NEXUS Aortic Arch Stent Graft System

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) # I. GENERAL INFORMATION | Device Generic Name: | Endovascular Graft | | --- | --- | | Device Trade Name: | NEXUS® Aortic Arch Stent Graft System | | Procode: | SDZ | | Applicant's Name and Address: | Endospan Ltd 4 Maskit St. Herzliya, ISRAEL 4673304 | | Date of Panel Recommendation: | None | | Premarket Approval Application (PMA) Number: | P250033 | | Date of FDA Notice of Approval: | April 2, 2026 | Breakthrough Device: Granted breakthrough device status on March 27, 2020, because of reasonable expectation that the device can provide more effective treatment of a life-threatening disease, as well as due to lack of approved or cleared endovascular device alternates. # II. INDICATIONS FOR USE The NEXUS® Aortic Arch Stent Graft System is indicated for the endovascular treatment of chronic dissections involving the aortic arch in patients who are at high risk for open surgical repair and who have appropriate anatomy including: - Adequate iliac or femoral artery access vessel morphology that is compatible with vascular access techniques, devices, or accessories. - Proximal/ascending native landing zone aortic anatomy including: - 30 mm to 39 mm diameter; - ≥ 30mm length - Landing zone cannot be aneurysmal, dissected, heavily thrombosed and tortuous - Proximal/ascending previously implanted surgical graft landing zone including: - 26 mm to 39 mm diameter; - ≥ 30mm length - Brachiocephalic trunk native landing zone anatomy including: - 12.5mm to 19.5 mm diameter; - ≥ 20mm length - Landing zone cannot be aneurysmal, dissected, heavily thrombosed and tortuous - Distal/descending native landing zone aortic anatomy including: - 28 mm to 42 mm diameter; 1 of 54 {1} – ≥ 30mm length ### III. CONTRAINDICATIONS - Patient with known sensitivities or allergies to the device materials. - Patient who has a condition that threatens to infect the graft. ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the NEXUS® Aortic Arch Stent Graft System labeling. ### V. DEVICE DESCRIPTION The NEXUS® Aortic Arch Stent Graft System is comprised of two primary implantable stent grafts, and an optional extension. All stent grafts are provided pre-loaded in a disposable 20 French (Fr) delivery system and each is provided sterilized and packaged individually. Each stent graft is introduced and implanted separately into the patient’s vascular system. The stent grafts that make up the NEXUS® Aortic Arch Stent Graft System are: - The **Arch Stent Graft**, whose cranial narrow end is intended to be deployed into the Brachiocephalic artery and whose distal end is to be deployed into the Descending Thoracic Aorta. - The **Ascending Curved Stent Graft** intended to be deployed in the Ascending Aorta. - Optional - **Descending Extension** can be used in case the aortic lesion elongates further distally and out of the covered length offered by the Arch Stent Graft. Multiple Descending Extensions can be used if needed to cover the entire length of the lesion. The pre-loaded stent graft components are sequentially advanced to the diseased location over a guide wire using fluoroscopic guidance. The sequence of delivery and implantation is the Arch Stent Graft System, followed by the Ascending Curved Stent Graft System and if needed the Descending Extension can be implanted overlapping and extending distally. In some cases, it may be decided in advance to implant the Descending Extension Stent Graft in advance of the Arch Stent Graft, in these cases the Arch Stent Graft would be implanted second and extending proximally from the Descending Extension, followed by an Ascending Curved Stent Graft implanted proximal to the Arch Stent Graft. The NEXUS® Stent Graft System is designed to be placed in the native vessel or within a previously implanted surgical graft such that the unconstrained stent graft diameter is larger than the internal diameter of the native vessel/surgical graft landing zone. This “oversizing” at the landing zone helps exclude the lesion from the aortic blood flow and ensures that the stent graft is held in place. The stent graft components are collectively intended to form proximal, distal and brachiocephalic artery (BCA) branch seal zones surrounding the diseased location (follow the shape and size of the true lumen and seal the primary entry tear). 2 of 54 {2}  *Figure 1. Configuration of the NEXUS® Arch & Ascending Curved Stent Grafts within the anatomy* Each stent graft is made of Nickel-Titanium (Nitinol) alloy stents, sewn to a polyester fabric, using surgical suture material. Each stent graft incorporates radiopaque markers to aid in visualization of the stent graft under fluoroscopy to facilitate accurate placement of the device components relative to each other and in relation to the patient’s vascular system. The radiopaque markers consist of tantalum and are described as the B-markers, Dot markers and the Docking radiopaque ring. The B-markers are used to determine rotational alignment, the Dot markers are used to determine axial positioning, and the Docking radiopaque ring, located on the Arch Stent Graft is used for axial alignment with the Locking Stent of the Ascending Curved Arch Stent. #### **A. Arch Stent Graft (Brachiocephalic Trunk to Descending Aorta)** The Arch Stent Graft is the main base stent graft, implanted from the brachiocephalic trunk (cranially) to the descending aorta (caudally), and is aligned with the aortic arch region (Figure 2). The Arch Stent Grafts are manufactured with equally spaced Nitinol stents which are sewn to the polyester graft using medical grade suture. The shape of the stent graft within the body is a thunderbolt shape which is designed to assist with stability and fixation. This stent graft contains a sleeve named the “Dock” or “Docking Sleeve” with a single fenestration which opens toward the ascending aorta. 3 of 54 {3}  *Figure 2. Arch Stent Graft (Brachiocephalic to Descending Aorta)* The positioning of the Arch Stent Graft should be such to allow blood flow to the brachiocephalic artery and to the descending aorta. Blood supply to the left carotid artery should flow through a bypass from the distal Brachiocephalic Trunk (BCT) or Right common carotid (RCC) artery. Blood supply to the left subclavian artery (LSA) should be made possible through bypass or it can be sacrificed, according to physician’s discretion. **Note:** Parallel Stent Grafts are not to be utilized with the NEXUS® System. The Arch Stent Graft implantation is done over a bracheo-femoral wire (known as “Through & Through” technique) in which a stiff guide wire is placed into the vasculature from the axillary/brachial artery to the iliac-femoral artery of the patient (see **Figure 3**).  *Figure 3. Through & Through Technique* 4 of 54 {4} ## **B. Ascending Curved Stent Graft** The Ascending Curved Stent Graft is the most proximal stent graft of the stent graft system and is implanted in the ascending aorta. The Ascending Curved Stent Grafts are manufactured with equally spaced Nitinol stents which are sewn to the polyester graft using medical grade suture. The Ascending Curved Stent Graft has additional Compression and Anti-Buckling Springs sewn to the graft material. The proximal stent of the Ascending Curved Stent Graft is slightly inwardly bent with the intent to prevent damage to the ascending aorta (**Figure 4**). The Ascending Curved Stent Graft is implanted distally to the coronary arteries and the sino-tubular junction, or distal to the most distal take-off of a coronary bypass and extends along the ascending aorta and into the Docking Sleeve of the Arch Stent Graft. The distal stent, called the Lock or Locking Stent is partially exposed and contains non traumatic, triangularly shaped latches. These latches are intermittently proximally and distally oriented, with the intent to provide bidirectional locking of the Ascending Curved Stent Graft inside the Dock of the Arch Stent Graft. The Sealing Stent of the Ascending Curved Stent Graft is located just proximal to the Locking Stent and is designed to seal against the proximal portion of the Arch Stent Graft Docking Sleeve (see **Figure 4**) for the location of the Locking and Sealing Stent). **Note:** The Locking and Sealing Stent are the exact same design for all sizes of Ascending Curved Stent Grafts. Once deployed, the Locking and Sealing Stents engage the Dock of the Arch Stent Graft, with the goal of creating a secure connection between the two stent grafts.  *Figure 4. Ascending Curved Stent Graft* ## **C. Descending Extension Stent Graft** The Descending Extension (DE) Stent Graft is used only in cases where the aortic lesion elongates further distally and out of the covered length offered by the distal portion of the Arch Stent Graft. The DE Stent Graft can be used in continuation to the Arch Stent Graft to ensure exclusion of the lesion from the blood flow. Multiple DE stent grafts may be utilized depending 5 of 54 {5} on the length of the aortic lesion. The DE Stent Graft is comprised of equally spaced Nitinol stents which are sewn to the polyester graft using medical grade suture. In addition, tantalum radiopaque markers; two opposite Dot markers indicate both ends of the prosthesis and a “B” shaped marker is positioned distal to the 4th stent and defines the minimum required overlap length. The minimum overlap length is defined by radiographically placing the B marker at the same axial level as the distal Dot marker on the Arch Stent Graft, this results in approximately a 6cm overlap. In all DE stent grafts, at both ends of the prosthesis, the graft follows the end stent’s exact circumference to create a crown-like shape. The DE Stent Graft is available in two configurations: Straight and Tapered (Figure 5).  Figure 5. Descending Extension Stent Graft (Straight and Tapered Configurations) # D. Delivery System The NEXUS® Delivery System (DS) is a single-use, disposable catheter-based delivery platform designed to facilitate controlled deployment of the NEXUS® Aortic Arch Stent Graft System components. Both the proximal shaft that contains the Stent Graft and the proximal tip are hydrophilic coated. The NEXUS® Delivery System has an outer diameter of 20 Fr. for all component sizes, supporting a percutaneous approach. The catheter assembly is flexible and compatible with a 0.035 inch (0.89 mm) guidewire. The delivery system used for the NEXUS® Arch Stent Graft component is pre-shaped (thunderbolt shape) (Figure 6). The delivery system used for the NEXUS® Ascending Curved Stent Graft is pre-curved (Figure 7). The delivery system used for the optional NEXUS® 6 of 54 {6} Descending Extension is straight.  Figure 6. NEXUS® Arch Stent Graft Delivery System – Pre-Shaped (thunderbolt shape)  Figure 7. NEXUS Ascending Stent Graft Delivery System – Pre-Curved # VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several alternative treatment options available for patients with chronic dissections involving the aortic arch, including: - Medical management - Open surgical repair - Hybrid Surgery with Thoracic Endovascular Aortic Repair (TEVAR) - Other commercially available endovascular devices Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with their physician to select the method that best meets expectations and lifestyle. # VII. MARKETING HISTORY The NEXUS® Aortic Arch Stent Graft System is currently approved in Europe, Serbia, New Zealand, Israel, Argentina, Peru, Chile, and Uruguay. Prior to US commercialization, the NEXUS System was the subject of one recall in Europe during July 2022 that resulted in a correction to ensure continued safe and effective performance of the device. There have been no market withdrawals of the NEXUS System in any geography. 7 of 54 {7} ## **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. - Abscess formation - Acute respiratory distress syndrome (ARDS) - Adverse foreign body response - Allergies (including - Amputation - Anesthetic complications and subsequent attendant problems - Aneurysm enlargement or rupture - Angina - Aortic damage - Aortic enlargement - Aortic regurgitation - Aortic valve damage and/or functional impairment - Arrhythmia - Arteriovenous fistula - Aortoesophageal fistula - Bleeding/bleeding complications - Cardiac complications and subsequent attendant problems - Claudication (e.g. buttock, lower limb) - Congestive heart failure - Contrast toxicity - Coronary arteries occlusion - Coronary arteries stenosis - Death - Dissection extension - Dissection of a vessel - Edema - Embolization (micro and macro) - Emergency operation including surgical conversion to open repair - Endoleak - Erosion - Fistula - Fever - Genitourinary complications and subsequent attendant problems including erosion - Hematoma - Hematuria - Hemorrhage, requiring blood transfusion - Hemorrhagic pleural effusion - Heparin-induced thrombocytopenia (HIT) - Hepatic Failure - Lymphatic complications and subsequent attendant problems (lymphocele) - Multiple organ failure syndrome (MOF) - Myocardial infarction (MI) - Myocardial perforation - Necrosis - Neurologic complications including lipothymy and encephalopathy - Obstruction/occlusion - Pain - Paralysis including vocal cords and diaphragm - Paralysis of vocal cords - Paraparesis - Paraplegia - Pericardial tamponade - Perforation of a vessel wall - Peritonitis - Persistent False Lumen - Pseudoaneurysm - Pulmonary complications and subsequent attendant problems - Radiation exposure risks / repetitive radiation sessions - Renal Insufficiency/failure - Rupture of a vessel - Sepsis - Seroma - Stenosis - Stent graft complications: improper component placement; incomplete component deployment; inadequate apposition, "beaking" and subsequent collapse of the component; clinically significant component migration; suture break; stent fracture; graft twisting or kinking; insertion and removal difficulties; graft material wear; dilatation; erosion; puncture and perigraft flow - Stroke - Syncope - Temporary Neurological Deficit (TND) - Thrombosis - Transient ischemic attack (TIA) - Vascular access site complications including lymphocele 8 of 54 {8} - Hypertension - Hypotension - Ileus - Impotence - Incontinence - Infarction - Infection - Inflammation (localized or general) - Ischemia transient or permanent - Ischemic effects to the limbs, genitourinary system including kidneys, myocardium, mesentery, brain and spinal cord - Vascular spasm or vascular trauma - Ventricular fibrillation - Ventricular tachycardia - Vessel damage - Wound complications including dehiscence and cellulitis For the specific adverse events that occurred in the clinical study, see Section X. # IX. SUMMARY OF NONCLINICAL STUDIES Nonclinical studies were completed to evaluate the NEXUS® Aortic Arch Stent Graft System including non-clinical bench testing, biocompatibility, sterilization, packaging, shelf-life, and animal studies. These are described in detail in the following sections. # A. Laboratory Studies In vitro bench testing to support the NEXUS® Aortic Arch Stent Graft System is summarized in Table 1. It was developed based on the device risk assessment and is consistent with FDA's Guidance Document Non-Clinical Tests and Recommended Labeling of Intravascular Stents and Associated Delivery Systems, April 18, 2010, its addendum, Select Updates for Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, August 18, 2015, and ISO 25539-1. Table 1. In Vitro Engineering Testing Summary | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | **Complete System Testing** | | | | | Simulated Use* | To evaluate the following attributes of the Nexus Aortic Arch Stent Graft System according to the Instructions for Use: - Compatibility with Accessories - Preparation for Use - Delivery to target location - Push-ability, flexibility, torque-ability, and trackability - Deploy at Target Location, including accuracy of deployment - Conformability - Withdrawal of the Delivery System - Occurrence of Particles | The following criteria were used: • **Packaging:** The packaging must allow for the removal of the loaded delivery system without damage. • **Degassing:** Guidewire lumen can be flushed with slip fit luer syringe and saline should exit at the tip of the catheter. • **Guidewire compatibility:** The guidewire should be able to pass through the guidewire lumen without kinking or damage to the delivery system. • **Sheath compatibility:** The delivery system should be able to pass through the introducer sheath without kinking or damage to the delivery system. • **Accessory Compatibility:** The stent-grafts | Pass | 9 of 54 {9} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | | | shall be compatible with accessory devices (e.g., balloons or pigtail catheters), including insertion, inflation, deflation, and withdrawal, without damage to or displacement of the implanted stent-grafts. • **Deliver to target location:** System can be advanced to the target location with adequate pushability, trackability, and torqueability without buckling or loss of function • **Deployment and accuracy:** Device can be deployed within +/- 5 mm of the target location. • **Conformability:** Stent-graft opposes the vessel wall at intended landing zones and regions of stent graft overlaps. • **Withdrawal:** Delivery system can be withdrawn without causing device migration or damage. • **Migration:** Device migrates ≤ 4 mm from its original implant location. • **Particles:** No clinically significant particle generation observed. | | | **Delivery System** | | | | | Dimensional Verification of the System | Verify the NEXUS Delivery System dimensions meet design specifications. | The measured dimensions shall be compared to the pre-determined specifications (dimension ± accepted tolerance) | Pass | | Force to Deploy* | Evaluate the maximum force required to deploy the NEXUS Aortic Arch Stent Graft System under simulated use conditions and confirm that deployment forces remain within the mechanical strength limits of the delivery system components. | The maximum deployment force shall remain below the minimum tensile strength of the delivery system structural components to ensure safe deployment without damage or failure of the delivery system. | Pass | | Stent-Graft Wire Release Force | Characterize and determine the force required to release the stent-graft by retracting the tether wires during deployment of the NEXUS Aortic Arch Stent-Graft System under simulated anatomical conditions. | Wire release torque ≤1.2 Nm | Pass | | Tubing Tensile Strength* | Determine the longitudinal tensile strength and associated elongation of the NEXUS Delivery System outer tube (shaft) as part of the delivery system. | The tensile strength of the delivery system shaft shall exceed the maximum forces expected during device deployment without impairing system function. | Pass | | Bond tensile strength* | Determine the bond strength of the joints and/or fixed connections of the delivery system. | Bond strength shall exceed the maximum forces expected during device deployment and use. | Pass | | Torsional bond strength* | Determine the torsional bond strength of the NEXUS Delivery System. | The torsional strength of the delivery system shall exceed the maximum torque expected during clinical use. | Pass | | Hemostasis* | Verify that the NEXUS Aortic Arch Stent Graft System provides adequate hemostasis during the implant procedure. | Leakage from the Delivery System shall not exceed the specified limit. | Pass | | Visibility | Evaluate the ability to visualize the NEXUS system (DS and the implant) | The implant and the delivery system shall be visualized under imaging techniques | Pass | 10 of 54 {10} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | | using imaging techniques specified in the instructions for use (IFU). | according to the instructions for use, radiopaque components shall be visualized and assessed. | | | **Implant** | | | | | Dimensional Verification of the Prosthesis* | Verify the NEXUS implant dimensions to meet design specifications. | Implant dimensions shall meet pre-determined specifications. | Pass | | Radial Force* | Evaluate the outward radial force of the NEXUS Stent Graft as a function of diameter. | Radial force shall be within the specified design range to ensure adequate vessel apposition without excessive vessel loading. | Pass | | Burst Strength* | Determine the pressurized burst strength of the NEXUS Stent-Graft. | The lower expected stent graft burst strength > 75 kPa | Pass | | Longitudinal tensile strength* | Determine the longitudinal tensile strength of the graft fabric used in the manufacturing of the NEXUS Aortic Arch Stent-Graft System. | Graft tensile strength shall exceed the maximum forces expected during device deployment (i.e., lower tolerance limit of strength measurement ≥ 2.17 N/mm). | Pass | | Water permeability (textile materials) | Determine the water flow rate through a given area of the NEXUS graft material under a given hydrostatic pressure. | Water permeability shall not exceed the specified maximum flow rate (i.e., upper tolerance limit of flow rate measurement < 600 ml/(min cm²) under 120mmHg.) | Pass | | Factory anastomosis – Seam strength | Determine the strength of the graft fabric used in the manufacturing of the NEXUS Aortic Arch Stent-Graft System. | The graft seam strength shall exceed the burst pressure loads expected for the largest diameter NEXUS stent graft configuration. | Pass | | Strength of Connection Between Stents and Graft Material | Determine the strength of connection between the graft material and the Locking Stent (fixation system) | The connection strength between the Locking Stent and the graft shall exceed the maximum forces expected during device deployment and use. The connection strength between the Dock Stent and the graft shall meet the minimum strength specification. | Pass | | Integral water leakage | Evaluate the water leakage between modular components of the NEXUS stent-grafts and holes in the graft material resulting from the construction of the endovascular prosthesis. | The water leakage through the entire NEXUS Stent-Graft shall be lower than the pre-determined specified flow rate (600 ml/(min cm²)) under a pressure of 120[mmHg]. | Pass | | NEXUS Migration resistance and Separation Force of Overlapping Stent Graft Components | Evaluate the resistance of overlapping NEXUS stent graft components to migration and separation under simulated physiological loading conditions representative of clinical use. | Separation Force: The separation force between overlapping stent-graft components shall exceed the minimum specified force required to maintain modular engagement. Migration: Migration shall not exceed clinically acceptable limits. | Pass | | Implant Resistance to kinking (flexibility) | Determine the radius of curvature required to begin “kinking” the NEXUS Stent-Graft and characterize the minimum BCT angulation of the Arch Stent-Graft | Characterization of the NEXUS Arch Stent-Graft resulted in the determination that the device shall maintain lumen continuity without kinking when subjected to a curvature corresponding to a mandrel diameter of ≥40 mm (radius ≥20 mm). For the branch segment, the device shall maintain lumen continuity at a branch-to-body angulation ≥125°. | Pass | | Pitting corrosion resistance and | Evaluate the pitting corrosion resistance and nickel release rate from the NEXUS implants over 60-day exposure | If the pre-specified acceptance criteria for pitting corrosion resistance are not met, Nickel release shall not exceed 35 μg/day, | Pass | 11 of 54 {11} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Nickel-ion release | | consistent with established safety thresholds for nickel exposure. | | | Nitinol Austenitic Transitional temperature (Af) | To verify that the austenitic transition temperature (Af) of all Nitinol components is below body temperature to ensure full transition to the austenite phase during clinical use. | The austenitic transition temperature (Af) of all Nitinol components shall meet the specified design requirements to ensure full transition to the austenite phase at physiological temperature. | Pass | | Magnetic Resonance Imaging (MRI) safety See | Ensure the system is compatible for MRI use. According to applicable standards | • Deflection angle <45° • Magnetically induced torque less than gravitational torque • RF-induced heating ≤2°C • Image artifact characterized | Pass | | Finite Element Analysis (FEA) modeling of Wire Stents and Laser-Cut Nitinol Components | Finite element modeling of wire stents and laser-cut stents including shape-setting, crimping & deployment, and fatigue at worst-case boundary conditions | Finite element analysis shall demonstrate peak strain amplitudes below the Nitinol fatigue limits reported in literature and internal testing, and a safety factor against fatigue failure ≥1. | Pass | | Fatigue-to-Failure of Worst-Case Laser-Cut Nitinol Component | Evaluate the fatigue strength of the representative worst-case laser-cut Nitinol component and confirm an adequate margin relative to expected in vivo loading conditions. | The fatigue strength of the component shall exceed the maximum strain expected under worst-case physiological loading conditions. | Pass | | Fatigue Resistance of Worst-Case Laser-Cut Nitinol Component | Verify long-term durability of the representative worst-case laser-cut Nitinol component under cyclic loading representative of physiological conditions. | No fatigue fractures shall occur after completion of the defined fatigue cycling test. | Pass | | Radial Fatigue and Durability of overlapping Arch and Descending Extension Stent Grafts | Evaluate the long-term structural integrity of the overlap region between the stent grafts under cyclic radial loading representative of physiological conditions for a simulated 10-year implant duration. | Test articles shall maintain structural integrity following completion of the durability testing, including no stent fractures, no separation of stents or markers from the graft, and graft integrity maintained within specification. | Pass | | Radial Fatigue and Durability of Overlapping Bent Stent Grafts | Evaluate the long-term structural integrity of overlapping stent grafts under cyclic radial loading in a fixed bent configuration representative of physiological conditions for a simulated 10-year implant duration. | Test articles shall maintain structural integrity following completion of the durability testing, including no stent fractures, no separation of stents or markers from the graft, and graft integrity maintained within specification. | Pass | | Axial Durability of Dock-Lock Interface Between the Ascending and Arch Stent Grafts | Evaluate the long-term durability and wear of the Dock-Lock interface between the Ascending and Arch stent grafts under cyclic axial motion representative of physiological cardiac motion for a simulated 10-year implant duration. | Test articles shall maintain structural integrity following completion of the durability testing, including no stent fractures, no separation of stents or markers from the graft, and graft integrity maintained within specification. | Pass | * Testing was also completed to support device shelf-life. 12 of 54 {12} ## B. Animal Studies The purpose of the GLP animal study was to evaluate the biological safety of the NEXUS® Aortic Arch Stent Graft System in a chronic swine model. A total of 12 mature swine (Male and Female) were evaluated chronically in this safety study (4 animals in each group – 30-day, 90-day and 180-day). Animals were implanted with the NEXUS Stent Graft and the study implant device was evaluated for biological safety. Study endpoints included assessments through 180 days for overall animal health, local tissue response to the device, and system toxicity. Thrombogenicity was evaluated on the delivery system and implant during the implant procedure, as well as through local (implant site) and downstream tissue evaluation during gross pathology and histopathology. The Good Laboratory Practices (GLP) animal study is summarized in **Table 2**. **Table 2. GLP Animal Study Summary** | Study Description and Sample Size | Evaluations | Outcome | | --- | --- | --- | | 30, 90, and 180 Day Safety Evaluation in the Swine Model. 4 animals were evaluated at each time point. One NEXUS Stent Graft* was placed in the thoracic aorta of each of 12 swine. | Acute Assessment: - Success of implantation - Following the dwell time, the delivery system was removed and scored for thrombogenicity - Post implant flow was scored based on the Arterial Flow Assessment (AFA) Flow scale. Chronic Assessments: - Physical examinations, body condition scores, body weights, clinical monitoring and clinical pathology were performed from prior to Day 0 through termination - Evaluation of patency. - Gross pathology. - Evaluation of the structural integrity of the NEXUS Stent Graft at the time of explant. - Evaluation of histology and pathology of explanted test article and surrounding tissue, as well as downstream. | - All animals survived until their scheduled termination time point. - A total of twelve animals were successfully implanted (4 animals per the 30, 90, and 180 day groups). - There was no evidence of thrombus on the delivery system post-implant. - All implanted vessels scored a '3' based on the AFA Flow scale. - All animal health assessments suggested that animals remained in good general health throughout the duration of the study. - There was no evidence of thromboembolism in the downstream organs/tissues in the chronic swine model at any time point. - There was no evidence of adverse systemic toxicity resulting from Test Article implantation in the chronic swine model at any time point. - All study objectives were met for this study. Therefore, the Aortic Arch Stent Graft System is considered safe at 30 days, 90 days, and 180 days following implant. | \*A cylindrical stent graft (ø31x125mm) representative of the materials and manufacturing process of the NEXUS device ## C. Biocompatibility Studies The NEXUS® Aortic Arch Stent Graft System biological safety was evaluated in accordance with the requirements of International Organization for Standardization (ISO) 10993-1:2018, *Biological evaluation of medical devices – Evaluation and testing*, and the FDA guidance document, *Use of International Standard ISO 10993-1, 'Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process.'* The NEXUS® Aortic Arch Stent Graft System consists of two (2) main components, the Stent Graft and the Delivery System. All NEXUS stent grafts are considered implants with long term contact (> 30 days). All the NEXUS delivery systems are considered an external 13 of 54 {13} communicating device, circulating blood with limited exposure (< 24 hours). All testing performed met the pre-specified acceptance criteria. A summary of the biocompatibility testing can be found in **Table 3**. **Table 3. Biocompatibility Testing Summary** | Test Performed | Test Description | Stent | Delivery System | Results | | --- | --- | --- | --- | --- | | Cytotoxicity | Minimum Essential Medium (MEM) Elution | X | X | Non-cytotoxic | | Sensitization | ISO Guinea Pig Maximization Sensitization | X | X | No evidence of causing delayed contact sensitization | | Irritation/ Intracutaneous Reactivity | ISO Intracutaneous study in Rabbits | X | X | Non-irritating | | Acute Systemic Toxicity | ISO Acute Systemic Toxicity study in Mice | X | X | No evidence of systemic toxicity | | Material-Mediated Pyrogenicity | Material Mediated Pyrogenicity Test International Organization for Standardization /United States Pharmacopeia (ISO/USP) | X | X | No evidence of material mediated pyrogenicity | | Subacute/ Subchronic Toxicity | ISO Two Week Toxicity Study in the Rat - Repeated Parenteral Administration of Two Extracts | X | N/A | No evidence of systemic toxicity | | Genotoxicity | Mouse Lymphoma Assay | X | N/A | Non-mutagenic | | Genotoxicity | Bacterial Reverse Mutation Study | X | N/A | Non-mutagenic | | Implantation | ISO Muscle Implantation Study in Rabbits, 13-Weeks* | X | N/A | Non- significant tissue contact irritation | | Hemocompatibility | ASTM F756 Hemolysis Study | X | X | Non-hemolytic | | Hemocompatibility | Soluble C5b-9 (SC5b-9) Complement Activation Assay | X | X | Non-Activator of the Complement System | | Hemocompatibility | In Vivo Thrombogenicity* | X | X | The test article average clot time was greater than the vehicle control | | Chronic Toxicity | Chemical Characterization/ Toxicological Risk Assessment | X | N/A | Non-toxic | | Carcinogenicity | Chemical Characterization/ Toxicological Risk Assessment | X | N/A | No carcinogenic risks | \* This was also evaluated as part of the GLP chronic safety animal study #### **D. Sterilization, Packaging, and Shelf-Life** The NEXUS® Aortic Arch Stent Graft System is sterilized by Ethylene Oxide (EO). Validation of the sterilization method to ensure a Sterility Assurance Level (SAL) of 10$^{-6}$ was conducted in accordance with EN ISO 11135:2014/ A1:2019 *Sterilization of health-care products Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices.* Packaging Validation demonstrated the ability of the packaging to protect the product and maintain a sterile barrier through shipping and shelf life. A shelf life of one (1) year has been established for the NEXUS® Aortic Arch Stent Graft System based on product performance and package shelf-life testing. The specific 14 of 54 {14} engineering tests completed to support the shelf-life are denoted by an asterisk (*) in Table 1. # X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the NEXUS® Aortic Arch Stent Graft System (NEXUS) for endovascular repair of chronic dissections of the aortic arch in the United States and New Zealand under IDE #G200105. Data from this clinical study were the basis for the Premarket Approval (PMA) approval decision. A summary of the clinical study is presented below. # A. Study Design Patients were treated between February 2021 and October 2024. The database for this PMA reflected data collected through November 12, 2025, and included 60 subjects with chronic dissection who were considered high risk for open repair. There were 31 investigational sites: 30 in the United States (US) and one (1) in New Zealand. The clinical study also included enrollment of subjects with aneurysms, penetrating aortic ulcers and intramural hematomas; those lesion types are not within scope of the current PMA. The TRIOMPHE study was a prospective, multi-center, non-randomized clinical study with comparison to a performance goal. There were two co-primary endpoints: 1) Device Technical Failure and 2) Clinical Failure. These co-primary endpoints were defined as: - Device Technical Failure (through 30 days): - Failure to accurately deliver, track and deploy all required endovascular device components at the intended implantation site and failure to retrieve the device delivery systems without the need for unplanned additional procedures - Device occlusion - Failed exclusion of primary entry tear - Additional unanticipated surgical or interventional procedure related to the device or procedure, to prevent life-threatening or permanent disabling event. Specifically, the below were counted against the endpoint: - Surgical conversion - Re-intervention to treat migration - Re-intervention to treat stenosis or occlusion - Re-intervention to treat type Ia, Ib, III, IV endoleaks. - Re-intervention for loss of device integrity - Clinical Failure (through 30 days): Subjects experiencing early mortality or at least one of the following major adverse events (MAEs) through 30-Day of Phase 1 Procedure* and 30-Day of Index procedure: - Disabling Stroke - Permanent Paralysis/Paraplegia - Renal Failure 15 of 54 {15} ○ Aortic Rupture ○ Development of new dissections in the thoracic aorta or brachiocephalic artery *Phase 1 Procedure was defined as the supra-aortic bypass procedure. If a subject has a supra-aortic bypass however, did not have Index Procedure due to non-device related issues or adverse events (e.g. voluntary withdrawal), the subject was excluded from the primary endpoint analysis. Also, any subjects where the Index Procedure was not initiated due to death after Phase 1 Procedure they were not included in the primary endpoint analysis because the analysis was conducted on subjects where there was an attempt to place the NEXUS device into the subject. The results of the study were tested against Performance Goals derived from published data on other approved devices and literature reported rates. The hypotheses tested for the co-primary endpoints are presented below: Device Technical Failure: ▪ Null Hypothesis (H₀): Pᵢ ≥ 0.30 ▪ Alternative Hypothesis (H₁): Pᵢ < 0.30 Where Pᵢ represents the proportion of subjects experiencing a device failure event. Clinical Failure: ▪ Null Hypothesis (H₀): Pᵢ ≥ 0.35 ▪ Alternative Hypothesis (H₁): Pᵢ < 0.35 Where Pᵢ represents the proportion of subjects experiencing a clinical failure event. The null hypothesis for both endpoints needed to be rejected for the study to be considered a success. The sample size was based on statistical power calculations for two co-primary endpoints, each evaluated at a one-sided alpha of 0.025, ensuring a minimum desired power of 80%. Sample size calculations were completed based on the exact binomial test calculated via the normal approximation. ▪ Device Technical Failure Endpoint: With an estimated device technical failure rate of 13%, a sample size of 51 evaluable subjects provided >80% power to test against the 30% performance goal. ▪ Clinical Failure Endpoint: With an estimated clinical failure rate of 18%, a sample size of 54 evaluable subjects provided ~80% power to test against the 35% performance goal. A total of 60 subjects were enrolled in the study. The co-primary endpoints were formally evaluated in the “as treated population” which was defined as “any subject where there is an 16 of 54 {16} attempt to place the device into the subject (Index procedure).” Accordingly, any subjects wherein the Index Procedure was not initiated due to adverse events or death after Phase 1 Procedure were not included in the primary endpoint analysis. Evaluation groups used during the course of the pivotal study are described below: - During the screening process, all subjects who were assessed by an Investigator to meet all inclusion/exclusion criteria were submitted to Endospan for review and case approval. A Subject Eligibility Committee (SEC) reviewed the pre-treatment Computed Tomography (CT) imaging and made recommendations to Endospan whether the subject should be excluded based on anatomical criteria. The SEC comprised of at least one physician with prior NEXUS experience. Members included an Interventional Radiologist, Vascular Surgeons and Cardiothoracic Surgeons. At the conclusion of the process, the site was notified by Endospan on the subject's eligibility (Accept/Reject). - An independent Clinical Events Committee (CEC) was established to provide unbiased adjudication. The CEC reviewed and adjudicated device and/or procedure related AEs, SAEs, MAEs, specified clinical endpoints and death data. Members included a Neurologist, Vascular Surgeons and Cardiothoracic Surgeons. - A Data Safety Monitoring Board (DSMB) was established to provide independent oversight of subject safety and study conduct throughout the TRIOMPHE study. The DSBM was responsible for periodic review of cumulative safety data, including Adverse Events (AEs), Serious Adverse Events (SAEs), Protocol Deviations (PDs), deaths, and device- or procedure-related complications. Members included an independent statistician, Vascular Surgeons and Cardiothoracic Surgeons. - All imaging data for the TRIOMPHE study were evaluated by an independent core laboratory. The core lab was responsible for evaluations on all CT images submitted by the clinical sites. The Core Lab reported all evaluations to Endospan. # 1. Clinical Inclusion and Exclusion Criteria Enrollment in the TRIOMPHE study was limited to patients who met the following inclusion criteria: - Male and female age ≥ 18. - Subject with chronic dissections who is considered to be at high risk for open repair, with at least one of the following conditions: - An aortic aneurysm with a maximum diameter ≥ 55 mm. - Rapidly expanding false lumen (growth of > 0.5 cm/6 months) - Compressed true lumen associated with end organ malperfusion - Symptomatic - Must have appropriate proximal, distal and brachiocephalic landing zone - Subject is willing and able to comply with procedures specified in the protocol and is able to return for follow-up visits as specified by the protocol Patients were not permitted to enroll in the TRIOMPHE study if they met any of the following exclusion criteria: 17 of 54 {17} - Acute dissection - Lesions that can be safely treated with TEVAR landing in zone 2 (with or without LSA vascularization) - Required emergent treatment (e.g., trauma, rupture) - Acute vascular injury of the aorta due to trauma - Aortic rupture - Received a previous stent or stent graft in the treated area (including planned landing area) - Any major surgical or interventional procedure 6 weeks before the NEXUS® implantation, exclusive of planned procedures that are needed for the safe and effective placement of the stent graft (e.g. supra-aortic bypass) - Subject has had a MI or cerebral vascular accident (CVA) within 90 days prior to the planned implantation - Subjects with severe aortic valvular insufficiency as determined by echocardiography - Mechanical valve that precludes safe delivery of NEXUS - Known Connective tissue disease (e.g., Marfan's or Ehler's-Danlos syndromes) - Subject has an active systemic infection at the time of the procedure documented by pain, fever, drainage, positive culture - Pregnant - Life expectancy of less than 2 years - Unsuitable vascular anatomy - Subject with hostile groins/axilla (scarring, obesity, or previous failed puncture) unless conduit are used. - Subjects with severe atherosclerosis, severe calcification or extensive intraluminal thrombus of the aorta or in the brachiocephalic trunk - Subject with known hypersensitivity or contraindication to anticoagulants, antiplatelets, or contrast media, which is not amenable to pre-treatment - Subject with known sensitivities or allergies to the device materials - Subject has history of bleeding diathesis or coagulopathy that may limit the use of dual antiplatelet or anticoagulant therapy by the decision of the investigator - Acute renal failure; chronic renal failure (excluding dialysis); Creatinine > 2.00 mg/dl # 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Table 4 outlines the required screening evaluations and follow-up visit procedures for subjects. Adverse events and complications were recorded at all visits. The key timepoints are shown below in the tables summarizing safety and effectiveness. 18 of 54 {18} **Table 4. Schedule of Events** | | Screening/ Baseline | Phase 1 Procedure | Index Procedure | Pre- discharge | 30 days | 6 Months | 1 year | Annual visits: 2-5 years | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Physical Exam | X | | | X | X | X | X | X | | Neurological Assessment | X | | | | X | X* | X* | X* | | Clinical Laboratory Tests | X | | | | X | X | | | | CT Angiogram of Chest, Abdomen and Pelvis | X | | | X | X | X | X | X | | CT Angiogram of Head and Neck | X | | | | | | | | | Ultrasound | X | | X | | | | | | | Angiography | | | X | | | | | | * Performed only if a neurologic problem occurred, subject has symptoms indicating a neurological issue or if suspected stroke was seen on imaging ### 3. Clinical Endpoints With regards to safety and effectiveness, there were two co-primary endpoints: 1) Device Technical Failure and 2) Clinical Failure. Device Technical Failure was defined as any of the following occurring through 30 days: - Failure to accurately deliver, track and deploy all required endovascular device components at the intended implantation site and failure to retrieve the device delivery systems without the need for unplanned additional procedures - Device occlusion - Failed exclusion of primary entry tear - Additional unanticipated surgical or interventional procedure related to the device or procedure, to prevent life-threatening or permanent disabling event. Specifically, the below were counted: - Surgical conversion - Re-intervention to treat migration - Re-intervention to treat stenosis or occlusion - Re-intervention to treat type Ia, Ib, III, IV endoleaks. - Type I: Perigraft blood flow caused by inadequate seal at either the proximal or distal graft end (Type Ia: Proximal; Type Ib: Distal) - Type III: Occurs in the midgraft region due to leakage through a defect in the graft fabric or between the segments of multisegmental graft (Type IIIa: Junctional leak or disconnect between devices; Type IIIb: through hole or tear) - Type IV: Blush of contrast that is presumed to emanate from 19 of 54 {19} blood diffusion across the porous graft fabric or through small holes in the graft caused by sutures or stent struts. - Re-intervention for loss of device integrity - Stent-Graft Fracture - Stent-Graft Kink - Stent-Graft Twist - Misalignment/Birdbeaking - Component Separation - Stent-Graft Docking - Stent-Graft Dilation - Suture Break The statistical analysis aimed to test the null hypothesis that the device failure rate was greater than or equal to the predefined Performance goal of 30%. Clinical Failure was defined as the occurrence of any MAEs within 30-Day of Phase 1 Procedure (supra-aortic bypass procedure) and 30-Day of Index Procedure (NEXUS procedure) in subjects where there is an attempt to place the NEXUS device into the subject: - Early Mortality: a lesion related death or any death that occurs within 30-Days or within initial hospitalization following the Index Procedure, unless there is evidence of accidental or self-inflicted death. - Disabling Stroke: a stroke with a modified Rankin Scale (mRS) score of two or more at 30 days and an increase in at least one mRS category from an individual's pre-stroke baseline - Permanent Paralysis/Paraplegia: Spinal Cord Ischemia Scale > 3 (Non-ambulatory and/or wheelchair bound), persisting at least 30 days. - Renal failure: new onset requiring permanent dialysis - Aortic rupture: catastrophic rupture or tear of the aorta as confirmed by new hematoma or pericardial effusion based upon CT, MRI or Echocardiographic imaging. - Development of new dissections in the thoracic aorta or brachiocephalic artery: any great vessel or brachiocephalic artery that clinically requires intervention The statistical analysis aimed to test the null hypothesis that the clinical failure rate was greater than or equal to the predefined Performance Goal of 35%. **B. Accountability of PMA Cohort** At the time of database lock, 60 subjects were eligible and included for analysis. **Table 5** below provides the disposition and compliance at the time of the database lock. 20 of 54 {20} Note: NA – Not Applicable, LTFU | Visit [1] | Subject Follow-Up [2] | | | | Imaging Performed [2] CT Scan | Imaging Adequate to Assess the Parameter [2] [3] | | | | | Subject Status [4] | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Eligible for follow-up [5] | Visit Performed | No Visit, Still in Window | Missed visit | | Size Changes | False Lumen Perfusion | Endoleak | Migration | Fracture | Death | LTFU/ Early Withdrawal | Surgical Conversion | Not due for next visit | One or More Reason for Future Visit Ineligibility [6] | | Index Procedure (1-27) | 60 | 100.0% (60/60) | 0.0% (0/60) | 0.0% (0/60) | 100.0% (60/60) | NA | NA | NA | NA | NA | 8.3% (5/60) | 0.0% (0/60) | 1.7% (1/60) | 0.0% (0/60) | 8.3% (5/60) | | 30 Days (28-45) [7] | 55 | 100.0% (55/55) | 0.0% (0/55) | 0.0% (0/55) | 100.0% (55/55) | NA | 92.7% (51/55) | 92.7% (51/55) | NA | 100.0% (55/55) | 0.0% (0/55) | 0.0% (0/55) | 0.0% (0/55) | 0.0% (0/55) | 0.0% (0/55) | | 6 Months (150-210) | 55 | 83.6% (46/55) | 0.0% (0/55) | 3.6% (2/55) | 83.6% (46/55) | 83.6% (46/55) | 76.4% (42/55) | 78.2% (43/55) | 80.0% (44/55) | 83.6% (46/55) | 10.9% (6/55) | 1.8% (1/55) | 3.6% (2/55) | 0.0% (0/55) | 12.7% (7/55) | | 1 Year (305-425) | 48 | 97.9% (47/48) | 0.0% (0/48) | 2.1% (1/48) | 97.9% (47/48) | 97.9% (47/48) | 93.8% (45/48) | 95.8% (46/48) | 93.8% (45/48) | 97.9% (47/48) | 4.2% (2/48) | 2.1% (1/48) | 0.0% (0/48) | 27.1% (13/48) | 33.3% (16/48) | | 2 Years (670-790) | 32 | 90.6% (29/32) | 6.3% (2/32) | 0.0% (0/32) | 87.5% (28/32) | 81.3% (26/32) | 75.0% (24/32) | 71.9% (23/32) | 81.3% (26/32) | 87.5% (28/32) | 3.1% (1/32) | 0.0% (0/32) | 0.0% (0/32) | 43.8% (14/32) | 46.9% (15/32) | | 3 Years (1035-1155) | 17 | 76.5% (13/17) | 11.8% (2/17) | 0.0% (0/17) | 76.5% (13/17) | 76.5% (13/17) | 76.5% (13/17) | 76.5% (13/17) | 76.5% (13/17) | 76.5% (13/17) | 5.9% (1/17) | 5.9% (1/17) | 0.0% (0/17) | 35.3% (6/17) | 47.1% (8/17) | | 4 Years (1400-1520) | 9 | 66.7% (6/9) | 33.3% (3/9) | 0.0% (0/9) | 66.7% (6/9) | 66.7% (6/9) | 66.7% (6/9) | 66.7% (6/9) | 66.7% (6/9) | 66.7% (6/9) | 0.0% (0/9) | 0.0% (0/9) | 0.0% (0/9) | 100.0% (9/9) | 100.0% (9/9) | | 5 Years (1825-1945) | 0 | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | 0.0% (0/0) | – Lost to Follow-Up[{"box_2d": [45, 559, 320, 574], "label": "text", "caption [1,2,3,4,5,6,7] Percentages = (Subjects with Adequate Imaging) / (Subjects Eligible)"}][{"box_2d": [45, 572, 877, 587], "label": "text", " [1] Windows for visits are as follows: Study period definitions: 30 Days (28-45 days) 6 Months (150-210 days) 1 Year (305-425 days) 2 Years (670-790 days) 3 Years (1035-1155) 4 Years (1400-1520 days) 5 Years (1825-1945 days)"}] NOTE: When reporting data for subjects with more than one imaging study in a window, all imaging observations should be reported, irrespective of which image is closest to the midpoint of the window. [2] Denominator is the number of subjects who are eligible. [3] Not the number of Subjects with these reported events, but rather, the number with adequate imaging as assessed by Core Lab. [4] These columns reflect subjects that are not eligible at the start of the next visit window due to death, loss to follow-up/ early withdrawal, open surgical conversion, or who are not yet due for the next visit (e.g., the duration between the index procedure and the date of analysis was less than the days for the start of the next window). The last column is necessary to calculate the number of subjects eligible for the subsequent interval, since subjects may experience more than one event (e.g. surgical conversion and death). NOTE: One subject (126001) had a surgical conversion at 6 months but stayed enrolled in the study. They are being included in subsequent visits. [5] Eligible subjects are those eligible at the prior interval minus those with one or more reason for future ineligibility within the prior visit window. [6] A subject with multiple reasons for ineligibility is only counted once. [7] When reporting 1-month endpoint data, the numerator is the number of subjects with an observation between the procedure and the end of the 1-month window. The denominator is includes subjects who did not have adequate imaging within the window but had an observation. 21 of 54 {21} ## C. Study Population Demographics and Baseline Parameters ### 1. Demographics The demographics of the study population are typical for a thoracic endovascular graft study performed in the US on high surgical risk subjects with chronic dissection involving the aortic arch. A summary of subject demographics can be found in **Table 6**. Across the study population (N=60), the mean age was 65.9 ± 9.61 years (range 41–89). The cohort was predominantly male, with 81.7% (49/60) men, and had a mean Body Mass Index (BMI) of 30.0 ± 7.01 kg/m². **Table 6. Baseline Demographics** | **Age, years** | | | --- | --- | | Mean ± SD (N) | 65.9 ± 9.61 (60) | | Median (Q1, Q3) | 67.0 (59.0, 74.0) | | (Min, Max) | (41.0, 89.0) | | **Gender** | | | Male | 81.7% (49/60) | | Female | 18.3% (11/60) | | **Race** | | | American Indian/Alaska Native | 0.0% (0/60) | | Asian | 3.3% (2/60) | | Black/African American | 38.3% (23/60) | | Native Hawaiian/Other Pacific Islander | 8.3% (5/60) | | White | 41.7% (25/60) | | Other | 6.7% (4/60) | | Not Answered | 1.7% (1/60) | | **Ethnicity** | | | Hispanic/Latino | 10.0% (6/60) | | Not Hispanic/Latino | 86.7% (52/60) | | Not Answered | 3.3% (2/60) | | **BMI (kg/m2)** | | | Mean ± SD (N) | 30.0 ± 7.01 (60) | | Median (Q1, Q3) | 28.6 (25.1, 33.7) | | (Min, Max) | (18.0, 48.8) | | **Clinical Presentation of Arch Pathology** | | | Asymptomatic | 88.3% (53/60) | | Symptomatic | 11.7% (7/60) | | **NEXUS Proximal Landing Zone** | | | Native Aorta | 38.3% (23/60) | | Previously Implanted Surgical Graft | 61.7% (37/60) | Note: Subjects may have more than one race indicated ### 2. Baseline Medical History Subjects were eligible for enrollment if they were classified as high-risk surgical candidates. Baseline medical history (**Table 8**) and Baseline Risk Factors (**Table 9**) confirmed a substantial burden of comorbidities. Coronary artery disease was present in 40.0% (24/60), significant valvular heart disease in 20.0% (12/60), and 33.3% (20/60) had a history of arrhythmia. A prior history of vascular intervention was reported in 28.3% (17/60). Additionally, 51.7% (31/60) of subjects were either current or former smokers, and 11.7% (7/60) were symptomatic at baseline. Other prevalent comorbidities included 22 of 54 {22} hypertension in 98.3% (59/60), hyperlipidemia in 80.0% (48/60), and chronic obstructive pulmonary disease (COPD) in 18.3% (11/60). Furthermore, 71.7% (43/60) had undergone a previous aortic intervention, and 70.0% (42/60) had a history of prior sternotomy. All subjects were classified as American Society of Anesthesiologist (ASA) Class IV (severe systemic disease that is a constant threat to life, e.g., unstable angina), or ASA Class III (severe systemic disease with definite functional limitation, e.g., chronic obstructive pulmonary disease), reflecting the high-risk nature of the treated population. Specifically, 55.0% (33/60) were ASA Class IV and 45.0% were ASA Class III (27/60). **Table 7. Subject Baseline Medical History** | Chronic Obstructive Pulmonary Disease (COPD) | 18.3% (11/60) | | --- | --- | | Diabetes Mellitus | 21.7% (13/60) | | Hypertension | 98.3% (59/60) | | Hyperlipidemia | 80.0% (48/60) | | Chronic Angina | 3.3% (2/60) | | Myocardial Infarction | 11.7% (7/60) | | Coronary Artery Disease (CAD) | 40.0% (24/60) | | Percutaneous Coronary Intervention (PCI) | 10.0% (6/60) | | Coronary Artery Bypass Graft | 8.3% (5/60) | | Congestive Heart Failure (CHF) | 15.0% (9/60) | | Transient Ischemic Attack | 8.3% (5/60) | | Cerebrovascular Accident | 16.7% (10/60) | | Peripheral Vascular Disease | 20.0% (12/60) | | Valvular Heart Disease | 20.0% (12/60) | | Arrhythmia | 33.3% (20/60) | | Carotid Arterial Disease | 10.0% (6/60) | | History of Malignancy | 20.0% (12/60) | | Previous Vascular Intervention | 28.3% (17/60) | | Previous Aortic Intervention | 71.7% (43/60) | | Previous Sternotomy | 70.0% (42/60) | | Previous Thoracotomy | 3.3% (2/60) | | Renal Insufficiency | 38.3% (23/60) | | Connective Tissue Disorder | 0.0% (0/60) | | Family History of Aortic Disease | 6.7% (4/60) | | Aortic Dissection | 91.7% (55/60) | | Paraplegia/Paraparesis | 1.7% (1/60) | **Table 8. Baseline Risk Factors** | Smoking Status | | | --- | --- | | Current (within 30 days) | 8.3% (5/60) | | Former (>30 days) | 43.3% (26/60) | | Never smoked | 48.3% (29/60) | | **Incomplete Circle of Willis [1]** | 12.1% (7/58) | 23 of 54 {23} | **ASA Classification** | | | --- | --- | | I – Healthy subject | 0.0% (0/60) | | II – Mild systemic disease – no functional limitation | 0.0% (0/60) | | III – Severe systemic disease – definite functional limitation | 45.0% (27/60) | | IV – Severe systemic disease that is constant threat to life | 55.0% (33/60) | | V – Moribund subject unlikely to survive 24 hours with or without operation | 0.0% (0/60) | | **New York Heart Association (NYHA) Classification** | | | I – Cardiac disease, physical activity not limited | 46.7% (28/60) | | II – Cardiac disease, physical activity slightly limited | 36.7% (22/60) | | III – Cardiac disease, physical activity markedly limited | 0.0% (0/60) | | IV – Cardiac disease, physical activity very limited | 0.0% (0/60) | | Not Applicable [2] | 16.7% (10/60) | [1] Restricted to those with information known [2] The Electronic Data Capture (EDC) allows you to indicate the NYHA classification as Not Applicable; however, a follow-up question asks “If Not Applicable, please confirm for eligibility that the subject does not have NYHA Classification of III or IV. Currently 15 patients have indicated they are not applicable and confirm the subject met the NYHA eligibility. Common reasons investigators deemed the subject as high surgical risk are listed in **Table 9**. Other reasons are refusal of open repair or general frailty; however, this information was not captured in the study. **Table 9. Reasons For High Risk in Open Repair** | ASA Score III or IV | 100% (60/60) | | --- | --- | | Current or Former Smoker | 51.7% (31/60) | | Prior Sternotomy | 70.0% (42/60) | | Advanced Age (>75) | 18.3% (11/60) | | COPD | 18.3% (11/60) | | BMI (>30) | 43.3% (26/60) | | Female | 18.3% (11/60) | | Arrythmia | 33.3% (20/60) | | Prior Cerebrovascular Event | 25.0% (15/60) | | Inadequate Cardiac Function | | | MI | 11.7% (7/60) | | PCI | 10.0% (6/60) | | CHF | 15.0% (9/60) | | Valvular Heart Disease | 20.0% (12/60) | | CAD | 40.0% (24/60) | ### 3. Lesion Characteristics **Table 10** presents core lab–reported baseline characteristics describing the extent of the aortic disease. Sixty percent (60.0%, 36/60) had proximal disease involvement beginning in Zone 0, and 80.4% (45/56) had distal disease extending to Zone 9 or beyond. All subjects in the TRIOMPHE study required a Zone 0 landing zone. **Table 10. Core Lab Reported Disease Extension** | **Proximal End of Disease** | | | --- | --- | | Zone 0 | 36/60 (60.0%) | | Zone 1 | 6/60 (10.0%) | | Zone 2 | 9/60 (15.0%) | | Zone 3 | 9/60 (15.0%) | | Other | - | | **Distal End of Disease** | | | Zone 0 | - | 24 of 54 {24} | Zone 1 | - | | --- | --- | | Zone 2 | - | | Zone 3 | 1/56 (1.8%) | | Zone 4 | 2/56 (3.6%) | | Zone 5 | 3/56 (5.4%) | | Zone 6 | 1/56 (1.8%) | | Zone 7 | 2/56 (3.6%) | | Zone 8 | 1/56 (1.8%) | | Zone 9 | 7/56 (12.5%) | | Zone 10 - Right | 4/56 (7.1%) | | Zone 10 - Left | 10/56 (17.9%) | | Zone 11 - Right | 12/56 (21.4%) | | Zone 11 - Left | 12/56 (21.4%) | | Other | 1/56 (1.8%) | Note: For subjects with the proximal extent of disease in Zone 2 or Zone 3, an adequate proximal landing zone was not available; therefore, device implantation required a proximal landing in Zone 0. #### 4. Device Usage **Table 11** provides a summary of the Stent Graft configurations implanted in subjects during the Index Procedure. Arch Stent Grafts implanted in subjects are summarized in **Table 12** Ascending Stent Grafts in **Table 13**, and optional Descending Extension Stent Grafts in **Table 14**. **Table 11. Stent Graft Configurations Implanted During Index Procedure** | | # implanted | | --- | --- | | Arch Stent Graft and 1 Ascending Stent Graft | 26.7% (16/60) | | Arch Stent Graft and 2 Ascending Stent Grafts | 0.0% (0/60) | | Arch Stent Graft, 1 Ascending Stent Graft, and 1 Descending Extension | 58.3% (35/60) | | Arch Stent Graft, 1 Ascending Stent Graft, and 2 Descending Extensions | 10.0% (6/60) | | Arch Stent Graft, 2 Ascending Stent Grafts, and 1 Descending Extension | 3.3% (2/60) | | Arch Stent Graft, 2 Ascending Stent Grafts, and 2 Descending Extensions | 1.7% (1/60) | **Table 12. Arch Stent Graft Implanted** | Branch Diameter | Branch Length | Descending Aorta Diameter | Descending Aorta Length | # Implanted | | --- | --- | --- | --- | --- | | 14 | 20 | 32 | 180 | 1.7% (1/60) | | 14 | 20 | 36 | 180 | 0.0% (0/60) | | 14 | 20 | 40 | 180 | 0.0% (0/60) | | 14 | 30 | 32 | 180 | 20.0% (12/60) | | 14 | 30 | 36 | 180 | 8.3% (5/60) | | 17 | 20 | 32 | 180 | 5.0% (3/60) | 25 of 54 {25} | Branch Diameter | Branch Length | Descending Aorta Diameter | Descending Aorta Length | # Implanted | | --- | --- | --- | --- | --- | | 17 | 20 | 36 | 180 | 1.7% (1/60) | | 17 | 30 | 32 | 180 | 21.7% (13/60) | | 17 | 30 | 36 | 180 | 10.0% (6/60) | | 17 | 30 | 40 | 180 | 1.7% (1/60) | | 17 | 40 | 32 | 180 | 1.7% (1/60) | | 17 | 40 | 36 | 180 | 5.0% (3/60) | | 20 | 20 | 32 | 180 | 1.7% (1/60) | | 20 | 20 | 36 | 180 | 5.0% (3/60) | | 20 | 30 | 32 | 180 | 8.3% (5/60) | | 20 | 30 | 36 | 180 | 1.7% (1/60) | | 20 | 30 | 40 | 180 | 1.7% (1/60) | | 20 | 40 | 32 | 180 | 5.0% (3/60) | | 20 | 40 | 36 | 180 | 0.0% (0/60) | **Table 13. Ascending Stent Graft Sizes Implanted** | Ascending Diameter | Length | Configuration | # Implanted | | --- | --- | --- | --- | | 36 | 40 | Curved | 12.7% (8/63) | | 36 | 55 | Curved | 20.6% (13/63) | | 36 | 70 | Curved | 3.2% (2/63) | | 40 | 40 | Curved | 7.9% (5/63) | | 40 | 55 | Curved | 25.4% (16/63) | | 40 | 70 | Curved | 12.7% (8/63) | | 43 | 55 | Curved | 9.5% (6/63) | | 43 | 70 | Curved | 7.9% (5/63) | Note: Denominators are based on the number of Ascending Stent Grafts used **Table 14. Descending Extension Stent Graft Sizes Implanted** | Tapered | | | | | --- | --- | --- | --- | | Proximal Diameter | Length | Distal Diameter | #Implanted | | 36 | 125 | 31 | 7.1% (3/42) | | 36 | 157 | 31 | 19.0% (8/42) | | 36 | 189 | 31 | 38.1% (16/42) | | 36 | 189 | 36 | 4.8% (2/42) | | 40 | 125 | 36 | 2.4% (1/42) | | 40 | 157 | 36 | 4.8% (2/42) | | 40 | 157 | 40 | 2.4% (1/42) | | 40 | 189 | 36 | 11.9% (5/42) | | 40 | 189 | 40 | 7.1% (3/42) | | 43 | 162 | 40 | 2.4% (1/42) | | 43 | 194 | 40 | 0.0% (0/42) | 26 of 54 {26} | Straight | | | | --- | --- | --- | | Diameter | Length | | | 31 | 189 | 0.0% (0/9) | | 36 | 125 | 11.1% (1/9) | | 36 | 157 | 0.0% (0/9) | | 36 | 189 | 22.2% (2/9) | | 40 | 157 | 11.1% (1/9) | | 40 | 189 | 33.3% (3/9) | | 43 | 166 | 11.1% (1/9) | | 43 | 200 | 11.1% (1/9) | Note: Denominators are based on the number of Descending Extension Stent Grafts used ## 5. Procedure Characteristics ### *Supra-aortic bypass (Phase 1)* Phase 1 Procedure was defined as the supra-aortic bypass procedure. Phase 1 Procedural information is provided in **Table 15**. **Table 15. Phase 1 Parameters** | **Length of Surgical Procedure (min)** | | | --- | --- | | Mean ± SD (N) | 230.9 ± 84.71 (60) | | Median (Q1, Q3) | 220.5 (178.5, 273.0) | | (Min, Max) | (73.0, 455.0) | | **Intubation Time (min)** | | | Mean ± SD (N) | 286.5 ± 80.07 (57) | | Median (Q1, Q3) | 287.0 (223.0, 324.0) | | (Min, Max) | (141.0, 466.0) | | **Estimated Blood Loss (ml)** | | | Mean ± SD (N) | 299.7 ± 307.38 (59) | | Median (Q1, Q3) | 200.0 (100.0, 350.0) | | (Min, Max) | (25.0, 1500.0) | | **Transfusion Required** | 8.3% (5/60) | | **Transfusion Amount (ml)** | | | Mean ± SD (N) | 535.8 ± 292.47 (4) | | Median (Q1, Q3) | 535.0 (285.0, 786.5) | | (Min, Max) | (250.0, 823.0) | | **RCC-Left Common Carotid (LCC)** | | | Native | 2.5% (1/40) | | Graft | 97.5% (39/40) | | Diameter | | | Mean ± SD (N) | 7.9 ± 0.27 (39) | | Median (Q1, Q3) | 8.0 (8.0, 8.0) | | (Min, Max) | (7.0, 8.0) | | **LCC-LSA** | | | Native | 11.1% (4/36) | | Graft | 88.9% (32/36) | | Diameter | | | Mean ± SD (N) | 7.8 ± 0.45 (32) | | Median (Q1, Q3) | 8.0 (8.0, 8.0) | | (Min, Max) | (6.0, 8.0) | | **RCC-LSA** | | | Native | 0.0% (0/20) | 27 of 54 {27} | Graft | 100.0% (20/20) | | --- | --- | | Diameter | | | Mean ± SD (N) | 7.9 ± 0.72 (20) | | Median (Q1, Q3) | 8.0 (8.0, 8.0) | | (Min, Max) | (6.0, 10.0) | | **Other Anatomic Locations** | | | Native | 50.0% (10/20) | | Graft | 50.0% (10/20) | | Diameter | | | Mean ± SD (N) | 8.0 ± 0.00 (10) | | Median (Q1, Q3) | 8.0 (8.0, 8.0) | | (Min, Max) | (8.0, 8.0) | | **Was Mini Sternotomy Performed?** | | | Yes | 6.7% (4/60) | | No | 93.3% (56/60) | | **Retropharyngeal bypass performed?** | | | Yes | 76.7% (46/60) | | No | 23.3% (14/60) | | **Bypass Patent at End** | 100.0% (60/60) | Note: Information in this table is limited to study subjects who proceeded to the index procedure. One subject was initially enrolled for treatment with NEXUS. This subject completed the Phase 1 Procedure, in preparation for the Index Procedure, it was noticed the subject no longer met anatomical eligibility. The subject was withdrawn from the study and was treated with NEXUS under expanded access/compassionate use. Data from this subject is not included in the analysis. All other subjects who underwent the Phase 1 procedure proceeded to the index procedure. ### *Index Procedure (NEXUS Procedure)* The mean time from insertion of the first stent graft delivery system to withdrawal of the final delivery system (Ascending, or Descending, if applicable) was 85 minutes overall. Use of the optional descending stent graft was implanted in 73.3% (44/60). Rapid pacing, performed at three predefined time points during the procedure, had an overall mean cumulative duration of 102.9 seconds. In 61.7% (37/60) the proximal landing zone was within a surgical graft. Conversely, the native aorta served as the proximal landing zone in 38.3% (23/60) of subjects (**Table 16**). **Table 16. Procedural Parameters** | **Device Deployment Time (min) [1]** | | | --- | --- | | Mean ± SD (N) | 85.0 ± 41.68 (59) | | Median (Q1, Q3) | 75.0 (57.0, 103.0) | | (Min, Max) | (21.0, 250.0) | | **Rapid Pace Time (Sec)** | | | Mean ± SD (N) | 102.9 ± 70.25 (60) | | Median (Q1, Q3) | 90.0 (63.0, 130.0) | | (Min, Max) | (12.0, 420.0) | | **Length of Procedure (min) [2]** | | | Mean ± SD (N) | 229.8 ± 69.61 (60) | | Median (Q1, Q3) | 213.0 (179.5, 263.0) | 28 of 54 {28} | (Min, Max) | (131.0, 470.0) | | --- | --- | | **Intubation Time (min)** | | | Mean ± SD (N) | 333.5 ± 194.73 (55) | | Median (Q1, Q3) | 305.0 (254.0, 352.0) | | (Min, Max) | (153.0, 1583.0) | | **Fluoroscopy Time (min)** | | | Mean ± SD (N) | 50.1 ± 18.97 (59) | | Median (Q1, Q3) | 46.0 (36.0, 64.0) | | (Min, Max) | (1.0, 96.0) | | **Volume of Contrast (ml)** | | | Mean ± SD (N) | 150.1 ± 68.70 (60) | | Median (Q1, Q3) | 135.0 (100.0, 190.0) | | (Min, Max) | (33.0, 337.0) | | **Estimated Blood Loss (ml)** | | | Mean ± SD (N) | 214.8 ± 185.88 (58) | | Median (Q1, Q3) | 200.0 (100.0, 300.0) | | (Min, Max) | (0.0, 900.0) | | **Transfusion Required** | 23.3% (14/60) | | **Transfusion Amount (ml)** | | | Mean ± SD (N) | 1214.6 ± 1994.16 (13) | | Median (Q1, Q3) | 620.0 (350.0, 1000.0) | | (Min, Max) | (340.0, 7750.0) | | **Anesthesia** | | | General | 100.0% (60/60) | | Local | 0.0% (0/60) | | **Main Access Method** | | | Cutdown | 95.0% (57/60) | | Percutaneous | 5.0% (3/60) | | **Main Access Vessel** | | | Right Femoral | 85.0% (51/60) | | Left Femoral | 15.0% (9/60) | | **Additional Access Sites** | | | Right Femoral | 15.3% (9/59) | | Left Femoral | 84.7% (50/59) | | **Axillary Access Method** | | | Cutdown | 33.9% (19/56) | | Percutaneous | 66.1% (37/56) | | **Axillary Access Sites** | | | Right | 94.5% (52/55) | | Left | 5.5% (3/55) | | **Additional Access Used?** | 60.0% (36/60) | | **Proximal Landing Zone** | | | Within Surgical Graft | 61.7% (37/60) | | Within Native Aorta | 38.3% (23/60) | | **Distal Extension Used?** | | | Yes | 73.3% (44/60) | | No | 26.7% (16/60) | | **Surgical Conversion [3]** | 0.0% (0/60) | [1] First insertion of Arch Stent Graft delivery to withdrawal of Ascending Stent graft delivery system. If Descending stent is being used, then withdrawal of Descending Stent graft delivery. [2] Skin to skin time. [3] At time of Index Procedure. [4] Extended procedure time due to non-device related adverse events, estimated blood loss was 250 mL, Hemoglobin decreased from 13.0 g/dL to a nadir of 10.5 g/dL. 29 of 54 {29} **Table 17** presents the hospitalization period. The median hospital stay after Index Procedure was 8.0 days (5.0, 12.0), with a median ICU stay of 3.0 days (1.0, 4.5). **Table 17. Hospitalization Period** | Number of Days between Phase 1 and Index Procedures | | | --- | --- | | Mean ± SD (N) | 11.6 ± 27.92 (60) | | Median (Q1, Q3) | 4.5 (3.0, 9.0) | | (Min, Max) | (2.0, 212.0) | | Phase 1 Procedure | | | Length of ICU Stay (days) | | | Mean ± SD (N) | 3.6 ± 5.04 (60) | | Median (Q1, Q3) | 2.0 (1.0, 4.0) | | (Min, Max) | (0.0, 23.0) | | Phase 1 and Index procedure in same admission? | | | Yes | 73.3% (44/60) | | No | 26.7% (16/60) | | Index Procedure | | | Length of Intensive Care Unit (ICU) Stay (days) [1] | | | Mean ± SD (N) | 3.8 ± 3.82 (56) | | Median (Q1, Q3) | 3.0 (1.0, 4.5) | | (Min, Max) | (0.0, 22.0) | | Length of Hospital Stay (days) [1] | | | Mean ± SD (N) | 9.4 ± 7.00 (56) | | Median (Q1, Q3) | 8.0 (5.0, 12.0) | | (Min, Max) | (1.0, 40.0) | [1] Subjects who experienced early mortality are not included in the length of ICU or hospital stay **Table 18** Lists the unanticipated and anticipated adjunctive procedures that occurred during the Phase 1 Procedure (5.0%, 3/60) or during the Index Procedure (15.0%, 9/60). **Table 18. Adjunctive Procedures by Subject** | | Time Point | Event (n) | Anticipated | Intervention | | --- | --- | --- | --- | --- | | 110003 | Phase 1 | Clamp injury | Yes | Stent | | 120011 | Phase 1 | Dissection flap seen on imaging of the right carotid artery | Yes | Patch angioplasty of right carotid artery | | 124011 | Phase 1 | Acute pulmonary oedema | Yes | Reintubation | | 102008 | Index Procedure | Femoral artery access was high | Yes | Stent across the access site via a contralateral approach | | 103002 | Index Procedure | Right brachial occlusion | Yes | Graft repair | | 103005 | Index Procedure | Right brachial dissection | Yes | Repair sutures and bovine patch | | 103013 | Index Procedure | Commercial catheter breakage | Yes | Retrieval | | 103020 | Index Procedure | Bend at the NEXUS BCT origin | Yes | Stent in BCT^{1} | | 105001 | Index Procedure | Left renal artery occlusion | Yes | Stent | | 111016 | Index Procedure | Cardiac perforation | Yes | Pericardial window, cardiopulmonary bypass | 30 of 54 {30} | | Time Point | Event (n) | Anticipated | Intervention | | --- | --- | --- | --- | --- | | 115012 | Index Procedure | 1) Acute compartment syndrome; 2) CVA | 1) No 2) Yes | 1) Forearm fasciotomy and decompression with carpal tunnel release 2) Reintubation | | 124011 | Index Procedure | Transient Paraparesis | Yes | Lumbar Drain Placed | ¹Subject also met device technical failure, site does not consider this an adverse event ### D. Safety and Effectiveness Results This study (CIP009) had two co-primary endpoints: 1) Device Technical Failure and 2) Clinical Failure through 30 days. These capture both safety and effectiveness. #### 1. Safety and Effectiveness Results The analysis of safety and effectiveness was based on the chronic dissection cohort of 60 subjects available for the 30-day evaluation. The co-primary endpoint results are presented below in Table 19 with details of each endpoint event in Table 20. Device Technical Failure (through 30-Day): - Failure to accurately deliver, track and deploy all required endovascular device components at the intended implantation site and failure to retrieve the delivery systems without the need for unplanned additional procedures - Including the placement of a commercial stent in the BCT - Device occlusion (complete absence of blood flow at any point) - Failed exclusion of primary entry tear - Additional unanticipated surgical or interventional procedure related to the device or procedure, to prevent life-threatening or permanent disabling event. - Surgical Conversion - Re-Intervention to treat migration (movement greater than 10mm) - Re-Intervention to treat stenosis (>50% narrowing) or occlusion (complete absence of blood flow at any point) - Re-Intervention to treat Type Ia, Ib, III, IV Endoleaks - Re-Intervention to treat for loss of device integrity Clinical Failure: Subjects experiencing at least one of the following MAEs through 30-Day of Phase 1 Procedure and 30-Day of Index Procedure: - Early Mortality - Disabling Stroke - Permanent Paralysis/Paraplegia - Renal failure - Aortic rupture - Development of new dissections in the thoracic aorta or brachiocephalic artery 31 of 54 {31} The null hypothesis was rejected for both co-primary endpoints. Freedom from device technical failure, was met in 95.0% (57/60) of subjects, with a failure rate of 5.0% (3/60; 95% CI: 1.04–13.92; p<0.001 versus the 30% performance goal). Technical failure events included failure to deliver/track/deploy system (3.3%, 2/60), additional unanticipated procedures: surgical conversion (1.7%, 1/60). Freedom from clinical failure, was met in 85.0% (51/60) of subjects, with a clinical failure rate of 15.0% (9/60; 95% CI: 7.10–26.57; p<0.001 versus the 35% performance goal). Contributing events included death (10.0%, 6/60), disabling stroke (8.3%, 5/60), and development of new dissection (1.7%, 1/60). Two strokes and the dissection resulted in fatalities. No cases of permanent paralysis/paraplegia, renal failure, or aortic rupture were reported. There were no occurrences of device occlusion, failed exclusion of the primary entry tear, or reinterventions for type I, III or IV endoleak, stenosis, migration, or loss of device integrity through 30 days. Of the two deployment-related failures, one involved intraoperative placement of a stent in the BCT following NEXUS deployment. In the second case, the device failed to deploy and was removed, and a new device was successfully implanted, all without any associated complications or adverse events. The Co-Primary Endpoints (30 Days) are provided in **Table 19**. The components of the primary endpoints over time are provided in **Table 22**. **Table 19. Co-Primary Endpoints (30 Days)** | | % (n/N) | 95% CI | p-value | | --- | --- | --- | --- | | **Device Technical Failure [1]** | 5.0% (3/60) | 1.04, 13.92 | <0.001 | | Failure to deliver/track/deploy components or retrieve delivery system | 3.3% (2/60) | 0.41, 11.53 | | | Device Occlusion | 0.0% (0/60) | 0.00, 5.96 | | | Failed Exclusion of Primary Entry Tear | 0.0% (0/60) | 0.00, 5.96 | | | Additional Unanticipated Procedure | 1.7% (1/60) | 0.04, 8.94 | | | Surgical Conversion | 1.7% (1/60) | 0.04, 8.94 | | | Re-intervention for Migration | 0.0% (0/60) | 0.00, 5.96 | | | Re-intervention for Stenosis or Occlusion | 0.0% (0/60) | 0.00, 5.96 | | | Re-intervention for Type Ia, Ib, III, IV Endoleaks | 0.0% (0/60) | 0.00, 5.96 | | | Re-intervention for Loss of Device Integrity | 0.0% (0/60) | 0.00, 5.96 | | | **Clinical Failure [2], [3]** | 15.0% (9/60) | 7.10, 26.57 | <0.001 | | Death | 10.0% (6/60) | 3.76, 20.51 | | | Disabling Stroke | 8.3% (5/60) | 2.76, 18.39 | | | Permanent Paralysis/Paraplegia | 0.0% (0/60) | 0.00, 5.96 | | | Renal Failure | 0.0% (0/60) | 0.00, 5.96 | | | Aortic Rupture | 0.0% (0/60) | 0.00, 5.96 | | | Development of New Dissection | 1.7% (1/60) | 0.04, 8.94 | | [1] p-value is derived from a one sample, one-sided exact binomial test against a reference safety goal of 30%. [2] p-value is derived from a one sample, one-sided exact binomial test against a reference safety goal of 35%. [3] The clinical failure events include any MAE occurring through 30 days of the Phase 1 (supra-aortic bypass) procedure and though 30 days of Index (NEXUS) procedure. One MAE (disabling stroke) occurred following the Phase 1 Procedure. All other MAEs occurred following the Index procedure. 32 of 54 {32} **Table 20** provides a description of the events considered device technical or clinical failure. **Table 22** Provides the primary endpoint components through 12 months. **Table 20. Event Descriptions for Subjects Who Met Endpoint** | Subject # | Device Technical Failure | Clinical Failure | Description of Event | | --- | --- | --- | --- | | 103002 | Yes – Surgical Conversion | Yes - Development of a New Dissection Requiring Treatment (Surgical Conversion) and Early Mortality (Anoxic Brain Injury) | Uneventful Phase 1 and Index Procedure. On Post Operative Day (POD) 1, Computed Tomography Angiography (CTA) demonstrated an acute Type A aortic dissection requiring surgical repair. The subject expired on POD 14 due to anoxic brain injury. | | 103020 | Yes - Failure to Deliver/Track/Deploy Components or Retrieve Delivery System (including placement of a commercial stent in the BCT) | No | Uneventful Phase 1 Procedure. During Index Procedure, imaging suggested a bend at the NEXUS BCT origin; a commercial stent was placed in the BCT without complication. Post-placement imaging showed good flow. No adverse events occurred. | | 110012 | No | Yes -Disabling Stroke | Uneventful Phase 1 and Index Procedure. On POD 2, CT demonstrated new hypodense foci in the right cerebellar hemisphere and left frontal lobe. mRS went from 1 to 3. | | 110018 | No | Yes – Disabling Stroke Resulting in Early Mortality | Uneventful Phase 1 and Index Procedure. On POD 3, a seizure occurred and imaging demonstrated a right temporoparietal intraparenchymal hemorrhage. Hemicraniectomy and hematoma evacuation were performed. Subject expired on POD 55 withou…