← Product Code MIH · P110032 # AORFIX FLEXIBLE STENT GRAFT SYSTEM (P110032) _Lombard Medical Limited · MIH · Feb 14, 2013 · Cardiovascular · APWD_ **Canonical URL:** https://fda.innolitics.com/device/P110032 ## Device Facts - **Applicant:** Lombard Medical Limited - **Product Code:** MIH - **Decision Date:** Feb 14, 2013 - **Decision:** APWD - **Device Class:** Class 3 - **Review Panel:** Cardiovascular - **Attributes:** Therapeutic ## Intended Use The Aorfix™ AAA Flexible Stent Graft System is indicated for treatment of patients with abdominal aortic and aorto-iliac aneurysms having vascular morphology suitable for endovascular repair, including: - Adequate iliac or femoral access that is compatible with vascular access techniques, implants, and accessories. - Aortic neck landing zone diameters with a range of 19mm to 29mm. - Non aneurysmal proximal neck center-line length of ≥15mm. - Infrarenal aortic neck angulations including those up to and including 90°. - Common iliac landing zone diameters with a range of 9mm to 19mm. - Distal fixation length of ≥15mm. ## Device Story Aorfix™ AAA Flexible Stent Graft System is a modular endovascular device for treating infra-renal aortic and aorto-iliac aneurysms; creates internal bypass to reduce rupture risk. System comprises implantable stent graft and disposable delivery system. Stent graft features bifurcated main body with ipsilateral leg, contralateral socket, and plug-in contralateral leg; uses Nitinol wire rings for radial force and polyester graft material. Radiopaque tantalum markers aid visualization. Delivery system allows single-operator deployment. Used in hospital settings by vascular surgeons. Physician uses fluoroscopy to guide placement; device provides internal seal against vessel wall. Benefits include minimally invasive aneurysm exclusion, particularly in highly angulated (up to 90°) aortic necks where traditional grafts may be unsuitable. ## Clinical Evidence Prospective, non-randomized, multi-center study (Pythagoras) under IDE #G050116. Enrolled 218 Aorfix subjects and 76 Concurrent Open Surgical (COS) controls. Primary effectiveness endpoint: composite of freedom from Type I/III endoleak, migration >10mm, and fixation zone fracture at 12 months. 90.7% success rate in all-angle group. Primary safety endpoint: freedom from Major Adverse Events (MAE) at 30 days (76% Aorfix vs 59% COS). ## Technological Characteristics Modular endovascular stent graft. Materials: Nitinol (stents/hooks), polyester (graft/sutures), tantalum (radiopaque markers). Design: Bifurcated main body with fishmouth shape for trans-renal placement; helical/ladder Nitinol wire construction. Delivery system: 20Fr/22Fr PTFE sheaths. Connectivity: None. Sterilization: ETO. Standards: EN 12006-3, ISO 7198, ISO 25539-1, ISO 10993-1. ## Reference Devices - SVS Lifeline registry ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION Device Generic Name: Endovascular Stent Graft Device Trade Name: Aorfix™ AAA Flexible Stent Graft System Device Product Code: MIH Applicant’s Name and Address: Lombard Medical Technologies Inc. 2050 East ASU Circle, Suite 103 Tempe, AZ 85284 USA Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P110032 Date of FDA Notice of Approval: February 14, 2013 Expedited: Not applicable ## II. INDICATIONS FOR USE The Aorfix™ AAA Flexible Stent Graft System is indicated for treatment of patients with abdominal aortic and aorto-iliac aneurysms having vascular morphology suitable for endovascular repair, including: - Adequate iliac or femoral access that is compatible with vascular access techniques, implants, and accessories. - Aortic neck landing zone diameters with a range of 19mm to 29mm. - Non aneurysmal proximal neck center-line length of ≥15mm. - Infrarenal aortic neck angulations including those up to and including 90°. - Common iliac landing zone diameters with a range of 9mm to 19mm. - Distal fixation length of ≥15mm. ## III. CONTRAINDICATIONS The Aorfix™ AAA Flexible Stent Graft System is contraindicated in: - Patients who have a condition that threatens to infect the graft. - Patients with known allergies or sensitivities to the implant materials (including polyester, Nitinol and tantalum). PMA P110032: FDA Summary of Safety and Effectiveness Data {1} PMA P110032: FDA Summary of Safety and Effectiveness Data Page 2 ## IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Aorfix™ AAA Flexible Stent graft System labeling. ## V. DEVICE DESCRIPTION The Aorfix™ AAA Flexible Stent Graft System is an endovascular stent graft system for treating infra-renal aortic and aorto-iliac aneurysms. When placed within the aneurysm, the Aorfix™ AAA Flexible Stent Graft System creates an internal bypass of the aneurysm to reduce the risk of rupture. The Aorfix™ AAA Flexible Stent Graft System is a modular system where each component comprises: an implantable stent graft (Aorfix™ Stent Graft) and a disposable delivery system (Aorfix™ Delivery System). The stent graft is a two-piece system consisting of 1) a main body incorporating an ipsilateral leg component and a contralateral socket and 2) a contralateral plug-in leg. The main body has four sets of hooks positioned at the proximal end to aid fixation. The contralateral socket is a standard 12mm diameter component, with an oblique distal end that is designed to assist cannulation with a guide-wire. Radiopaque markers made of tantalum wire rings are located at the open ends of graft components. A bifurcated main body implant, with contralateral leg, is shown in Figure 1. Distal and proximal extension stent graft implants are available and may be used as required. For bailout, an aorto-uni-iliac (AUI) converter is also available. The delivery systems for the proximal extender and AUI converter are the same as the main body delivery system while the delivery systems for the distal extenders are the same as the contralateral leg delivery system. Each implant has a dedicated delivery system (22Fr main body and 20Fr contralateral leg). The delivery systems are designed to provide accurate placement of each implant and can be used by a single operator. See Instructions for Use (IFU) for the full range of sizes for the aortic body, ipsilateral limb, contralateral leg, iliac and proximal extensions, and AUI converter. Nitinol (nickel / titanium alloy) is used for all stent and hook components, tantalum is used for all radiopaque markers and polyester is used for the graft and suture materials. {2} ![img-0.jpeg](img-0.jpeg) Figure 1 Bifurcated Main Body of Graft with Contralateral Leg ## A. Main Body The main body stent graft has three sections – the body top, the ipsilateral leg and the contralateral socket as described below. It is available with proximal diameters from 24mm to 31mm. The key features of the body top are shown in Figure 2. Four pairs of hooks are positioned circumferentially 90° apart at the proximal end and are designed to resist migration. The reinforcing wire is in ring form, rather than a traditional zig-zag or diamond mesh stent. At the proximal end, the wire rings are placed closer together than in the body to increase radial force and they are also placed on the inside of the graft to improve the seal between the graft and the vessel wall. There is a radiopaque ring around the top of the device. PMA P110032: FDA Summary of Safety and Effectiveness Data {3} ![img-1.jpeg](img-1.jpeg) Figure 2 Main Body Hooks Figure 3 shows that the reinforcing wire in the main body is continuous and, between stent rings, the wire is bent to run longitudinally in an offset, stepwise fashion. The longitudinal parts of the wire run in the seam of the device. Note that when implanted, the stent graft rings are deformed to have a saddle or 'fishmouth' shape, also shown in Figure 3 and photographed in Figure 4. This shape allows the stent graft to be placed trans-renally, with the fishmouth trough aligned with the renal arteries juxtarenally and the fishmouth peak extending suprarenally. Note that the seam referred to above is part of the fishmouth peak. The seam is less flexible than the rest of the graft and, in curved vessels, placing the seam on the inner curve should be avoided. This requirement and the orientation of the seam to the fishmouth are usually met by placing the device with the seam anteriorly in the patient with exact alignment determined by the orientation of the renal arteries. To aid this orientation, there is a longitudinal radiopaque wire running within the seam of the main body. ![img-2.jpeg](img-2.jpeg) Figure 3 Shape of Nitinol Wire Used to Form Stent Rings PMA P110032: FDA Summary of Safety and Effectiveness Data {4} ![img-3.jpeg](img-3.jpeg) Figure 4 Lateral View of Stent Graft Once Deployed, Showing the Fishmouth Shape. ## B. Ipsilateral Leg All ipsilateral legs have a standard 12mm internal diameter at their proximal ends. The distal ends are flared on legs with distal diameters larger than 12mm and taper down for the 10mm distal diameter. The range of sizes for the distal diameter of this implant is from 10mm to 20mm in 2mm steps. There are no hooks on the leg. All leg components in the Aorfix™ AAA Flexible Stent Graft System are reinforced with Nitinol wire that is wound in a continuous helical shape. ## C. Contralateral Socket The socket also has a standard 12mm internal diameter and has an oblique distal end. There is a proximal radiopaque wire ring as well as the distal radiopaque ring to provide a visual guide to the physician when cannulating the contralateral socket. Note that the oblique entrance to the contralateral socket is not present in the 81mm long main body implant. Figure 5 Contralateral Sockets | | | | --- | --- | | Contralateral Socket used on Body lengths: 96mm, 111mm, 128mm, 142mm | Contralateral Socket used on Body length: 81mm | ## D. Contralateral (Plug-In) Leg All contralateral legs have a standard 12mm internal diameter at their proximal ends. The distal ends are flared on legs with distal diameters larger than 12mm and taper down for the 10mm distal diameter. The range of sizes for the distal diameter of this implant is from 10mm to 20mm in 2mm steps. There are no hooks on the leg. PMA P110032: FDA Summary of Safety and Effectiveness Data {5} The specified length of the leg is the Working Length and is the length of implant that projects beyond the contralateral socket; the actual length of the implant is 40mm longer than the working length to provide for full over-lap in the socket. Note: When using the 81mm body, the socket is 15mm shorter than on all other body lengths, making the Working Length of the contralateral legs 15mm longer (See Figure 5 and Figure 6). For example, Figure 6 shows a 64mm contralateral leg. Its overall length is 104mm and it has a Working Length of 64mm when plugged into a 40mm socket. This socket is found on all main body grafts apart from the 81mm graft. This shortest graft has a 25mm socket and this has the effect of increasing the working length of the contralateral leg to 79mm. The working length for both socket sizes is indicated on the box label for contralateral legs. ![img-4.jpeg](img-4.jpeg) Figure 6 Dimensions of a Contralateral plug in leg ## E. Proximal and Distal Extender Components All extension pieces (shown in Figure 7) have the same diameter at both ends and have radiopaque wire rings at the proximal and distal openings to aid visualization. Like the main body, the proximal extension pieces have hooks at the proximal end, the same design of Nitinol rings, and radiopaque wire along the seam. They are available in diameters 24mm through 31mm. Shown in Figure 8, the proximal extender also has a fishmouth shape which should be deployed with the same orientation as the fishmouth of the main body. PMA P110032: FDA Summary of Safety and Effectiveness Data {6} The distal extender has the same construction as the leg components using helical wound Nitinol wire. It is available in diameters 10mm through 20mm. ![img-5.jpeg](img-5.jpeg) Proximal Extender ![img-6.jpeg](img-6.jpeg) Figure 7 Proximal and Distal Extension Pieces Distal Extender ![img-7.jpeg](img-7.jpeg) Figure 8 Use of Proximal Extender with Main Bifurcated Graft ![img-8.jpeg](img-8.jpeg) ## F. Aorto-Uni-Iliac Converter (AUI Converter) The AUI converter (Figure 9) is for use as a ‘bail-out’ device in procedures where it has not been possible to gain access for the contralateral delivery system to the contralateral gate. Like the main body, the AUI converter consists of a body component and a leg component. The AUI converter body component is fabricated in the same way as the body component for the main body of the primary graft, and the leg component of the AUI converter is fabricated in the same way as the ipsilateral leg component. The AUI converter is designed to fit on the flow divider of the Aorfix™ main body and it has a fishmouth which should have the same orientation as the primary graft. Proximal diameters are 25mm, 27mm, 29mm and 31mm. Converters are designed to use the same size as, or 1mm larger than, the aortic diameter of the primary graft. PMA P110032: FDA Summary of Safety and Effectiveness Data {7} ![img-9.jpeg](img-9.jpeg) Figure 9 AUI converter Figure 10 illustrates correct position of the AUI converter in the main body graft. The top of the AUI converter leg should be aligned with the flow divider in the main body, the top of the converter should be below the top of the main graft and, in order to avoid inadvertent coverage of the renal arteries, the fishmouth at the top of the AUI converter should have the same orientation as the fishmouth of the main body graft. ![img-10.jpeg](img-10.jpeg) Figure 10 Use of AUI converter in Main Bifurcated Body ![img-11.jpeg](img-11.jpeg) PMA P110032: FDA Summary of Safety and Effectiveness Data {8} # G. Aorfix™ AAA Flexible Stent Graft System Main Body Delivery System ![img-12.jpeg](img-12.jpeg) Figure 11 Main Body Delivery System The main components of the Aorfix™ AAA Flexible Stent Graft System delivery system are shown above and are listed below in Table 1. The delivery system is operated by the sheath control which pulls the sheath back to deploy the stent graft. The control is rotated counter-clockwise while the fishmouth is being positioned. There is a ratchet which clicks while the control is being rotated. At the end of the ratchet, the Sheath Control spins freely at which point the mouth of the graft will have been fully deployed. The rest of the graft is deployed by pulling the sheath control distally. PMA P110032: FDA Summary of Safety and Effectiveness Data {9} Table 1 Components of the Main Body Delivery System | Part | Description | | --- | --- | | Stent Graft | The stent graft is compressed within the sheath. Its proximal and distal ends can be clearly seen, as well as the entrance to the contralateral gate which is a plain white oval of fabric midway down the graft. | | PTFE Sheath | The PTFE sheath has a 22Fr Diameter and contains the stent graft and attachments to it. The sheath is translucent and allows the key parts of the stent graft to be seen through it. | | Handle | The handle is firmly attached to and stabilizes the body tube while the sheath control and support tube controls are adjusted. | | Sheath Control | This control retracts the sheath in two stages; stage one uses a counterclockwise screw thread to release the proximal end slowly and stage two uses a simple pull back to deploy the rest of the graft. | | Body Tube | This is a blue colored tube that is attached to the handle and which carries all the controls of the deployment mechanism. When the seam on the main body graft is anterior, a full length slot in the body tube should face towards the patient. | | Support Tube Control | This control was initially intended to aid dilation of the mouth of the graft but was found to be ineffective in highly angled necks. It is recommended that the control is not used during deployment. | | Support Tube Release | This control disconnects the support tubes from the proximal end of the stent graft. | | Distal Stop | This clip prevents the support tube controls from moving during deployment. It must be removed before operating the support tube release. | PMA P110032: FDA Summary of Safety and Effectiveness Data {10} H. Contralateral Delivery System ![img-13.jpeg](img-13.jpeg) Figure 12 Contralateral Leg Delivery System When the proximal end of the contralateral plug-in leg (Figure 12) is aligned with the proximal radiopaque marker on the contralateral socket of the main body, the sheath control is moved directly back, i.e. without a twisting action, to deploy the implant. Once the contralateral leg is fully deployed, the support tube release is detached from the support tube control to release the implant. The delivery system is then withdrawn. Table 2 lists all components of the contralateral delivery system. PMA P110032: FDA Summary of Safety and Effectiveness Data {11} Table 2 Components of the Contralateral Delivery System | Part | Description | | --- | --- | | Stent Graft | The stent graft is compressed within the sheath. Its proximal and distal ends can be clearly seen. | | PTFE Sheath | The PTFE sheath has a 20Fr Diameter and contains the stent graft and attachments to it. The sheath is translucent and allows the key parts of the stent graft to be seen through it. | | Sheath Control | This control pulls the sheath back to deploy the stent graft. The stent graft is deployed by pulling the sheath control distally. | | Body Tube | This is a blue colored tube that is attached to the handle and which carries all the controls of the deployment mechanism. | | Support Tube Control | This control is locked and inoperable on this delivery system. | | Support Tube Release | This control disconnects the support tubes from the proximal end of the stent graft. | I. Ancillary Components Delivery System The proximal extender and AUI converter have the same delivery system as the main body implant. Distal extender pieces have the same delivery system as the contralateral leg. VI. ALTERNATIVE PRACTICES AND PROCEDURES There are three primary alternatives to using the Aorfix™ AAA Flexible Stent Graft System for the correction of abdominal aortic aneurysms (AAA). These include: endovascular repair using a commercially available endovascular grafting system (note: currently, not all endovascular grafting systems are approved in the US for treating necks angled more than 60°); surgical implantation of a synthetic graft within the aneurysmal vessel; and medical management. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. VII. MARKETING HISTORY The Aorfix™ AAA Flexible Stent Graft System has been commercially available outside the United States since March 2006 and is currently available in the following countries: Argentina, Austria, Brazil, Cyprus, Czech Republic, Germany, Great Britain, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Russia, Slovakia, Slovenia, Spain, Sweden, Turkey and Uruguay. It has never been withdrawn from any market as a result of risk of serious adverse health consequences. PMA P110032: FDA Summary of Safety and Effectiveness Data {12} VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. - Insertion and other vascular access site complications for example infection, dissection, bleeding, pain, delayed healing, hematoma, dehiscence, seroma, cellulitis, nerve injury/damage, arteriovenous fistula; - Allergic reaction and/or anaphylactic response for example to x-ray contrast dye, anti-platelet therapy, device materials; - Anesthetic complications and subsequent attendant problems; - Blood or bleeding events for example hemorrhage, anemia, gastrointestinal bleeding, coagulopathy; - Bowel events for example bowel ischemia, paralytic or adynamic ileus, obstruction, fistulae; - Cardiac events consequent to general anesthesia and abdominal surgery and, for example, transient aortic occlusion during ballooning; - Death; - Loss of stent graft function arising from, for example, improper component placement or deployment, component migration, occlusion, infection, loss of integrity requiring surgical revision, perforation and endoleak; - Embolic and thrombotic events (with transient or permanent ischemia or infarction), for example, deep vein thrombosis, renal embolism, micro embolic shower; - Arterial fistulae with, for example, vein, lymphatic, bowel; - Infection, for example urinary tract, systemic or localized, endograft, sepsis; - Generalized inflammatory response, for example, elevated temperature (post implantation syndrome); - Ischemic losses arising from, for example, planned or inadvertent occlusion of branch vessels including complications to systems such as: hepatic, gastric, splenic, bowel, neurologic, genitourinary and musculoskeletal; - Hepatic failure; - Lymphatic complications and subsequent attendant problems, for example, lymphocele, lymphatic fistula; - Multi-system organ failure; - Neurologic or cerebral events and subsequent attendant problems, for example, transient ischemic attacks, cerebrovascular accident (hemorrhagic or embolic), reversible ischemic neurologic deficit, nerve injury, paraparesis and paraplegia; - Pulmonary events consequent to general anesthesia and abdominal surgery; - Renal complications, for example, acute and chronic renal failure, renal microembolism, renal insufficiency, renal artery occlusion, contrast toxicity; - Endovascular or surgical reintervention to correct deficit caused by, or loss of performance of, stent graft including surgical conversion to open repair; - Impotence/ sexual dysfunction; - Shock; - Vessel damage, for example, dissection, plaque disruption, rupture, thrombosis, occlusion and fistulae. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 13 {13} For the specific adverse events that occurred in the clinical studies, please see Section X below. ## IX. SUMMARY OF PRECLINICAL STUDIES Lombard Medical completed comprehensive biocompatibility (Section A), in vitro bench and analytical testing (Section B), animal studies (Section C), and Sterility, Packaging and Shelf Life testing (Section D) on the Aorfix™ AAA Flexible Stent Graft System to support the safety and effectiveness of the device. The testing included the stent graft, iliac limbs, extensions and delivery system following recognized standards and guidance documents. ## A. Biocompatibility Biocompatibility testing was conducted on the Aorfix™ AAA Flexible Stent Graft System to ensure that the finished device is safe and biocompatible. Testing was performed in accordance with ISO 10993-1. The Aorfix™ Stent Graft was categorized as an implant device with permanent blood contact (>30 days). The Aorfix™ Delivery System was categorized as an external communicating device in limited contact with circulating blood (<24 hours). All testing performed met the requirements as specified within the applicable standard. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 14 {14} Table 3 Biocompatibility Testing | Test | What Tested | Method | Purpose | Results | | --- | --- | --- | --- | --- | | S. typhimurium* Reverse Mutation Assay (Ames) | Implant | Extracting Media: A) 0.9% sodium chloride B) DMSO Conditions: 70°C / 24 hours | Evaluate the potential of the test article to induce reverse mutations in five strains of Salmonella typhimurium in the presence and absence of exogenous mammalian metabolic activation system (S-9) | Pass Non-Mutagenic Test article extracts did not produce a two-fold increase in the number of revertants in any of the 5 extracts. | | Mouse Lymphoma* | Implant | Extracting Media: A) 0.9% sodium chloride injection USP B) DMSO Conditions: 70°C / 24 hours | Determine the ability of the stent graft to induce forward mutations at the thymidine kinase (TK) locus as assayed by colony growth of L5178Y mouse lymphoma cells in the presence of trifluorothymidine (TFT) | Pass Non-Mutagenic None of the test article treatments induced substantial increases in the number of revertant colonies. | | In vitro Chromosomal Aberration* | Implant | Extracting Media: A) Physiological Saline B) DMSO Conditions: 70°C / 24 hours | Determine whether the test article extract causes genotoxicity in Chinese hamster ovary cells | Pass Non-genotoxic | | ISO Implant test* | Implant | New Zealand White Rabbits Test articles implanted 2.5-5cm from midline, parallel to spinal column about 2.5cm apart. Control articles implanted in same manner on other side of spinal column. Control: USP Reference Standard HDPE (1x10mm) | Evaluate the potential of the test article to induce irritancy effects after implantation in muscle tissue of rabbits for 7, 30, 90 and 365 days | Acceptable No gross evidence of local irritancy | | ISO Dog Thrombogenicity | Implant and functional end of delivery system | Two purebred female beagles Test article surgically inserted into jugular vein. The control article was inserted into the opposing jugular vein of the test subject. Control article: Negative Control | Evaluate the potential of the test article to resist thrombus formation when placed in the vasculature of dogs | Acceptable The amount of thrombosis formed was not considered significant and was comparable to negative control. | PMA P110032: FDA Summary of Safety and Effectiveness Data {15} | Test | What Tested | Method | Purpose | Results | | --- | --- | --- | --- | --- | | | | Plastic (ex Toxikon) Implantation time of 4 ± 1/2hrs | | | | Complement Activation Assay, C3a and SC5b-9 | Implant and functional end of delivery system | Extraction Media: NaCl Conditions: 37°C for 72 hours. Test then exposed to plasma and incubated at 37°C for 90 minutes prior to assaying for complement proteins. | Measure complement activation in human plasma as a result of exposure of the plasma to the test article | Acceptable Concentration of C3a and SC5b-9 in the test extract was not significantly greater as compared to both negative and plasma controls. | | ISO MEM Elution | Implant and functional end of delivery system | Extracting Media: MEM Conditions: 37°C / 24 hours | Evaluate cytotoxic effects of the test article on a mouse fibroblast monolayer | Pass Non-cytotoxic | | Murine Local Node Assay | Implant and functional end of delivery system | Extracting Media: A) 0.9% sodium chloride injection USP B) acetone in olive oil Conditions: 70°C / 24 hours or 50°C /72hrs | Evaluate the allergenic potential or sensitizing capacity of the test article | Pass No evidence of sensitization | | ISO Intracutaneous Reactivity | Implant and functional end of delivery system | Extracting Media: A) 0.9% sodium chloride injection USP B) cottonseed oil (OIL) Conditions: 70°C / 24 hours or 50°C /72hrs | Evaluation of irritation or toxic effects of leachables extracted from the test articles in rabbits | Pass Non- irritant | | USP Systemic Injection Test | Implant and functional end of delivery system | Extracting Media: A) sodium chloride injection USP (IV administered) B) cottonseed oil (IP administered) Conditions: 70°C / 24 hours or 50°C /72hrs | Evaluate the test article for potential toxic effects after single dose injection into mice | Pass Non-toxic | | Hemolysis - direct contact method | Implant and functional end of delivery system | Negative Control: 0.9% sodium chloride injection USP Positive Control: 0.1% sodium carbonate solution Conditions: Incubation in rabbit blood | Evaluate hemolytic activity of the test article in rabbits | Pass Non-hemolytic | PMA P110032: FDA Summary of Safety and Effectiveness Data {16} | Test | What Tested | Method | Purpose | Results | | --- | --- | --- | --- | --- | | | | at 37°C for 60 minutes | | | | Partial Thromboplastin Time (PTT) | Implant and functional end of delivery system | Negative Control: Human plasma Positive Control: Crushed glass beads 0.4g/2.0ml Conditions: Incubation in plasma at room temperature for 60minutes. 0.2ml aliquots were incubated at 37°C for 60secs. 0.2ml PTT reagent was added and samples incubated for exactly 3mins before clotting induced. | Measure the effect of the test article on clotting time of human plasma | Acceptable Difference between test sample and negative control = 3 seconds, difference between test sample and positive control = 30 seconds | | Prothrombin Time (PT) | Implant and functional end of delivery system | Negative Control: Human plasma Positive Control: AcculotTM Control II Incubation in plasma at room temperature for 60minutes. 0.2ml aliquots were incubated at 37°C for 3-4minutes before clotting induced. | To measure the effect of the test article on clotting time of human plasma | Acceptable Test sample demonstrated a similar clotting time when compared to the negative control. | PMA P110032: FDA Summary of Safety and Effectiveness Data {17} # B. Laboratory Studies # 1. Bench Testing Lombard conducted bench testing on the Aorfix™ AAA Flexible Stent Graft System including both the stent graft and the delivery system. All testing was conducted in accordance with national and international standards and guidance documents, primarily EN 12006-3 (Non-active surgical implants – particular requirements for cardiac and vascular implants. Endovascular Devices), ISO 7198 (Cardiovascular implants – Tubular vascular prostheses) and ISO 25539-1 (Cardiovascular Implants. Endovascular devices. Endovascular Prosthesis). The testing details include results from $\mathrm{T} = 0$ (baseline, no ageing) as well as results using samples accelerated aged to 2 years $(\mathrm{T} = 2)$ . Testing verified that the Aorfix™ AAA Flexible Stent Graft System (implant and delivery systems) met its product performance and design specifications. Results obtained from in vitro testing provided evidence supporting the safety and effectiveness of the Aorfix™ AAA Flexible Stent Graft System, see Table 4. Table 4 Bench Testing Summary | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Dimensional Verification and Component Dimension Compatibility* | (72) Main Body (72) Leg | Dimensional Verification: Maximum effective length (handle to tip) for: A5-22 Delivery System is 595mm maximum. A6-20 Delivery System is 555mm maximum. | Dimensional Verification: All samples met acceptance criteria. | | | | Dimensional Compatibility: Guide-wire to pass completely through the central lumen of the delivery system without any impediment. | Dimensional Compatibility: All samples met acceptance criteria. | | | | Luer lock mating connector to indicate acceptable function. | All samples met acceptance criteria. | | Profile/Diameter Test* | (72) Main Body (72) Leg | Profile – The diameter of the effective length for: A5-22 Delivery System is 7.6mm ±0.2mm. A6-20 Delivery System is 6.6mm ±0.2mm. | The profile of the effective length was found to be acceptable for clinical use. | | Assessment of Haemostasis* | (33) Main Body (33) Leg | Leakage from the test delivery systems must be ≤10cm3/minute in all cases. | The leakage from the delivery system was found to be acceptable for clinical use. | | Simulated Use Models* | (22) Main Body (22) Leg | The tester must be in agreement with all statements listed below: | Testing was carried out in a pulsatile flow model with tortuous iliacs and a highly angulated neck. | PMA P110032: FDA Summary of Safety and Effectiveness Data {18} PMA P110032: FDA Summary of Safety and Effectiveness Data Page 19 | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | | | Pushability: The delivery system is able to advance into position in the anatomical model without bending or buckling. | Results of the testing were found to be sufficient for clinical use. | | | | Torquability: The delivery system handle transmits sufficient rotational rigidity to the implant end of the catheter. | Results of the testing were found to be sufficient for clinical use. | | | | Trackability: The delivery system is able to advance over the guide wire, following the guidewire tip, along the path of the vessel. | Results of the testing were found to be sufficient for clinical use. | | | | Flex/Kink: The delivery system and implant are able to bend in order to accommodate the minimum radius or angle negotiated during access and delivery. | Results of the testing were found to be sufficient for clinical use. | | | | Ability to access the intended deployment site: The delivery system enables access to the deployment site. | Results of the testing were found to be sufficient for clinical use. | | | | Deployment accuracy: Stent Graft Body: At its closest, the proximal wire rung is less than 7mm from the left renal artery marker. The implant has not occluded the target renal artery marker. | Stent Graft Body: Results of the testing were found to be sufficient for clinical use. | | | | Proximal Extender: The HPE implant successfully extended the stent graft body implant. | Proximal Extender: Results of the testing were found to be sufficient for clinical use. | | | | Contralateral Leg: The HBL implant was successfully positioned in the stent graft body implant. | Contralateral Leg: Results of the testing were found to be sufficient for clinical use. | {19} PMA P110032: FDA Summary of Safety and Effectiveness Data Page 20 | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | | | Visual inspection of deployed prosthesis: The implant maintains adequate contact with the vessel wall. There are no unacceptable kinks, bends, or twists. There is no unacceptable component separation between modular implant or components of the implant. | Results of the testing were found to be sufficient for clinical use. | | | | Ability to deploy: The delivery system enables the user to deploy the implant as intended. | Results of the testing were found to be sufficient for clinical use. | | | | Ability to withdraw: The delivery system is able to be successfully withdrawn. | Results of the testing were found to be sufficient for clinical use. | | | | Condition of delivery system: The delivery system is in an acceptable condition i.e. all joints are intact and there is no material damage that could cause harm to a subject. | Results of the testing were found to be sufficient for clinical use. | | | | Final statements: The delivery system can successfully deploy the stent graft as described in the IFU. The delivery systems, implants and ancillary implants were all compatible when used in accordance with the IFU. The process is practical for use in operating conditions. The expanded implant (when used with other implant modules) is patent and excludes the aneurysm. | Results of the testing were found to be sufficient for clinical use. | | Visibility | (6 ) Main Body | Characterization Study. | The radiopaque markers on the delivery system and implant were evaluated under fluoroscopy. The results indicate that the radiopacity of the delivery system and implant were found to be sufficient for clinical use. | {20} | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Force to Deploy* | (17) Main Body(17) Leg(11) Distal Extender | Characterization Study. | All stent grafts were successfully deployed. The unsheathing force did not exceed the minimum tensile strength of the sheath tubing. | | Bond strength / Torsional Bond Strength* | (64) Each joint | Varies depending upon specific test (Acceptance criteria ranged from 15N to 180N tensile and 4.84cNm torsional). | All joints met the pass criteria. | | Tip Connector to Center Tube Joint* | (32) Joints | Minimum joint strength 70N. | All samples met pass criteria. | | Tubing Longitudinal Tensile Strength | (64) 22Fr(64) 20Fr | 22Fr Outer Sheath Material. All Samples >115N at 10% Offset Yield.20Fr Outer Sheath Material. All Samples >77N at 10% Offset Yield. | All samples met pass criteria. | | Dimensional Verification (implant)* | (72) Main Body(72) Leg | All implant dimensions within the defined tolerances. | All samples met pass criteria. | | Integral Water permeability/leakage* | (22) Main Body(22) Leg | Characterization Study. | Stent graft permeability testing was characterized to evaluate the rate of water flow through the Aorfix™ stent graft under pressure of 120mmHg. The mean rate of leakage was 551ml/cm2/min. | | Circumferential Strength* | (22) Main Body(22) Leg | Characterization Study. | The minimum circumferential strength was determined to be 9N/mm, which corresponds to 4366mmHg blood pressure.The failure mode in each case was a graft fabric tear adjacent to the seam.These results demonstrate the circumferential strength of the Aorfix™ stent graft is adequate for the intended clinical use. | | Flex Kink* | (17) Main Body(17) Leg(22) Distal Extender | Characterization Study | It was determined that patency was maintained at a radius of curvature of 4mm. Results of the testing were found to be sufficient for clinical use demonstrating the ability of the stent graft to maintain an open lumen in tortuous anatomy. | PMA P110032: FDA Summary of Safety and Effectiveness Data {21} | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Longitudinal Tensile Strength (implant)* | (17) Main Body (17) Leg (11) Distal Extender | Characterization Study | Mean values for Longitudinal Tensile Strength are as follows: Main Body: 241.8N Leg: 224.7N Distal extender:203.14N The failure mode in each case was fabric tear in the smallest diameter region of the implant. The longitudinal tensile strength is sufficient to ensure the integrity of the implant is maintained in clinical use. | | Migration Resistance | (10) Main Body | Characterization Study | The testing characterized the ability of the bifurcated stent graft to resist migration. The peak force required to displace the proximal section of the bifurcated stent graft ranged from 16.47N to 22.66N. The migration resistance is higher than anticipated hemodynamic forces of 8.8N for a 29mm vessel, mean blood pressure 100mmHg. | | Migration Resistance | (18) Distal Extenders covering range. | Characterization Study | The testing characterized the ability of the distal extender devices to resist migration. The average force to displace a distal extender across the size range (10mm – 20mm diameter) is 6.7N. | | Pull Test for Modular Components* Leg devices | (11) Main Body (11) Leg | Characterization Study | The mean pull out force for modular components (plug-in leg) was 25.15N, which corresponds to a calculated blood pressure of 1668mmHg. Results of the testing are therefore sufficient for clinical use. | PMA P110032: FDA Summary of Safety and Effectiveness Data {22} | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Pull Test for Modular Components. | (19) Distal Extender | Characterization Study | The mean pull out force for modular components (distal extender) was 11.16 – 36.02N across the range, which corresponds to a minimum calculated blood pressure of 266mmHg. | | Distal Extender | | | Results of the testing are therefore sufficient for clinical use. | | Pull Test for Modular Components. | (12) Proximal Extender | Characterization Study | The mean pull out force for modular components (proximal extender) was 7.24N, which corresponds to a minimum calculated blood pressure of 82mmHg. | | Proximal Extender | | The proximal extender is intended to provide an adjunctive seal to the primary graft. It is not intended to resist migration forces on the primary graft, which has its own fixation. | In clinical use fixation of the primary implant is adequate to resist migration. The Proximal Extender is used to extend the sealing zone of the primary implant. | | Radial Force | (11) Main Body | Characterization Study | Main body:30% over-sizing: 1.49N10% over-sizing 0.43NDistal leg:20% over-sizing: 1.42N1 mm over-sizing: 0.21NThis testing demonstrates the ability of the Aorfix™ stent graft to exert an outward non-zero radial force, allowing the graft to expand, provide an adequate seal and maintain an open lumen. | | Strength of graft to stent bond* | (33) Helical construction(33) Ladder construction | Characterization Study | The mean force to break a single suture is 27.1NThe forces necessary to break the sutures are higher than the whole graft migratory forces that the graft will be subjected to in clinical use. | | Strength of attachment system bond | (11) Helical construction(11) Ladder construction | Characterization Study | The mean force to initiate separation of the hook is 52.9NThe forces necessary to detach the hooks are higher than the whole graft migratory forces that the graft will be subjected to in clinical use. | PMA P110032: FDA Summary of Safety and Effectiveness Data {23} | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Corrosion Assessment | (6) Main Body (6) Leg | Equivalent or better corrosion behavior when compared to a legally marketed device. | Results of the testing were found to be sufficient for clinical use. | | Fatigue and Durability Test (Pulsatile) Whole implant, full physiological simulation. | (8) Main Body, 24mm diameter with (8)Legs plugged into Main Bodies (8) Main Body, 31mm diameter with (8)Legs plugged into Main Bodies | Testing to identify evidence of macroscopic damage that would compromise its functional integrity as indicated in the failure modes identified in the risk analysis. | All devices successfully completed 400,000,000 test cycles. There was no visible deterioration of the devices. Independent examination concluded that the integrity of all devices was maintained. No unexpected failure modes were observed. | | 90° Neck Angle Fatigue and Durability Test (Pulsatile) Whole implant, full physiological simulation. | (8) Main Body | The test article must not exhibit evidence of macroscopic damage that would compromise its functional integrity as indicated in the failure modes identified in the risk analysis. | All devices successfully completed 400,000,000 test cycles. All samples met the acceptance criteria. The test articles did not exhibit any evidence of macroscopic damage that would compromise the implants' functional integrity as indicated in the failure modes identified in the risk analysis. There was no evidence of any of the following failure modes which would compromise the functional integrity of the implant. • Wire failure in the proximal seal zone. • Wire break / Wire Erosion. • Implant migration. • Fabric wear. • Seam Failure. • Suture Break. | PMA P110032: FDA Summary of Safety and Effectiveness Data {24} | Test | Samples Tested | Specification / acceptance criteria | Summary Test results | | --- | --- | --- | --- | | Stress Strain Analyses (e.g., Finite Element Analysis) | 24mm and 31mm devices plus the helical leg construction which is representative of the Aorfix™ AAA Flexible Stent Graft System | Characterization Study Finite element models of segments of a range of device diameters and pitch were selected to assess the sensitivity of the key design parameters to • manufacturing processes • simulated deployment • cyclical fatigue loading | Within the limits of FEA: • All configurations considered are satisfactory under the uniform radial fatigue conditions. • All configurations have adequate margins of safety, with the larger factors of safety occurring in the larger diameter device segments. | | MRI | (6) Main Body (6) Leg | The outcome of the testing provided the recommended scan settings for use with the device. These conditions are included in the device labeling. | The device has been determined to be MR conditional when scanned under the recommended conditions. | (*) Indicates testing was performed at both T=0 and/or T=2. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 25 {25} # C. Animal Studies Two preclinical in vivo animal studies were conducted, 1 ovine (12 animals) and 1 bovine (8 animals), using adaptations of the final device design. The ovine animal model required that human sized grafts be scaled to fit the smaller vessels of a sheep. The ovine stent grafts used Aorfix™ AAA Flexible Stent Graft System graft material. Narrower gauge Nitinol wire was used and the wire diameter and spacing of adjacent rings was scaled in proportion to the diameter of the vessel being treated. Hooks were reduced in width from the clinical design to fit onto the smaller implant. All Nitinol wire was treated using the same processes as the human devices and all machine stitching was completed using the same sewing machines and set ups. The bovine model had vessels that were slightly smaller than the clinical range. Thus the aortic diameter was reduced from $24\mathrm{mm}$ to $22\mathrm{mm}$ , the ipsilateral leg diameter was reduced from $12\mathrm{mm}$ to $10\mathrm{mm}$ and the contralateral leg reduced from $12\mathrm{mm}$ to $11\mathrm{mm}$ . The study data evaluated acute technical success (deployment), stent graft integrity and the histopathological response to the Aorfix™ AAA Flexible Stent Graft System for up to 26 weeks. The results demonstrated the accurate deployment of the endovascular graft and the capacity of the prosthesis to maintain physiological function. The responses of both the host and prosthesis were acceptable and support the safety and expected performance of the Aorfix™ AAA Flexible Stent Graft System. Table 5 Summary of Animal Studies | Study | Model | Samples | Details | Outcomes | | --- | --- | --- | --- | --- | | Ovine | Adult female sheep 65kg to 75kg | 12 tube devices implanted | Phase 1a: 3 x Stand alone aneurysm model. 3 Months | Patent, unchanged at 3 months. Conclude model is viable. | | | | 2 sizes of tubular implant: 7cm x 14mm (majority) and 10cm x 12mm. Delivery system 18Fr outside diameter from standard sheath with modified core. | Phase 1b: 3 x implant into normal aorta. 6 Months | 100% deployment succes, widely patent, free from migration at 6 months. | | | | | Phase 2 a: 6 x implant placed to exclude preplaced aneurysm. 6 Months | 100% deployment success but 2/9 early paraplegia secondary to access vessel thrombosis. Out of 7 stented aneurysms, 5 showed continuous shrinkage and became unrecognisable on 4-months scans. In two cases the size of aneurysm remained unchanged i.e. 6 cm and, Doppler studies suggested endoleak. On explantation the causes were revealed to be inadequate over-size (1) and inadequate length (1). Necropsy at 6 months showed stents were either partially or entirely covered by neointima. No migration was observed, with all hooks penetrating through aortic wall. | | | | | Phase 2b: 3 x implant placed to exclude preplaced aneurysm from Phase 1a. 6 Months | | PMA P110032: FDA Summary of Safety and Effectiveness Data {26} | Study | Model | Samples | Details | Outcomes | | --- | --- | --- | --- | --- | | Bovine | Young adult female calves approximately 200kg | 8 Bifurcated endovascular stent grafts implanted in 8 animals | 4 x acute animals < 1.5 hours | The device was successfully delivered to the target site within the infrarenal aorta with no related morbidity or mortality. The device delivery caused no vascular damage. | | | | | 4 x chronic animals followed for 100 to 115 days | The Aorfix™ AAA endoluminal stent graft system appears to be safe when implanted into the aortic bifurcation of young adult cattle. The healing response was normal. The histologic findings were comparable between animals and consistent with the implant of foreign material in the vascular system of a ruminant animal. All grafts were well incorporated into the intima of the native vessel and covered with a smooth neo-intima. | ## D. Sterilization, Packaging and Shelf-life The Aorfix™ AAA Flexible Stent Graft System is a single-use device that is provided sterile to the end user. The Aorfix™ AAA Flexible Stent Graft System is sterilized using ETO sterilization and is validated to demonstrate a Sterility Assurance Level (SAL) of $10^{-6}$. Packaging performance and stability testing demonstrate that the packaging designs for the Aorfix™ AAA Flexible Stent Graft System are sufficient to adequately protect the device and maintain the integrity of the Aorfix™ AAA Flexible Stent Graft System package throughout its 2-year shelf-life claim. Shelf-life testing results are presented alongside the in-vitro bench test results as part of Table 4. Accelerated shelf-life product testing conducted on the Aorfix™ AAA Flexible Stent Graft System supports a 2-year shelf-life claim. ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study (Pythagoras) to establish a reasonable assurance of safety and effectiveness of endovascular stent grafting with the Aorfix™ AAA Flexible Stent Graft System for infrarenal aortic and aorto-iliac aneurysms; however an adequate number of isolated iliac aneurysms were not enrolled in the study to demonstrate safety and effectiveness for this indication. The study anticipated enrolling a limited number of neck angles of $<60^{\circ}$ (for training purposes) and a majority of $60^{\circ}-90^{\circ}$ neck angles. The study was conducted under IDE #G050116 and was a controlled, prospective, non-randomized, multi-center study. Two hundred eighteen (218) Aorfix™ subjects and 76 Concurrent Open Surgical (COS) subjects were enrolled in this study. The study was carried out at 41 hospitals in the US, 3 in Canada and 1 in Poland. Two hundred ten (210) Aorfix™ procedures were initiated in the US, 6 in Canada and 2 in PMA P110032: FDA Summary of Safety and Effectiveness Data {27} Poland. The most frequent number of procedures completed at each site was 2, illustrating low levels of experience with the Aorfix™ at many sites. ## A. Study Design The Pythagoras study was an open label, non-randomized study of Aorfix™. The Aorfix™ arm was compared with the COS control and with historical data from the Society for Vascular Surgery (SVS) Lifeline registry. The control group used open surgery because it is currently the only approved intervention for AAA subjects with aortic neck angles greater than 60° in the U.S. Subjects were treated between April 28, 2006 and September 30, 2011. The database for this PMA reflected data collected through July 13, 2012 and included 218 Aorfix™ subjects and 76 COS subjects. An independent core lab reviewed CT scans and abdominal x-rays to assess all components of the primary efficacy endpoint including aneurysm changes, device integrity and position, and the presence of endoleaks. An independent Data Monitoring Committee (DMC) was established to ensure overall safety of the study and to classify secondary endpoints requiring clinical judgment. The determination of the safety and effectiveness of the Aorfix™ AAA Flexible Stent Graft System was based on the data collected in the first year post-implant. Additionally, Lombard Medical has been following and will continue to follow the subjects enrolled in the Pythagoras study for a total of 5 years. The Aorfix™ arm was divided into three sub-groups according to angle of the aortic neck. The first was based on the pre-specified hypotheses to be tested, including those subjects with neck angles from 60° to 90°. The other 2 were defined post-hoc, and included those subjects with neck angles less than 60° and those subjects with neck angles equal to or greater than 60°. The objective of the Aorfix™ AAA Flexible Stent Graft System Pythagoras study was to evaluate the safety and effectiveness of the Aorfix™ AAA Flexible Stent Graft System in the treatment of aortic, iliac, and abdominal aorto-iliac aneurysms. As a result of low numbers of subjects (3) recruited with aneurysms only in their iliac vessels, the study did not have the power to support an indication for patients with iliac aneurysms who did not also have aortic aneurysms. Effectiveness was assessed at 12 months in Aorfix™ AAA Flexible Stent Graft System subjects by a composite of those subjects free of Type I or Type III endoleak, free from migration >10mm and free from fracture in the fixation zone. Safety was assessed in Aorfix™ and COS subjects by evaluating the proportion of Aorfix™ subjects free from any Major Adverse Event (MAE) in the first 30 days postoperative and first 12 months postoperative compared with the control arm. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 28 {28} PMA P110032: FDA Summary of Safety and Effectiveness Data Page 29 # Pre-Specified Analysis Although the study enrolled subjects with neck angles of less than 60° and greater than 90°, the study protocol's pre-specified analyses plan defined the primary analysis group as subjects with neck angles of 60° to 90°. For effectiveness, a sample size of 120 subjects was considered to be sufficient to achieve a minimum of 85% statistical power with a Type I error rate of 2.5%. The null hypothesis was that the proportion of subjects with aortic neck angles between 60° and 90° who were free of all components of the primary composite outcome at 12 months would be at least 80%. The components of the effectiveness composite endpoints were: - Type I and Type III endoleaks - Migration of the proximal end of the device of more than 10mm - Fracture in the fixation zone. The primary safety hypothesis was that the proportion of subjects free from the occurrence of any Major Adverse Event (MAE) within 30 days of the implantation would be superior to the control group. The primary safety endpoint was defined as the rate of MAEs (as described below) within 30 days of the procedure. The sample size would provide 85% power to detect a rate difference of 0.14 for the 30-day Major Adverse Events between the two groups with an alpha of 0.05, using a two-sided two-sample chi-square test. # Changes to Pre-Specified Analysis The study anticipated enrolling a limited number of neck angles of <60° (for training purposes) and a majority of subjects with neck angles of 60° to 90°. Subjects of >90° neck angles were inadvertently enrolled into the study due to variations in measuring techniques used at the clinical sites and the core laboratory. For purposes of analysis, the subjects were assigned to a neck angle group on the basis of the neck angle measured by the core lab. In this sense, the study was blinded to neck angle group but a consequence was that a substantial number of subjects were found to have higher neck angles than the study required. The study ultimately enrolled 67 subjects with neck angles less than 60°, 109 with 60° to 90°, and 42 with >90°. Table 9 provides the distribution of neck angles of subjects enrolled in the study. After consultation with the FDA, it was decided that the post-hoc safety analysis would be conducted on the <60° population, the ≥60° population, and the <60° and ≥60° subjects combined (218). These three groups are presented below. When pertinent, the 60° to 90° results are also discussed to address the requirements of the pre-specified analysis. The effectiveness analysis presented below was conducted on the subjects who successfully received an Aorfix™ graft (210 subjects) who also had adequate data to evaluate the effectiveness endpoints. All endpoints described in the pre-specified analysis plan were evaluated. Additional analysis requested by the FDA was also performed. Of specific note, due to missing data {29} the primary effectiveness endpoint employs a substitution assessment where later follow-up data is used to increase the robustness of the primary analysis. The prospectively defined analysis also stipulated that the open control group would be the SVS Lifeline registry augmented by the COS control group. Due to limitations of the SVS registry including the lack of core lab defined neck angle measurements and the temporal differences in treatment between the Aorfix™ arm and the SVS registry, after consultation with the FDA it was decided that the COS arm would be the primary comparator for the study. In addition, the prospective analysis allowed for expanded follow-up windows of: 30 days –7/+15 days; 6 months (defined as 180 days ± 1 month); 12 months (365 days ± 2 months); yearly to 5 years (365 days ± 2 months). In order to account for all visits, including those that occurred in between the visits noted above, expanded windows were defined and used in the analysis as noted in Table 6 and Table 7. Finally, after consultation with the FDA, in addition to the substitution imputation discussed above, a tipping point analysis was performed to address missing data. ## 1. All Subjects Clinical Inclusion and Exclusion Criteria Enrollment in the Aorfix™ AAA Flexible Stent Graft System Pythagoras Study was limited to subjects who met the following selection criteria as listed below: - Diagnosed abdominal aortic aneurysm > 4.5 cm in diameter, OR 4.0 cm or larger in diameter if symptomatic (i.e. pain, embolisation), OR documented AAA growth of more than 5 mm within the previous 6 months, and/or including extension into common iliac artery(ies); and/or - Iliac aneurysm greater than, or equal to 3.5 cm in maximum diameter. Patients were not permitted to enroll in the Aorfix™ AAA Flexible Stent Graft System Pythagoras Study if they met any of the following exclusion criteria: - Less than 21 years of age; - Patient not expected to live more than 2 years from enrollment; - Pregnant; - Religious, cultural or other objection to the receipt of blood or blood products; - Unwillingness to comply with follow-up schedule; - Unwillingness or inability to provide informed consent to both trial and procedure; - Patient had a ruptured aneurysm; - Aneurysm extended above renal arteries; - Aorta between superior mesenteric artery (SMA) and aneurysm had significant loose thrombus associated with it; PMA P110032: FDA Summary of Safety and Effectiveness Data {30} - Patient with an acute or chronic aortic dissection or mycotic aneurysm, - Patient had current non-localized infection (may be recruited following remission of the infection); - Patient was allergic to device materials; - Patient was allergic to or intolerant of use of contrast media and could not be exposed to suitable remedial treatment such as steroids and/or Benadryl; - Patient was clinically and morbidly obese such that imaging would be severely adversely affected; - Patient had renal failure (serum creatinine > 2.5mg/dL); - Patient had an uncorrectable bleeding abnormality; - Patient had unstable angina; - Patient was receiving dialysis; - Inflammatory aneurysm; - MI in prior 6 months; - End stage COPD; - Patient had connective tissue disease (e.g., Marfan syndrome, Ehlers Danlos syndrome); or - Significant (>80%) renal artery stenosis which could not be readily treated. ## Endovascular Arm Exclusion Criteria - Patient had co-morbidities that deny vascular access, or small access vessels; - Patient had highly calcified and/or tortuous proximal neck or distal landing zones or iliac arteries; - Patient had insufficient length of proximal aneurysm neck (< 15mm from lowest renal artery) or SMA to aneurysm distance is less than 20mm; - Patient had insufficient length of distal landing zone (< 15mm); - Proximal neck was outside of device range indicated in IFU; - The iliac artery diameter (landing zone) was larger than 19 mm in diameter (reference sizing tables); - Indispensable Inferior Mesenteric Artery (IMA); - Inability to maintain at least 1 patent hypogastric artery; or - Excessive calcification, such as a ring or near ring of calcified plaque around an iliac artery. Prospective participants excluded from the endovascular study arms could still be eligible for inclusion in the open arm. The acceptability of excessive tortuosity, calcification and thrombus was determined by the principal investigator at each site. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 31 {31} Open Arm Exclusion Criteria - Excessive calcification or occlusive disease which would prevent open repair in the opinion of the principal site investigator; - Any portion of the aneurysm was supra-renal; - Aneurysm involved visceral arteries; or - Otherwise eligible for the endovascular arm. 2. Follow-up Schedule All subjects were scheduled to return for follow-up examinations at the following intervals postoperatively: - 1 month following index procedure - 6 months following index procedure - 12 months following the index procedure; and - Annually thereafter, for total of 5 years from the index procedure At the 1 month and 12 month visits, abdominal X-ray and CT with contrast medium were required. Only an abdominal X-ray was required at the 6 months visit unless an endoleak was present at 30 days and then a CT was required. The alternative imaging modality, Duplex Ultrasound was recommended in subjects with impaired renal function or intolerance to contrast media. ‘KUB’ refers to a plane film abdominal X-ray covering the kidneys, ureters and bladder which was used to evaluate the device for possible fracture. 3. Clinical Endpoints The analysis included clinically relevant endpoints for subjects with abdominal aortic disease. The endpoints used by Lombard Medical to demonstrate the safety of their device were adequate to describe the adverse events resulting from using the Aorfix™ AAA Flexible Stent Graft System. Similarly, endpoints used by Lombard Medical to demonstrate the effectiveness of their device were adequate to demonstrate the treatment effect. With regards to safety, the primary safety post-hoc endpoint of the study evaluated all Aorfix™ subjects (<60° and ≥60°). The primary post-hoc safety endpoint compares the proportion of Aorfix™ subjects free from any MAE in the first 30 days postoperative with the rate in the COS arm. The primary safety endpoint was further supported by a secondary safety analysis that was performed comparing Aorfix™ groups with results from the SVS Lifeline registry of open control subjects. This registry uses its own set of body system-related MAEs, referred to as SVS MAEs. The SVS MAE definition is less inclusive than the definition used by the study protocol for MAEs, principally because it defines no implant-specific events, such as ‘Device replacement or revision.’ PMA P110032: FDA Summary of Safety and Effectiveness Data {32} 12 month secondary analyses included the proportion of Aorfix™ subjects free from: any MAE, all-cause mortality, aneurysm-related mortality, graft migration, graft fracture and endoleaks. In addition, changes in volume of aneurysms, changes in diameter of aneurysms, stent graft patency, conversions, aneurysm ruptures, secondary procedures, and procedural success were analyzed. With regards to effectiveness, the primary effectiveness endpoint was the proportion of subjects in the Aorfix™ group classified as being free of all components of the primary composite endpoint at 12 months and was compared with 0.80. The components of the primary composite endpoint were migration > 10mm, fracture in the fixation zone and Type I or Type III endoleaks. A core lab was used to standardize all measurements and assessments made from all images, including endoleak identification and classification and the determination of assessability of CTs. Core lab derived angle measurements were used to define the groups. Post-hoc secondary outcomes included technical success at 30 days as adjudicated by an independent data monitoring committee (DMC). ## B. Accountability of PMA Cohort Follow-up evaluations were conducted at 1 month, 6 months (if needed), 12 months, and annually thereafter for a total of 5 years from the index procedure. Although at 12 months, 86% of subjects had CT follow-up and 81% had KUB follow-up, detailed imaging deficits, such as lack of contrast enhancement or poor KUB image quality, substantially reduced the proportion of subjects with assessable data for the effectiveness endpoint. At the time of database lock, 221 Aorfix™ subjects were consented in the PMA study. Of these, Aorfix™ implantation was not attempted in 2 subjects due to scheduling and graft availability and in 1 subject due to deteriorating health. Therefore, 218 subjects had an Aorfix™ procedure initiated with the Intention To Treat (ITT Population). Of these, 8 subjects did not have an Aorfix™ graft successfully deployed, leaving 210 subjects that completed the Aorfix™ procedure (As Treated population). Subjects were unable to be followed-up for effectiveness purposes if they had not had an Aorfix™ graft implanted, had died or withdrawn from the study, had their Aorfix™ repair converted to an open repair, were lost to follow-up or were not yet due for follow-up. Two hundred seven (207) subjects who received the stent graft were eligible for follow-up at 30 days. Of these, 189 (91%) had a clinical follow-up visit and 173 (84%) had CT scans. The 30 day follow-up window extended from 23 to 150 postoperative days. PMA P110032: FDA Summary of Safety and Effectiveness Data {33} One hundred forty-eight (148) subjects presented for a 6 month clinical visit. Although the protocol did not require a CT scan at the 6 month visit, 109 subjects had a CT performed. At the 12 month follow-up interval, 196 subjects were eligible for clinical and imaging follow-up. Of these, 171 (87%) had clinical follow-up visits and 168 (86%) had CT scans performed. The 12 month follow-up window extended from 10 months to 22 months. Table 6 summarizes subject and scan accountability. In the pre-specified analysis group of neck angles of 60° to 90°, 108 were eligible for 30 day follow-up, 99 subjects (92%) presented for a clinical follow-up and 91 (84%) had CT scans performed. One hundred and one (101) were eligible for a 12 month follow-up, 91 (90%) presented for a clinical follow-up and 87 (86%) had CT scans performed. In the COS group, 76 were eligible for 30 day follow-up, 76 subjects (100%) presented for a clinical follow-up. Seventy one (71) were eligible for a 12 month follow-up, 62 (87%) presented for a clinical follow-up. Data analysis sample sizes vary for each of the time points below and in the following tables. This variability is due to subject availability for follow-up as well as quality of images available from specific time points for evaluation. Although measures were undertaken to attempt 100% follow-up, this did not occur due to subject's health status, geographic proximity to evaluating physician, and core lab determined imaging quality. PMA P110032: FDA Summary of Safety and Effectiveness Data Page 34 {34} Table 6 Subject Accountability and Follow-up, for Patients with an Aorfix™ Implanted | N (%) All Aorfix™ Subjects | Number of Subjects | | | | | Assessable Endpoints | | | | | Before Next Visit | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Expected^{1} | Clinical Evaluation | CT | KUB | Pending^{2} | All Assessable^{3} | Change in Aneurysm size^{4} | Endoleak and Patency | Migration^{4} | Fracture | Death | Withdrawal | Conversion | Lost to Follow-up | Not due for next visit | | Subjects Implanted | 210 | 210 (100) | | | | | | | | | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 3 | | | | | | 30 days expanded (23 to 150 days) | 207 | 189 (91.3) | 173 (83.6) | 166 (80.2) | | 138 (66.7) | | 163 (78.7) | | 160 (77.3) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 2 | 1 | 1 | | | | 6 months (5 to 7 months) | 203 | 148 (72.9) | 109^{5} (53.7) | 139 (68.5) | | 81 (39.9) | | 101 (49.8) | | 136 (67) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 4 | | | | 3 | | 12 months expanded (10 to 22 months) | 196 | 171 (87.2) | 168 (85.7) | 158 (80.6) | 6 (3.1) | 124 (63.3) | 168 (85.7) | 143 (73) | 160 (81.6) | 150 (76.5) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 14 | 4 | | 3 | 23 | | 24 months expanded (22 to 34 months) | 152 | 134 (88.2) | 127 (83.6) | 116 (76.3) | 8 (5.3) | 79 (52) | 127 (83.6) | 102 (67.1) | 119 (78.3) | 103 (67.8) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 9 | 2 | | 1 | 28 | | 36 months expanded (34 to 46 months) | 112 | 85 (75.9) | 80 (71.4) | 76 (67.9) | 17 (15.2) | 55 (49.1) | 79 (70.5) | 69 (61.6) | 75 (67) | 67 (59.8) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 7 | 2 | | 2 | 51 | | 48 months expanded (46 to 58 months) | 50 | 21 (42) | 19 (38) | 16 (32) | 25 (50) | 12 (24) | 19 (38) | 16 (32) | 19 (38) | 14 (28) | | | | | | | Reasons not eligible for next visit | | | | | | | | | | | 2 | 1 | | 1 | 37 | | 60 months expanded (>58 months) | 9 | 6 (66.7) | 4 (44.4) | 4 (44.4) | 3 (33.3) | 3 (33.3) | 4 (44.4) | 3 (33.3) | 4 (44.4) | 4 (44.4) | | | | | | 1 N Expected is the number of subjects previously eligible for follow-up, minus those that have terminated or are not yet due for the visit. 2 Subjects within visit window, but no data yet available. 3 Subjects with data assessable for stent graft patency, endoleak, and stent fracture through 6 months plus change in aneurysm size and migration from 12 months onward. PMA P110032: FDA Summary of Safety and Effectiveness Data {35} 4 Subjects with scans 1-150 days postoperative and respective follow-up. 5 Not required by protocol. Table 7 Subject Accountability and Follow-up in the COS Arm | N (%)All COSSubjects | Subjects | | Before next visit | | | --- | --- | --- | --- | --- | | | Expected1 | Clinical Evaluation | Death | Withdrawal | | Subjects | 76 | 76(100) | 0 | 0 | | Events after implant but before a 30 day visit | 0 | 0 | 1 | | | 30 days expanded (23 to 150 days) | 75 | 69(92) | 0 | 0 | | Events after 30 day visit but before a 6 month visit | 0 | 0 | 2 | 0 | | 6 months (5 to 7 months) | 73 | 422(57.5) | 0 | 0 | | Events after 6 month visit but before a 12 month visit | 0 | 0 | 1 | 1 | | 12 months expanded (10-22 months) | 71 | 62(87.3) | | | 1 N Expected is the number of subjects previously eligible for follow-up, minus those that have terminated or are not yet due for the visit. 2 Not required by protocol. # C. Study Population Demographics and Baseline Parameters The demographic data for the Aorfix™ ITT population and the COS ITT population are presented and compared in Table 8 while the medical histories of the two populations are presented in Table 9. On average the Aorfix™ ITT subjects represent a significantly older subject population (76 vs. 69; $p < 0.001$ ). The proportion of female subjects treated was substantially higher in the Aorfix™ ITT population compared with the COS ITT population (29% vs. 20%). This difference is particularly influenced by the Aorfix™ ITT ≥60° group in which 35% of subjects were female, which was significantly more than the COS ITT population ( $p = 0.017$ ). A significantly higher proportion of the COS ITT population presented with history of tobacco use (97% vs. 87%; $p = 0.008$ ). There were also several notable differences in baseline medical history between the Aorfix™ ITT population and the COS ITT population which failed to reach significance because of limited subject numbers. Comparing Aorfix™ ITT with COS ITT, Congestive heart failure (13% vs. 5.4%), Angina (11% vs. 5.3%), Liver disease (4.6% vs. 1.3%) and Renal disease (14.3% vs. 6.7%) have more than double the incidence in the Aorfix™ ITT population than in the COS ITT. Coagulopathy (1.4% vs. 5.3%), alcohol abuse (3.2% vs. 8%) and peripheral PMA P110032: FDA Summary of Safety and Effectiveness Data {36} artery occlusive disease (10% vs. 17%) had lower incidence in the Aorfix™ ITT population than in the COS ITT. The data presented below is grouped in the post-hoc analysis groups. The pre-defined group of 60° to 90° showed a similar mean age of 76 years and similar percent females at 28%. The baseline medical histories of the 60° to 90° group were similar to those of the ≥60° group. Table 8 Demographics | N Mean ±STD % (n/N) | Aorfix™ <60° N=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | Mean Age | | | | | | Age | n=67 74.0▲ ±7.92 | n=151 76.3▲ ±7.24 | n=218 75.6▲ ±7.51 | n=76 69.2 ±7.04 | | Age Category▲▲ | | | | | | ≤55 years | 1.5% (1/67) | 0 | 0.5% (1/218) | 3.9% (3/76) | | 56-65 years | 16.4% (11/67) | 9.3% (14/151) | 11.5% (25/218) | 26.3% (20/76) | | 66-75 years | 34.3% (23/67) | 35.8% (54/151) | 35.3% (77/218) | 48.7% (37/76) | | 76-85 years | 43.3% (29/67) | 47.7% (72/151) | 46.3% (101/218) | 21.1% (16/76) | | ≥86 years | 4.5% (3/67) | 7.3% (11/151) | 6.4% (14/218) | 0 | | Gender | | | | | | Male | 85.1% (57/67) | 64.9%▲ (98/151) | 71.1% (155/218) | 80.3% (61/76) | | Female | 14.9% (10/67) | 35.1%▲ (52/151) | 28.9% (63/218) | 19.7% (15/76) | | Ethnicity | | | | | | White, non-Hispanic | 94.0% (63/67) | 91.4% (138/151) | 92.2% (201/218) | 90.8% (69/76) | | Non-White | 6.0% (4/67) | 8.6% (13/151) | 7.8% (17/218) | 9.2% (7/76) | ▲ indicates difference between each Aorfix™ ITT group and the COS ITT population p≤0.05 ▲▲ The distribution of ages is significantly different from COS ITT for all Aorfix™ ITT subgroups PMA P110032: FDA Summary of Safety and Effectiveness Data {37} Table 9 Baseline Medical History | % (n/N▲▲) Body System/Condition | Aorfix™ <60° N=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | Patients with at Least One Condition | 100.0% (67/67) | 99.3% (150/151) | 99.5% (217/218) | 100.0% (76/76) | | Cardiovascular | 94.0% (63/67) | 94.0% (142/151) | 94.0% (205/218) | 88.2% (67/76) | | Angina | 9.0% (6/67) | 11.9% (18/151) | 11.0% (24/218) | 5.3% (4/67) | | Arrhythmia | 16.4% (11/67) | 23.8% (36/151) | 21.6% (47/218) | 21.1% (16/76) | | Coagulopathy | 4.5% (3/67) | 0▲ | 1.4% (3/215) | 5.3% (4/76) | | Congestive Heart Failure | 10.8% (7/65) | 13.4% (20/149) | 12.6% (7/214) | 5.4% (4/74) | | Coronary Artery Disease | 50.7% (34/67) | 43.6% (65/149) | 45.8% (99/216) | 37.0% (27/73) | | History of Stroke or TIA | 15.4% (10/65) | 12.6% (19/ 151) | 13.4% (29/216) | 7.9% (6/76) | | Hypertension | 89.6% (60/67) | 83.3% (125/150) | 85.3% (185/217) | 80.3% (61/76) | | Myocardial Infarction | 32.8% (22/67) | 20.8% (31/149) | 24.5% (53/216) | 25.0% (19/76) | | Peripheral Arterial Occlusive Disease | 10.8% (7/65) | 9.9% (14/142) | 10.1% (21/207) | 17.1% (12/70) | | Valvular Disease | 9.0% (6/67) | 11.3% (17/151) | 10.6% (23/218) | 7.9% (6/76) | | Other | 98.5% (66/67) | 98.0% (148/ 151) | 98.2% (214/218) | 98.7% (75/76) | | Alcohol Abuse | 6.0% (4/67) | 2.0% (3/150) | 3.2% (7/217) | 8.0% (6/75) | | Allergy to Contrast | 6.0% (4/67) | 3.3% (5/151) | 4.1% (9/218) | 2.6% (2/76) | | Allergy to Nickel | 0 | 0 | 0 | 0 | | Allergy to Penicillin | 9.0% (6/67) | 11.9% (18/151) | 11.0% (24/218) | 9.2% (7/76) | | Cancer | 27.3% (18/66) | 30.5% (46/151) | 29.5% (64/217) | 23.7% (18/76) | | Diabetes | 19.4% (13/67) | 16.7% (25/150) | 17.5% (38/217) | 12.0% (9/75) | | Family History of AAA Disease | 27.6% (16/58) | 20.1% (27/134) | 22.4% (43/192) | 25.4% (17/67) | | Liver Disease | 7.5% (5/67) | 3.3% (5/151) | 4.6% (10/218) | 1.3% (1/75) | | Obesity | 19.4% (13/67) | 13.9% (21/151) | 15.6% (34/218) | 21.1% (16/76) | | Other Chronic Disease | 15.4% (10/65) | 30.7% (46/150) | 26.0% (56/215) | 22.7% (17/75) | | Pulmonary Insufficiency | 28.4% (19/67) | 33.3% (49/147) | 31.8% (68/214) | 28.2% (20/71) | | Seasonal/Other Allergies | 25.4% (17/67) | 29.8% (45/151) | 28.4% (62/218) | 17.1% (13/76) | | Tobacco Use | 97.0% (65/67) | 82.8%▲ (125/151) | 87.2%▲ (190/218) | 97.4% (74/76) | | Wound Infection | 0 | 0.7% (1/151) | 0.5% (1/218) | 0 | | Renal Disease | 13.4% (9/67) | 14.7% (22/150) | 14.3% (31/217) | 6.7% (5/75) | $\triangle$ indicates difference between each Aorfix™ ITT group and the COS ITT population p≤0.05 Sample sizes vary for specific baseline medical conditions due to missing data at the time of report writing. PMA P110032: FDA Summary of Safety and Effectiveness Data {38} Average neck length in the COS ITT was shorter than in the Aorfix™ ITT population while average neck angles were higher in the Aorfix™ ITT population than in the COS ITT population. These measurements apart, the preoperative CT measurements showed all other dimensions, including the range and distribution of aneurysm diameters, to be generally comparable across the control population and the Aorfix™ population. Table 10 to Table 12 summarize aneurysm and access vessel characteristics. Table 10 Baseline Aneurysm and Access Vessel Characteristics | N Mean ± SD | Aorfix™ <60° N=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | Iliac Aneurysm without AAA | 0 | 2.0% (3/151) | 1.4% (3/218) | 0 | | Iliac Aneurysm with AAA | 3.0% (2/67) | 2.0% (3/151) | 2.3% (5/218) | 6.6% (5/76) | | Proximal Neck Diameter 1mm Infrarenal (mm) | n=67 23.41 ± 3.41 | n=151 22.23▲ ± 2.72 | n=218 22.59▲ ± 2.99 | n=75 24.82 ± 5.17 | | Proximal Neck Diameter 7mm Infrarenal (mm) | n=67 23.25▲ ± 3.12 | n=151 22.44▲ ± 3.15 | n=218 22.69▲ ± 3.16 | n=75 27.90 ± 6.79 | | Proximal Neck Diameter 15mm Infrarenal (mm) | n=67 25.08▲ ± 4.30 | n=151 24.14▲ ± 5.64 | n=218 24.43▲ ± 5.27 | n=75 32.90 ± 8.77 | | Proximal Neck Length (mm) | n=67 24.04▲ ± 15.38 | n=151 21.91▲ ± 12.60 | n=218 22.56▲ ± 13.51 | n=75 13.34 ± 12.74 | | Proximal Neck Angle (°) | n=67 44.75 ± 12.32 | n=151 83.26▲ ± 14.51 | n=218 71.42▲ ± 22.56 | n=75 48.24 ± 23.26 | | Sac Diameter (mm) | n=67 54.31▲ ± 8.98 | n=151 58.95 ± 11.93 | n=218 57.53 ± 11.29 | n=75 57.69 ± 8.76 | | Sac Volume (cc) | n=66 168.01▲ ± 68.36 | n=151 218.37 ± 108.21 | n=217 203.05 ± 100.38 | n=74 200.82 ± 88.68 | | Maximum Left Iliac Diameter (mm) | n=66 17.28 ± 4.50 | n=151 19.73▲ ± 9.50 | n=217 18.99 ± 8.37 | n=72 17.27 ± 6.38 | | Maximum Right Iliac Diameter (mm) | n=66 17.53 ± 4.60 | n=151 21.02▲ ± 9.06 | n=217 19.96 ± 8.12 | n=74 18.54 ± 7.69 | | Proximal Neck Diameter (mm) | n=67 25.79▲ ± 3.18 | n=151 24.27▲ ± 3.02 | n=218 24.74▲ ± 3.14 | n=75 27.49 ± 5.48 | $\triangle$ indicates difference between each Aorfix™ ITT group and the COS ITT population p≤0.05 PMA P110032: FDA Summary of Safety and Effectiveness Data {39} Table 11 Distribution of Aneurysm Diameters | % (n/N) Max. Aneurysm Diameter (mm) | Aorfix™ <60° N'=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | <30 | 0 | 0.7% (1/151) | 0.5% (1/218) | 0 | | 30 to <40 | 0 | 1.3% (2/151) | 0.9% (2/218) | 1.3% (1/76) | | 40 to <50 | 38.8% (26/67) | 14.6% (22/151) | 22% (48/218) | 14.7% (11/76) | | 50 to <60 | 40.3% (27/67) | 47.0% (71/151) | 45.0% (98/218) | 46.7% (35/76) | | 60 to <70 | 14.9% (10/67) | 20.5% (31/151) | 18.8% (41/218) | 25.3% (19/76) | | 70 to <80 | 4.5% (3/67) | 10.6% (16/151) | 8.7% (19/218) | 10.7% (8/76) | | 80 to <90 | 1.5% (1/67) | 3.3% (5/151) | 2.8% (6/218) | 1.3% (1/76) | | ≥90 | 0 | 2.0% (3/151) | 1.4% (3/218) | 0 | Table 12 Distribution of Aortic Neck Angles | % (n/N) Aneurysm Neck Angles (°) | Aorfix™ <60° N=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | <40° | 26.9% (18/67) | | 8.3% (18/218) | 37.3% (28/76) | | 40° to <50° | 26.9% (18/67) | | 8.3% (18/218) | 18.7% (14/76) | | 50° to <60° | 46.3% (31/67) | | 14.2% (31/218) | 17.3% (13/76) | | 60° to <70° | | 15.9% (24/151) | 11.0% (24/218) | 10.7% (8/76) | | 70° to <80° | | 29.1% (44/151) | 20.2% (44/218) | 9.3% (7/76) | | 80° to <90° | | 23.8% (36/151) | 16.5% (36/218) | 1.3% (1/76) | | 90° to <100° | | 22.5% (34/151) | 15.6% (34/218) | 2.7% (2/76) | | ≥100° | | 8.6% (13/151) | 6.0% (13/218) | 2.7% (2/76) | Tortuosity index is used to provide a ratio of the tortuosity of a vessel. It represents the extra length of a vessel between its origin and terminus, caused by tortuosity, compared with the length it would have had if it took a straight path. Aorto-iliac tortuosity is calculated from the distal renal artery to the right or left femoral artery bifurcation and Iliac tortuosity is calculated from the aortic bifurcation to the right or left femoral artery bifurcation. For each group there is a substantial range of tortuosities. Tortuosity indices in the all angle Aorfix™ group are larger than the COS ITT group. PMA P110032: FDA Summary of Safety and Effectiveness Data {40} Table 13 Tortuosity Indices | N Mean ± SD | Aorfix™ <60° N=67 | Aorfix™ ≥60° N=151 | Aorfix™ ITT N=218 | COS ITT N=76 | | --- | --- | --- | --- | --- | | Right Aorto-Iliac Tortuosity Index | n=66 1.239▲ ± 0.077 | n=149 1.330▲ ± 0.101 | n=215 1.302▲ ± 0.103 | n=73 1.243 ± 0.107 | | Left Aorto-Iliac Tortuosity Index | n=66 1.251▲ ± 0.081 | n=149 1.333▲ ± 0.114 | n=215 1.308▲ ± 0.111 | n=72 1.244 ± 0.105 | | Right Iliac Tortuosity Index | n=65 1.291 ± 0.121 | n=149 1.325 ± 0.143 | n=214 1.315 ± 0.137 | Not Calculated | | Left Iliac Tortuosity Index | n=65 1.272 ± 0.105 | n=149 1.322 ± 0.154 | n=214 1.307 ± 0.143 | Not Calculated | $\triangle$ indicates difference between each AorfixTM ITT group and the COS ITT population $\mathrm{p}\leq 0.05$ # D. Devices Implanted The Aorfix™ device is a two piece device comprising an aortic body with conjoined ipsilateral leg and a modular contralateral leg. 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