, as provided in Table 1. Table 1 also lists the corresponding delivery system sheath sizes. Table 1. Proximal body graft sizes and corresponding delivery system sizes | Proximal Body Graft | Diameter (mm) | Body Length (mm) | Introducer Sheath (Fr) | Introducer Sheath Length (cm) | | --- | --- | --- | --- | --- | | | 24 | 76 / 91 / 94 / 106 / 109 / 121 / 124 | 20 | 50 | | | 26 | 76 / 91 / 94 / 106 / 109 / 121 / 124 | 20 | 50 | | | 28 | 76 / 91 / 94 / 106 / 109 / 121 / 124 | 20 | 50 | | | 30 | 76 / 91 / 94 / 106 / 109 / 121 / 124 | 20 | 50 | | | 32 | 76 / 91 / 94 / 106 / 109 / 121 / 124 | 20 | 50 | | | 34 | 84 / 99 / 114 / 129 / 107 / 122 / 137 | 20 | 50 | | | 36 | 84 / 99 / 114 / 129 / 107 / 122 / 137 | 20 | 50 | 4 April 2012 13 {6} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-7 ### B. Proximal Body Graft Delivery System The Zenith® Fenestrated AAA Endovascular Graft proximal graft is shipped preloaded onto the H&L-B One-Shot™ Introduction System (Figure 5). The H&L-B One-Shot™ Introduction System is constructed from identical materials and is similar in design and deployment characteristics to the H&L-B One-Shot™ Introduction System that the standard Zenith Flex AAA Endovascular Graft is loaded on. It has a sequential deployment method to provide control of the endovascular graft throughout the deployment procedure. During manufacture, the graft is reduced in diameter by an independent wire tied to removable diameter reducing ties (Figure 6). This is unique to the Fenestrated device and allows the partially constrained graft to be manipulated within the aorta to allow positioning of the graft so that the fenestrations can line up with the desired arteries before complete device deployment. Same as with the standard device, the bare suprarenal stent is constrained within a top cap and held there by a trigger wire. The distal end of the graft is also attached to the delivery system and held by an independent wire. The H&L-B One-Shot™ Introduction System allows readjustment of the final graft position before deployment of the bare barbed suprarenal stent. The delivery system uses a 20 French H&L-B One-Shot™ Introduction System. All systems are compatible with a 0.035 inch wire guide.  Figure 5. Proximal introduction system 4 April 2012 14 {7} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-8  Figure 6. Diameter reducing ties on the proximal main body component ### C. Distal Bifurcated Body Graft The Zenith Fenestrated AAA Endovascular Distal Bifurcated Body Graft has one long ipsilateral iliac limb and one short contralateral limb. There is a radiopaque marker at the proximal end of the graft as well as at the graft bifurcation and at the distal end of the contralateral limb (Figure 7).  Figure 7. Gold markers on distal bifurcated body The distal main body graft is available in a number of diameters and lengths, as listed in Table 2. Table 2 also lists the corresponding delivery system sheath sizes. Table 2. Distal body graft sizes and corresponding delivery system sizes | Distal Bifurcated Body Graft | Diameter (mm) | Body Length (mm) | Leg Length (mm) | Introducer Sheath (Fr) | Introducer Sheath Length (cm) | | --- | --- | --- | --- | --- | --- | | | 12 | 76/91/106/121 | 28/45/62 | 20 | 40 | | | 16 | 76/91/106/121 | 28/45/62 | 20 | 40 | | | 20 | 76/91/106/121 | 28/45/62 | 20 | 40 | | | 24 | 76/91/106/121 | 28/45/62 | 20 | 40 | 4 April 2012 15 {8} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-9 ### D. Distal Bifurcated Body Graft Delivery System The Zenith® Fenestrated AAA Endovascular Graft distal body graft is shipped preloaded onto the H&L-B One-Shot™ Introduction System (Figure 8). Both the proximal and distal ends of the graft are attached to the delivery system and held by independent wires. The H&L-B One-Shot™ Introduction System allows readjustment of the final graft position before deployment of the stent-graft. The delivery system uses a 20 French H&L-B One-Shot™ Introduction System. All systems are compatible with a 0.035 inch wire guide.  Figure 8. Distal introduction system ### E. Iliac Leg Graft and Delivery System The fenestrated Zenith graft uses the same iliac legs as the standard Zenith graft. The iliac legs are tubular grafts which are used to extend the fenestrated graft into the iliac arteries. An iliac leg must be placed into the short limb from the contralateral side. 4 April 2012 16 {9} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-10 # F. Ancillary Components and Delivery System The fenestrated Zenith graft is compatible with the same ancillary components as the standard Zenith graft. The following ancillary endovascular components are available: - Main body extensions - Leg extensions - Converters - Iliac occluders # G. Zenith Alignment Stent Zenith Alignment Stents may be placed in branch vessels targeted by fenestrations or scallops to secure positive alignment. The Zenith Alignment Stent is a balloon-expandable stent that can be deployed through scallops or small fenestrations in a Zenith Fenestrated AAA Endovascular Graft into branch vessels of the aorta. The stent is constructed of 316L stainless steel. The distal segment of the stent is designed to be expanded into the target vessel. The flarable proximal segment of the stent is designed to extend into the lumen of a Zenith Fenestrated AAA Endovascular Graft already deployed in the aorta and can be flared using a standard non-compliant balloon, to allow for ease in reintervention. The margin between the flarable proximal segment and non-flarable distal segment of the Zenith Alignment Stent is denoted by circumferentially arranged gold markers on the stent that are to be aligned with the graft fenestrations. As depicted in Figure 9, the region/zone of the stent likely to be in contact with the fenestration is reinforced. The Zenith Alignment Stent is available in lengths of 18 and 26 mm, and nominal expanded diameters of 3, 4, 5, 6, 7, and 8 mm (Table 3). Figure 7 depicts the Zenith Alignment Stent before and after flaring. 4 April 2012 17 {10} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-11  Figure 9. Zenith Alignment Stent (a) flarable proximal segment, (b) non-flarable distal segment, and (c) reinforced zone Table 3. Available diameters and lengths of the Zenith Alignment Stent and corresponding sheath compatibility | Nominal Stent Size (Diameter x Length) | Crimped Stent | Expanded Stent | | Introducer Sheath Compatibility | | --- | --- | --- | --- | --- | | | Total Length (mm) | Total Length (mm) | Non-flarable Segment Length (mm) | | | 3 x 18 mm | 18.4 | 18.3 | 13.3 | 6 Fr | | 3 x 26 mm | 25.3 | 25.3 | 20.2 | 6 Fr | | 4 x 18 mm | 18.3 | 18.1 | 13.2 | 6 Fr | | 4 x 26 mm | 25.3 | 25.2 | 20.3 | 6 Fr | | 5 x 18 mm | 17.7 | 17.7 | 12.2 | 6 Fr | | 5 x 26 mm | 26.3 | 26.7 | 20.8 | 6 Fr | | 6 x 18 mm | 17.8 | 17.8 | 12.3 | 6 Fr | | 6 x 26 mm | 26.4 | 26.6 | 20.9 | 6 Fr | | 7 x 18 mm | 18.3 | 18.2 | 12.2 | 6 Fr | | 7 x 26 mm | 26.9 | 27.0 | 20.8 | 6 Fr | | 8 x 18 mm | 18.3 | 17.9 | 12.2 | 7 Fr | | 8 x 26 mm | 26.9 | 27.1 | 20.8 | 7 Fr | 4 April 2012 18 {11} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-12 ### H. Zenith Alignment Stent Balloon Delivery System The Zenith Alignment Stent is pre-mounted and positioned between two radiopaque (platinum) marker bands on the balloon catheter, which serves as the delivery system. The delivery system is advanced through an introducer sheath into a target artery. The sheath is withdrawn and the gold markers on the stent are aligned with the gold markers designating a fenestration or scallop. The stent is then deployed by inflating the balloon to the recommended expansion pressure as indicated in the stent IFU. After removal of the Zenith Alignment Stent balloon catheter, a 10 mm non-compliant balloon catheter is inserted within the flarable proximal segment of the stent and inflated to the recommended expansion pressure indicated in the balloon IFU. The delivery system is 80 cm in length and its profile permits vascular access via 6.0 or 7.0 French introducer sheaths (dependent on the selected Zenith Alignment Stent size). A depiction of the delivery system is presented in Figure 10.  Figure 10. Zenith Alignment Stent delivery system. ### VI. ALTERNATIVE PRACTICES AND PROCEDURES There are no approved endovascular graft options for the treatment of patients with a short infrarenal aortic neck. The available treatment options for patients with an abdominal aortic aneurysm and a short infrarenal aortic neck are conventional surgical repair and medical management. Each alternative has advantages and disadvantages. The physician should fully discuss these alternatives with the patient to select the method that best meets expectations and lifestyle. 4 April 2012 19 {12} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-13 # VII. MARKETING HISTORY The Zenith Fenestrated AAA Endovascular Graft has been commercially available outside the US since November 2002. The Zenith Fenestrated AAA Endovascular Graft is available in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Dominican Republic, European Union, Hong Kong, India, Malaysia, New Zealand, Serbia, Singapore, Taiwan, Thailand, Turkey, and Uruguay. The Zenith Fenestrated AAA Endovascular Graft has not been withdrawn from any market for reasons related to safety and effectiveness. # VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Adverse events that may occur and/or require intervention include, but are not limited to: Amputation Anesthetic complications and subsequent attendant problems (e.g., aspiration) Aneurysm enlargement Aneurysm rupture and death Aortic damage, including perforation, dissection, bleeding, rupture, and death - Arterial or venous thrombus and/or pseudoaneurysm - Bleeding, hematoma or coagulopathy - Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis) - Cardiac complications and subsequent attendant problems (e.g., arrhythmia, myocardial infarction, congestive heart failure, hypotension, hypertension) Claudication (e.g. buttock, lower limb) Death Edema - Embolization (micro and macro) with transient or permanent ischemia or infarction Endoleak Endoprosthesis: improper component placement; incomplete component deployment; component migration; suture break; occlusion; infection; stent fracture; graft material wear; dilation; erosion; puncture; perigraft flow; barb separation and corrosion Fever and localized inflammation Fistula (e.g., aortoenteric, arteriovenous) 4 April 2012 20 {13} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-14 - Genitourinary complications and subsequent attendant problems (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection) - Hepatic failure - Impotence - Infection of the aneurysm, device or access site, including abscess formation, transient fever and pain - Lymphatic complications and subsequent attendant problems (e.g., lymph fistula) - Neurologic local or systemic complications and subsequent attendant problems (e.g., confusion, stroke, transient ischemic attack, paraplegia, paraparesis, paralysis) - Occlusion of device or native vessel - Organ impairment/loss due to side-branch vessel occlusion (in particular, renal and/or gastrointestinal impairment/loss) - Pulmonary/respiratory complications and subsequent attendant problems (e.g., pneumonia, respiratory failure, prolonged intubation) - Renal complications and subsequent attendant problems (e.g., artery stenosis or occlusion, contrast toxicity, insufficiency, failure) - Surgical conversion to open repair - Vascular access site complications, including infection, pain, hematoma, pseudoaneurysm, arteriovenous fistula - Vascular spasm or vascular trauma (e.g., iliofemoral vessel dissection, bleeding, rupture, death) - Vessel damage - Wound complications and subsequent attendant problems (e.g., dehiscence, infection, hematoma, seroma, cellulitis) For the specific adverse events that occurred in the clinical studies, please see Section X below. 4 April 2012 21 {14} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-15 # IX. SUMMARY OF NON-CLINICAL STUDIES # A. Biocompatibility # 1. Zenith Fenestrated AAA Endovascular Graft The Zenith Fenestrated AAA Endovascular Graft System is a product line extension of the Zenith Flex AAA Endovascular Graft System and utilizes the same materials as with the currently-approved system. Therefore, additional biocompatibility testing was not necessary for the Zenith Fenestrated AAA Endovascular Graft. # 2. Zenith Alignment Stent A panel of biocompatibility testing was performed on the Zenith Alignment Stent and delivery system in accordance with FDA's biocompatibility testing guidance, ISO 10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing, and 21 CFR 58 Good Laboratory Practice (GLP) requirements. The stent was assessed by tests considered appropriate for a permanent (>30 days) blood-contacting implant, and the delivery systems were assessed by tests considered appropriate for a limited time, circulating-blood contacting, externally-communicating device. Biocompatibility testing performed on the Zenith Alignment Stent and the delivery system are summarized in Table 4. The test articles in each of the following biocompatibility tests consisted of the Zenith Alignment Stent and delivery system. The stents included in this testing did not have gold markers; however, gold radiopaque markers have been included on every Zenith device to date, with no adverse clinical sequelae related to the presence of gold markers. Therefore, additional testing of the Zenith Alignment Stent with gold markers was not considered necessary. Longer-term biocompatibility testing for the Zenith Alignment Stent was leveraged from the Formula™ Balloon-Expandable Stent (approved for renal use under P100028) and has been reviewed by FDA previously. Test results for the Formula™ Balloon-Expandable Stent are considered applicable as the stent is manufactured from the same material and is the same design as the segment of the Zenith Alignment Stent intended for vessel contact. The leveraged testing included genotoxicity, ISO muscle implantation, 4 April 2012 22 {15} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-16 and plasma recalcification time coagulation. Compared to the Formula Balloon-Expandable Stent, the delivery system for the Zenith Alignment Stent utilizes different color additives for the balloon catheter tip and shaft, which contact the body for a limited period of time and were shown to be biocompatible based on the results from testing described in Table 4. Table 4. Summary of biocompatibility testing – Zenith Alignment Stent and delivery system | Test Type | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | USP and ISO Acute Systemic Toxicity (extracts) | Determine whether extracts would cause acute systemic toxicity | The device/ material shall show no evidence of significant systemic toxicity | Pass | | Cytotoxicity: ISO Elution Method (1X MEM Extract) | Determine whether extracts would cause cytotoxicity | The device/ material shall not show more than 50% lysis (grade 2, mild cell lysis) | Pass | | In vivo Thrombo-resistance Study (carotid artery) | Determine whether the device triggers thrombus formation | The device/ material shall be considered thrombo-resistant and there shall be no evidence of thrombus formation | Pass | | In vitro Hemolysis Study (modified ASTM-extraction method) | Determine whether extracts would cause hemolysis in vitro | The device/ material shall be considered nonhemolytic (hemolytic index 0-2%) | Pass | | ISO Intracutaneous Study (extract) | Determine whether extracts would cause local dermal irritant or toxic effects | The device/ material shall not exhibit significant irritation | Pass | | ISO Maximization Sensitization Study (extract) | Evaluate the potential for delayed dermal contact sensitization | The device/ material shall show no evidence of causing delayed dermal contact sensitization | Pass | ### B. Laboratory (in vitro) Studies As a product line extension, much of the testing previously performed on the Zenith Flex AAA Endovascular Graft is applicable to the Zenith Fenestrated AAA Endovascular Graft. A comprehensive preclinical testing plan was conducted to evaluate any differences in design and verify that the performance attributes of the Fenestrated Graft System are acceptable. All testing was conducted in accordance with national and international standards and guidance 4 April 2012 23 {16} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-17 documents. The results obtained from in vitro testing provided evidence supporting safety and effectiveness of the Fenestrated Graft System # 1. Zenith Fenestrated AAA Endovascular Graft The results of in vitro bench testing performed on the Zenith Fenestrated AAA Endovascular Graft (implant) are summarized in Table 5. Table 5. Results of testing performed for the implant | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Dimensional verification | Determine the outer diameters and lengths of the endovascular prosthesis in the deployed state for verification to design specifications | • Length must be ± 5% of the nominal length; • The diameter of the proximal vessel seal site (D1) must be ± 5% of the nominal outer diameter (NOD); • D2 (maximum measured outer diameter) < D3 (minimum measured outer diameter) + 1.432 mm; • D3 (minimum measured outer diameter) > D2 (maximum measured outer diameter) - 1.432 mm; • D4 (maximum measured outer diameter) < iliac leg graft (minimum measured outer diameter) + 1.34 mm; and • The diameter of the distal vessel seal site (D5) must be ± 10% of the nominal diameter (NOD) for nominal diameters < 20 mm or ± 5% of the nominal diameter for nominal diameters ≥ 20 mm | Pass | | Flex/kink | Determine the minimum radius that the endovascular prosthesis can accommodate without kinking | Maximum kink radius must be < 50.8 mm | Pass | | Pull test for modular components | Determine the force required to separate the modular components of an endovascular prosthesis or to separate overlapping endoprostheses in the deployed state | Separation force must be ≥ 5.1 N | Pass | 4 April 2012 24 {17} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-18 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Radial Force | Demonstrate that when grafts are sized correctly, the z-stents are expected to exert a radial force sufficient enough to maintain graft patency and apposition to the vessel wall without causing vessel damage | Radial force must be between 7.7 N and 14.3 N. | Pass | | Fatigue & durability (pulsatile) | Evaluate the fatigue life of the Fenestrated Graft in combination with Alignment Stent during physiologic pulsatile loading for 400 million cycles (10 year simulated fatigue) | No stent fractures;External stents must not have more than six suture attachment failures in a row;Internal stents must not completely separate from the graft;Graft material wear around a small fenestration and at the graft to fenestration stent interface shall not show any opening up of the weave construction that is wider than the stent wire at that location;Nitinol ring shall remain in location around the small fenestration and shall not develop fractures leading to a free floating piece of wire;Fenestration ring retention sutures shall not develop a suture fracture(s) leading to a free floating detached suture after 10-year time-accelerated radial fatigue test;Zenith Alignment Stent must maintain position within the fenestrated stent-graft such that the cross-sectional area of the orifice is reduced by no more than 60%; andZenith Alignment Stent must not have any fractures not present in the non-Cook stents tested. | Pass | 4 April 2012 25 {18} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-19 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Fatigue and durability (bending) | Evaluate the fatigue life of the Fenestrated Graft in combination with Alignment Stent during simulated respiration for 85 million cycles (10 year simulated fatigue) | • Graft material wear around a small fenestration, and the graft to fenestration stent interface shall not show any opening up of the weave construction that is wider than the stent wire at that location • Nitinol ring shall remain in location around the small fenestration and shall not develop fractures leading to a free floating piece of wire • Fenestration ring retention sutures shall not develop a suture fracture(s) leading to a free floating detached suture after 10-year time accelerated respiratory motion test • Zenith Alignment Stent must not have any fractures not present in the non-Zenith stents tested | Pass | | Stress/strain analysis | To determine and locate the maximum stresses and strains in the implant when subjected to worst-case catheter loading, deployment, and physiological pulsatile loading | The fatigue safety factors must be >1.0 | Pass | The results of in vitro bench testing performed on the Zenith Fenestrated AAA Endovascular Graft H&L-B One Shot Introduction System (delivery system/complete assembly) are summarized in Table 6. Table 6. Results of testing performed for the delivery system/complete assembly | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Simulated use models (deployment) | Demonstrate that the Zenith® Fenestrated AAA Endovascular Graft and delivery system perform as intended with respect to dimensional compatibility, trackability, pushability, torquability, and deployability in a simulated use model | 100% success for each of the deployment parameters assessed | Pass | 4 April 2012 26 {19} Supplement to P020018. Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-20 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Visibility | Demonstrate that the Zenith® Fenestrated AAA Endovascular Graft and delivery system perform as intended with respect to visibility in a simulated use model | 100% success for each of the visibility parameters assessed | Pass | | Force to deploy | The purpose of this test is to determine the force to deploy the endovascular prostheses, including the force necessary for sheath retraction, trigger wire withdrawal, and top cap advancement | • Sheath retraction must be < 100 N • Trigger wire withdrawal must be < 35 N • Top cap advancement must be < 15 N | Pass | | Bond strength | Determine tensile characteristics of the delivery system using a tensile testing machine | • Inner cannula/dilator tip must be ≥ 60.4 N • Hub/inner cannula must be ≥ 60.4 N • Pin vise handle/dilator must be ≥ 60.4 N • Valve/sheath must be ≥ 100 N • Trigger wire/trigger knob ≥ 35 N | Pass | | Torsional bond strength | Determine the maximum torque required to cause failure of the delivery system components | • Needle hub/threaded cannula must be > 0.02 N·m; • Threaded dilator tip/threaded cannula must be > 0.068 N·m; • Threaded dilator tip/threaded cap must be > 0.068 N·m; • Pin vise handle/dilator must be > 0.068 N·m | Pass | ## 2. Zenith Alignment Stent The results of in vitro bench testing performed on the Zenith Alignment Stent (implant) are summarized in Table 7. Table 7. Results of testing performed for the implant | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Stent Corrosion Resistance | Evaluate the susceptibility of the metallic components of the stent to corrosion in a simulated physiological environment | The mean breakdown potential of the Zenith Alignment Stent shall be ≥ 586 mV_{SCE} | Pass | 4 April 2012 27 {20} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-21 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Foreshortening | Determine the amount a stent will foreshorten upon deployment | For the non-flatable (arterial) region of the stent, the calculated maximum length change between the expanded (post-deployed) stent length and crimped (undeployed) stent length must be less than 5% | Pass | | Dimensional Verification | Determine the outer diameter of the stent in the deployed state | On an expanded stent, O.D_{max} - O.D_{min} must be less than or equal to 0.5 mm for the non-flatable segment of the stent | Pass | | Recoil for Balloon Expandable Stents | Determine the amount of elastic recoil after the deployment of a balloon-expandable stent | For the arterial segment of the stent, the stent recoil must be less than 6% | Pass | | Stent Integrity | Evaluate the integrity of the stent following deployment | There must be no microscopic evidence of structural deficiency at 50-63X magnification after deployment | Pass | | Percent Surface Area | Determine the percentage of vessel surface area covered by the stent struts (abluminal surface area) when the stent is expanded to its nominal diameter | No acceptance criteria - for characterization of stent design criteria | Surface area was between 13.11% and 21.31% depending on stent size | | Radial Stiffness and Radial Strength | Determine the ability of a stent to withstand deformation due to external radial forces. | Radial strength > π x D_{Nom} x 0.02133 N/mm² and radial stiffness >0.134 N/mm² | Pass | | Crush Resistance | Determine the crush resistance of the Zenith Alignment Stent when subjected to external focal loading | The shear force required to reduce the cross-sectional area of the 6, 7, and 8 mm diameter stents by 60% must be >2.37 N. Testing of 3, 4, and 5 mm diameter stents was performed for characterization purposes only. | Pass | | Shelf Life | Establish an expiration period for the product | No sign of stent fractures at a magnification of 50x following balloon burst testing after aging | Pass | 4 April 2012 28 {21} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-22 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Stress/strain Analysis | To determine and locate the maximum stresses and strains in the implant after crimping, deployment, and physiological pulsatile loading, bending loading, and combined (pulsatile and bending) loading | The fatigue safety factors must be >1.0 | Pass | | Fatigue and Durability (pulsatile) | Evaluate the fatigue life of the stent by subjecting it to time-accelerated, physiologically modeled, controlled displacement pulsatile loading for 400 million cycles | No stent fractures | Pass | | Fatigue and Durability (bending) | To determine the bending fatigue endurance limit of the stent, defined as the bending angle/radius of curvature at which six out of six test articles achieved run-out to 85 million cycles without fracture | The endurance limit radius of curvature must be less than the physiologically relevant curvature during respiration | Pass | The results of in vitro bench testing performed on the Zenith Alignment Stent Balloon Catheter (balloon catheter/complete assembly) are summarized in Table 8. Table 8. Results of testing performed for the balloon catheter/complete assembly | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Crossing profile | Determine the undeployed stent outer diameters | No acceptance criteria – for characterization of sheath compatibility | Stents will fit in specified sheaths | | Balloon profile | Determine the undeployed balloon outer diameters | No acceptance criteria – for characterization of sheath compatibility | Stents will fit in specified sheaths | | Stent Diameter vs. Balloon Pressure (Compliance Chart) | The purpose of this test was to determine the relationship between stent diameter and balloon inflation pressure | At nominal inflation pressure (8 atm), stent inner diameter must equal the labeled diameter + 10% with a confidence interval of 95% and a reliability interval of 99% | Pass | 4 April 2012 29 {22} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-23 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Balloon Rated Burst Pressure | Determine the rated burst pressure (RBP) of the delivery system balloon | • With the stent mounted on the balloon, 99.9% of balloons must survive at least 12 atm of pressure (the labeled rated burst pressure) with a confidence of 95%; • Balloon failure must occur linearly and not at the balloon bond sites; and • There must be no microscopic evidence of structural deficiency of the stent at 50-63X magnification after balloon burst | Pass | | Deployment and Sheath Compatibility Testing | Evaluate performance of the endovascular system using a model that simulates deployment under the intended use conditions | 100% success for all deployment parameters assessed | Pass | | Dogboning Measurement | Evaluate the diameter of the balloon at rated burst pressure compared to the diameter of the stent during deployment | No acceptance criteria - for characterization related to geometry and deployment of the stents | Balloon diameter is smaller than the outer diameter of the stents | | Balloon Fatigue | Determine the ability of the balloon to withstand repeated inflation cycles. | All test samples must inflate to 12 atm and deflate 10 times without bursting | Pass | | Catheter Bond Strength | Determine the longitudinal strength of various joints/subassemblies used in the delivery system | All bonds must have a strength ≥ 10 N | Pass | | Balloon Inflation and Deflation Time | Determine the time required to inflate the balloon to the maximum recommended inflation pressure, volume, or diameter, and to measure the time required to deflate the balloon | Each balloon must be inflated with a 1:1 mixture of contrast and saline within 30 seconds, and each balloon must be evacuated of the same mixture within 30 seconds of a negative pressure being applied to the balloon | Pass | 4 April 2012 30 {23} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-24 | Test Method | Purpose | Acceptance Criteria | Result | | --- | --- | --- | --- | | Stent Securement for Unsheathed Stents | Determine if the stent will become displaced or dislodged from the balloon and to determine the force required to displace or dislodge the stent from the balloon | The device must be able to pass through an anatomical model, an appropriately sized sheath, and a simulated stricture without the stent being dislodged or displaced so that it is no longer between the markers on the balloon catheter. The force to dislodge the stent was measured for characterization only | Pass | | Shelf Life | Establish an expiration period for the product | • All bonds must have a strength ≥ 10 N after aging • Balloons must survive at least 12 atm of pressure | Pass | ### C. Animal Studies #### 1. Zenith Fenestrated AAA Endovascular Graft Considerable in vivo testing addressing patency, histopathology, and survival at 1, 3, and 6 months of the Zenith® AAA Endovascular Graft in animal models has been previously reported to the Agency. The need for animal studies to assess deployability and biological response to the Zenith® Fenestrated AAA Endovascular Graft was considered during development of the in vitro bench testing and non-clinical studies testing plan. However, based on several factors (i.e., similarities in materials of construction with other devices, limitations of appropriate animal models, and extensive clinical experience), animal studies specific to the Zenith® Fenestrated AAA Endovascular Graft were considered not necessary. #### 2. Zenith Alignment Stent The purpose of the animal study (summarized in Table 9) was to evaluate the functional biocompatibility and safety of Zenith Alignment Stents. Up to four prototype stents were implanted in each domestic pig, one each, in the left and right renal arteries, celiac artery and superior mesenteric artery (SMA) for one month. Primary safety endpoints included quantitative angiographic evaluation of early (immediately after implant) and late (at one-month follow-up) patency of the stented arteries as well as qualitative histopathologic evaluation and 4 April 2012 31 {24} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-25 quantitative histomorphometric analysis of the stented arteries characterizing the response of the stented vessels to the stents. A one-month follow-up time point is supported based on the demonstrated safety and effectiveness of the Formula Balloon-Expandable Renal Stent (P100028), which is the same design as the segment of the Zenith Alignment Stent intended for vessel contact. Secondary endpoints in the study included a qualitative evaluation of the performance characteristics of the delivery system. Performance parameters evaluated included preparation, introduction, pushability, trackability, flexibility, radiopacity and appearance on inspection. The Zenith Alignment Stent was evaluated under conditions that simulated the intended clinical use of the device. The animal testing complied with 21 CFR 58, Good Laboratory Practices (GLP). Table 9. Animal testing summary for the Zenith Alignment Stent | One-Month Study of Balloon Expandable Fenestration Stents in Domestic Swine Arteries | | | | --- | --- | --- | | Study Objectives | Number of Animals Timepoints Devices Tested | Relevant Findings | | Evaluate the functional biocompatibility and safety of Zenith Alignment Stents under conditions that simulated the intended clinical use of the device | • 9 pigs • 1 month • 16 stents evaluated | • All animals were healthy at 1 month follow up • Performance of stent delivery systems was rated as “adequate” or better for all parameters • Stented vessels remained widely patent throughout the study. • Stented vessels appeared to be healing adequately at 1 month. • No stent fractures were observed 1 month following implantation. | The animal study revealed no safety problems or negative sequelae associated with the Zenith Alignment Stent following a 1 month implantation period. ### D. Sterilization, Packaging and Shelf Life The Zenith Fenestrated AAA Endovascular Graft and H&L-B One-Shot Introduction System is sterilized by a validated ethylene oxide (EtO) sterilization process to achieve a minimal sterility assurance level (SAL) of 10⁻⁶. The Zenith Fenestrated AAA Endovascular Graft system is packaged in the same packaging system that is currently used for other marketed products produced by Cook Incorporated and William Cook Australia. The shelf life studies on file for these 4 April 2012 32 {25} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-26 packaging materials reveal that the package configuration and materials provide an acceptable bacterial barrier and that three years is an appropriate sterility expiration period. The Zenith Fenestrated AAA Endovascular Graft and H&L-B One-Shot Introduction System is constructed from identical materials using similar manufacturing processes as the Zenith Flex AAA Endovascular Graft and H&L-B One-Shot Introduction System which previously performed as intended following 3-years aging, supporting a 3-year shelf life for the Zenith Fenestrated AAA Endovascular Graft. The Zenith Alignment Stent is sterilized by a validated ethylene oxide (EtO) sterilization process to achieve a minimal sterility assurance level (SAL) of 10⁻⁶. The Zenith Alignment Stent is packaged in the same packaging system that is currently used for the Formula Stent produced by Cook Incorporated. The shelf life studies on file for these packaging materials reveal that the package configuration and materials provide an acceptable bacterial barrier and that 3 years is an appropriate sterility expiration period. The additional shelf life studies referred to in Tables 7 and 8 further support a 3 year shelf life for the Zenith Alignment Stent. # X. SUMMARY OF CLINICAL STUDY The applicant performed a clinical study in the US under G040063 to help establish a reasonable assurance of safety and effectiveness of the Zenith Fenestrated AAA Endovascular Graft for the endovascular treatment of abdominal aortic or aorto-iliac aneurysms. Data from the pivotal clinical study support the PMA approval decision. The study was initially approved for 30 patients and use of available balloon-expandable stents in combination with the Fenestrated Graft. Following completion of the initial 30 patient enrollment, the study hypothesis and requirements for approval were agreed upon. The study was then expanded to include the Zenith Alignment Stent and enrollment of 12 additional patients, thus providing 42 total patients, which was the pre-specified study sample size. A summary of the clinical study is presented below. # A. Clinical Study Design 4 April 2012 33 {26} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-27 Patients were treated between January 2005 and August 2010. The database for this PMA supplement reflected data collected through June 2011 and included 42 patients. There were 7 investigational sites. The study was a prospective, multi-center, two-armed clinical study. One study arm consisted of investigational patients implanted with the Zenith Fenestrated AAA Endovascular Graft and the second arm consisted of historical, case-matched controls treated with the standard Zenith AAA Endovascular Graft (identified from patients treated with the Zenith AAA Endovascular Graft under G990135). Taking into consideration the Zenith AAA study results, expected attrition, and a goal of achieving at least a minimum of 80% statistical power at a significance level of 5%, a sample size of 42 subjects was considered sufficient using a 10% margin. Propensity score methods with a pre-specified matching algorithm were used to select the control patients from the Zenith AAA endovascular cohorts. The covariates for matching were pre-specified and included the following relevant demographic, comorbid, and anatomic characteristics, all of which were comparable between the two groups: age, gender, height, weight, arrhythmia, cancer, chronic heart failure, chronic obstructive pulmonary disease, cerebrovascular disease, diabetes, hypertension, previous diagnosis of systemic infection, previous myocardial infarction, peripheral vascular disease, previous surgeries at access site, thromboembolic event, maximum aneurysm diameter, minimum aneurysm diameter, and neck diameter. Patient imaging underwent independent core laboratory analysis. All patient deaths and any associated adverse events were adjudicated by an independent clinical events committee (CEC). The clinical trial was monitored by an independent data safety monitoring board (DSMB) according to an established safety monitoring plan. ### 1. Inclusion and Exclusion Criteria Enrollment in clinical study was limited to patients who met the following selection criteria: - Aortic or aortoiliac aneurysm with diameter ≥5 cm; or - Aortic or aortoiliac aneurysm with a history of growth ≥0.5 cm per year, or clinical indication for AAA repair 4 April 2012 34 {27} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-28 Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: # General Exclusion Criteria - Less than 18 years of age - Life expectancy less than 2 years - Pregnant or breastfeeding - Unwilling to comply with the follow-up schedule - Inability or refusal to give informed consent # Medical Exclusion Criteria - Baseline creatinine >2.0 mg/dl - Cultural objection to receipt of blood or blood products - Allergy to stainless steel, polyester, solder, gold, or nitinol - Anaphylactic reaction to contrast that cannot be adequately pre-medicated - Leaking/ruptured or symptomatic aneurysm - Uncorrectable coagulopathy - Previous stent in any renal or visceral artery to be accommodated with a small fenestration # Anatomical Exclusion Criteria - Significant occlusive disease, tortuosity, or calcification - Proximal neck <4 mm, or ≥15 mm in length unless otherwise compromised to preclude seal (i.e., unsuitable for a non-fenestrated graft) - Proximal neck, measured outer wall to outer wall on a sectional image (CT), >31 mm in diameter or <19 mm in diameter - Proximal neck angulated more than 45 degrees relative to the long axis of the aneurysm - Immediate suprarenal neck angulated more than 45 degrees relative to the immediate infrarenal neck - Proximal neck diameter change over the length of the proximal seal zone ≥4 mm - Proximal seal site with circumferential thrombus/atheroma above the renal arteries - Iliac artery diameter, measured inner wall to inner wall on a sectional image (CT), <7.5 mm at any point along access length (prior to deployment) - Ipsilateral iliac artery fixation site diameter, measured inner wall to inner wall on a sectional image (CT), <9.0 mm (prior to deployment) - Iliac artery diameter, measured outer wall to outer wall on a sectional image (CT), >21 mm at distal fixation site 4 April 2012 35 {28} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-29 - Iliac artery distal fixation site <30 mm in length - Inability to maintain at least one patent hypogastric artery - Renal artery stenosis >50% - Non-bifurcated segment of any artery to be stented <15 mm in length - Artery to be stented with a maximum diameter <3 mm or >8 mm at the vessel ostium - Unsuitable arterial anatomy 4 April 2012 36 {29} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-30 ## 2. Study Follow-up Schedule The study follow-up schedule for patients consisted of imaging (CT and X-ray) and clinical assessments at post-procedure (pre-discharge), 30 days, 6 months, 12 months, and yearly thereafter through 5 years. ## 3. Clinical Endpoints The primary safety and effectiveness endpoint was based on treatment success, which is defined as technical success (i.e., successful access of the aneurysm site and deployment of the Zenith Fenestrated AAA Endovascular Graft in the intended location, with all vessels targeted by fenestrations patent at the completion of the procedure) plus freedom from the following at 6 months: Type I and Type III endoleak, aneurysm growth >0.5 cm, any AAA-related serious adverse event (death, rupture, conversion), and any AAA-related major complication (Q-wave MI; congestive heart failure; cardiac ischemia requiring intervention; renal failure requiring permanent dialysis; bowel obstruction, ischemia, or fistula; stroke with permanent deficit; paralysis). The study results for the primary endpoint, 6-month treatment success, were explored in patients treated with the Zenith Fenestrated AAA Endovascular Graft and in matched patients treated with the standard Zenith AAA Endovascular Graft. The study additionally provided for assessment of morbidity, mortality, aneurysm size change, endoleak, migration, device integrity, and secondary interventions. ## B. Patient Accountability Of 42 patients enrolled in the clinical study, 95% (40) were evaluable for the primary endpoint analysis. The 42 patient cohort, combines patient data from the feasibility study (n = 30; implanted device between January 2005 – January 2006) with pivotal study data (n = 12). Table 10 reports the patient accountability for study follow-up as of the database lock. The data in the follow-up accountability table is site reported and reflects data available for endpoints that are assessed with imaging. As such, denominators for core lab reported analyses and for events that are not imaging dependant in the results tables below may differ from the information in this table. 4 April 2012 37 {30} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-31 Table 10. Follow-up compliance | Follow-up Visit | Patients Eligible for Follow-up^{1} | Percent of Data Available^{1} | | | Adequate Imaging to Assess the Parameter^{2} | | | | Events Occurring Before Next Interval | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Clinical | X-ray | CT | Size Increase | Endoleak | Migration | Fracture | Death | Conversion | Lost to Follow-up (LTF) or Withdrawal | Refused Consent for 3-5 Year Follow-up^{3} | Not Due for Next Visit | | Pre-discharge | 42 (0) | 100.0% (42/42) | 95.2% (40/42) | 95.2% (40/42) | 95.2% (40/42) | 92.9% (39/42) | 95.2% (40/42) | 100.0% (42/42) | 0 | 0 | 0 | 0 | 0 | | 30-day | 42 (0) | 97.6% (41/42) | 88.1% (37/42) | 97.6% (41/42) | 97.6% (41/42) | 92.9% (39/42) | 95.2% (40/42) | 97.6% (41/42) | 1 | 0 | 1 | 0 | 0 | | 6-month | 40 (0) | 97.5% (39/40) | 95.0% (38/40) | 95.0% (38/40) | 95.0% (38/40) | 87.5% (35/40) | 95.0% (38/40) | 97.5% (39/40) | 0 | 0 | 1 | 0 | 4 | | 12-month | 35 (3) | 91.4% (32/35) | 82.9% (29/35) | 88.6% (31/35) | 82.9% (29/35) | 80.0% (28/35) | 82.9% (29/35) | 82.9% (29/35) | 1 | 0 | 0 | 0 | 7 | | 24-month | 27 (0) | 96.3% (26/27) | 85.2% (23/27) | 96.3% (26/27) | 96.3% (26/27) | 81.5% (22/27) | 96.3% (26/27) | 96.3% (26/27) | 1 | 0 | 0 | 6 | 0 | | 3-year | 20 (0) | 90.0% (18/20) | 70.0% (14/20) | 90.0% (18/20) | 75.0% (15/20) | 70.0% (14/20) | 80.0% (16/20) | 75.0% (15/20) | 0 | 0 | 1 | 0 | 0 | | 4-year | 19 (0) | 94.7% (18/19) | 73.7% (14/19) | 89.5% (17/19) | 84.2% (16/19) | 63.2% (12/19) | 84.2% (16/19) | 89.5% (17/19) | 0 | 0 | 2 | 0 | 0 | | 5-year | 17 (0) | 100.0% (17/17) | 70.6% (12/17) | 82.4% (14/17) | 64.7% (11/17) | 52.9% (9/17) | 64.7% (11/17) | 64.7% (11/17) | 0 | 0 | 0 | 0 | 0 | $^{1}$Site submitted data. $^{2}$Based on core lab analysis – does not include imaging exams received by the core lab for analysis, but that have not yet been analyzed. $^{3}$Number in parenthesis indicates the number of patients without submitted data who are still eligible for follow-up. $^{4}$Initial cohort of 30 patients consented only for 2-year follow-up and therefore were asked to reconsent for 3-5 year follow-up. 4 April 2012 38 {31} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-32 ### C. Study Population Demographics and Baseline Parameters Table 11 summarizes the demographics and patient characteristics for the Zenith Fenestrated group. Table 11. Demographics and patient characteristics | Demographic | Result^{1} | | --- | --- | | Age (years) | 75.3 ± 7.4 (58 - 86), 42 | | Gender | | | Male | 78.6% (33/42) | | Female | 21.4% (9/42) | | Ethnicity | | | White | 92.9% (39/42) | | Hispanic or Latino | 2.4% (1/42) | | Black or African American | 0.0% (0/42) | | American Indian or Alaska Native | 2.4% (1/42) | | Asian | 2.4% (1/42) | | Native Hawaiian or other Pacific Islander | 0.0% (0/42) | | Other | 0.0% (0/42) | | Height (in) | 67.5 ± 4.4 (51 - 74), 41 | | Weight (lbs) | 190.6 ± 46.9 (110 - 342), 42 | | Body mass index | 28.7 ± 4.8 (19.5 - 40.8), 41 | $^{1}$ Mean values +/- the standard deviation, with the range of values shown in parentheses, followed by the number of patients evaluated Table 12 presents the medical history of patients in the Zenith Fenestrated group. Table 12. Pre-existing comorbid medical conditions | Medical History | Percent Patients (number/total number) | | --- | --- | | Cardiovascular | | | Previous myocardial infarction | 23.8% (10/42) | | Previous diagnosis of symptomatic congestive heart failure | 9.5% (4/42) | | Previous diagnosis of coronary artery disease | 52.4% (22/42) | | Previous diagnosis of cardiac arrhythmia | 40.5% (17/42) | | Vascular | | | Thromboembolic event | 11.9% (5/42) | | Peripheral vascular disease | 23.8% (10/42) | | Family history of aneurysmal disease | 14.3% (6/42)^{1} | | Hypertension | 92.9% (39/42) | 4 April 2012 39 {32} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-33 | Medical History | | Percent Patients (number/total number) | | --- | --- | --- | | Pulmonary | Chronic obstructive pulmonary disease | 33.3% (14/42) | | Renal | Diagnosis of renal failure requiring dialysis | 0.0% (0/42) | | | Renal insufficiency | 9.5% (4/42) | | | GFR ≤ 60 ml/min/1.73 m² | 21.4% (9/42) | | Endocrine | Diabetes | 26.2% (11/42) | | Infectious disease | Previous diagnosis of sepsis | 7.1% (3/42) | | Gastrointestinal | Gastrointestinal disease | 40.5% (17/42) | | Hepatobiliary | Previous diagnosis of liver disease | 2.4% (1/42) | | Neoplasms | Previous diagnosis of cancer | 35.7% (15/42) | | Neurologic | Previous diagnosis of cerebrovascular disease | 16.7% (7/42) | | | Previous endarterectomy | 2.4% (1/42) | | Substance use | Excessive alcohol use | 0.0% (0/42) | | | Tobacco use: currently smokes | 28.6% (12/42) | | | quit smoking | 57.1% (24/42) | | | never smoked | 14.3% (6/42) | | Access site | Previous surgery at the intended access site | 11.9% (5/42)² | | | Previous radiation at the intended access site | 0.0% (0/42) | ¹ In 11.9% (5/42) of patients family history of aneurysmal disease was reported as unknown. ² In 2.4% (1/42) of patients previous surgery at intended access site was reported as unknown. Table 13 lists the anatomical characteristics of patients in the Zenith Fenestrated group, as assessed by the core lab. 4 April 2012 40 {33} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-34 Table 13. Presenting anatomical dimensions, as assessed by core lab | Measure | Mean ± S.D. (range), N=42 | | --- | --- | | Aortic diameters (mm) | | | Diameter at celiac artery | 28.2 ± 3.2 (21.2 - 35.9) | | Diameter at SMA | 28 ± 3.5 (22.3 - 39.8) | | Diameter at lowest patent renal artery | 25.7 ± 3.2 (19.2 - 33.2) | | Diameter at midpoint of renal arteries | 25.5 ± 5.1 (0.0 - 32.2) | | Maximum aneurysm diameter – long axis | 61.1 ± 10.9 (45.2 - 94.2) | | Maximum aneurysm diameter – short axis | 56.8 ± 10.3 (43.4 - 90.4) | | Proximal neck length (mm) | 9.7 ± 3.5 (2.4 - 19.1) | | Angles (°) | | | Angle between immediate suprarenal neck and immediate infrarenal neck | 15.9 ± 9.6 (2 - 40) | | Angle between the proximal neck and the longitudinal axis of the aneurysm | 34 ± 14.2 (7 - 57) | | Diameter of renal artery ostia (mm) | | | Right renal artery | 6.5 ± 1.2 (4.6 - 8.9) | | Left renal artery | 6.8 ± 1.3 (4.0 - 9.4) | # D. Devices Implanted # 1.0 Stent-graft Components Table 14 reports the type of stent-graft components that were deployed during the index procedure. All but one patient received the standard 3-piece system (proximal graft, distal graft, contralateral leg) – one patient received only a proximal graft, which landed in a previous open surgical graft and thus did not require a distal graft or contralateral leg. Table 14. Stent-graft components deployed | Type | Percent Patients (number/total number) | | --- | --- | | Proximal graft | 100% (42/42) | | Distal graft | 97.6% (41/42)^{1} | | Contralateral leg | 97.6% (41/42)^{1} | | Ancillary components | | | Main body extension | 0.0% (0/42) | | Additional iliac leg | 7.1% (3/42) | | Ipsilateral iliac leg extension | 2.4% (1/42) | | Contralateral iliac leg extension | 7.1% (3/42) | | Occluder | 0.0% (0/42) | | Converter | 0.0% (0/42) | $^{1}$One patient that had undergone prior open surgical AAA repair received only the proximal fenestrated component 4 April 2012 41 {34} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-35 Table 15 reports the sizes (diameters and lengths) of the proximal grafts used during the initial implant procedure. The full range of available graft diameters and lengths was utilized. Table 15. Proximal graft sizes used | Diameter (mm) | Length (mm) | | | | | Total | | --- | --- | --- | --- | --- | --- | --- | | | 97 | 107 | 109 | 122 | 124 | | | 24 | 0 | 0 | 0 | 0 | 2 | 2 | | 26 | 0 | 0 | 4 | 0 | 0 | 4 | | 28 | 1 | 0 | 7 | 0 | 4 | 12 | | 30 | 1 | 0 | 6 | 0 | 9 | 16 | | 32 | 0 | 0 | 1 | 0 | 2 | 3 | | 34 | 0 | 2 | 0 | 2 | 0 | 4 | | 36 | 0 | 0 | 0 | 1 | 0 | 1 | | Total | 2 | 2 | 18 | 3 | 17 | 42 | Table 16 reports the sizes (diameters and lengths) of the distal grafts used during the initial implant procedure. The full range of available graft diameters and lengths was utilized. Table 16. Distal graft sizes used | Diameter (mm) | Length (mm) | | | | | | | Total | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | 119 | 121 | 136 | 138 | 151 | 153 | 168 | | | 12 | 0 | 2 | 2 | 1 | 0 | 3 | 0 | 8 | | 16 | 0 | 2 | 3 | 4 | 2 | 2 | 4 | 17 | | 20 | 1 | 0 | 1 | 3 | 1 | 5 | 3 | 14 | | 24 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | | Total | 1 | 4 | 7 | 8 | 4 | 10 | 7 | 41 | Table 17 reports the sizes (diameters and lengths) of the contralateral leg grafts used during the initial implant procedure. 4 April 2012 42 {35} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-36 Table 17. Contralateral leg sizes used | Diameter (mm) | Length (mm) | | | | | | Total | | --- | --- | --- | --- | --- | --- | --- | --- | | | 54 | 56 | 71 | 73 | 88 | 90 | | | 12 | 3 | 1 | 2 | 0 | 0 | 0 | 6 | | 14 | 1 | 0 | 10 | 0 | 1 | 0 | 12 | | 16 | 3 | 0 | 3 | 1 | 0 | 0 | 7 | | 18 | 6 | 0 | 3 | 0 | 1 | 0 | 10 | | 20 | 0 | 0 | 3 | 0 | 0 | 1 | 4 | | 22 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | | 24 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | | Total | 13 | 1 | 23 | 1 | 2 | 1 | 41 | The location of the most proximal graft margin relative to the renal arteries, SMA, and celiac artery is provided in Table 18. The proximal margin of the graft was above the renal arteries in all patients. Table 18. Graft location | Location of proximal graft margin relative to specified vessel | | Percent Patients (number/total number) | | --- | --- | --- | | Renal arteries | Above | 100.0% (42/42) | | | Below | 0.0% (0/42) | | SMA | Above | 66.7% (28/42) | | | Below | 33.3% (14/42) | | Celiac | Above | 0.0% (0/42) | | | Below | 100.0% (42/42) | The specific graft fenestration/scallop configurations that were utilized to accommodate the vessels intended to remain patent are provided in Table 19. The most commonly used configuration was 2 fenestrations and 1 scallop. Table 19. Fenestrated configurations used | Configurations | % (n/N) | | --- | --- | | 1 scallop | 9.5% (4/42) | | 1 small fenestration and 1 scallop | 11.9% (5/42) | | 2 small fenestrations | 4.8% (2/42) | | 2 small fenestrations and 1 scallop | 69.0% (29/42) | | 2 small fenestrations and 1 large fenestration | 4.8% (2/42) | 4 April 2012 43 {36} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-37 ### 2.0 Fenestration Stents Table 20 provides the total number of each stent type used during the initial implant procedure. Eleven (11) patients received a Zenith Alignment Stent. Table 20. Type and number of fenestration stents used | Stent type/description | (n) | | --- | --- | | Zenith Alignment Stent(uncovered, balloon-expandable, 316 L stainless steel) | 22 | | Uncovered, balloon-expandable,316L stainless steel biliary stent | 28 | | Uncovered, balloon-expandable,316L stainless steel biliary/iliac stent | 20 | | Uncovered, balloon-expandable,316L stainless steel biliary/renal stent | 8 | | Covered, balloon-expandable,316L stainless steel tracheobronchial stent | 2 | Table 21 indicates which vessels were targeted by either a fenestration or scallop and were either stented or unstented. All vessels accommodated by a small fenestration were stented. Table 21. Fenestration and vessel stenting | Vessel | Small fenestration | | Large fenestration | | Scallop | | Total | | --- | --- | --- | --- | --- | --- | --- | --- | | | Stented | Unstented | Stented | Unstented | Stented | Unstented | | | Celiac | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | SMA | 0 | 0 | 0 | 2 | 0 | 29 | 31 | | Right renal | 35 | 0 | 0 | 0 | 3 | 0 | 38 | | Left renal | 36 | 0 | 0 | 0 | 4 | 2 | 42 | | Accessory | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Total | 71 | 0 | 0 | 2 | 7 | 31 | 111 | ## E. Safety and Effectiveness Results The analysis of safety and effectiveness was based on the cohort of 42 patients/procedures, etc available for 6 month evaluations. The primary safety and effectiveness endpoints are based on treatment success, plus freedom from the following at 6 months: Type I and Type III endoleak, aneurysm growth >0.5 cm, any AAA-related serious adverse event (death, rupture, conversion), and any AAA-related major complication (Q-wave MI; congestive heart failure; cardiac Comment [dxh1]: Incorporated template language- 4 April 2012 44 {37} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-38 ischemia requiring intervention; renal failure requiring permanent dialysis; bowel obstruction, ischemia, or fistula; stroke with permanent deficit; paralysis). The study results for the primary endpoint, 6-month treatment success, were explored in patients treated with the Zenith Fenestrated AAA Endovascular Graft and in matched patients treated with the standard Zenith AAA Endovascular Graft. The study additionally provided for assessment of morbidity, mortality, aneurysm size change, endoleak, migration, device integrity, and secondary interventions. The key safety and effectiveness outcomes for this study are presented below in tables 22-33. ### 1.0 Technical Success Technical success is defined as successful access of the aneurysm site and deployment of the Zenith Fenestrated AAA Endovascular Graft in the intended location, with all vessels targeted by fenestrations patent at the completion of the procedure. Table 22 reports the technical success results for the Zenith Fenestrated AAA Endovascular Graft. Table 22. Technical success | Measure | Percent (n/N) | | --- | --- | | Technical success | 100.0% (42/42) | ### 2.0 6-month Treatment Success (Primary Endpoint) Treatment success is defined as technical success plus freedom from the following at 6 months: Type I and Type III endoleak, aneurysm growth >0.5 cm, any AAA-related serious adverse event (death, rupture, conversion), and any AAA-related major complication (Q-wave MI; congestive heart failure; cardiac ischemia requiring intervention; renal failure requiring permanent dialysis; bowel obstruction, ischemia, or fistula; stroke with permanent deficit; paralysis). Of 42 patients enrolled in the clinical study, 40 were evaluable for the primary endpoint analysis (two patients were lost to follow-up). Table 23 reports the 6-month treatment success for the Zenith Fenestrated AAA Endovascular Graft, as compared to the matched patients treated with the standard Zenith AAA Endovascular Graft. Propensity score methods with a pre-specified one-to-one global matching algorithm were used to select patients from the Zenith AAA Endovascular Graft multicenter study. The 6-month treatment success was 97.5% 4 April 2012 45 {38} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-39 in the Fenestrated endovascular treatment group compared to 95% in the matched Zenith AAA cohort. Table 23. Results for 6-month treatment success | Measure | Zenith Fenestrated | Zenith AAA | | --- | --- | --- | | Treatment success | 97.5% (39/40)1 | 95.0% (38/40)2 | \( ^{1} \) Failure due to bowel ischemia \( ^{2} \) Failure due to congestive heart failure in one and congestive heart failure as well as cardiac ischemia requiring intervention in another ### 3.0 Adverse Events #### 3.1 Major Adverse Events Table 24 reports the Kaplan-Meier survival estimates for freedom from major adverse events (MAE) within 30 days (death, Q-wave MI, bowel ischemia, paralysis, stroke, reintubation, renal failure requiring dialysis). One Zenith Fenestrated patient experienced a major adverse event within 30 days (bowel ischemia, which resolved with antibiotics and IV fluids). There were no MAEs in the Zenith AAA group within 30 days. Table 24. Results from Kaplan-Meier analysis for freedom from 30-day MAE | Event | Parameter | Zenith Fenestrated | | --- | --- | --- | | Any MAE | Number at risk | 41 | | | Cumulative events | 1 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 0.976 | | | Standard error | 0.024 | | Death | Number at risk | 42 | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | | Q-wave MI | Number at risk | 42 | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | | Bowel ischemia | Number at risk | 41 | | | Cumulative events | 1 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 0.976 | | | Standard error | 0.024 | | Paralysis | Number at risk | 42 | 4 April 2012 46 {39} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-40 | Event | Parameter | Zenith Fenestrated | | --- | --- | --- | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | | Stroke | Number at risk | 42 | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | | Re-intubation | Number at risk | 42 | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | | Renal failure requiring dialysis | Number at risk | 42 | | | Cumulative events | 0 | | | Cumulative censored | 0 | | | Kaplan-Meier estimate | 1.000 | | | Standard error | 0.000 | # 3.2 Serious Adverse Events Table 25 provides the Kaplan-Meier estimates for freedom from death (all-cause and AAA-related, which was defined as any death occurring within 30 days of the initial implant procedure or secondary intervention, or any death determined by an independent clinical events committee (CEC) to be related to the AAA repair), rupture, and conversion. The cause of death was unknown in one patient from the Zenith Fenestrated group, which the CEC was therefore unable to adjudicate – this was the only patient death counted as AAA-related in the Zenith Fenestrated group. No aneurysm ruptures or conversions to open repair where reported in the Zenith Fenestrated group. Table 25. Results from Kaplan-Meier analysis for serious adverse events | Event | Group | Parameter | 30 Days | 365 Days | 730 Days | 1095 Days | 1460 Days | 1825 Days | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | All-cause mortality | Zenith Fenestrated | Number at risk | 42 | 36 | 27 | 20 | 19 | 14 | | | | Cumulative events | 0 | 1 | 2 | 4 | 4 | 4 | | | | Cumulative censored | 0 | 5 | 13 | 18 | 19 | 24 | | | | Kaplan-Meier estimate | 1.000 | 0.976 | 0.943 | 0.861 | 0.861 | 0.861 | | | | Standard error | 0.000 | 0.024 | 0.040 | 0.066 | 0.066 | 0.066 | | | Zenith AAA | Number at risk | 33 | 32 | 30 | 30 | 28 | 17 | | | | Cumulative events | 0 | 0 | 2 | 2 | 2 | 2 | | | | Cumulative censored | 0 | 1 | 1 | 1 | 3 | 14 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 0.938 | 0.938 | 0.938 | 0.938 | | | | Standard error | 0.000 | 0.000 | 0.043 | 0.043 | 0.043 | 0.043 | 4 April 2012 47 {40} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-41 | Event | Group | Parameter | 30 Days | 365 Days | 730 Days | 1095 Days | 1460 Days | 1825 Days | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | AAA-related mortality | Zenith Fenestrated | Number at risk | 42 | 36 | 27 | 20 | 19 | 14 | | | | Cumulative events | 0 | 0 | 0 | 1^{1} | 1 | 1 | | | | Cumulative censored | 0 | 6 | 15 | 21 | 22 | 27 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 1.000 | 0.955 | 0.955 | 0.955 | | | | Standard error | 0.000 | 0.000 | 0.000 | 0.044 | 0.044 | 0.044 | | | Zenith AAA | Number at risk | 33 | 32 | 30 | 30 | 28 | 17 | | | | Cumulative events | 0 | 0 | 0 | 0 | 0 | 0 | | | | Cumulative censored | 0 | 1 | 3 | 3 | 5 | 16 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | | | | Standard error | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | | Rupture | Zenith Fenestrated | Number at risk | 42 | 37 | 28 | 21 | 21 | 18 | | | | Cumulative events | 0 | 0 | 0 | 0 | 0 | 0 | | | | Cumulative censored | 0 | 5 | 14 | 21 | 21 | 24 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | | | | Standard error | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | | | Zenith AAA | Number at risk | 33 | 32 | 30 | 30 | 28 | 17 | | | | Cumulative events | 0 | 1 | 1 | 1 | 1 | 1 | | | | Cumulative censored | 0 | 0 | 2 | 2 | 4 | 15 | | | | Kaplan-Meier estimate | 1.000 | 0.970 | 0.970 | 0.970 | 0.970 | 0.970 | | | | Standard error | 0.000 | 0.030 | 0.030 | 0.030 | 0.030 | 0.030 | | Conversion | Zenith Fenestrated | Number at risk | 42 | 37 | 28 | 21 | 21 | 18 | | | | Cumulative events | 0 | 0 | 0 | 0 | 0 | 0 | | | | Cumulative censored | 0 | 5 | 14 | 21 | 21 | 24 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | 1.000 | | | | Standard error | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | | | Zenith AAA | Number at risk | 33 | 32 | 30 | 30 | 28 | 17 | | | | Cumulative events | 0 | 1 | 1 | 1 | 1 | 1 | | | | Cumulative censored | 0 | 0 | 2 | 2 | 4 | 15 | | | | Kaplan-Meier estimate | 1.000 | 0.970 | 0.970 | 0.970 | 0.970 | 0.970 | | | | Standard error | 0.000 | 0.030 | 0.030 | 0.030 | 0.030 | 0.030 | $^{1}$1 case of death that the CEC was unable to adjudicate, which was conservatively counted as AAA-related for the purpose of analysis. ### 3.3 Pre-specified Adverse Events by Organ System Table 26 reports the Kaplan-Meier survival estimates for freedom from pre-specified cardiovascular, pulmonary, renal, GI, wound, neurologic, and vascular events reported by the investigative sites. The procedure-related incidence (i.e., within 30 days) of cardiovascular, pulmonary, gastrointestinal, wound, and neurologic events appeared comparable between Zenith Fenestrated and Zenith AAA, and the occurrence of events in these categories beyond 30 days was not surprising given the pre-existing comorbid conditions of the patient populations. The percent of patients experiencing renal events or vascular events within 30 days trended higher for Zenith Fenestrated compared to Zenith AAA patients, the details of which are discussed further in Sections 3.4 and 3.5, respectively. 4 April 2012 48 {41} Supplement to P020018: Zenith® Fenestrated AAA Endovascular Graft Appendix K: SSED K-42 Table 26. Kaplan-Meier estimates (freedom from morbidity, by category) | Category | Group | Parameter | 30 Days | 365 Days | 730 Days | 1095 Days | 1460 Days | 1825 Days | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Cardiovascular^{1} | Zenith Fenestrated | Number at risk | 40 | 30 | 21 | 15 | 15 | 10 | | | | Cumulative events | 2 | 6 | 7 | 8 | 8 | 10 | | | | Cumulative censored | 0 | 6 | 14 | 19 | 19 | 22 | | | | Kaplan-Meier estimate | 0.952 | 0.854 | 0.817 | 0.766 | 0.766 | 0.656 | | | | Standard error | 0.033 | 0.055 | 0.064 | 0.078 | 0.078 | 0.098 | | | Zenith AAA | Number at risk | 29 | 27 | 24 | 24 | 23 | 14 | | | | Cumulative events | 4 | 5 | 6 | 6 | 6 | 6 | | | | Cumulative censored | 0 | 1 | 3 | 3 | 4 | 13 | | | | Kaplan-Meier estimate | 0.879 | 0.848 | 0.817 | 0.817 | 0.817 | 0.817 | | | | Standard error | 0.057 | 0.062 | 0.068 | 0.068 | 0.068 | 0.068 | | Pulmonary^{2} | Zenith Fenestrated | Number at risk | 41 | 32 | 24 | 18 | 17 | 12 | | | | Cumulative events | 1 | 4 | 4 | 5 | 5 | 6 | | | | Cumulative censored | 0 | 6 | 14 | 19 | 20 | 24 | | | | Kaplan-Meier estimate | 0.976 | 0.903 | 0.903 | 0.855 | 0.855 | 0.798 | | | | Standard error | 0.024 | 0.046 | 0.046 | 0.064 | 0.064 | 0.081 | | | Zenith AAA | Number at risk | 33 | 32 | 29 | 29 | 28 | 17 | | | | Cumulative events | 0 | 0 | 1 | 1 | 1 | 1 | | | | Cumulative censored | 0 | 1 | 3 | 3 | 4 | 15 | | | | Kaplan-Meier estimate | 1.000 | 1.000 | 0.969 | 0.969 | 0.969 | 0.969 | | | | Standard error | 0.000 | 0.000 | 0.031 | 0.031 | 0.031 | 0.031 | | Renal^{3} | Zenith Fenestrated | Number at risk | 37 | 30 | 21 | 15 | 14 | 10 | | | | Cumulative events | 5 | 6 | 8 | 9 | 10 | 10 | | | | Cumulative censored | 0 | 6 | 13 | 18 | 18 | 22 | | | | Kaplan-Meier estimate | 0.881 | 0.856 | 0.791 | 0.742 | 0.692 | 0.692 | | | | Standard error | 0.050 | 0.054 | 0.067 | 0.079 | 0.088 | 0.088 | | | Zenith AAA | Number at risk | 33 | 31 | 29 | 29 | 27 | 16 | | | | Cumulative events | 0 | 1 | 1 | 1 | 1 | 1 | | | | Cumulative censored | 0 | 1 | 3 | 3 | 5 | 16 | | | | Kaplan-Meier estimate | 1.000 | 0.970 | 0.970 | 0.970 | 0.970 | 0.970 | | | | Standard error | 0.000 | 0.030 | 0.030 | 0.030 | 0.030 | 0.030 | | GI^{4} | Zenith Fenestrated | Number at risk | 40 | 33 | 25 | 20 | 19 | 14 | | | | Cumulative events | 2 | 2 | 2 | 2 | 2 | 2 | | | | Cumulative censored | 0 | 7 | 15 | 20 | 21 | 26 | | | | Kaplan-Meier estimate | 0.952 | 0.952 | 0.952 | 0.952 | 0.952 | 0.952 | | | | Stand…