← Product Code [SDZ](/productcode/SDZ) · P210032S015 # GORE TAG Thoracic Branch Endoprosthesis (TBE Device) (P210032S015) _W. L. Gore & Associates, Inc. · SDZ · Apr 11, 2025 · Cardiovascular · APPR_ **Canonical URL:** https://fda-staging.innolitics.com/device/P210032S015 ## Device Facts - **Applicant:** W. L. Gore & Associates, Inc. - **Product Code:** [SDZ](/productcode/SDZ.md) - **Decision Date:** Apr 11, 2025 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Cardiovascular - **Attributes:** Therapeutic, Real-World Evidence ## Real-World Evidence | Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags | | --- | --- | --- | --- | --- | --- | | P210032S015 · Apr 11, 2025 | GORE TAG Thoracic Branch Endoprosthesis (TBE Device) | W. L. Gore & Associates, Inc. | Systematic review of hybrid TEVAR repair literature | A systematic literature review was used to derive a performance goal (60%) for the primary endpoint (Strategy Success) of the aneurysm cohort in the pivotal clinical study. | Performance Goal; Literature Review; Hybrid TEVAR | ### Clinical Evidence | Study Design | Population | Comparator | Key Endpoints | | --- | --- | --- | --- | | Systematic review of hybrid TEVAR repair literature; Systematic literature review | Patients undergoing hybrid TEVAR repair in Zone 0/1; Number of Sites: Not applicable | Not applicable for this study | Primary endpoint success (Strategy Success) | ## Indications for Use The GORE® TAG® Thoracic Branch Endoprosthesis is indicated for endovascular repair of lesions of the aortic arch and descending thoracic aorta, while maintaining flow into a single aortic arch branch vessel, in patients who have: Adequate iliac/femoral access Proximal Aortic Landing Zones: For Isolated Lesion Patients: Proximal landing zone cannot be aneurysmal, dissected, heavily calcified, or heavily thrombosed For Dissection Patients: Primary entry tear must be distal to the target branch vessel and the proximal extent of the landing zone must not be dissected Aortic inner diameter range 16-42 mm Proximal segment length (length from distal edge of target branch vessel to the midpoint of any proximal branch vessel) of at least 2.0-4.0 cm, depending on Aortic Component selection Proximal covered length (measured from distal edge of target branch vessel to the midpoint of any proximal branch vessel) of at least 15–36 mm, depending on Aortic Component selection For patients with prior ascending aorta or aortic arch repair with a surgical graft: at least 2 cm landing zone proximal to the distal anastomosis Target Branch Vessel Landing Zone: Landing zone cannot be aneurysmal, dissected, heavily thrombosed and severely tortuous (180 degree turn within the treated length) Target branch vessel inner diameter of 6–18 mm, depending on Side Branch Portal diameter selected Target branch vessel minimum length of 2.5–3.0 cm, depending on Side Branch Portal diameter selected Distal Landing Zone (Isolated Lesion Patients only) Outer curve length must be ≥ 2 cm proximal to celiac artery Aortic inner diameter range 16-42 mm Cannot be aneurysmal, dissected, heavily calcified, or heavily thrombosed Native Aorta or previously placed GORE® TAG® Conformable Thoracic Stent Graft ## Device Story Modular endovascular graft system for aortic arch/descending thoracic aorta repair; consists of Aortic Component (AC), Side Branch (SB) Component, and optional Aortic Extender. AC features internal portal for SB seal/fixation. Components comprise ePTFE/FEP graft on nitinol wire frame with radiopaque gold bands. Delivered via catheter through single distal access site over 0.035" guidewires. SB component includes CBAS® Heparin Surface. Used in clinic/OR by vascular/cardiothoracic surgeons. System allows endovascular repair while maintaining branch vessel flow, avoiding deep hypothermic circulatory arrest/cardiopulmonary bypass. Output is radiographic visualization of device placement; clinical decision-making relies on pre-procedural CT imaging and intra-procedural angiography to ensure accurate landing zone alignment and seal, reducing risk of aortic rupture/lesion progression. ## Clinical Evidence Prospective, multicenter, non-randomized clinical study (IDE #G130120) with 77 patients (Aneurysm, Dissection, Other Isolated Lesion cohorts). Primary endpoint: Strategy Success (composite of technical success and freedom from major adverse events through 1 month). Aneurysm cohort success: 74.5% (95% LCL 61.9%), meeting 60% performance goal. Dissection cohort success: 81.8%. Other Isolated Lesion cohort success: 100%. Key safety events through 12 months: aortic rupture (2.6%), lesion-related mortality (6.5%), disabling stroke (7.8% through 30 days). ## Technological Characteristics Modular endovascular graft; ePTFE/FEP graft material; nitinol wire frame (stent); radiopaque gold bands for imaging. Delivery system compatible with 0.035" guidewires; 20-26 Fr profile. CBAS® Heparin Surface on SB component. Sterilization method not specified. Standalone or used with GORE® TAG® Conformable Thoracic Endoprosthesis. ## Regulatory Identification Endovascular Repair of Ascending Aorta and Aortic Arch Lesions ## Predicate Devices - GORE® TAG® Conformable Thoracic Endoprosthesis ([P040043](/device/P040043.md)) ## 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 Graft Device Trade Name: GORE® TAG® Thoracic Branch Endoprosthesis (TBE Device) Device Procode: SDZ Applicant’s Name and Address: W. L. Gore & Associates, Inc. 3450 W. Kiltie Lane Flagstaff, AZ 86005, USA Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P210032/S015 Date of FDA Notice of Approval: April 11, 2025 Priority Review: Granted priority review status on July 17, 2015 because the device is intended to treat a potentially life threatening disease and because of reasonable expectation that the device represents a breakthrough technology with the potential to provide a clinically meaningful advantage over existing legally marketed technology, offers significant, clinically meaningful advantages over existing legally marketed alternatives and the availability of the device is in the best interest of patients. The original PMA (P210032) was approved on May 13, 2022 and was indicated for endovascular repair of lesions of the descending thoracic aorta, while maintaining flow into the left subclavian artery, in patients who are at high risk for debranching subclavian procedures and have appropriate anatomy. In P210032/S007, which was approved on May 2, 2023, the indication was expanded to no longer limit use to patients at high risk for debranching subclavian procedures. The SSED to support these indications is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the indication for the TBE device to include repair of lesions of the aortic arch. ## II. INDICATIONS FOR USE The GORE® TAG® Thoracic Branch Endoprosthesis is indicated for endovascular repair of lesions of the aortic arch and descending thoracic aorta, while maintaining flow into a single aortic arch branch vessel, in patients who have: - Adequate iliac/femoral access P210032/S015 FDA Summary of Safety and Effectiveness Data Page 1 of 70 {1} • Proximal Aortic Landing Zones: ○ For Isolated Lesion Patients: Proximal landing zone cannot be aneurysmal, dissected, heavily calcified, or heavily thrombosed ○ For Dissection Patients: Primary entry tear must be distal to the target branch vessel and the proximal extent of the landing zone must not be dissected ○ Aortic inner diameter range 16-42 mm ○ Proximal segment length (length from distal edge of target branch vessel to the midpoint of any proximal branch vessel) of at least 2.0-4.0 cm, depending on Aortic Component selection ○ Proximal covered length (measured from distal edge of target branch vessel to the midpoint of any proximal branch vessel) of at least 15–36 mm, depending on Aortic Component selection ○ For patients with prior ascending aorta or aortic arch repair with a surgical graft: at least 2 cm landing zone proximal to the distal anastomosis • Target Branch Vessel Landing Zone: ○ Landing zone cannot be aneurysmal, dissected, heavily thrombosed and severely tortuous (180 degree turn within the treated length) ○ Target branch vessel inner diameter of 6–18 mm, depending on Side Branch Portal diameter selected ○ Target branch vessel minimum length of 2.5–3.0 cm, depending on Side Branch Portal diameter selected • Distal Landing Zone (Isolated Lesion Patients only) ○ Outer curve length must be ≥ 2 cm proximal to celiac artery ○ Aortic inner diameter range 16-42 mm ○ Cannot be aneurysmal, dissected, heavily calcified, or heavily thrombosed ○ Native Aorta or previously placed GORE® TAG® Conformable Thoracic Stent Graft ### III. CONTRAINDICATIONS The GORE® TAG® Thoracic Branch Endoprosthesis is contraindicated in: • Patients with known sensitivities or allergies to the device materials • Patients who have a condition that threatens to infect the graft • Patients with known hypersensitivity to heparin, including those patients who have had a previous incident of Heparin-Induced Thrombocytopenia (HIT) Type II ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the GORE® TAG® Thoracic Branch Endoprosthesis labeling. ### V. DEVICE DESCRIPTION The GORE® TAG® Thoracic Branch Endoprosthesis (TBE Device) provides P210032/S015 FDA Summary of Safety and Effectiveness Data Page 2 of 70 {2} endovascular repair of pathologies of the aortic arch and descending thoracic aorta requiring a proximal landing zone including the brachiocephalic, left common carotid, or left subclavian artery. The GORE® TAG® Thoracic Branch Endoprosthesis is a modular device consisting of the Aortic Component, the Side Branch (SB) Component, and an optional Aortic Extender, as shown in Figure 1. These components may be used together as a stand-alone device or in conjunction with the GORE® TAG® Conformable Thoracic Endoprosthesis (P040043) in multiple device combinations to accommodate the intended treatment site. Each component of the endoprosthesis consists of an ePTFE/FEP graft supported over its entire length by a nitinol wire frame (stent). Radiopaque gold bands are embedded in the graft material for device imaging. The stent is attached to the external surface of the graft by laminated ePTFE/FEP bonding tape. For delivery, all device components are constrained on the leading end of a delivery catheter compatible with 0.035" guidewires and are delivered through a single distal access site. All device components are intended to be delivered through an appropriately sized GORE® DrySeal Flex Sheath family of devices. ![img-0.jpeg](img-0.jpeg) Figure 1: GORE® TAG® Thoracic Branch Endoprosthesis System and Key Features ### A. Aortic Component (AC) The Aortic Component (see Figure 2) incorporates an internal portal that opens to the outer device surface, allowing for seal and fixation of the SB Component. Embedded in both ends of the Aortic Component and the internal portal are radiopaque gold bands that provide radiographic visibility. The leading end of the endoprosthesis consists of partially uncovered stent apices, while the trailing end of the stent is in line with the graft material, with each end including a sealing cuff bonded over the stent. This component is mounted onto a catheter delivery system for delivery from a distal access site over a primary aortic guidewire. A Removable Guidewire Tube is provided to facilitate loading of the constrained device over a secondary branch guidewire that is pre-positioned from the distal access site to the target branch vessel. The constrained profile of these components on a delivery catheter ranges from 20 to 26 Fr. The Aortic Component is constrained by a P210032/S015 FDA Summary of Safety and Effectiveness Data Page 3 of 70 {3} sewn deployment sleeve, which unlaces to allow device expansion by pulling the deployment knob on the hub of the catheter. Aortic Component deployment initiates from the portal opening and extends simultaneously to the proximal and distal ends. Following deployment, the deployment sleeve remains implanted with the endoprosthesis. ![img-1.jpeg](img-1.jpeg) **Figure 2: Aortic Component and Aortic Component Delivery** ### **B. System Side Branch Component (SB)** The SB Component (see **Figure 3**) includes the CBAS® Heparin Surface which consists of stable, covalent, end-point attached heparin of porcine origin. A radiopaque gold band is embedded in the graft material at each end of the device. A third embedded radiopaque band is located 5 mm from the trailing end of the device. This inner radiopaque marker facilitates alignment of the SB Component with the Aortic Component internal portal and denotes the position of three flared stent apices. The flared stent apices protrude slightly from the underlying graft material. The SB Component is mounted onto a catheter delivery system and constrained by a sewn deployment sleeve. The device component expands from its constrained profile by pulling the deployment knob on the hub of the catheter, which unlaces the constraining sleeve from the trailing end toward the leading end. The SB Component should be selected such that the diameter of the trailing portion of the graft is the same as the portal diameter of the chosen Aortic Component. The diameter of the leading portion of the SB Component should be selected such that it is compatible with the branch vessel diameter. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 4 of 70 {4} ![img-2.jpeg](img-2.jpeg) Figure 3: Side Branch (SB) Component and SB Component Delivery System ### C. Aortic Extender (AE) The Aortic Extender (see Figure 4) is a short, tubular device with radiopaque gold bands at each end for radiographic visibility. Both the leading and trailing ends consist of partially uncovered stent apices. This device is intended to be used to improve sealing of the Aortic Component and/or add seal length proximally within the aorta, if necessary. The compressed profile of these devices on the delivery catheter ranges from 20 to 26Fr. The device is mounted onto a catheter delivery system. A longitudinal radiopaque marker is embedded in the deployment sleeve to allow visualization during delivery catheter withdrawal. ![img-3.jpeg](img-3.jpeg) Figure 4: Aortic Extender (AE) Component and AE Component Delivery System P210032/S015 FDA Summary of Safety and Effectiveness Data Page 5 of 70 {5} ## **VI. ALTERNATIVE PRACTICES AND PROCEDURES** There are several other alternatives for the treatment of lesions of the aortic arch and descending thoracic aorta including: - Medical management - Open surgical repair - Thoracic endovascular aortic repair (TEVAR) using other endovascular devices - Hybrid surgery with TEVAR 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 TBE Device is currently approved/available for use in the United States, European Union, Australia, New Zealand, Canada, China, Japan, and Taiwan. The TBE Device has not been withdrawn from marketing for any reason related to its safety or effectiveness. ## **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. For the specific adverse events that occurred in the clinical study, please see Section X. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 6 of 70 {6} - aortic valve injury, - access, delivery and deployment events (e.g. access failure; deployment difficulties/failures; failure to deliver the stent graft; and insertion or removal difficulty), - adynamic ileus, - allergic reaction (to contrast, anti-platelet therapy, stent graft material), - amputation, - anesthetic complications, - aortic expansion, - aortic rupture, - angina, - atelectasis/pneumonia, - bleeding (procedural and post-treatment), - bowel complications (e.g., ileus, transient ischemia, infarction, necrosis), - branch vessel occlusion or obstruction, - cardiac complications (e.g., arrhythmia, myocardial infarction, congestive heart failure, hypotension or hypertension), - catheter breakage, change in mental status, - coagulopathy, - contrast toxicity, - death, - dissection, perforation, or rupture of the aortic vessel and/or surrounding vasculature, - edema (e.g., leg), - embolism (micro and macro) with transient or permanent ischemia, - endoleak, - endoprosthesis: collapse, improper placement; incomplete deployment; migration; material failure; occlusion; infection; stent fracture; dilatation; perigraft flow, - erectile dysfunction, - erosion - extension of dissection, - femoral neuropathy, - fever and localized inflammation, - fistula (e.g., aortoenteric, arteriovenous, aortoesophageal, aortobronchial), - genitourinary (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection), - hematoma, - heparin-induced thrombocytopenia (HIT), - infection (e.g., aortic, device, or access sites), - lymphocele/lymph fistula, - myocardial infarction, - neurologic damage, local or systemic (e.g., stroke, paraplegia, paraparesis), - nerve injury, - peripheral malperfusion or ischemia, - persistent false lumen flow, - post-implant syndrome, - prosthesis dilatation/rupture, - prosthetic thrombosis, - pseudoaneurysm, - pulmonary complications (e.g., pneumonia, respiratory failure), - pulmonary embolism, - radiation injury, - renal complications (e.g., artery occlusion, contrast toxicity, insufficiency, failure), - reoperation, - stenosis, - surgical conversion, - thrombosis, - transient ischemic attack, - vascular spasm, - vascular trauma (e.g., ilio-femoral vessel dissection, bleeding, rupture), - wound (e.g., infection, dehiscence) P210032/S015 FDA Summary of Safety and Effectiveness Data Page 7 of 70 {7} For Zone 0/1 Patients Only - aortic valve injury - coronary artery occlusion or obstruction ### IX. SUMMARY OF NON-CLINICAL STUDIES Nonclinical studies were completed to evaluate the TBE Device, including non-clinical bench testing, biocompatibility, sterilization, packaging, shelf-life, and animal studies. Previously conducted bench testing incorporated evaluation of device in worst case conditions reflective of device use in the aortic arch as well as the descending thoracic aorta. The SSED containing the nonclinical studies to support the original PMA is available on the CDRH website and is incorporated by reference here. No changes have been made to the TBE Device for the expansion of the indication. These data remain applicable and support the revised indications for use. ### X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the GORE® TAG® Thoracic Branch Endoprosthesis (TBE Device) for the endovascular repair of lesions of the aortic arch, while maintaining flow into a single aortic arch branch vessel (brachiocephalic or left common carotid) in the US and Japan under IDE # G130120. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ### A. Study Design Patients were treated between December 28, 2016 and March 2, 2023. The database for this Panel Track Supplement reflected data collected through April 10, 2024 and included 77 patients. There were 31 investigational sites: 26 in the United States (U.S.) and five (5) in Japan. The study was a prospective, multicenter, non-randomized clinical study with two (2) study arms specific to proximal placement of the device in Zones 0 and 1 with a total of three (3) cohorts. The arms are described as follows: - Zone 0/1 – Aneurysm, hypothesis-driven analysis - Zone 0/1 – Non-aneurysm aortic lesions which are anatomically suitable for treatment with the TBE Device, descriptive analysis - Dissection cohort - Other isolated lesion types Each cohort was analyzed separately by lesion type. The primary endpoint was Strategy Success for planned staged procedures (landing zone optimization, transposition, and device placement) through one month following last planned procedure. Strategy Success is defined as a composite of the following events from the time of enrollment through one month following the index endovascular procedure: - Initiation of the index endovascular procedure following the debranching procedure P210032/S015 FDA Summary of Safety and Effectiveness Data Page 8 of 70 {8} - Device technical success for the index endovascular procedure - Absence of the following: o Aortic rupture o Lesion-related mortality o Disabling Stroke o Permanent paraplegia o Permanent paraparesis o New onset renal failure requiring permanent dialysis o Additional unanticipated post-procedural surgical or interventional procedure related to the device, procedure, or withdrawal of the delivery system. Primary endpoint success (mixture of safety and effectiveness endpoints) was defined as the proportion of analysis-eligible subjects without a primary endpoint event that met any of the endpoint failure components (described above) and with imaging in the one-month window. The results of the Aneurysm Cohort were tested against a performance goal of 60%, derived from outcomes from a systematic review of hybrid TEVAR repair literature. Using the performance goal of 60% with Primary Endpoint success through one month, the following hypothesis was tested: $$\mathrm{H}_{\mathrm{O}}: \quad \mathrm{P}_{\mathrm{s01}} \leq 0.60$$ $$\mathrm{H}_{\mathrm{A}}: \quad \mathrm{P}_{\mathrm{s01}} > 0.60$$ Where P_s01 is the proportion of subjects with primary endpoint success, as described above. A 95% one-sided lower Exact confidence limit for binomial proportions was calculated. The null hypothesis was to be rejected if the lower bound exceeded the performance goal. No hypotheses were planned for the Non-Aneurysm Cohorts. Literature review,[1-23] inclusive of the outcomes from both the surgical revascularization and TEVAR procedures required for hybrid Thoracic Endovascular Repair (TEVAR) procedures in Zone 0/1, was used to estimate primary endpoint success to be 78% in the Aneurysm cohort. Using the Exact Binomial Test and assuming a one-sided alpha of 0.05, a performance goal of 60%, and power of at least 80%, the sample size needed was 50 patients. Evaluation groups used during the course of the pivotal study are described below: - During the screening process, all patients who were assessed by an Investigator to meet all inclusion / exclusion criteria were submitted to Gore for review and case approval. A Screening Committee reviewed the pre-treatment CT imaging, head/neck imaging or imaging report and patient medical history (including atrial fibrillation and other comorbidities) and made recommendations to Gore regarding whether the patient should be excluded based on high risk of adverse neurological events (e.g. stroke). The Screening Committee was comprised of at least one physician with prior TBE experience that reviewed the patient information and imaging; Screening Committee members included an Interventional Radiologist, Vascular Surgeons, and P210032/S015 FDA Summary of Safety and Effectiveness Data Page 9 of 70 {9} Cardiothoracic Surgeons. At the conclusion of the process, the Site was notified by Gore on the patient's eligibility (Accept / Reject). - All subjects were required to have a consultation with a Surgeon or other physician with experience in ascending aortic and arch surgery (such as a Cardiothoracic Surgeon in the US and a Cardiovascular Surgeon in Japan) within 90 days of enrollment for a discussion of other treatment options, such as open surgical repair based on the subject's medical history and the subject's (high) risk for open surgical repair. - An independent external Core Laboratory (Core Lab) was used to perform evaluations on all medical imagery submitted by clinical sites. The Core Lab reported all measurements and device assessments to Gore. - An external Clinical Events Committee (CEC) adjudicated safety and certain effectiveness endpoint events for the study as well as reviewed inclusion / exclusion violations for potential impact on subject safety. Effectiveness endpoint events not adjudicated by the CEC were determined by the Core Lab. - The Gore Office of Medical Affairs (OMA) provided adjudication of key adverse events where event onset was after day 546. The OMA is comprised of healthcare professionals whose responsibilities include providing healthcare provider perspective, medical expertise and judgment, and objectivity in review of patient and product safety matters, including human clinical data. - An independent Data Safety Monitoring Board (DSMB) reviewed all available safety data on a regular basis and provided recommendations on the continuing safety, validity and scientific merit of the study. # 1. Clinical Inclusion and Exclusion Criteria Enrollment in the clinical study was limited to patients who met the following inclusion criteria. - Presence of thoracic aortic pathology deemed to warrant surgical repair which requires proximal graft placement in Zone 0/1 - Age ≥18 years at time of informed consent signature - Subject is capable of complying with protocol requirements, including follow-up - Informed Consent Form (ICF) is signed by subject or legal representative - Must have appropriate proximal aortic landing zone - Must have appropriate target branch vessel landing zone - For patients with aneurysm/isolated lesion, must have appropriate distal aortic landing zone - Subject does not have a mechanical aortic valve - Subject is considered a high-risk candidate for conventional open surgical repair at the discretion of the investigator Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - Concomitant disease of the ascending aorta or aneurysm of the abdominal aorta P210032/S015 FDA Summary of Safety and Effectiveness Data Page 10 of 70 {10} requiring repair - Previous endovascular repair of the ascending aorta - Previous endovascular repair of the descending thoracic aorta (DTA) with a non-Gore device - Surgery within 30 days prior to enrollment with the exception of surgery for Ascending Aortic Dissection and/or placement of vascular conduit for access - Infected aorta - Life expectancy <2 years - Myocardial infarction within 6 weeks prior to treatment - Stroke within 6 weeks prior to treatment, stroke defined as rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin. - Patient has an active systemic infection (e.g., infection requiring treatment with parenteral anti-infective medication) that may place the patient at increased risk of endovascular infection. Patients with a chronic infection (such as HIV, Hepatitis C, etc.) that is well controlled under their current treatment regimen may be eligible. - Pregnant female at time of informed consent signature - Degenerative connective tissue disease, e.g., Marfan's or Ehler-Danlos Syndrome - Participation in another drug or medical device study within one year of study enrollment - Known history of drug abuse within one year of treatment - Presence of protruding and/or irregular thrombus and/or atheroma in the aortic arch or ascending aorta - Tortuous or stenotic iliac and/or femoral arteries preventing introducer sheath insertion and the inability to use a conduit for vascular access - Planned coverage of celiac artery - Patient has known sensitivities or allergies to the device materials - Patient has known hypersensitivity or contraindication to anticoagulants or contrast media, which is not amenable to pre-treatment - Previous instance of Heparin Induced Thrombocytopenia type 2 (HIT-2) or known hypersensitivity to heparin - Patient with a history of a hypercoagulability disorder and/or hypercoagulability state - Diameter taper outside of the device sizing range between proximal and distal landing zones of aorta and the inability to use additional devices of different diameters to compensate for the taper - Mycotic aneurysm - Persistent refractory shock (systolic blood pressure \(< 90\mathrm{mmHg}\)) P210032/S015 FDA Summary of Safety and Effectiveness Data Page 11 of 70 {11} - Patient has body habitus or other medical condition which prevents adequate visualization of the aorta - Renal failure defined as patients with an estimated Glomerular Filtration Rate (eGFR) <30 (ml/min/1.73 m²) or currently requiring dialysis - Patient at high risk for a neurological event, e.g., stroke ## 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 1, 6, 12, 24, 36, 48 and 60 months. Table 1 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. Table 1. Schedule of Events | | Screening | Treatment | | | Discharge | 1 month | 6 months | 12 months | 24, 36, 48, and 60 months | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Phase 1 Procedure | Phase 1 Evaluation^{a} | Phase 2 Procedure | | | | | | | Physical Examination | X | | X^{b} | | X | X | X | X | X | | Serum Creatinine Concentration | X | | | | | | | | | | Spiral CTA (contrast) | X^{c} | | | | | X | X | X | X | | Spiral CT (non-contrast) | | | | | | X | | | | | CTA of the Head/Neck^{d} | X | | | | | | | | | | Angiogram at Completion of Procedure | | | | X | | | | | | | ^{a} Phase 1 Evaluation should be performed at least 24 hours after completion of the revascularization procedure but within 60 days post treatment. ^{b} Subjects who are withdrawn prior to the Phase 2 Procedure should also have a Physical Exam at one month post Phase 1 procedure. ^{c} Screening CTA must be ≤90 days prior to Phase 2 procedure. ^{d} Screening CTA of Head/Neck must be ≤90 days prior to Phase 1 procedure. If CT of Head/Neck is not consistent with Site's standard of care then radiological modality of evaluation is at investigator discretion (Ultrasound, MR, etc.). However, imaging of head/neck vasculature is required ≤90 days prior to Phase 1 procedure. | | | | | | | | | | ## 3. Clinical Endpoints With regards to safety and effectiveness, the primary endpoint for all cohorts was Strategy Success for planned staged procedures (landing zone optimization, transposition, and device placement) through one month following last planned procedure (through day 59 unless otherwise specified in the component definitions below): - Initiation of the index endovascular procedure following the debranching procedure - Device Technical Success for the index endovascular procedure - Successful access and delivery to the intended implantation site, and retrieval of the device delivery system, and; P210032/S015 FDA Summary of Safety and Effectiveness Data Page 12 of 70 {12} ○ Patency of the graft; ○ The absence of unanticipated additional procedure related to the device, procedure, or withdrawal of the delivery system. • Absence of the following: ○ Aortic rupture ○ Lesion-related mortality ○ Disabling stroke ▪ Stroke was assessed using the Modified Rankin Scale (mRS). Stroke identified as having occurred within 30 days of the index endovascular procedure, combined with mRS≥2 with an increase from baseline of at least one grade due to neurological deficits at no more than 120 days post index endovascular procedure. ○ Permanent paraplegia ▪ Paraplegia secondary to Spinal Cord Ischemia (SCI) identified within 30 days of the index endovascular procedure combined with SCI scale grade = 3 at the one month follow-up visit. ○ Permanent paraparesis ▪ Paraparesis secondary to SCI identified within 30 days of the index endovascular procedure, combined with SCI scale grade = 2 at the one month follow-up visit. ○ New onset renal failure requiring permanent dialysis ▪ New onset sustained renal failure identified within 30 days of the index endovascular procedure, combined with need/requirement for dialysis at the one month follow-up visit. ○ Additional unanticipated post-procedural surgical or interventional procedure related to the device, procedure, or withdrawal of the delivery system With regard to overall study success, the primary endpoint performance goal of 60% for the Aneurysm cohort needed to be met in order to achieve study success. The primary endpoint analysis for the other cohorts (Dissection and Other Isolated Lesion) was analyzed for each cohort and was reported descriptively (no hypothesis tests). In addition to the primary endpoint analysis, Procedural and Treatment Success data was collected and analyzed for each cohort and were reported descriptively and independent of the performance goal. Procedural Success was defined as Device Technical Success, with absence of the following events occurring from the initiation of the index endovascular procedure through 1 month (through day 59 unless otherwise specified below or in the Primary Endpoint component definitions): • Death (Through 30 days only) • Aortic rupture (Through 30 days only) • Disabling stroke P210032/S015 FDA Summary of Safety and Effectiveness Data Page 13 of 70 {13} - Paraplegia (Through 30 days only) - Paraparesis (Through 30 days only) - New onset renal failure requiring permanent dialysis - Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system - New ischemia - Distal device-related thromboembolic adverse event requiring intervention or surgery - Extension of a dissection (proximally or distally) (Dissection cohort only) - New dissection - Life-threatening bleed - Myocardial infarction - Prolonged intubation - Laryngeal or Phrenic Nerve injury - Renal dysfunction or volume overload requiring ultrafiltration - Severe Heart Failure/Hypotension Treatment Success was defined as Device Technical Success, with absence of the following events occurring from the initiation of the index endovascular procedure and at all appropriate follow-up windows: - Aortic enlargement in the region encompassed by the initial lesion - Aortic rupture - Extension of a dissection (proximally or distally) (Dissection cohort only) - New dissection - False lumen perfusion through the primary entry tear (Dissection cohort only) - False lumen perfusion through an aortic arch branch vessel (Dissection cohort only) - Type I or III endoleak - Fistula formation - Lesion-related mortality - Loss of device integrity - Loss of aortic or aortic branch patency - Migration - Disabling stroke within 30 days of the index endovascular procedure only - Paraplegia within 30 days of the index endovascular procedure only - Paraparesis within 30 days of the index endovascular procedure only - New ischemia P210032/S015 FDA Summary of Safety and Effectiveness Data Page 14 of 70 {14} - Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system The following outcomes, which were not components of Procedural or Treatment Success, were pre-defined as additional outcomes within the study protocol and collected: - Type II or IV endoleak - Significant Blood Loss (≥1000ml) during initial endovascular treatment intervention (excluding autologous blood transfusion or cell salvage) - False Lumen Status in treated and untreated segments (Dissection cohort only) - False Lumen perfusion through a non-aortic arch branch vessel (Dissection cohort only) **B. Accountability of PMA Cohort** At the time of database lock, 77 subjects were eligible and included for analysis. Two subjects were excluded from analysis due to being treated with device sizes (i.e., 49 mm and 53 mm) that were removed from the TBE Device size portfolio. **Table 2** and **Table 3** summarize compliance with the follow-up visit and imaging requirements directed by the investigational plan for enrolled Aneurysm and Dissection subjects. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 15 of 70 {15} **Table 2: Subject Disposition and Compliance by Analysis Study Window for Aneurysm Cohort** | Visit | Eligible for Follow-Up | Subjects with Data for Visit | | | | | Adequate Imaging to Assess Parameter^{2} | | | | | Subject Status | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Subjects with Data for that Visit | Physical Exam | CT | MRA | Subjects with Follow-Up Pending^{1} | Size Increase (Aortic Enlargement) | Endoleak | Device Migration | Wire Fracture | Device Patency | Death | Conversion | LTF^{3} | Not Due for Next Visit^{4} | | Phase 1 | 50 | 50 (100.0%) | - | - | - | 0 (0%) | - | - | - | - | - | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Endovascular Procedure | 50 | 50 (100.0%) | - | - | - | 0 (0%) | - | - | - | - | 50 (100.0%) | 1 (2.0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Post-Procedure | 49 | 47 (95.9%) | 45 (91.8%) | 5 (10.2%) | 0 (0%) | 0 (0%) | - | 3 (6.1%) | 5 (10.2%) | 5 (10.2%) | 4 (8.2%) | 2 (4.1%) | 0 (0%) | 0 (0%) | 0 (0%) | | 1 Month | 47 | 45 (95.7%) | 45 (95.7%) | 43 (91.5%) | 0 (0%) | 0 (0%) | - | 43 (91.5%) | 43 (91.5%) | 42 (89.4%) | 43 (91.5%) | 1 (2.1%) | 0 (0%) | 0 (0%) | 0 (0%) | | 6 Months | 46 | 41 (89.1%) | 37 (80.4%) | 39 (84.8%) | 0 (0%) | 0 (0%) | 38 (82.6%) | 36 (78.3%) | 39 (84.8%) | 38 (82.6%) | 37 (80.4%) | 2 (4.3%) | 0 (0%) | 1 (2.2%) | 0 (0%) | | 12 Months | 43 | 39 (90.7%) | 39 (90.7%) | 39 (90.7%) | 0 (0%) | 0 (0%) | 36 (83.7%) | 38 (88.4%) | 38 (88.4%) | 38 (88.4%) | 38 (88.4%) | 2 (4.7%) | 1 (2.3%) | 1 (2.3%) | 5 (11.6%) | | 24 Months | 34 | 24 (70.6%) | 22 (64.7%) | 23 (67.6%) | 0 (0%) | 6 (17.6%) | 22 (64.7%) | 20 (58.8%) | 22 (64.7%) | 21 (61.8%) | 21 (61.8%) | 1 (2.9%) | 0 (0%) | 0 (0%) | 13 (38.2%) | | 36 Months | 20 | 15 (75.0%) | 13 (65.0%) | 15 (75.0%) | 0 (0%) | 2 (10.0%) | 13 (65.0%) | 13 (65.0%) | 14 (70.0%) | 14 (70.0%) | 13 (65.0%) | 3 (15.0%) | 0 (0%) | 0 (0%) | 2 (10.0%) | | 48 Months | 15 | 10 (66.7%) | 8 (53.3%) | 9 (60.0%) | 0 (0%) | 1 (6.7%) | 8 (53.3%) | 9 (60.0%) | 9 (60.0%) | 9 (60.0%) | 9 (60.0%) | 1 (6.7%) | 0 (0%) | 3 (20.0%) | 1 (6.7%) | | 60 Months | 10 | 6 (60.0%) | 6 (60.0%) | 6 (60.0%) | 0 (0%) | 3 (30.0%) | 5 (50.0%) | 6 (60.0%) | 6 (60.0%) | 6 (60.0%) | 6 (60.0%) | 1 (10.0%) | 0 (0%) | 0 (0%) | 3 (30.0%) | $^{1}$Subjects still within follow-up window, but data not yet available. $^{2}$Not the number of Subjects with these reported events, but rather, the number with adequate imaging as assessed by Core Lab, such as paired size data to evaluate aneurysm growth. Wire fracture is if at least partially evaluable. $^{3}$In this table, lost to follow-up (LTF) includes all other reasons for study discontinuation including Subjects that have withdrawn from the study. $^{4}$Those Subjects that are 'Not due for next visit' are those Subjects that are not within the follow-up window for the next interval. Study period definitions: Phase 1 (revascularization procedure, prior to endovascular procedure) Endovascular Procedure(0 days) Post-Procedure(1-14 days) 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days) 24 Months(547-911 days) 36 Months(912-1275 days) 48 Months(1276-1640 days) 60 Months(1641-2006 days) **Table 3: Subject Disposition and Compliance by Analysis Study Window for Dissection Cohort** | Visit | Eligible for Follow-Up | Subjects with Data for Visit | | | | | Adequate Imaging to Assess Parameter^{2} | | | | | Subject Status | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Subjects with Data for that Visit | Physical Exam | CT | MRA | Subjects with Follow-Up Pending^{1} | Size Increase (Aortic Enlargement) | Endoleak | Device Migration | Wire Fracture | Device Patency | Death | Conversion | LTF^{3} | Not Due for Next Visit^{4} | | Phase 1 | 24 | 23 (95.8%) | - | - | - | 0 (0%) | - | - | - | - | - | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Endovascular Procedure | 24 | 24 (100.0%) | - | - | - | 0 (0%) | - | - | - | - | 24 (100.0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Post-Procedure | 24 | 24 (100.0%) | 24 (100.0%) | 2 (8.3%) | 0 (0%) | 0 (0%) | - | 2 (8.3%) | 2 (8.3%) | 2 (8.3%) | 2 (8.3%) | 1 (4.2%) | 0 (0%) | 0 (0%) | 0 (0%) | | 1 Month | 23 | 21 (91.3%) | 19 (82.6%) | 21 (91.3%) | 0 (0%) | 0 (0%) | - | 21 (91.3%) | 21 (91.3%) | 20 (87.0%) | 21 (91.3%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | 6 Months | 23 | 22 (95.7%) | 19 (82.6%) | 22 (95.7%) | 0 (0%) | 0 (0%) | 19 (82.6%) | 20 (87.0%) | 21 (91.3%) | 21 (91.3%) | 21 (91.3%) | 1 (4.3%) | 0 (0%) | 0 (0%) | 0 (0%) | | 12 Months | 22 | 20 (90.9%) | 18 (81.8%) | 20 (90.9%) | 0 (0%) | 0 (0%) | 17 (77.3%) | 19 (86.4%) | 19 (86.4%) | 19 (86.4%) | 19 (86.4%) | 3 (13.6%) | 0 (0%) | 0 (0%) | 3 (13.6%) | | 24 Months | 16 | 9 (56.3%) | 7 (43.8%) | 8 (50.0%) | 0 (0%) | 5 (31.3%) | 6 (37.5%) | 7 (43.8%) | 7 (43.8%) | 7 (43.8%) | 7 (43.8%) | 1 (6.3%) | 0 (0%) | 0 (0%) | 6 (37.5%) | | 36 Months | 9 | 7 (77.8%) | 6 (66.7%) | 7 (77.8%) | 0 (0%) | 0 (0%) | 6 (66.7%) | 6 (66.7%) | 7 (77.8%) | 6 (66.7%) | 6 (66.7%) | 0 (0%) | 0 (0%) | 1 (11.1%) | 0 (0%) | | 48 Months | 8 | 7 (87.5%) | 6 (75.0%) | 6 (75.0%) | 0 (0%) | 0 (0%) | 4 (50.0%) | 6 (75.0%) | 6 (75.0%) | 6 (75.0%) | 6 (75.0%) | 1 (12.5%) | 0 (0%) | 2 (25.0%) | 1 (12.5%) | | 60 Months | 4 | 4 (100.0%) | 4 (100.0%) | 4 (100.0%) | 0 (0%) | 0 (0%) | 4 (100.0%) | 4 (100.0%) | 4 (100.0%) | 4 (100.0%) | 4 (100.0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | $^{1}$Subjects still within follow-up window, but data not yet available. $^{2}$Not the number of Subjects with these reported events, but rather, the number with adequate imaging as assessed by Core Lab, such as paired size data to evaluate aneurysm growth. Wire fracture is if at least partially evaluable. $^{3}$In this table, lost to follow-up (LTF) includes all other reasons for study discontinuation including Subjects that have withdrawn from the study. $^{4}$Those Subjects that are 'Not due for next visit' are those Subjects that are not within the follow-up window for the next interval. Study period definitions: Phase 1 (revascularization procedure, prior to endovascular procedure) Endovascular Procedure(0 days) Post-Procedure(1-14 days) 1 Month(15-59 days) 6 Months(60-242 days) 12 Months(243-546 days) 24 Months(547-911 days) 36 Months(912-1275 days) 48 Months(1276-1640 days) 60 Months(1641-2006 days) P210032/S015 FDA Summary of Safety and Effectiveness Data Page 16 of 70 {16} Subject compliance with follow-up visits and imaging requirements for the Other Isolated Lesion Cohort is summarized below: - All three (100%) eligible subjects had a 1-Month visit (100%) and imaging. Three subjects were eligible for a 6-Month follow-up visit, of which two (66.7%) subjects had their 6-Month visit and completed imaging. Three subjects were eligible for a 12-Month follow-up visit, and two (66.7%) subjects had their 12-Month visit and completed imaging. Two subjects were eligible for a 24-Month follow-up visit, of which one (50%) subject had their visit and imaging. One subject (100%) completed the 36-Month and 48-Month visits and imaging. There has been one death (at 48 months) and one non-death discontinuation (at 12 months) in this cohort. ### 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, with the exception of the proportion of Asian subjects. This is due to subjects being enrolled in both the US and Japan. A summary of subject demographics can be found in **Table 4**. The majority (66.2%) of subjects were male (64.0% for Aneurysm, 70.8% for Dissection, and 66.7% for Other Isolated Lesion). Most subjects (57.1%) also specified white as their race (54% for Aneurysm, 58.3% for Dissection, and 100% for Other Isolated Lesion). The median ages reported were 75 years for Aneurysm, 63 years for Dissection, and 73 years for Other Isolated Lesion. **Table 4: Baseline Demographics** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Sex** | | | | | | Male | 32 (64.0%) | 17 (70.8%) | 2 (66.7%) | 51 (66.2%) | | Female | 18 (36.0%) | 7 (29.2%) | 1 (33.3%) | 26 (33.8%) | | **Ethnicity** | | | | | | Not Hispanic or Latino | 47 (94.0%) | 23 (95.8%) | 3 (100.0%) | 73 (94.8%) | | Hispanic or Latino | 3 (6.0%) | 1 (4.2%) | 0 (0%) | 4 (5.2%) | | Unknown | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | **Race^{1}** | | | | | | White | 27 (54.0%) | 14 (58.3%) | 3 (100.0%) | 44 (57.1%) | | Black or African American | 6 (12.0%) | 6 (25.0%) | 0 (0%) | 12 (15.6%) | | Asian | 16 (32.0%) | 2 (8.3%) | 0 (0%) | 18 (23.4%) | | American Indian or Alaska Native | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Hawaiian or Pacific Islander | 1 (2.0%) | 1 (4.2%) | 0 (0%) | 2 (2.6%) | | Other | 0 (0%) | 2 (8.3%) | 0 (0%) | 2 (2.6%) | | **Age (yrs)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 74.3 (8.56) | 63.0 (11.31) | 73.7 (9.02) | 70.8 (10.75) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 17 of 70 {17} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | Median | 75.0 | 63.0 | 73.0 | 72.0 | | Range | (50, 89) | (41, 86) | (65, 83) | (41, 89) | | BMI² | | | | | | n | 49 | 24 | 3 | 76 | | Mean (Std Dev) | 27.3 (5.94) | 29.9 (4.44) | 23.4 (2.01) | 27.9 (5.57) | | Median | 25.6 | 29.0 | 24.4 | 26.9 | | Range | (16.8, 44.4) | (21.7, 40.2) | (21.1, 24.8) | (16.8, 44.4) | | ¹More than one option can be selected. ²Site was queried and the weight for one Subject is unavailable. | | | | | ## 2. Subject Baseline Medical History A summary of subject baseline medical history is provided in Table 5 and summary of subject risk factors prior to enrollment is provided in Table 6. Table 5: Baseline Medical History | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | Number of Enrolled Subjects¹ | 50 | 24 | 3 | 77 | | Stroke | 6/50 (12.0%) | 3/24 (12.5%) | 1/3 (33.3%) | 10/77 (13.0%) | | Transient ischemic attack | 2/50 (4.0%) | 1/24 (4.2%) | 0/3 (0%) | 3/77 (3.9%) | | Myocardial infarction | 6/50 (12.0%) | 2/24 (8.3%) | 0/3 (0%) | 8/77 (10.4%) | | Coronary artery bypass graft | 7/50 (14.0%) | 3/24 (12.5%) | 1/3 (33.3%) | 11/77 (14.3%) | | Percutaneous coronary intervention | 12/50 (24.0%) | 1/24 (4.2%) | 0/3 (0%) | 13/77 (16.9%) | | Coronary artery disease | 19/50 (38.0%) | 3/24 (12.5%) | 1/3 (33.3%) | 23/77 (29.9%) | | Great vessel stenosis | 2/50 (4.0%) | 0/24 (0%) | 0/3 (0%) | 2/77 (2.6%) | | Subclavian steal | 0/49 (0%) | 1/24 (4.2%) | 0/3 (0%) | 1/76 (1.3%) | | Congestive heart failure | 6/50 (12.0%) | 2/24 (8.3%) | 1/3 (33.3%) | 9/77 (11.7%) | | Hypercholesterolemia | 32/49 (65.3%) | 15/24 (62.5%) | 2/3 (66.7%) | 49/76 (64.5%) | | Hypertension | 46/50 (92.0%) | 24/24 (100.0%) | 3/3 (100.0%) | 73/77 (94.8%) | | Atrial fibrillation | 8/50 (16.0%) | 7/24 (29.2%) | 1/3 (33.3%) | 16/77 (20.8%) | | Chronic obstructive pulmonary disease | 19/50 (38.0%) | 4/24 (16.7%) | 1/3 (33.3%) | 24/77 (31.2%) | | Nicotine use | 32/50 (64.0%) | 8/24 (33.3%) | 1/3 (33.3%) | 41/77 (53.2%) | | Diabetes mellitus | 5/50 (10.0%) | 1/24 (4.2%) | 0/3 (0%) | 6/77 (7.8%) | | Renal insufficiency | 8/50 (16.0%) | 5/24 (20.8%) | 1/3 (33.3%) | 14/77 (18.2%) | | Renal dialysis | 0/50 (0%) | 0/24 (0%) | 0/3 (0%) | 0/77 (0%) | | Valvular heart disease | 7/50 (14.0%) | 1/23 (4.3%) | 1/3 (33.3%) | 9/76 (11.8%) | | Cardiac arrhythmia | 10/50 (20.0%) | 3/23 (13.0%) | 1/3 (33.3%) | 14/76 (18.4%) | | Paraplegia | 0/50 (0%) | 0/24 (0%) | 0/3 (0%) | 0/77 (0%) | | Thromboembolic event | 0/49 (0%) | 3/23 (13.0%) | 1/3 (33.3%) | 4/75 (5.3%) | | Prior aortic surgery | 19/50 (38.0%) | 21/24 (87.5%) | 1/3 (33.3%) | 41/77 (53.2%) | | Other vascular intervention | 5/50 (10.0%) | 1/24 (4.2%) | 1/3 (33.3%) | 7/77 (9.1%) | | Peripheral vascular disease | 6/49 (12.2%) | 0/24 (0%) | 1/3 (33.3%) | 7/76 (9.2%) | | Erectile dysfunction (males only) | 2/18 (11.1%) | 0/9 (0%) | 0/1 (0%) | 2/28 (7.1%) | | Cancer | 11/50 (22.0%) | 0/24 (0%) | 1/3 (33.3%) | 12/77 (15.6%) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 18 of 70 {18} **Table 6: Baseline Risk Factors** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Reason High Risk for Open Repair** | | | | | | Prior sternotomy | 5/50 (10.0%) | 14/24 (58.3%) | 1/3 (33.3%) | 20/77 (26.0%) | | Advanced age (>80 years) | 13/50 (26.0%) | 3/24 (12.5%) | 0/3 (0%) | 16/77 (20.8%) | | Inadequate pulmonary function | 12/50 (24.0%) | 1/24 (4.2%) | 1/3 (33.3%) | 14/77 (18.2%) | | Inadequate cardiac function | 2/50 (4.0%) | 2/24 (8.3%) | 0/3 (0%) | 4/77 (5.2%) | | Other^{1} | 18/50 (36.0%) | 4/24 (16.7%) | 1/3 (33.3%) | 23/77 (29.9%) | | **Aberrant Anatomy Risk Criteria (any below)^{2}** | | | | | | | 14/50 (28.0%) | 3/24 (12.5%) | 0/3 (0%) | 17/77 (22.1%) | | Dominant left vertebral artery | 5/46 (10.9%) | 2/23 (8.7%) | 0/1 (0%) | 7/70 (10.0%) | | Occluded/stenosed right vertebral artery | 0/50 (0%) | 0/23 (0%) | 0/3 (0%) | 0/76 (0%) | | Aberrant right subclavian artery | 0/50 (0%) | 0/24 (0%) | 0/3 (0%) | 0/77 (0%) | | Bilateral carotid artery disease | 2/50 (4.0%) | 2/23 (8.7%) | 0/3 (0%) | 4/76 (5.3%) | | Presence of a left internal mammary artery graft | 3/49 (6.1%) | 0/24 (0%) | 0/3 (0%) | 3/76 (3.9%) | | Incomplete circle of willis | 6/41 (14.6%) | 0/15 (0%) | 0/3 (0%) | 6/59 (10.2%) | | Left vertebral artery ending in posterior inferior cerebellar artery | 1/37 (2.7%) | 0/11 (0%) | 0/2 (0%) | 1/50 (2.0%) | | **Clinical Frailty Scale Score (1-9, higher is more frail)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 3.3 (1.10) | 2.9 (0.95) | 3.7 (1.53) | 3.2 (1.08) | | Median | 3.0 | 3.0 | 4.0 | 3.0 | | Range | (1, 6) | (1, 5) | (2, 5) | (1, 6) | | **SVS Score (0-24, higher is worse)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 5.4 (3.30) | 4.9 (2.59) | 5.7 (2.52) | 5.3 (3.05) | | Median | 5.0 | 6.0 | 6.0 | 6.0 | | Range | (0.0, 15.0) | (1.0, 11.0) | (3.0, 8.0) | (0.0, 15.0) | | **ASA Classification** | | | | | | I - Healthy patient | 7/50 (14.0%) | 2/24 (8.3%) | 0/3 (0%) | 9/77 (11.7%) | | II - Mild systemic disease - no functional limitation | 11/50 (22.0%) | 8/24 (33.3%) | 0/3 (0%) | 19/77 (24.7%) | | III - Severe systemic disease - definite functional limitation | 19/50 (38.0%) | 10/24 (41.7%) | 3/3 (100.0%) | 32/77 (41.6%) | | IV - Severe systemic disease that is a constant threat to life | 13/50 (26.0%) | 4/24 (16.7%) | 0/3 (0%) | 17/77 (22.1%) | | V - Moribund patient unlikely to survive 24 hours with or without operation | 0/50 (0%) | 0/24 (0%) | 0/3 (0%) | 0/77 (0%) | | **NYHA Classification** | | | | | | No cardiac disease | 20/50 (40.0%) | 13/24 (54.2%) | 2/3 (66.7%) | 35/77 (45.5%) | | I - Cardiac disease, physical activity not limited | 19/50 (38.0%) | 8/24 (33.3%) | 0/3 (0%) | 27/77 (35.1%) | | II - Cardiac disease, physical activity slightly limited | 10/50 (20.0%) | 3/24 (12.5%) | 0/3 (0%) | 13/77 (16.9%) | | III - Cardiac disease, physical activity markedly limited | 1/50 (2.0%) | 0/24 (0%) | 1/3 (33.3%) | 2/77 (2.6%) | | IV - Cardiac disease, physical activity very limited | 0/50 (0%) | 0/24 (0%) | 0/3 (0%) | 0/77 (0%) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 19 of 70 {19} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | ¹Other reasons for high risk for open repair included subjects with more than one reason, body habitus/anatomic reasons, other prior repairs, refuse open operation or general frailty ²Restricted to those with information known. | | | | | ### 3. Subject Presenting Characteristics A summary of the subjects, by cohort, further presented with differing characteristics by their pathology are presented in Table 7 through Table 9 (Site reported). Table 7: Type of Aneurysm Treated for Aneurysm Cohort | | Aneurysm | | --- | --- | | Number of Enrolled Subjects | 50 | | Fusiform (>55mm) aneurysm | 26/50 (52.0%) | | Fusiform (>2 times native aortic diameter) aneurysm | 2/50 (4.0%) | | Saccular aneurysm | 22/50 (44.0%) | Table 8: Presenting Dissection Characteristics for Dissection Cohort | | Dissection | | --- | --- | | Number of Enrolled Subjects | 24 | | Dissection Type | | | Acute (≤14 days¹) Complicated² Type B | 0 (0%) | | Chronic (>14 days¹) Complicated² Type B | 0 (0%) | | Residual³ Complicated² Dissection | 2 (8.3%) | | Acute (≤14 days¹) Uncomplicated² Type B | 0 (0%) | | Chronic (>14 days¹) Uncomplicated² Type B | 8 (33.3%) | | Residual³ Uncomplicated² Dissection | 14 (58.3%) | | Complication of Aortic Dissection | 2 (8.3%) | | Visceral ischemia | 0 (0%) | | Renal ischemia | 0 (0%) | | Lower limb ischemia | 1 (4.2%) | | Spinal cord ischemia | 0 (0%) | | Other ischemia | 1 (4.2%) | | Rupture | 0 (0%) | | Other issues of Aortic Dissection | 21 (87.5%) | | Rapid enlargement | 4 (16.7%) | | Caused aneurysm | 13 (54.2%) | | Pain | 4 (16.7%) | | Hypertension | 4 (16.7%) | | Days from Onset to Treatment - Chronic Type B Dissection⁴ | | | n | 4 | | Mean (Std Dev) | 247.0 (249.5) | | Median | 153.5 | | Range | (75, 606) | | Days Since Previous Repair - Residual Dissection | | | n | 16 | | Mean (Std Dev) | 1082.2 (1327.0) | | Median | 479.0 | | Range | (34, 4024) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 20 of 70 {20} | | Dissection | | --- | --- | | **TBE Device Procedure Part of Planned Staged Procedure for Residual Dissection Subjects (following ascending procedure)** | 5/16 (31.3%) | | **Proximal Extent of Dissection (Pre-Imaging, Corelab)** | | | Zone 0 | 15 (62.5%) | | Zone 1 | 3 (12.5%) | | Zone 2 | 5 (20.8%) | | Zone 3 | 0 (0%) | | Zone 4 | 0 (0%) | | Zone 5 | 0 (0%) | | Unknown | 1 (4.2%) | | **Distal Extent of Dissection (Pre-Imaging, Corelab)** | | | Aortic Arch (Zone 0,1,2) | 0 (0%) | | Descending Thoracic (Zone 3,4,5) | 4 (16.7%) | | Celiac (Zone 6) | 0 (0%) | | SMA (Zone 7) | 0 (0%) | | Renal(s) (Zone 8) | 0 (0%) | | Abdominal (Zone 9) | 4 (16.7%) | | Iliac(s) (Zone 10,11) | 15 (62.5%) | | Unknown | 1 (4.2%) | | ^{1}Acute Type B Dissection is defined as a newly presenting dissection being ≤14 days between reported dissection onset and treatment date (endovascular procedure for Zone 2, revascularization procedure for Zone 0/1). Chronic Type B Dissection is defined as being a newly presenting dissection >14 days. | | | ^{2}Complicated Dissection is defined as having ischemia or rupture. Uncomplicated dissection are all others. | | | ^{3}Residual Dissection is defined as dissection that remains after previous surgical repair of the ascending aorta and/or aortic arch. | | | ^{4}The count of Subjects with this information can be less than those defined as acute or chronic since there is an additional question which asks whether this date is unknown but the dissection is chronic. | | **Table 9: Type of Other Isolated Lesions for Zone 0/1 Other Isolated Lesion Cohort** | | Zone 0/1 Other Isolated Lesion | | --- | --- | | **Number of Enrolled Subjects** | 3 | | **Aortic Intramural Hematoma** | 0/3 (0%) | | **Penetrating Aortic Ulcer** | 1/3 (33.3%) | | **Aortic Other Isolated Lesion** | 2/3 (66.7%) | #### 4. Device Usage **Table 10** describes the initial treatment devices implanted in subjects enrolled in the study. All subjects had both the Aortic Component (AC) and Side Branch (SB) devices implanted. **Table 11** shows a summary of TBE Aortic Component sizes implanted during the index endovascular procedure (Phase 2). **Table 10: Initial Treatment Devices Implanted** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Number of Subjects with Both TBE Devices Implanted^{1}** | 50 (100.0%) | 24 (100.0%) | 3 (100.0%) | 77 (100.0%) | | **Subjects with Aortic Extender Implanted** | 4 (8.0%) | 2 (8.3%) | 0 (0%) | 6 (7.8%) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 21 of 70 {21} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Subjects with Conformable TAG Device as Distal Extension Implanted** | 35 (70.0%) | 17 (70.8%) | 1 (33.3%) | 53 (68.8%) | | **Subjects with >1 Aortic Component Implanted** | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | **Subjects with Other ^{2} Device Implanted** | 3 (6.0%) | 0 (0%) | 0 (0%) | 3 (3.9%) | | **Number of SB Components Implanted Per Subject** | | | | | | **1 SB Component Implanted** | 33 (66.0%) | 19 (79.2%) | 3 (100.0%) | 55 (71.4%) | | **2 SB Components Implanted** | 14 (28.0%) | 4 (16.7%) | 0 (0%) | 18 (23.4%) | | **3+ SB Components Implanted^{3}** | 3 (6.0%) | 1 (4.2%) | 0 (0%) | 4 (5.2%) | | **Number of Aortic Extenders Implanted Per Subject** | | | | | | **0 Aortic Extenders Implanted** | 46 (92.0%) | 22 (91.7%) | 3 (100.0%) | 71 (92.2%) | | **1 Aortic Extender Implanted** | 3 (6.0%) | 1 (4.2%) | 0 (0%) | 4 (5.2%) | | **2 Aortic Extenders Implanted** | 0 (0%) | 1 (4.2%) | 0 (0%) | 1 (1.3%) | | **3+ Aortic Extenders Implanted^{4}** | 1 (2.0%) | 0 (0%) | 0 (0%) | 1 (1.3%) | | **Number of Conformable TAG Devices Implanted Per Subject** | | | | | | **0 Conformable TAG Devices Implanted** | 15 (30.0%) | 7 (29.2%) | 2 (66.7%) | 24 (31.2%) | | **1 Conformable TAG Device Implanted** | 20 (40.0%) | 12 (50.0%) | 1 (33.3%) | 33 (42.9%) | | **2 Conformable TAG Device Implanted** | 12 (24.0%) | 5 (20.8%) | 0 (0%) | 17 (22.1%) | | **3+ Conformable TAG Devices Implanted** | 3 (6.0%) | 0 (0%) | 0 (0%) | 3 (3.9%) | | ^{1}This includes both the aortic component and side branch component devices. | | | | | | ^{2} These include one Viabahn, one Viabahn VBX, and one Excluder Contralateral Limb | | | | | | ^{3} For one subject, physician encountered difficulty rotationally aligning the AC portal to the target branch vessel. Three SB Components and a GORE® VIABAHN® Endoprosthesis were used to further extend into the innominate artery. One subject had two TBE SB Components accurately positioned and deployed. At one month an SB component and Viabahn were placed to address a Type III endoleak discussed further in the Endoleak section. Two subjects had three SB Components as part of index procedure due to unknown reasons or contributing factors. | | | | | | ^{4} Discussion of this subject has been included in Table 19 and Aneurysm: Technical Success | | | | | **Table 11: Initial Treatment TBE Aortic Component Sizing for Zone 0/1 All Cohorts** | Device Diameter (mm) | Internal Portal^{1} Diameter (mm) | Overall Device Length (cm) | Subjects (N=77) | Devices (N=77) | | --- | --- | --- | --- | --- | | 21 | 8 | 10 | 0 | 0 | | 21 | 8 | 15 | 0 | 0 | | 21 | 8 | 20 | 0 | 0 | | 26 | 8 | 10 | 0 | 0 | | 26 | 8 | 15 | 0 | 0 | | 26 | 8 | 20 | 0 | 0 | | 28 | 8 | 10 | 0 | 0 | | 28 | 8 | 15 | 0 | 0 | | 28 | 8 | 20 | 0 | 0 | | 31 | 8 | 10 | 0 | 0 | | 31 | 8 | 15 | 2 (2.6%) | 2 (2.6%) | | 31 | 8 | 20 | 0 | 0 | | 31 | 12 | 10 | 0 | 0 | | 31 | 12 | 15 | 4 (5.2%) | 4 (5.2%) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 22 of 70 {22} | Device Diameter (mm) | Internal Portal^{1} Diameter (mm) | Overall Device Length (cm) | Subjects (N=77) | Devices (N=77) | | --- | --- | --- | --- | --- | | 31 | 12 | 20 | 0 | 0 | | 34 | 8 | 10 | 0 | 0 | | 34 | 8 | 15 | 4 (5.2%) | 4 (5.2%) | | 34 | 8 | 20 | 0 | 0 | | 34 | 12 | 10 | 0 | 0 | | 34 | 12 | 15 | 4 (5.2%) | 4 (5.2%) | | 34 | 12 | 20 | 1 (1.3%) | 1 (1.3%) | | 37 | 8 | 10 | 0 | 0 | | 37 | 8 | 15 | 0 | 0 | | 37 | 8 | 20 | 0 | 0 | | 37 | 12 | 10 | 0 | 0 | | 37 | 12 | 15 | 11 (14.3%) | 11 (14.3%) | | 37 | 12 | 20 | 6 (7.8%) | 6 (7.8%) | | 40 | 8 | 10 | 0 | 0 | | 40 | 8 | 15 | 0 | 0 | | 40 | 8 | 20 | 0 | 0 | | 40 | 12 | 10 | 0 | 0 | | 40 | 12 | 15 | 12 (15.6%) | 12 (15.6%) | | 40 | 12 | 20 | 5 (6.5%) | 5 (6.5%) | | 45 | 8 | 10 | 0 | 0 | | 45 | 8 | 15 | 1 (1.3%) | 1 (1.3%) | | 45 | 8 | 20 | 0 | 0 | | 45 | 12 | 10 | 0 | 0 | | 45 | 12 | 15 | 14 (18.2%) | 14 (18.2%) | | 45 | 12 | 20 | 13 (16.9%) | 13 (16.9%) | $^{1}$ For Patients in whom the target branch vessel is the brachiocephalic artery, an Aortic Component with a 12mm internal portal is required. **Table 12: Initial Treatment TBE Side Branch Sizing$^{1}$** | Device Diameter (mm) | SB Portal^{1} Diameter (mm) | Device Length (cm) | Subjects (N=77) | Devices (N=103) | | --- | --- | --- | --- | --- | | 8 | 8 | 6 | 3 (3.9%) | 4 (3.9%) | | 10 | 8 | 6 | 3 (3.9%) | 3 (2.9%) | | 12 | 8 | 6 | 1 (1.3%) | 1 (1.0%) | | 15 | 8 | 6 | 0 | 0 | | 15 | 12 | 6 | 23 (29.9%) | 32 (31.1%) | | 17 | 8 | 6 | 0 | 0 | | 17 | 12 | 6 | 28 (36.4%) | 38 (36.9%) | | 20 | 12 | 6 | 21 (27.3%) | 25 (24.3%) | $^{1}$ For patients in whom the target branch vessel is the brachiocephalic artery, a Side Branch Component with a 12mm portal segment diameter is required. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 23 of 70 {23} **Table 13: Initial Treatment TBE Aortic Extender Sizing$^{1}$** | Device Diameter (mm) | Device Length (cm) | Subjects (N=6) | Devices (N=9) | | --- | --- | --- | --- | | 21 | 3.6 | 0 | 0 | | 26 | 3.8 | 0 | 0 | | 28 | 4.0 | 0 | 0 | | 31 | 4.0 | 0 | 0 | | 34 | 4.2 | 0 | 0 | | 37 | 4.2 | 2 (33.3%) | 2 (22.2%) | | 40 | 4.3 | 0 | 0 | | 45 | 4.6 | 5 (83.3%) | 7 (77.8%) | ### 5. Procedure Characteristics Subject treatment occurred in two phases. During the first phase (Phase 1, Revascularization), the great vessels distal to the target branch vessel were revascularized through bypass and/ or transposition. Subjects were considered enrolled at the initiation of the Phase 1 procedure. Following at least 24 hours of observation, and no greater than 60 days after the Phase 1 procedure, the subjects underwent the second phase of the procedure, the index endovascular procedure with the TBE Device (Phase 2). A subject was considered to have entered the second phase of treatment once a device delivery catheter has been introduced into the subject’s vasculature. #### *Revascularization Procedure Results (Phase 1)* **Table 14** provides a summary of revascularization procedure information for all enrolled subjects. All subjects survived the Phase 1 procedure and entered Phase 2. **Table 14: Revascularization (Phase 1) Procedure Data** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Revascularization Type^{1}** | | | | | | Bypass | 47 (94.0%) | 23 (95.8%) | 3 (100.0%) | 73 (94.8%) | | Transposition | 20 (40.0%) | 11 (45.8%) | 0 (0%) | 31 (40.3%) | | **Procedure Time (minutes)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 208.3 (83.14) | 193.7 (83.28) | 152.7 (20.50) | 201.6 (81.92) | | Median | 193.5 | 173.0 | 164.0 | 181.0 | | Range | (42, 499) | (65, 408) | (129, 165) | (42, 499) | | **Anesthesia Method** | | | | | | General | 50 (100.0%) | 24 (100.0%) | 3 (100.0%) | 77 (100.0%) | | **Revascularization Successful^{2}** | 49 (98.0%) | 24 (100.0%) | 3 (100.0%) | 76 (98.7%) | | **Estimated Blood Loss During Procedure (mL)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 302.3 (400.06) | 172.0 (192.69) | 66.7 (41.63) | 252.5 (345.70) | | Median | 190.0 | 100.0 | 80.0 | 130.0 | | Range | (0, 2400)^{3} | (20, 900) | (20, 100) | (0, 2400) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 24 of 70 {24} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Transfusion Required** | 6 (12.0%) | 2 (8.3%) | 0 (0%) | 8 (10.4%) | | **Anticoagulant Administered** | 49 (98.0%) | 24 (100.0%) | 3 (100.0%) | 76 (98.7%) | | **Additional Procedures Performed^{1}** | 12 (24.0%) | 1 (4.2%) | 0 (0%) | 13 (16.9%) | | **Subject Survived Procedure** | 50 (100.0%) | 24 (100.0%) | 3 (100.0%) | 77 (100.0%) | | **Discharged Before Phase 2 Endovascular Procedure** | 21 (42.0%) | 8 (33.3%) | 2 (66.7%) | 31 (40.3%) | | **Length of Stay (days) if discharged** | | | | | | n | 21 | 8 | 2 | 31 | | Mean (Std Dev) | 4.2 (4.77) | 2.6 (1.19) | 8.0 (9.90) | 4.0 (4.51) | | Median | 3.0 | 3.0 | 8.0 | 3.0 | | Range | (1, 22) | (1, 4) | (1, 15) | (1, 22) | | **Length of Stay for Revascularization (days)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 4.3 (3.95) | 5.1 (8.78) | 6.7 (7.37) | 4.7 (5.93) | | Median | 3.0 | 3.0 | 4.0 | 3.0 | | Range | (1, 22) | (1, 44) | (1, 15) | (1, 44) | | ^{1}More than one option can be selected. | | | | | | ^{2}One Subject required a re-do revascularization procedure prior to Phase 2 because of a 'carotid-subclavian bypass graft stenosis' | | | | | | ^{3}One subject had a subclavian vein injury during the revascularization procedure that led to high blood loss. | | | | | | ^{4}Additional procedures included embolizations or vessel ligations | | | | | ### Endovascular Procedure Results (Phase 2) **Table 15** summarizes the endovascular procedure information by cohort. The majority (70.1 %) of all subjects' proximal landing zone was within native aortic tissue and 29.9% landed in a surgical graft. All subjects received general anesthesia. The median procedure time was 147 minutes. **Table 15: Endovascular Procedure Information– Part 1** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Time Since Phase 1 Revascularization Procedure (days)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 15.5 (19.31) | 11.3 (25.24) | 22.2 (23.92) | 14.5 (21.32) | | Median | 5.8 | 3.5 | 14.8 | 4.2 | | Range | (1, 74) | (1, 126) | (3, 49) | (1, 126) | | **Aortic Arch Zone Treated** | | | | | | Zone 0 | 45 (90.0%) | 22 (91.7%) | 3 (100.0%) | 70 (90.9%) | | Zone 1 | 5 (10.0%) | 2 (8.3%) | 0 (0%) | 7 (9.1%) | | **Proximal Landing Zone** | | | | | | Within Surgical Graft | 7 (14.0%) | 15 (62.5%) | 1 (33.3%) | 23 (29.9%) | | Within Native Aorta | 43 (86.0%) | 9 (37.5%) | 2 (66.7%) | 54 (70.1%) | | **Procedure Time (minutes)^{1}** | | | | | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 25 of 70 {25} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 168.6 (71.51) | 168.7 (78.83) | 118.0 (29.87) | 166.7 (72.79) | | Median | 148.0 | 148.5 | 106.0 | 147.0 | | Range | (79, 401) | (81, 423) | (96, 152) | (79, 423) | | **Anesthesia Method** | | | | | | General | 50 (100.0%) | 24 (100.0%) | 3 (100.0%) | 77 (100.0%) | | **Access Method** | | | | | | Percutaneous | 25 (50.0%) | 15 (62.5%) | 1 (33.3%) | 41 (53.2%) | | Cut-down | 22 (44.0%) | 9 (37.5%) | 1 (33.3%) | 32 (41.6%) | | Cut-down and conduit | 3 (6.0%) | 0 (0%) | 1 (33.3%) | 4 (5.2%) | | **Access Vessel** | | | | | | Left femoral | 9 (18.0%) | 7 (29.2%) | 1 (33.3%) | 17 (22.1%) | | Right femoral | 33 (66.0%) | 17 (70.8%) | 1 (33.3%) | 51 (66.2%) | | Left iliac | 2 (4.0%) | 0 (0%) | 1 (33.3%) | 3 (3.9%) | | Right iliac | 5 (10.0%) | 0 (0%) | 0 (0%) | 5 (6.5%) | | Aortic | 1 (2.0%) | 0 (0%) | 0 (0%) | 1 (1.3%) | | Unknown | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | **Additional Access Sites** | | | | | | Left brachial | 0 (0%) | 2 (8.3%) | 0 (0%) | 2 (2.6%) | | Right brachial | 33 (66.0%) | 13 (54.2%) | 3 (100.0%) | 49 (63.6%) | | Left axial | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Right axial | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Other^{2} | 15 (30.0%) | 8 (33.3%) | 0 (0%) | 23 (29.9%) | | None reported | 2 (4.0%) | 1 (4.2%) | 0 (0%) | 3 (3.9%) | $^{1}$Procedure Time (min) was captured as the time the first incision was made through the time the access site was closed. $^{2}$Other access sites may include a combination of multiple access sites including radial access and/or a combination of multiple access sites **Table 16** highlights estimated blood loss, heparin usage, and endovascular procedures for the subjects. Eight (10.4 %) Subjects had site-reported blood loss ≥1000mL during the TBE Device procedure (an Other Outcome). In total, 17 (22.1 %) subjects required a transfusion with a median replaced blood volume of 600mL. Heparin was administered to all subjects with median dose administered of 12,000 units per mL. Twenty-one subjects had additional procedures to prevent Type II endoleaks. Twenty-nine (37.7%) subjects had adjunctive technique used to prevent paraplegia, with cerebral spinal fluid (CSF) drainage being the most common procedure. **Table 16: Endovascular Procedure Information - Part 2** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Contrast Used During Procedure (mL)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 125.3 (65.53) | 108.3 (39.15) | 80.0 (59.03) | 118.3 (58.71) | | Median | 107.5 | 100.0 | 50.0 | 100.0 | | Range | (24, 265) | (50, 200) | (42, 148) | (24, 265) | | **Estimated Blood Loss During Procedure (mL)** | | | | | | n | 49 | 24 | 3 | 76 | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 26 of 70 {26} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | Mean (Std Dev) | 338.8 (525.06) | 278.1 (506.32) | 173.3 (219.39) | 313.1 (507.88) | | Median | 150.0 | 100.0 | 100.0 | 120.0 | | Range | (0, 2440) | (10, 2500) | (0, 420) | (0, 2500) | | **Blood Loss ≥ 1000mL^{1}** | 7 (14.0%) | 1 (4.2%) | 0 (0%) | 8 (10.4%) | | **Transfusion Required, blood volume replaced (mL)** | | | | | | n | 12 | 4 | 1 | 17 | | Mean (Std Dev) | 847.5 (640.71) | 1260.0 (1532.67) | 300.0 (-) | 912.4 (882.88) | | Median | 600.0 | 650.0 | 300.0 | 600.0 | | Range | (200, 2080) | (240, 3500) | (300, 300) | (200, 3500) | | **Heparin Administered, dose (units per mL)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 12100.0 (6488.61) | 11925.0 (5103.64) | 11666.7 (5507.57) | 12028.6 (5986.45) | | Median | 11500.0 | 12000.0 | 9000.0 | 12000.0 | | Range | (1000, 30000) | (100, 20000) | (8000, 18000) | (100, 30000) | | **Procedure Used to Prevent Type II Endoleaks^{2}** | 13 (56.5%) | 6 (66.7%) | 2 (100.0%) | 21 (61.8%) | | **Adjunctive Technique Used to Prevent Paraplegia** | | | | | | None | 34 (68.0%) | 11 (45.8%) | 3 (100.0%) | 48 (62.3%) | | Yes, CSF drainage | 10 (20.0%) | 7 (29.2%) | 0 (0%) | 17 (22.1%) | | Yes, induced hypertension | 3 (6.0%) | 4 (16.7%) | 0 (0%) | 7 (9.1%) | | Yes, CSF drainage and induced hypertension | 1 (2.0%) | 1 (4.2%) | 0 (0%) | 2 (2.6%) | | Yes, other | 2 (4.0%) | 1 (4.2%) | 0 (0%) | 3 (3.9%) | $^{1}$Estimated blood loss ≥ 1000mL were primarily due to complicated femoral access and/or surgical interventions associated with the aortic branch vessel revascularization. A discussion of Life Threatening Bleeds is included in the Key Events section. $^{2}$Among those who responded yes or no to 'If vessels distal to the target vessel were not ligated in Phase 1, was an endovascular procedure performed to prevent type II endoleaks?'. These procedures included coils and/or plugs. **Table 17** outlines the length of hospital stay, with the median time being four days. Most subjects (81.8 %) were discharged home, 11.7 % were sent to a rehab facility/nursing home, and 3.9% died in hospital (all three of these subjects were in the Aneurysm cohort). The median time to return to normal activities was 27 days (21 days for Aneurysm Subjects, 28 days for Dissection Subjects, and 26 days for Other Isolated Lesion Subjects). **Table 17: Endovascular Procedure Information - Part 3** | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects** | 50 | 24 | 3 | 77 | | **Endovascular Length of Stay (days)** | | | | | | n | 50 | 24 | 3 | 77 | | Mean (Std Dev) | 6.1 (4.84) | 6.2 (6.31) | 3.7 (1.53) | 6.0 (5.24) | | Median | 5.0 | 4.0 | 4.0 | 4.0 | | Range | (0, 31) | (1, 29) | (2, 5) | (0, 31) | | **Discharge Location** | | | | | | Home | 38 (76.0%) | 22 (91.7%) | 3 (100.0%) | 63 (81.8%) | P210032/S015 FDA Summary of Safety and Effectiveness Data Page 27 of 70 {27} | | Aneurysm | Dissection | Other Isolated Lesion | All | | --- | --- | --- | --- | --- | | Rehabilitation center/nursing facility | 8 (16.0%) | 1 (4.2%) | 0 (0%) | 9 (11.7%) | | Acute care facility | 1 (2.0%) | 1 (4.2%) | 0 (0%) | 2 (2.6%) | | N/A - Subject died in hospital | 3 (6.0%) | 0 (0%) | 0 (0%) | 3 (3.9%) | | **Return to Normal Activities (days)^{1}** | | | | | | n | 40 | 19 | 3 | 62 | | Mean (Std Dev) | 39.7 (51.40) | 31.2 (29.19) | 22.0 (17.35) | 36.2 (44.45) | | Median | 21.0 | 28.0 | 26.0 | 27.0 | | Range | (1, 229) | (2, 108) | (3, 37) | (1, 229) | $^{1}$Earliest reported time was used to calculate return to normal. ## D. Safety and Effectiveness Results The primary safety and effectiveness endpoint was Strategy Success for planned staged procedures (landing zone optimization, transposition, and device placement) through one month following last planned procedure. Strategy Success is defined as a composite of the following events from the time of enrollment through one month following the index endovascular procedure: initiation of the index endovascular procedure following the debranching procedure, device technical success for the index procedure and freedom from the following: aortic rupture, lesion-related mortality, disabling stroke, permanent paraplegia or paraparesis, new onset renal failure requiring permanent dialysis, and additional unanticipated procedure related to the device/procedure or withdrawal of the delivery system (i.e., protocol-defined reintervention). ### 1. Aneurysm: Primary Endpoint Composite The pre-specified performance goal (PG) for freedom from primary endpoint events in the Aneurysm arm of 60% was met (n=47 subjects eligible for Primary Analysis, Table 18). The overall rate of freedom from a primary endpoint event was 74.5% with a 95% one-sided Exact lower confidence limit of 61.9%. There were 52 subjects enrolled in this hypothesis-driven arm and 47 subjects were eligible for the primary endpoint analysis. Two subjects were excluded from analysis due to being treated with a 49/53 mm diameter device; two additional subjects were included (bringing the total subjects enrolled to 52) to keep the planned enrollment of 50 subjects for device sizes intended to be marketed. Three subjects were not eligible for the primary endpoint analysis since they did not have a primary endpoint event and did not have imaging within the 1-Month window. The denominator is comprised of the 43 subjects with imaging performed in the 1-Month window and an additional 4 subjects with a primary endpoint event who did not have 1-Month imaging performed. Table 18: Primary Endpoint Composite Success (Through 1-Month) Aneurysm Cohort | Primary Endpoint Analysis | Endpoint Denominator | Endpoint Event | Percent Free from Endpoint Event (95% Exact LCL) | Reject Null Hypothesis (LCL > 60% PG) | | --- | --- | --- | --- | --- | | Endpoint Eligible^{1} | 47 | 12 | 74.5% (61.9%) | Yes | $^{1}$Primary Endpoint composite (Through 1 Month) denominator is restricted to those with primary endpoint event or 1 Month imaging performed. NOTE: 95% LCL represents one-sided 95% Lower Confidence Limit by exact method. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 28 of 70 {28} **Table 19: Primary Endpoint Component Events (Through 1 Month) Aneurysm Cohort** | | Phase 1 | Endovascular Procedure | Post-Procedure | 1 Month | Total (Through 1 Month) | | --- | --- | --- | --- | --- | --- | | **Number of Enrolled Subjects^{1}** | 50 | 50 | 49 | 47 | 50 | | **Number of Subjects with Imaging in Follow-Up Window** | - | - | 5 | 43 | 45 | | **Number of Subjects with Imaging or Primary Endpoint Event in Window** | - | - | 8 | 43 | 48 | | **Subjects with Primary Endpoint Event Below^{2}** | 1/50 (2.0%) | 8/50 (16.0%) | 3/8 (37.5%) | 2/43 (4.7%) | 12/47 (25.5%) | | **Initiation of index endovascular procedure failure^{3}** | 0/50 (0%) | - | - | - | 0/50 (0%) | | **Device technical failure^{4}** | - | 3/50 (6.0%) | - | - | 3/50 (6.0%) | | Access or Device Delivery failure | - | 1/50 (2.0%) | - | - | - | | Access failure | - | 0/50 (0%) | - | - | - | | Accurate deployment failure | - | 1/50 (2.0%) | - | - | - | | Device delivery system retrieval failure | - | 0/50 (0%) | - | - | - | | Patency failure | - | 0/50 (0%) | - | - | - | | Unanticipated additional procedure related to device/procedure^{4} | - | 3/50 (6.0%) | - | - | - | | **Aortic rupture** | 0/50 (0%) | 0/50 (0%) | 0/49 (0%) | 0/47 (0%) | 0/50 (0%) | | **Lesion-related mortality** | 0/50 (0%) | 1/50 (2.0%) | 1/49 (2.0%) | 0/47 (0%) | 2/50 (4.0%) | | **Disabling stroke^{5}** | 0/50 (0%) | 4/50 (8.0%) | 1/49 (2.0%) | 1/47 (2.1%) | 6/50 (12.0%) | | **Permanent paraplegia^{3}** | 0/50 (0%) | 0/50 (0%) | 0/49 (0%) | 0/47 (0%) | 0/50 (0%) | | **Permanent paraparesis^{3}** | 0/50 (0%) | 0/50 (0%) | 0/49 (0%) | 0/47 (0%) | 0/50 (0%) | | **New onset renal failure requiring dialysis^{3}** | 0/50 (0%) | 0/50 (0%) | 1/49 (2.0%) | 0/47 (0%) | 1/50 (2.0%) | | **Unanticipated additional procedure related to device/procedure (Protocol-Defined Reintervention)** | 1/50 (2.0%) | 0/50 (0%) | 0/49 (0%) | 1/47 (2.1%) | 2/50 (4.0%) | $^{1}$Subjects at risk at the start of each interval. $^{2}$Primary endpoint composite denominator is restricted to Subjects either with a primary endpoint event within window and/or imaging done in window (except Phase 1 and Endovascular Procedure are among all enrolled). Primary endpoint composite Total (Through 1 Month) denominator is further restricted to primary endpoint event in timeframe (i.e., anytime ≤ 59 days; exceptions indicated with a '-' per Protocol definitions) and/or imaging done in 1 Month window (15-59 days). $^{3}$Initiation of index endovascular procedure failures counted as occurring in Phase 1. Device technical failure events on day 0 only, others are events with onset through day 30. Study period definitions: Phase 1 (revascularization procedure, prior to endovascular procedure) Endovascular Procedure(0 days) Post-Procedure(1-14 days) 1 Month(15-59 days) Total(Phase1-59 days) $^{4}$During the treatment of one subject, the investigator noticed infolding in one of two extenders and a third Aortic Extender was required to resolve this. Although the protocol states that placement of additional TBE devices would not constitute technical failure, the investigator determined it was an unanticipated additional procedure and therefore is considered a Technical Success Failure. At the time of the index endovascular operation one Subject had a bilateral neck exploration, thrombectomy of left and right CCA, thrombectomy of LSA for occluded bypass graft. The investigator did not consider this an unanticipated procedure and therefore it is not counted as a device technical failure. The core lab reported event was CEC adjudicated as a loss of patency and is considered a Treatment Success failure. There have been 12 Aneurysm Subjects (25.5% (12/47); 74.5% free from endpoint event) that had any primary endpoint event occur. Two of these 12 subjects had more than one type of primary endpoint event: one subject had disabling stroke and lesion-related mortality and one subject had disabling stroke and new renal failure. The index endovascular procedure was successfully initiated for all subjects and there were no reports of aortic rupture, permanent paraplegia, or permanent paraparesis through the 1-Month follow-up timeframe. #### Aneurysm: Device Technical Success Device Technical Success was achieved in 94.0% of subjects in the Aneurysm Cohort. Three subjects failed to meet the technical success criteria: - In one subject, upon deployment, the AC portal device rotationally misaligned to the target branch vessel requiring implantation of additional Side Branch components and a GORE® VIABAHN® device. P210032/S015 FDA Summary of Safety and Effectiveness Data Page 29 of 70 {29} placement for a right common carotid dissection occurring immediately following closure post TBE procedure. - In one subject, two AEs were placed proximal to AC in the ascending aorta to correct bird beaking of the AC. The AEs were ballooned, at which point in-folding of the second proximal cuff was noted, causing aortic stenosis, which did not resolve with ballooning. Further deployment of a third TBE AE was used in the ascending aorta, correcting the in-folding. As noted in the footnote of Table 19, although the protocol states that placement of additional TBE devices would not constitute technical failure, the investigator considered this event to be an unanticipated additional procedure related to the device/procedure. There were no access failure or device delivery system retrieval failures and there were no issues with establishing Aortic Component or Side Branch graft patency during the procedure. ### Aneurysm: Lesion-Related Mortality through 1-Month There were two Aneurysm Subjects (4.0%; 2/50), as adjudicated by the CEC, which died and met the definition of lesion-related mortality within the 1-Month follow-up timeframe. - One subject experienced infarcts in the high right frontal lobe, bilateral (left greater than right) parietal occipital regions, and broad right cerebellar infarction (with associated right tonsillar herniation) on POD 0. The subject received drug therapy. The subject died on POD 6. This event was also adjudicated for Disabling Stroke through 30 days in the Aneurysm - Disabling Stroke through 30 days section below. CEC adjudicated the event as related to the device and endovascular procedure. - One subject experienced pulseless electrical activity arrest on POD 0. The subject received drug therapy and fluid/blood/oxygen therapy the same day. The subject died on POD 0. CEC adjudicated the event as related to the endovascular procedure. ### Aneurysm: Disabling Stroke through 30 days There were six subjects (12.0%; 6/50) that experienced disabling stroke events from the time of enrollment through 30 days post-index endovascular procedure. Any potential adverse event meeting this component definition through the timeframe was sent to the independent CEC neurologist for event adjudication. - One subject experienced a left hemispheric stroke on POD 0 and received physical therapy/rehabilitation treatment. The event was reported by the site to be 'related to the endovascular procedure' and was ongoing at discharge on POD 9. - One subject experienced an ischemic stroke in left MCA territory with pattern consistent with embolism on POD 0. The subject received physical therapy/rehabilitation on POD 0 and POD 9. This event resolved with sequelae on POD 0, and the site reported a relationship of 'unknown'. - One subject experienced infarcts in the high right frontal lobe, bilateral (left greater than right) parietal occipital regions, and broad right… --- **Source:** [https://fda-staging.innolitics.com/device/P210032S015](https://fda-staging.innolitics.com/device/P210032S015) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [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/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com