ZENITH TX2 THORACIC TAA ENDOVASCULAR GRAFT WITH THE H&LB ONE-SHOT INTRODUCTION SYSTEM

P070016 · William Cook Europe Aps · MIH · May 21, 2008 · Cardiovascular

Device Facts

• Record ID: P070016
• Device Name: ZENITH TX2 THORACIC TAA ENDOVASCULAR GRAFT WITH THE H&LB ONE-SHOT INTRODUCTION SYSTEM
• Applicant: William Cook Europe Aps
• Product Code: MIH · Cardiovascular
• Decision Date: May 21, 2008
• Decision: APWD
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Zenith TX2® TAA Endovascular Graft with the H&L-B One-Shot™ Introduction System is indicated for the endovascular treatment of patients with aneurysms or ulcers of the descending thoracic aorta having vascular morphology suitable for endovascular repair, including: - Adequate iliac/femoral access compatible with the required introduction systems, - Non-aneurysmal aortic segments (fixation sites) proximal and distal to the aneurysm or ulcer: - with a length of at least 25 mm, and - with a diameter measured outer wall to outer wall of no greater than 38 mm and no less than 24 mm.

Device Story

Zenith TX2 TAA Endovascular Graft is a cylindrical, modular (one- or two-piece) endovascular prosthesis. It consists of woven polyester fabric sewn to self-expanding stainless steel Cook-Z stents. Proximal and distal components feature barbs for fixation. Gold radiopaque markers facilitate fluoroscopic visualization. The device is preloaded onto the H&L-B One-Shot Introduction System, which utilizes trigger-wire release mechanisms for sequential, controlled deployment. The system includes a Flexor introducer sheath and Captor hemostatic valve to enhance trackability and hemostasis. Used in a hospital setting by physicians (e.g., vascular surgeons) to treat thoracic aortic aneurysms or ulcers. The graft is deployed endovascularly via iliac/femoral access; it expands to line the aorta, excluding the aneurysm/ulcer from blood flow. This minimally invasive approach reduces surgical trauma, blood loss, and recovery time compared to open surgical repair. Clinical output is monitored via follow-up imaging (CT/X-ray) to assess graft position, patency, and absence of endoleaks.

Clinical Evidence

Pivotal STARZ-TX2 clinical trial: non-randomized, multi-center study comparing endovascular treatment (n=160) to open surgical control (n=70). Primary safety endpoint: 30-day survival (98.1% endovascular vs 94.3% open, p<0.01). Primary effectiveness endpoint: 30-day rupture-free survival (100% in both). Secondary endpoints: 30-day morbidity score (1.3 endovascular vs 2.9 open, p<0.01) and clinical utility measures (all superior for endovascular, p<0.01). Follow-up through 730 days showed 89.1% freedom from device events. Bench testing (ISO 25539-1) and animal studies (bovine) confirmed mechanical integrity, biocompatibility, and deployment functionality.

Technological Characteristics

Materials: Woven polyester fabric, stainless steel Cook-Z stents, braided polyester/polypropylene sutures, gold radiopaque markers. Energy: Self-expanding stents. Dimensions: 28-42 mm diameters. Delivery: 20 Fr or 22 Fr H&L-B One-Shot system, .035 inch wire guide compatible. Connectivity: None. Sterilization: Ethylene Oxide. Software: None.

Indications for Use

Indicated for endovascular treatment of patients with descending thoracic aortic aneurysms or ulcers with suitable vascular morphology (adequate iliac/femoral access; proximal/distal non-aneurysmal fixation sites ≥25 mm length and 24-38 mm diameter). Contraindicated in patients with known sensitivities to stainless steel, polyester, solder (tin, silver), polypropylene, nitinol, or gold, or systemic infection.

Submission Summary (Full Text)

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# Summary of Safety and Effectiveness Data (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Thoracic Endovascular Graft

Device Trade Name: Zenith TX2® TAA Endovascular Graft

Applicant Name and Address: William Cook Europe, ApS
Sandet 6, DK 4632
Bjaeverskov, Denmark

Premarket Approval Application (PMA) Number: P070016

Date of Panel Recommendation: None

Date of Notice of Approval to Applicant: May 21, 2008

Expedited: Not applicable

## II. INDICATIONS FOR USE

The Zenith TX2® TAA Endovascular Graft with the H&amp;L-B One-Shot™ Introduction System is indicated for the endovascular treatment of patients with aneurysms or ulcers of the descending thoracic aorta having vascular morphology suitable for endovascular repair, including:

- Adequate iliac/femoral access compatible with the required introduction systems,
- Non-aneurysmal aortic segments (fixation sites) proximal and distal to the aneurysm or ulcer:
- with a length of at least 25 mm, and
- with a diameter measured outer wall to outer wall of no greater than 38 mm and no less than 24 mm.

## II. CONTRAINDICATIONS

The Zenith TX2 TAA Endovascular Graft with the H&amp;L-B One-Shot Introduction System is contraindicated in:

- Patients with known sensitivities or allergies to stainless steel, polyester, solder (tin, silver), polypropylene, nitinol, or gold.
- Patients with a systemic infection which may be at increased risk of endovascular graft infection.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Zenith TX2® TAA Endovascular Graft labeling (Instructions for Use).

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# V. DEVICE DESCRIPTION

## Main Body Component Description

The Zenith TX2® TAA Endovascular Graft is a two- or one-piece cylindrical endovascular graft. The two-piece system consists of a proximal main body component and overlapping distal main body component. The one-piece system may consist of either a one-piece main body component or a proximal main body component (without use of a distal main body component). The proximal main body components can be either tapered (by 4 mm) or non-tapered. All main body components are shown in Figure 1.

Figure 1. Zenith TX2® TAA Endovascular Graft main body components.

As listed in Table 1, the Zenith TX2® TAA Endovascular Graft main body components are available in a variety of standard stock sizes.

Table 1. Zenith TX2® TAA Endovascular Graft main body components by diameter

| Graft diameter (mm) | Length of non-tapered proximal component (mm) | Length of tapered proximal component (mm) | Length of distal component (mm) | Length of one-piece component (mm) |
| --- | --- | --- | --- | --- |
| 28 | 120 / 140 / 200 | n/a | 127 / 147 / 207 | 84 |
| 30 | 120 / 140 / 200 | n/a | 127 / 147 / 207 | 84 |
| 32 | 120 / 140 / 200 | 160 / 200 | 127 / 147 / 207 | 84 |
| 34 | 127 / 152 / 202 | 157 / 197 | 136 / 186 | 81 |
| 36 | 127 / 152 / 202 | 157 / 197 | 136 / 186 | 81 |
| 38 | 127 / 152 / 202 | 152 / 202 | 136 / 186 | 81 |
| 40 | 108 / 135 / 162 / 216 | 158 / 208 | 144 / 198 | 85 |
| 42 | 108 / 135 / 162 / 216 | 158 / 208 | 144 / 198 | 85 |

The stent-grafts are constructed of full-thickness woven polyester fabric sewn to self-expanding stainless steel Cook-Z® stents with braided polyester and monofilament polypropylene sutures. The Zenith TX2® TAA Endovascular Graft is fully stented to provide stability and the expansile force necessary to open the lumen of the graft during deployment. Additionally, the Cook-Z® stents provide the necessary attachment and seal of the graft to the vessel wall. For added fixation, the covered stent at the proximal end of the proximal main body component

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(tapered and non-tapered) and one-piece main body component contains barbs placed at a 2 mm stagger, which protrude through the graft material (Figure 2a). The bare stent at the distal end of the distal main body component and one-piece main body component also contains barbs (Figure 2b). The number of barbs per covered or uncovered stent depends on component diameter, such that barbed stents on 28 to 40 mm diameter components contain 12 barbs and barbed stents on 42 mm diameter components contain 14 barbs.

(a)

(b)
Figure 2. Proximal (a) and distal (b) barbed stents.

To facilitate fluoroscopic visualization of the endovascular graft, four gold radiopaque markers are positioned on each end of every main body component. These markers are threaded on the stent wires and placed in a circumferential orientation within 1 mm of the most proximal aspect of the graft material and within 1 mm of the most distal aspect of the graft material, such as shown in Figure 3.

Figure 3. Positioning of gold radiopaque markers.

## Main Body Component Delivery System Description

The Zenith TX2® TAA Endovascular Graft is shipped preloaded onto the H&amp;L-B One-Shot™ Introduction System. It has a sequential deployment method with built-in features to provide continuous control of the endovascular graft throughout the deployment procedure. The H&amp;L-B One-Shot™ Introduction System enables precise positioning before deployment of its loaded component.

Depending on component diameter, the main body components are deployed from either a 20 Fr or 22 Fr H&amp;L-B One-Shot™ Introduction System. All 28 to 34 mm diameter components are deployed using a 20 Fr system, and all 36 to 42 mm diameter components are deployed using a 22 Fr system.

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All proximal main body components are deployed from an H&amp;L-B One-Shot™ Introduction System that utilizes a single trigger-wire release mechanism to secure the endovascular graft onto the delivery system until released by the physician. Additionally, the delivery system is pre-curved to facilitate positioning within the aortic arch. An illustration of the proximal main body component delivery system is shown in Figure 4.

Figure 4. Proximal main body component delivery system.

All distal main body components are deployed from an H&amp;L-B One-Shot™ Introduction System that utilizes a dual trigger-wire release mechanism to secure the endovascular graft onto the delivery system until released by the physician. The delivery system is straight with a pre-curved tip. An illustration of the distal main body component delivery system is shown in Figure 5.

Figure 5. Distal main body component delivery system.

All one-piece main body components are deployed from an H&amp;L-B One-Shot™ Introduction System that utilizes a dual trigger-wire release mechanism to secure the endovascular graft onto the delivery system until released by the physician. Additionally, the delivery system is pre-curved to facilitate positioning within the aortic arch. An illustration of the one-piece main body component delivery system is shown in Figure 6.

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Figure 6. One-piece main body component delivery system.

All delivery systems are compatible with a .035 inch wire guide. For added hemostasis, the Captor™ Hemostatic Valve can be loosened or tightened for the introduction and/or removal of ancillary devices into and out of the sheath. All delivery systems feature the Flexor® introducer sheath, which resist kinking and are hydrophilically coated. Both features of the introducer sheath are intended to enhance trackability from the iliac arteries to the thoracic aorta. The hydrophilic coating, in particular, is intended to minimize access site complications. The Flexor® introducer sheath has a marker at the tip to facilitate visualization during introduction. The trigger-wire release mechanisms of the respective systems work in tandem to deliver sequential, controlled release of the Zenith TX2® TAA Endovascular Graft during deployment. Once the sheath is withdrawn, the proximal end of all main body components remain attached to their respective delivery systems with the use of three trigger-wires, which keep the proximal end of the graft in a ‘tri-fold’ configuration (Figure 7), thus maintaining position of the endovascular graft with respect to target anatomy by allowing for blood flow around the graft.

Figure 7. Configuration of unsheathed proximal end constrained by trigger-wires.

The distal end of each main body component is also attached to the delivery system by trigger-wires. As shown in Figure 8(a), the proximal main body components are attached at the distal end by a single trigger-wire. Figure 8(b) depicts the distal end attachment for the distal main body components and one-piece main body components, which utilize a bottom cap to contain the distal bare stent as well as a trigger-wire to fix the graft to the delivery system bottom cap.

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(a)

(b)
Figure 8. Distal trigger-wire attachments for proximal main body components (a) and distal main body components/one-piece main body components (b).

## Ancillary Component Description

Ancillary devices comprising the Zenith TX2® TAA Endovascular Graft product line consist of proximal main body extensions and distal main body extensions, as shown in Figure 9. Both the proximal and distal main body extensions can be used to provide additional length to their respective portions of the main body components. Additionally, the distal main body extension can be used to increase the overlap length between components.

(a)

(b)
Figure 9. Proximal (a) and distal (b) main body extensions.

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As listed in Table 2, the Zenith TX2® TAA Endovascular Graft proximal and distal main body extensions are available in a variety of standard stock sizes.

Table 2. Zenith TX2® TAA Endovascular Graft main body extensions by diameter

| Graft diameter (mm) | Length of proximal extension (mm) | Length of distal extension (mm) |
| --- | --- | --- |
| 28 | 80 | 80 |
| 30 | 80 | 80 |
| 32 | 80 | 80 |
| 34 | 77 | 77 |
| 36 | 77 | 77 |
| 38 | 77 | 77 |
| 40 | 81 | 81 |
| 42 | 81 | 81 |

The main body extensions are constructed of the same materials as are used to construct the main body components. As with the proximal main body component and one-piece main body component, the covered stent at the proximal end of the proximal main body extension contains barbs for added fixation. The distal main body extension does not contain any barbs. Same as the main body components, the main body extensions contain four gold radiopaque markers at each end of the graft to facilitate fluoroscopic visualization.

## Ancillary Component Delivery System Description

The Zenith TX2® TAA Endovascular Graft proximal and distal main body extensions are also shipped preloaded onto the H&amp;L-B One-Shot™ Introduction System. Same as the main body components, all 28 to 34 mm diameter main body extensions are deployed using a 20 Fr system, and all 36 to 42 mm diameter main body extensions are deployed using a 22 Fr system.

The proximal main body extension uses the same H&amp;L-B One-Shot™ Introduction System design as that used for the proximal main body components, i.e., pre-curved delivery system with a single trigger-wire release mechanism.

All distal main body extensions are deployed from an H&amp;L-B One-Shot™ Introduction System that utilizes a single trigger-wire release mechanism to secure the endovascular graft onto the delivery system until released by the physician. The delivery system is straight with a pre-curved tip. An illustration of the distal main body extension delivery system is shown in Figure 10.

Figure 10. Distal main body extension delivery system.

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As with the main body components, all delivery systems are compatible with a .035 inch wire guide, feature the Captor™ Hemostatic Valve, and incorporate the Flexor® introducer sheath. Additionally, the proximal and distal ends of both proximal and distal main body extensions remain tethered to the delivery in the same fashion as the proximal main body components.

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

The traditional standard of care for treatment of thoracic aortic aneurysms or ulcers is surgical implantation of a synthetic graft within the diseased vessel, use of another commercially-available endovascular graft for the treatment of thoracic aortic aneurysms, and medical management. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

## VII. MARKETING HISTORY

The Zenith TX2® TAA Endovascular Graft with the H&amp;L-B One-Shot™ Introduction System is currently available throughout much of the world following approval by the Therapeutic Goods Administration in 2002 and CE marking in 2004. The Zenith TX2® TAA Endovascular Graft has not been withdrawn from any market for reasons related to safety or effectiveness.

## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Adverse events that may occur and/or require intervention include, but are not limited to:

- Amputation
- Anesthetic complications and subsequent attendant problems (e.g., aspiration)
- Aneurysm enlargement
- Aneurysm rupture and death
- Aortic damage, including perforation, dissection, bleeding, rupture and death
- Aorto-bronchial fistula
- Aorto-esophageal fistula
- Arterial or venous thrombosis and/or pseudoaneurysm
- Arteriovenous fistula
- Bleeding, hematoma, or coagulopathy
- Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis)
- Cardiac complications and subsequent attendant problems (e.g., arrhythmia, tamponade, myocardial infarction, congestive heart failure, hypotension, hypertension)
- Claudication (e.g., buttock, lower limb)
- Compartment Syndrome
- Death
- Edema
- Embolization (micro and macro) with transient or permanent ischemia or infarction
- Endoleak
- Endoprosthesis: improper component placement; incomplete component deployment; component migration and/or separation; suture break; occlusion; infection; stent fracture; graft material wear; dilatation; erosion; puncture; perigraft flow; barb separation and corrosion
- Femoral neuropathy

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- Fever and localized inflammation
- Genitourinary complications and subsequent attendant problems (e.g., ischemia, erosion, fistula, urinary incontinence, hematuria, infection)
- Hepatic failure
- Impotence
- Infection of the aneurysm, device or access site, including abscess formation, transient fever and pain
- Lymphatic complications and subsequent attendant problems (e.g., lymph fistula, lymphocele)
- Local or systemic neurologic complications and subsequent attendant problems (e.g., stroke, transient ischemic attack, paraplegia, paraparesis/spinal cord shock, paralysis)
- Occlusion of device or native vessel
- Pulmonary Embolism
- Pulmonary/respiratory complications and subsequent attendant problems (e.g., pneumonia, respiratory failure, prolonged intubation)
- Renal complications and subsequent attendant problems (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- Surgical conversion to open repair
- Vascular access site complications, including infection, pain, hematoma, pseudoaneurysm, arteriovenous fistula
- Vascular spasm or vascular trauma (e.g., ilio-femoral vessel dissection, bleeding, rupture, death)
- Wound complications and subsequent attendant problems (e.g., dehiscence, infection).

## IX. SUMMARY OF NON-CLINICAL STUDIES

### A. Biocompatibility

Biocompatibility of the Zenith TX2® TAA Endovascular Graft implant was assessed by testing specified in the ISO standard 10993-1 Biological Evaluation of Medical Devices including cytotoxicity, sensitization, skin irritation or intracutaneous reactivity, acute systemic toxicity, pyrogenicity, genotoxicity, and mutagenicity, hemocompatibility (hemolysis, coagulation, and complement activation), subchronic toxicity, and reaction toward implantation (4-week, 12-week, and 16-week muscle implant). Testing for carcinogenicity was considered unnecessary given the significant history of long-term biocompatibility of these implantable materials. Neither reproductive/developmental nor biodegradation testing were suggested by the standard for implantable blood-contacting devices.

Likewise, the biocompatibility of the H&amp;L-B One-Shot™ Introduction System was assessed by testing specified in the ISO standard 10993-1 Biological Evaluation of Medical Devices including cytotoxicity, sensitization, skin irritation or intracutaneous reactivity, acute systemic toxicity, and hemocompatibility.

Testing was performed by an independent laboratory (NAMSA; Northwood, OH). Results of these tests, as listed in Tables 3a and 3b, support the biocompatibility of the Zenith TX2® TAA Endovascular Graft and the H&amp;L-B One-Shot™ Introduction System.

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Table 3a. Summary of Biocompatibility Testing – Zenith TX2® TAA Endovascular Graft

| Test Type | Purpose | Results | Pass/Fail |
| --- | --- | --- | --- |
| Cytotoxicity: ISO Elution Method (1X MEM Extract) | Determine whether extracts would cause cytotoxicity | Extract grade less than 2 on a scale of 0-4 | Passed |
| Sensitization Study in the Guinea Pig (Maximization Method) | Evaluate the potential for delayed dermal contact sensitization | Test article extracts showed no evidence of causing delayed dermal contact sensitization in the guinea pig | Passed |
| Acute Intracutaneous Reactivity Study in the Rabbit (Extracts) | Determine whether extracts would cause local dermal irritant or toxic effects | Test scores were all ≤ 0.1 | Passed |
| Acute Systemic Toxicity Study in the Mouse (Extracts) | Determine whether extracts would cause acute systemic toxicity | No mortality or evidence of systemic toxicity from the extracts was observed | Passed |
| Subchronic Intravenous Toxicity Study in the Rat (14 day, Saline Extract) | Evaluate the potential for an extract to cause systemic toxicity following repeated intravenous injections | No significant evidence of systemic toxicity from the test extract | Passed |
| Genotoxicity: Bacterial Reverse Mutation Study (Extracts) | Evaluate whether extracts would cause mutagenic changes in S. typhimurium and E. coli strains | Spot plate inhibition screen – no inhibition observed; Standard plate incorporation assay – no 2 fold increase in mean number of revertants | Passed |
| Genotoxicity: In Vitro Chromosomal Aberration Study in Mammalian Cells (Extract) | Determine whether the extract would cause genotoxicity in Chinese Hampster ovary cells | Test extracts were concluded to be negative for the induction of structural chromosome aberrations: χ² = 0.0 and 1.5 | Passed |
| Mouse Bone Marrow Micronucleus Study | Determine whether an extract would cause genotoxic changes in chromosomes or the mitotic apparatus of murine polychromatic erythrocytes | No statistically significant dose related increase in the number of micronucleated polychromatic erythrocytes was noted | Passed |
| Muscle Implantation Study in the Rabbit with Histopathology (Surgical Method, 4, 12, and 26 weeks) | Evaluate the potential for a local irritant or toxic response to material implanted in direct contact with muscle tissue | Macroscopic score – non-irritant
Microscopic score – slight to moderate irritant | Acceptable |
| In Vitro Hemolysis Study (Modified ASTM – Extraction Method) | Determine whether extracts would cause hemolysis in vitro | 0.0% hemolysis at 4 hrs | Passed |
| Plasma Recalcification Time Coagulation Study | Determine the potential of the test article to cause an effect on the coagulation cascade | Mild decrease in recalcification time | Passed |
| C3a Complement Activation Assay | Evaluate the potential to activate the complement system | Complement activation was comparable to the biomaterial control | Passed |
| Rabbit Pyrogen Study (Material Mediated) | Determine whether an extract induced a pyrogenic response following intravenous injection in rabbits | No temperature increase of 0.5 °C for any animal | Passed |

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Table 3b. Summary of Biocompatibility Testing – H&amp;L-B One-Shot™ Introduction System

| Test Type | Purpose | Results | Pass/Fail |
| --- | --- | --- | --- |
| Cytotoxicity Study Using the ISO Elution Method (1X MEM Extract)^{†} | Determine whether extracts would cause cytotoxicity | Extract grade less than grade 2 on a scale of 0-4 | Passed |
| Sensitization Study in the Guinea Pig (Maximization Method) | Evaluate the potential for delayed dermal contact sensitization | Test article extracts showed no evidence of causing delayed dermal contact sensitization | Passed |
| Acute Intracutaneous Reactivity Study in the Rabbit (Extracts) | Determine whether extracts would cause local dermal irritant or toxic effects following injections into skin | Test scores were all ≤ 0.5 | Passed |
| Acute Systemic Toxicity Study in the Mouse (Extracts) | Determine whether extracts would cause acute systemic toxicity following injection | No mortality or evidence of systemic toxicity from the extracts was observed | Passed |
| In Vitro Hemolysis Study (Modified ASTM – Extraction Method) | Determine whether the test article would cause hemolysis in vitro | Hemolytic index ≤ 2% for all samples | Passed |

## B. Product Testing

A comprehensive laboratory (in vitro) testing plan for the Zenith TX2® TAA Endovascular Graft and H&amp;L-B One-Shot™ Introduction System was developed to provide an assessment of device deployability, clinical/mechanical function, and integrity. The specific in vitro tests that were considered in assessing the Zenith TX2® TAA Endovascular Graft and H&amp;L-B One-Shot™ Introduction System included tests listed in the testing standard ISO 25539-1, Cardiovascular implants — Endovascular devices — Part 1: Endovascular prostheses. The testing detailed in Table 4 verified the Zenith TX2® TAA Endovascular Graft and H&amp;L-B One-Shot™ Introduction System met the product performance and design specifications. Results obtained from the in vitro testing provided evidence supporting the safety and effectiveness of the Zenith TX2® TAA Endovascular Graft and H&amp;L-B One-Shot™ Introduction System.

Table 4. Summary of Product Testing of the Zenith TX2® TAA Endovascular Graft and H&amp;L-B One-Shot™ Introduction System

| Test | Samples Tested | Specification / Acceptance Criteria | Summary of Test Results |
| --- | --- | --- | --- |
| Profile/Diameter Test | (24) 20 Fr systems
(24) 22 Fr systems | Characterization study | Testing demonstrated the largest outer diameters for 20 Fr and 22 Fr systems were 7.70 mm and 8.68 mm, respectively. |
| Assessment of Hemostasis | (30) Check-Flo® Valves
(30) Captor™ Valves | Significantly less leakage with Captor™ valve compared to established Check-Flo® valve | The established acceptance criterion was met. |
| Simulated Use Models | (24) Proximal components
(24) Distal components | 100% successful operation of each parameter pre-specified as important to proper deployment. | The established acceptance criteria were met. |

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| Test | Samples Tested | Specification / Acceptance Criteria | Summary of Test Results |
| --- | --- | --- | --- |
| Visibility | (24) Proximal components
(24) Distal components | 100% successful visualization of each parameter pre-specified as important to proper deployment. | The established acceptance criteria were met. |
| Force to Deploy | (9) 22 Fr systems | Sheath Withdrawal < 100 N
Trigger Knob Removal < 36 N | The established acceptance criteria were met. |
| Bond Strength | At least 12 samples for each subassembly/bond type | Specified for each subassembly/bond type (minimum bond strength acceptance criteria ranged from >23N to >100N) | The established acceptance criteria were met. |
| Torsional Bond Strength | At least 9 samples for each subassembly/bond type | Minimum bond strength >0.068 N·m | The established acceptance criterion was met. |
| Bending Test | (30) Cannula subassemblies/bonds | Bond must not fail after cannula is bent 90° | The established acceptance criterion was met. |
| Bottom Cap Microscopic Inspection | (12) 22 Fr systems | Free from damage (e.g., pitting/gouging) | The established acceptance criterion was met. |
| Dimensional Verification | (12) Proximal components
(12) Distal components
(24) Tapered components
(12) Proximal extensions
(12) Distal extensions | Mean component length +/- 5% of stated length on package label
Mean component diameter +/- 5% of diameter stated on package label | The established acceptance criteria were met. |
| Water Permeability | (9) Graft material samples with sutures
(24) Graft material samples without sutures | Mean permeability ≤350 ml/cm²/min | The established acceptance criterion was met. |
| Graft Material Mechanical Property Testing | Varies depending upon property | Characterization study | Mean longitudinal tensile strength ranged from 53.8 N/mm to 55.8 N/mm
Mean circumferential tensile strength ranged from 11.51 N/mm to 16.30 N/mm
Mean suture retention strength ranged from 13.6 N to 14.1 N |
| Flex/kink | (36) Proximal components
(24) Tapered components
(36) Proximal component / distal component pairs
(24) Proximal component / proximal extension pairs
(24) Distal component / distal extension pairs | Mean kink radius <35 mm | The established acceptance criterion was met. |

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| Test | Samples Tested | Specification / Acceptance Criteria | Summary of Test Results |
| --- | --- | --- | --- |
| Migration Resistance | 12 each of the barbed z-stent configurations | Mean pull-out force >8.14 N | The established acceptance criterion was met. |
| Pull Test for Modular Components | Multiple overlap conditions for each pair:
(36) Proximal component / distal component pairs
(24) Tapered component / distal component pairs
(24) Proximal component / proximal extension pairs
(24) Distal component / distal extension pairs | Characterization study | Mean separation forces for the conditions and combinations tested ranged from 2.4 N to 37 N. |
| Radial Force | 3 of each z-stent configuration | Varies depending upon z-stent location with respect to graft material (acceptance criteria ranged from ≥0.8 N to ≤13.4 N) | The established acceptance criteria were met. |
| Graft-to-stent Attachment | (9) monofilament
(9) braided – (intermediate knot)
(9) braided – (start of knot) | >0.68 N for monofilament
>6.7 N for braided | The established acceptance criteria were met. |
| Corrosion | (9) barb attachments at each of the following time-equivalent periods: 1, 3, 6, and 12 years
(3) cannula attachments at each of the following time-equivalent periods: 1, 6, and 12 years; and
(2) cannula attachments at the 3 year time-equivalent period | >0.68 N for barb attachment
>0.68 N for cannula attachment | The established acceptance criteria were met. |
| Fatigue and Durability (pulsatile) | (8) Proximal component / distal component pairs | 95% confidence that 95% of stents will not fracture after 10 years of cyclic (pulsatile) radial loading | The established acceptance criterion was met. |
| Fatigue and Durability (longitudinal) | (3) covered stents with barbs
(3) uncovered stents with barbs | Failure of ≤ 4 consecutive barbs at 400 million cycles (10 year time-equivalent) | The established acceptance criterion was met. |
| Stress/strain Analysis (FEA) | Computer analysis of each z-stent | Fatigue factor of safety >1.0 | The established acceptance criterion was met. |
| Tensile Strength | (10) 0.020” stent wire samples
(10) 0.011” barb wire samples
N/A for 0.014”, 0.016”, and 0.018” wires – properties reported by vendor | Characterization study | Mean ultimate tensile strength ranged from 331 to 353 ksi. |
| MRI | (1) Proximal component / distal component pair | Demonstrates no known hazards to patients when subjected to 1.5T and 3.0T magnetic fields | The established acceptance criterion was met, supporting the device is MR Conditional |

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# C. Animal Studies

Table 5 summarizes the results of the definitive animal study.

Table 5. Summary of definitive non-clinical in vivo study

| Animal Study | Number &Type of Animal | Test Article | Methods | Results/Conclusions |
| --- | --- | --- | --- | --- |
| Sub-chronic and chronic study of tubular endoprostheses | 12 bovine animals | Zenith® components and the H&L-B™ Introduction System sized for the animal anatomy | Catheter delivery and functionality were assessed sub-chronically and chronically in 12 animals. Three animals were maintained for 30 days, three were maintained for 90 days and six were maintained for 180 days. | All acceptance criteria were met. 100% successful deployment of the TX2® in the intended position was achieved. 100% of the delivery systems and implants were able to be visualized. Patency was maintained in all devices until their explant at either 30, 90, or 180 days as evidenced by angiography and morphometric analysis. There was a 0% rate of migration in the animal study. Qualitative histopathological evaluation performed by an independent board-certified pathologist demonstrated minimal injury and inflammation |

The Zenith TX2® TAA Endovascular Graft was evaluated in a focused animal study that evaluated the deployment procedure, the ability to visualize the delivery system and the implant in an in vivo setting, the migration resistance of the graft, the patency of the vessel and graft after implantation, animal survival, and histological evaluation of the biological response. This study demonstrates that the delivery system is capable of accessing the arterial vasculature, accurately deploying the Zenith TX2® TAA Endovascular Graft in its intended position, and effectively withdrawing it. The implant was shown to be capable of self-expanding into its deployed position and remaining patent and in position after implantation and throughout follow-up, demonstrating the effectiveness of the design. With the exception of one transient episode of mild fever, there were no adverse events in this study. Histological and pathological analyses demonstrated implantation of the Zenith TX2® TAA Endovascular Graft to be minimally traumatic and non-reactive in this study.

# D. Packaging, Shelf Life, and Sterilization Testing

Sterilization is accomplished with a validated sterilization process using Ethylene Oxide. This process has demonstrated a sterility assurance level of $10^{-6}$. Product and package stability testing of the Zenith TX2® TAA Endovascular Graft was performed and validated for a 3-year shelf life.

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# X. SUMMARY OF CLINICAL STUDIES

## A. Study Design

The STARZ-TX2 Clinical Trial is a non-randomized, controlled, multi-center, study that was conducted to evaluate safety and effectiveness of the Zenith TX2® TAA Endovascular Graft in the elective treatment of patients with descending thoracic aortic aneurysms or ulcers, as compared to open surgical repair. The study consisted of an endovascular treatment group and an open surgical control group. The open surgical control group was comprised of both prospectively enrolled and retrospectively enrolled patients. The same inclusion/exclusion criteria applied to both the endovascular treatment group and open surgical control group, except that patients in the open surgical control group were not required to have anatomy amenable to endovascular repair with the Zenith TX2® TAA Endovascular Graft.

The study was designed to assess two primary and two secondary hypotheses regarding the endovascular treatment group compared to the open surgical control group. The primary hypothesis for safety was non-inferior 30-day survival, and the primary hypothesis for effectiveness was non-inferior 30-day rupture-free survival (i.e., freedom from rupture). The secondary hypotheses were superior clinical utility in the endovascular treatment group and non-inferior 30-day morbidity, expressed as a composite morbidity score including 57 prespecified events. In addition, the study assessed survival, morbidity, and device performance through 12 months, and will continue these assessments at yearly intervals through 5 years.

In addition to covariate analysis, propensity score analysis was used to assess comparability of the groups. The control group was analyzed to justify the use of both retrospectively and prospectively enrolled patients.

FDA requested additional analyses, including the analysis of a composite effectiveness endpoint (freedom from a device event) and separate analyses of patients with aneurysms and patients with ulcers. The separate analyses for aneurysm patients and ulcer patients did not show any findings unique to the specific indications. Data for aneurysm and ulcer patients are presented separately where appropriate.

Patient imaging underwent independent core laboratory analysis. Adverse events, including all patient deaths, were adjudicated by an independent clinical events committee. A data safety monitoring board, comprised of independent physicians and a biostatistician, monitored the safety of the study.

## B. Patient Enrollment and Availability for Follow-up

Forty-two (42) institutions enrolled a total of 160 endovascular treatment patients and 70 (19 prospective and 51 retrospective) open surgical control patients, including 20 institutions that enrolled both endovascular treatment and open surgical control patients, 16 institutions that enrolled only endovascular treatment patients, and 6 institutions that enrolled only open surgical control patients. Although nearly 75% of the open surgical control patients were enrolled retrospectively, the endovascular treatment group and open surgical control groups proved to be largely contemporaneous; the earliest open surgical control patient was treated less than one year prior to investigational device exemption application (IDE) initiation, and 81% of the open surgical control patients were treated on or after the date on which the first endovascular patient was treated.

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The study follow-up schedule for patients enrolled in the endovascular treatment group consisted of radiographic (CT scan and X-ray) and clinical assessments at pre-discharge, 30 days, 6 months, 12 months, and yearly thereafter through 5 years. The study follow-up schedule for patients enrolled in the open surgical control group consisted of radiographic (CT scan) and clinical assessments at pre-discharge (or 30 days) and 12 months, with an interim telephone contact at 6 months. Patient availability for study follow-up through 12 months as of September 12, 2007 is summarized in Table 6. Available data from on-going 24-month follow-up are also provided.

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Table 6. Follow-up Availability

| Timepoint | Eligible for follow-up (n) | Subjects with submitted data | | | Adequate imaging to assess parameter per core lab | | | | Events occurring before next visit | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Clinical % (n) | CT % (n) | X-ray % (n) | Size increase % (n) | Endoleak % (n) | Migration % (n) | Fracture % (n) | Death (n) | Conversion (n) | LTF (n) | Not due for next visit (n) |
| Endovascular | | | | | | | | | | | | |
| Pre-discharge | 158^{a} | 100% (158) | 94% (149) | 98% (154) | n/a | 85% (135) | n/a | 96% (152) | 3 | 0 | 0 | 0 |
| 30-day | 155 | 94% (146) | 92% (142) | 87% (134) | 78% (121) | 81% (126) | 72% (111) | 88% (136) | 5 | 0 | 5 | 0 |
| 6-month | 145 | 90% (130) | 89% (129) | 85% (123) | 81% (117) | 79% (114) | 77% (112) | 88% (127) | 5 | 0 | 5 | 0 |
| 12-month | 135 | 94% (127) | 92% (124) | 85% (115) | 83% (112) | 76% (103) | 79% (107) | 91% (123) | 10 | 0 | 4 | 25 |
| 24-month | 96 | 70% (67) | 61% (59) | 63% (60) | 58% (56) | 59% (57) | 57% (55) | 66% (63) | n/a | n/a | n/a | n/a |
| Open Surgical | | | | | | | | | | | | |
| Pre-discharge / 30-day | 70 | 100% (70) | n/a | n/a | n/a | n/a | n/a | n/a | 8 | n/a | 0 | 0 |
| 6-month | 62 | 60% (37) | n/a | n/a | n/a | n/a | n/a | n/a | 2 | n/a | 0 | 0 |
| 12-month | 60 | 65% (39) | n/a | n/a | n/a | n/a | n/a | n/a | 0 | n/a | 1 | 29^{b} |
| 24-month | 30 | 27% (8) | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a |

n/a – not applicable
a Device insertion was not achieved in two patients.
b IRB/EC-approved follow-up was limited to 12 months at 11 sites that enrolled open surgical control patients (n=24); 5 patients not due for next visit.

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# C. Demographic and Baseline Medical History Data

Table 7 compares the demographics and patient characteristics between the endovascular treatment group and open surgical control group.

Table 7. Demographics and Patient Characteristics

| Demographic/characteristic | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| Age (years) | 72.4 ± 9.6 (160) | 67.6 ± 11.6 (70) | 4.8 (1.9, 7.7) | <0.01 |
| Gender | | | | 0.09 |
| Male | 72% (115/160) | 60% (42/70) | 12 (-1.6, 25) | |
| Female | 28% (45/160) | 40% (28/70) | -12 (-25, 1.6) | |
| Ethnicity^{3} | | | | 0.82 |
| Asian | 2.5% (4/159) | 1.4% (1/70) | 1.1 (-2.6, 4.8) | |
| Black/African American | 12% (19/159) | 8.6% (6/70) | 3.4 (-4.9, 12) | |
| Hispanic/Latino | 3.8% (6/159) | 4.3% (3/70) | -0.5 (-6.1, 5.1) | |
| White/Caucasian | 80% (127/159) | 86% (60/70) | -5.8 (-16, 4.5) | |
| Other | 1.9% (3/159) | 0.0% (0/70) | 1.9 (n/a) | |
| Height (in) | 67.5 ± 4.0 (154) | 66.9 ± 3.6 (69) | 0.6 (-0.5, 1.8) | 0.26 |
| Weight (lbs) | 177 ± 35 (158) | 167 ± 32 (70) | 11 (1.1, 20) | 0.02 |
| Body mass index | 27.2 ± 4.9 (153) | 25.9 ± 3.7 (69) | 1.3 (0.1, 2.5) | 0.03 |

n/a – not applicable
1 Confidence intervals are unadjusted for multiplicity and are based on the difference in means for continuous variables utilizing the T-distribution and the difference in percentages for categorical variables utilizing the Z-distribution.
2 $p$ values are based on Fisher’s exact test for categorical variables and t-test for continuous variables and are unadjusted for multiplicity.
3 Ethnicity reported as unknown in one patient.

Table 8 compares the medical history between the endovascular treatment group and open surgical control group.

Table 8. Medical History

| Medical history | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| Cardiovascular | | | | |
| Myocardial infarction | 22.2% (35/158) | 25% (17/68) | -2.9 (-15, 9.3) | 0.73 |
| Congestive heart failure | 12.5% (20/160) | 11.6% (8/69) | 0.9 (-8.2, 10) | >0.99 |
| Coronary artery disease | 43.7% (69/158) | 42% (29/69) | 1.6 (-12, 16) | 0.88 |
| Arrhythmia | 30.2% (48/159) | 18.8% (13/69) | 11 (-0.3, 23) | 0.10 |
| Vascular | | | | |
| Thromboembolic event | 10.1% (16/159) | 8.7% (6/69) | 1.4 (-6.8, 9.5) | >0.99 |
| Peripheral vascular disease | 24.4% (39/160) | 26.1% (18/69) | -1.7 (-14, 11) | 0.86 |
| Family history of aneurysm | 17.1% (24/140) | 20.4% (11/54) | -3.2 (-16, 9.2) | 0.67 |
| Hypertension | 89.4% (143/160) | 82.9% (58/70) | 6.5 (-3.5, 17) | 0.19 |
| Thoracic surgery/trauma | 10% (16/160) | 25.7% (18/70) | -16 (-27, -4.5) | <0.01 |
| Diagnosed AAA | 31.3% (50/160) | 22.9% (16/70) | 8.4 (-3.8, 21) | 0.20 |
| Repaired AAA | 19.4% (31/160) | 14.3% (10/70) | 5.1 (-5.1, 15) | 0.47 |
| Chronic obstructive pulmonary disease | 44.7% (71/159) | 42.9% (30/70) | 1.8 (-12, 16) | 0.88 |
| Renal failure requiring dialysis | 3.1% (5/160) | 2.9% (2/70) | 0.3 (-4.5, 5.0) | >0.99 |
| Diabetes | 18.8% (30/160) | 14.3% (10/70) | 4.5 (-5.7, 15) | 0.45 |

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| Medical history | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| Sepsis | 1.9% (3/156) | 1.5% (1/68) | 0.5 (-3.1, 4.0) | >0.99 |
| Neurologic | | | | |
| Cerebrovascular accident | 15.0% (24/160) | 14.7% (10/68) | 0.3 (-9.8, 10) | >0.99 |
| Carotid endarterectomy | 5.7% (9/159) | 2.9% (2/70) | 2.8 (-2.5, 8.1) | 0.51 |
| Gastrointestinal disease | 40.5% (64/158) | 30% (21/70) | 11 (-2.7, 24) | 0.14 |
| Liver disease | 6.3% (10/160) | 4.3% (3/70) | 2.0 (-4.1, 8.0) | 0.75 |
| Cancer | 25.2% (40/159) | 15.7% (11/70) | 9.4 (-1.4, 20) | 0.12 |
| Excessive alcohol use | 3.2% (5/157) | 0.0% (0/67) | 3.2 (n/a) | 0.32 |
| Tobacco use | | | | 0.19 |
| Current smoker | 22.4% (35/156) | 17.6% (12/68) | 4.8 (-6.4, 16) | |
| Quit smoking | 66% (103/156) | 61.8% (42/68) | 4.3 (-9.5, 18) | |
| Never smoked | 11.5% (18/156) | 20.6% (14/68) | -9.1 (-20, 1.8) | |
| Access site | | | | |
| Previous surgery | 10.1% (16/159) | 1.4% (1/69) | 8.6 (3.2, 14) | 0.02 |
| Previous radiation | 0.0% (0/159) | 0.0% (0/69) | 0 (n/a) | n/a |
| Allergies | 43.8% (70/160) | 40% (28/70) | 3.8 (-10, 18) | 0.66 |

n/a – not applicable
1 Confidence intervals are unadjusted for multiplicity and are based on the difference in means for continuous variables utilizing the T-distribution and the difference in percentages for categorical variables utilizing the Z-distribution.
2 p values are based on Fisher’s exact test for categorical variables and t-test for continuous variables and are unadjusted for multiplicity.

Table 9 compares the results from patient risk assessment between the endovascular treatment group and open surgical control group.

Table 9. Patient Risk Assessment

| Item^{1} | Endovascular | Open Surgical | Diff (95% CI)^{2} | p value^{3} |
| --- | --- | --- | --- | --- |
| ASA classification | | | | < 0.01 |
| Healthy patient (1) | 8.8% (14/160) | 7.1% (5/70) | 1.6 (-5.9, 9.1) | |
| Mild systemic disease (2) | 50% (80/160) | 41.4% (29/70) | 8.6 (-5.3, 22) | |
| Severe systemic disease (3) | 36.9% (59/160) | 28.6% (20/70) | 8.3 (-4.7, 21) | |
| Incapacitating systemic disease (4) | 4.4% (7/160) | 22.9% (16/70) | -18 (-29, -8.2) | |
| Moribund patient (5) | 0% (0/160) | 0% (0/70) | 0 (n/a) | |
| Total SVS-ISCVS risk score | 6.4 ± 3.0 (159) | 5.4 ± 3.5 (68) | 1.0 (0.1, 1.9) | 0.03 |

n/a – not applicable
1 The SVS-ISCVS scoring system may be considered more objective than the ASA classification; however, direct comparisons of key patient characteristics are provided in Tables 7 and 8.
2 Confidence intervals are unadjusted for multiplicity and are based on the difference in means for continuous variables utilizing the T-distribution and the difference in percentages for categorical variables utilizing the Z-distribution.
3 p values are based on Fisher’s exact test for categorical variables and t-test for continuous variables and are unadjusted for multiplicity.

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Covariate and propensity score analyses supported the appropriateness of comparisons between study groups. A representative plot of propensity score quartiles is presented in Figure 11.

Figure 11. Quartiles of the Propensity Scores for the Two Study Groups

## D. Baseline Anatomical Data

Table 10 compares the morphology type, location, and size between the endovascular treatment group and open surgical control group based on the results from core lab analysis.

Table 10. Morphology Type, Location and Size

| Item | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| Morphology type | | | | 0.40 |
| Aneurysm | 85.6% (137/160) | 90.0% (63/70)^{4} | -4.4 (-13,4.5) | |
| Ulcer^{5} | 14.4% (23/160) | 10.0% (7/70) | 4.4 (-4.5, 13) | |
| Morphology location^{5} | | | | 0.02 |
| Proximal | 22.5% (36/160) | 36.9% (24/65) | -14 (-28, -1.0) | |
| Middle | 55.0% (88/160) | 52.3% (34/65) | 2.7 (-12, 17) | |
| Distal | 22.5% (36/160) | 10.8% (7/65) | 12 (1.8, 22) | |
| Aneurysm size | | | | |
| Major axis diameter (mm) | 60.8 ± 10.7 (137) | 63.0 ± 10.8 (53) | -2.2 (-5.6, 1.2) | 0.20 |
| Minor axis diameter (mm) | 50.8 ± 10.5 (137) | 57.5 ± 9.3 (49) | -6.7 (-10, -3.3) | <0.01 |
| Length (mm) | 151 ± 71.3 (132) | 158.6 ± 81.0 (46) | -7.9 (-33, 17) | 0.53 |
| Ulcer size | | | | |
| Major axis diameter (mm) | 28.7 ± 9.7 (22) | 29.0 ± 7.3 (7) | -0.2 (-8.4, 8.0) | 0.95 |
| Minor axis diameter (mm) | 20.9 ± 7.7 (23) | 21.1 ± 9.8 (7) | -0.1 (-7.4, 7.1) | 0.96 |
| Depth (mm) | 14.4 ± 4.7 (22) | 20.7 ± 7.8 (7) | -6.3 (-11, -1.4) | 0.01 |

n/a – not applicable
1 Confidence intervals are unadjusted for multiplicity and are based on the difference in means for continuous variables utilizing the T-distribution and the difference in percentages for categorical variables utilizing the Z-distribution.
2 p values are based on Fisher’s exact test for categorical variables and t-test for continuous variables and are unadjusted for multiplicity.
3 Ulcers ≥10 mm in depth and 20 mm in diameter were eligible for study inclusion.

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4 As determined by site assessment for 7 open surgical patients without available imaging for core lab analysis.
5 Primary location described as proximal one-third (i.e., arch to T6), middle one-third (i.e., T6-T8), or distal one-third (i.e., T9-L2).

## E. Devices Implanted

Endovascular patients were treated using either a two-piece main body (proximal main body component in combination with a distal main body component) or a one-piece main body (either a proximal main body component only or a one-piece main body component). Table 11 reports the percent of endovascular patients treated with a two-piece main body and the percent of patients treated with a one-piece main body. Also reported is the total number of components deployed during the initial implant procedure for patients treated with a two-piece main body and for patients treated with a one-piece main body in order to account for ancillary component use.

Table 11. Main Body System Type and Total Number of Components

| Type | % (n) | Total number of components (main body and ancillary) | | | |
| --- | --- | --- | --- | --- | --- |
| | | 1 | 2 | 3 | 4 |
| Two-piece | 59.5% (94/158) | n/a | 88.3% (83/94) | 11.7% (11/94) | 0% (0/94) |
| One-piece | 40.5% (64/158) | 90.6% (58/64)¹ | 7.8% (5/64) | 1.6% (1/64) | 0% (0/64) |

¹ One patient received a proximal extension as the principal endograft.

Table 12 reports the number of components (main body components and main body extensions) used during the initial implant procedure, by diameter.

Table 12. Graft Diameters Implanted during Initial Procedure

| Diameter (mm) | Non-tapered proximal main body component¹ (n) | Tapered proximal main body component¹ (n) | Distal main body component¹ (n) | One-piece main body component (n) | Proximal extension (n) | Distal extension (n) |
| --- | --- | --- | --- | --- | --- | --- |
| 28 | 4 | n/a | 2 | 0 | 0 | 1 |
| 30 | 8 | n/a | 2 | 2 | 1 | 0 |
| 32 | 13 | 2 | 7 | 0 | 1 | 1 |
| 34 | 22 | 1 | 14 | 1 | 2 | 2 |
| 36 | 19 | 3 | 17 | 0 | 3 | 1 |
| 38 | 22 | 7 | 22 | 0 | 0 | 0 |
| 40 | 29 | 5 | 20 | 0 | 0 | 4 |
| 42 | 12 | 7 | 10 | 0 | 2 | 1 |

¹ Multiple length increments available for each diameter.

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# F. Safety Results

## Survival

The primary safety hypothesis was based on 30-day survival, which was non-inferior ($p&lt;0.01$) in the endovascular treatment group compared to the open surgical control group (98.1% vs. 94.3%). As illustrated by Figure 12 and presented in Table 13, 365-day survival from all-cause mortality was 91.6% in the endovascular treatment group and 85.5% in the open surgical control group. Survival from all-cause mortality at 730 days is 79.8% in the endovascular treatment group and 85.5% in the open surgical control group, with follow-up on-going.

Survival from aneurysm-related mortality (i.e., death occurring within 30 days of the initial implant procedure or a secondary intervention, or any death adjudicated to be aneurysm-related by the independent clinical events committee) through 365 days was 94.2% in the endovascular treatment group and 88.2% in the open surgical control group, as illustrated by Figure 13 and presented in Table 14. Survival from aneurysm-related mortality at 730 days is 92.9% in the endovascular treatment group and 88.2% in the open surgical control group, with follow-up on-going.

Figure 12. Survival from All-Cause Mortality through 730 Days

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Table 13. Kaplan-Meier All-cause Mortality Survival Estimates

| Arm | Days | Kaplan-Meier Estimate | Standard Error | Cumulative Events | Cumulative Censored | Patients Remaining |
| --- | --- | --- | --- | --- | --- | --- |
| Endovascular | 0 | 1.000 | 0.0000 | 0 | 0 | 160 |
| | 30 | 0.981 | 0.0107 | 3 | 1 | 156 |
| | 365 | 0.916 | 0.0223 | 13 | 28 | 119 |
| | 730 | 0.798 | 0.0387 | 24 | 78 | 58 |
| Open Surgical | 0 | 1.000 | 0.0000 | 0 | 0 | 70 |
| | 30 | 0.943 | 0.0277 | 4 | 0 | 66 |
| | 365 | 0.855 | 0.0423 | 10 | 7 | 53 |
| | 730 | 0.855 | 0.0423 | 10 | 45 | 15 |

Figure 13. Survival from Aneurysm-Related Mortality through 730 Days

Table 14. Kaplan-Meier TAA-related Mortality Survival Estimates

| Arm | Days | Kaplan-Meier Estimate | Standard Error | Cumulative Events | Cumulative Censored | Patients Remaining |
| --- | --- | --- | --- | --- | --- | --- |
| Endovascular | 0 | 1.000 | 0.0000 | 0 | 0 | 160 |
| | 30 | 0.981 | 0.0107 | 3 | 1 | 156 |
| | 365 | 0.942 | 0.0187 | 9 | 32 | 119 |
| | 730 | 0.929 | 0.0229 | 10 | 92 | 58 |
| Open Surgical | 0 | 1.000 | 0.0000 | 0 | 0 | 70 |
| | 30 | 0.943 | 0.0277 | 4 | 0 | 66 |
| | 365 | 0.882 | 0.0391 | 8 | 9 | 53 |
| | 730 | 0.882 | 0.0391 | 8 | 47 | 15 |

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# Morbidity

A secondary hypothesis was based on 30-day morbidity with endovascular treatment, expressed as a composite morbidity score (mean number of events per patient), which, as shown in Table 15, was non-inferior in the endovascular treatment group compared to the open surgical control group ($p&lt;0.01$).

Table 15. Total Morbidity Score within 0-30 Days

| Item | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| 30-day morbidity score (events^{3} per patient) | 1.3 ± 3.0 (160) | 2.9 ± 3.6 (70) | -1.6 (-2.5, -0.7) | <0.01 |

1 Confidence interval on the difference in means utilized the T-distribution and is unadjusted for multiplicity.
2 $p$ value is based on test for non-inferiority and is unadjusted for multiplicity.
3 Pre-specified events that were considered for the morbidity score included: cardiovascular events (Q-wave myocardial infarction; non-Q-wave myocardial infarction; congestive heart failure; arrhythmia requiring intervention or new treatment; cardiac ischemia requiring intervention; inotropic support; refractory hypertension [systolic BP of &gt;160 despite receiving medication]; cardiac event involving arrest, resuscitation, or balloon pump); pulmonary events (ventilation &gt;24 hours; re-intubation; pneumonia requiring antibiotics; supplemental oxygen at time of discharge; chronic obstructive pulmonary disease; pleural effusion requiring treatment; pulmonary edema requiring treatment; pneumothorax; hemothorax; pulmonary event requiring tracheostomy or chest tube); renal events (urinary tract infection requiring antibiotic treatment; renal failure requiring dialysis; renal insufficiency [serum creatinine rise &gt;30% from baseline resulting in a persistent value &gt;2.0 mg/dL]; permanent dialysis, hemofiltration, or kidney transplant in patient with normal pre-procedure creatinine); gastrointestinal events (bowel/mesenteric ischemia; gastrointestinal infection requiring treatment; gastrointestinal bleeding requiring treatment; paralytic ileus &gt;4 days; bowel resection); neurological events (stroke; TIA/RIND; carotid artery embolization/occlusion; paraparesis/spinal cord shock; paraplegia); vascular events (pulmonary embolism; pulmonary embolism involving hemodynamic instability or surgery; vascular injury; aneurysm leak/rupture; aneurysm or vessel leak requiring re-operation; pseudoaneurysm requiring surgical repair; increase in aneurysm size &gt;0.5 cm relative to first post-procedure measurement; aorto-esophageal fistula; aorto-bronchial fistula; aorto-enteric fistula; arterial thrombosis; embolization resulting in tissue loss or requiring intervention; amputation involving more than the toes; deep vein thrombosis; deep vein thrombosis requiring surgical or lytic therapy; hematoma requiring surgical repair; hematoma requiring receipt of blood products; coagulopathy requiring surgery; post-procedure transfusion); wound events (wound infection requiring antibiotic treatment; incisional hernia; lymph fistula; wound breakdown requiring debridement; seroma requiring treatment; wound complication requiring return to the operating room).

The 30-day and 365-day Kaplan-Meier estimates for freedom from any one of the following pre-specified events (representing a subset of the events listed in Table 15) are illustrated in Figure 14 and reported in Table 16, along with the estimates for each individual event: Q-wave MI; cardiac event involving arrest, resuscitation, or balloon pump; ventilation &gt;72 hours; re-intubation; pulmonary event requiring a tracheostomy or chest tube; permanent dialysis, hemofiltration, or transplant [in a patient with normal pre-procedure creatinine]; bowel resection; stroke; paraplegia; pulmonary embolism involving hemodynamic instability or requiring surgery; aneurysm or vessel leak requiring re-operation; amputation involving more than the toes; deep vein thrombosis requiring surgery or lytic therapy; coagulopathy requiring surgery; and wound complication requiring return to OR.

The 30-day estimate for freedom from any of the events from this pre-specified subset was 90.6% in the endovascular treatment group and 67.1% in the open surgical control group. The 365-day estimate for freedom from these events was 87.3% in the endovascular treatment group and 64.3% in the open surgical control group. The 730 day estimate for freedom from any of the events from the pre-specified subset is 83.6% in the endovascular treatment group and 64.3% in the open surgical control group, with follow-up on-going.

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Figure 14. Freedom from Pre-specified Subset of Morbid Events through 730 Days

Table 16. Summary of Kaplan-Meier Estimates for Freedom from Pre-specified Subset of Morbid Events*

| Event | Parameter | 30 days | | 365 days | | 730 days | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Endo | Open | Endo | Open | Endo | Open |
| Any event | Number at risk^{1} | 160 | 70 | 144 | 47 | 109 | 39 |
| | Cumulative events | 15 | 23 | 20 | 25 | 23 | 25 |
| | Cumulative | 1 | 0 | 31 | 6 | 84 | 35 |
| | censored^{2} | 0.91 | 0.67 | 0.87 | 0.64 | 0.84 | 0.64 |
| | Kaplan-Meier est.^{3} | 0.02 | 0.06 | 0.03 | 0.06 | 0.3 | 0.06 |
| | Standard error | | | | | | |
| Q-wave MI | Number at risk^{1} | 160 | 70 | 156 | 66 | 119 | 53 |
| | Cumulative events | 0 | 0 | 0 | 0 | 0 | 0 |
| | Cumulative | 4 | 4 | 41 | 17 | 102 | 55 |
| | censored^{2} | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| | Kaplan-Meier est.^{3} | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| | Standard error | | | | | | |
| Cardiac event involving arrest, resuscitation or balloon pump | Number at risk^{1} | 160 | 70 | 153 | 66 | 118 | 53 |
| | Cumulative events | 4 | 1 | 4 | 2 | 5 | 2 |
| | Cumulative | 3 | 3 | 38 | 15 | 98 | 53 |
| | censored^{2} | 0.98 | 0.99 | 0.98 | 0.97 | 0.96 | 0.97 |
| | Kaplan-Meier est.^{3} | 0.01 | 0.01 | 0.01 | 0.02 | 0.02 | 0.02 |
| | Standard error | | | | | | |
| Vcnt. >72 hours | Number at risk^{1} | 160 | 70 | 155 | 57 | 119 | 46 |
| | Cumulative events | 1 | 11 | 1 | 11 | 1 | 11 |
| | Cumulative | 4 | 2 | 40 | 13 | 101 | 47 |
| | censored^{2} | 0.99 | 0.84 | 0.99 | 0.84 | 0.99 | 0.84 |

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P070016: FDA Summary of Safety and Effectiveness Data
page 26
37

| Event | Parameter | 30 days | | 365 days | | 730 days | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Endo | Open | Endo | Open | Endo | Open |
| | Kaplan-Meier est.³
Standard error | 0.01 | 0.04 | 0.01 | 0.04 | 0.01 | 0.04 |
| Re-intubation | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
8
2
0.95
0.02 | 70
10
3
0.86
0.04 | 150
8
35
0.95
0.02 | 57
11
12
0.84
0.04 | 117
9
94
0.94
0.02 | 47
11
47
0.84
0.04 |
| Pulmonary
event requiring
tracheostomy or
chest tube | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
2
4
0.99
0.01 | 70
9
2
0.87
0.04 | 154
4
38
0.97
0.01 | 59
12
9
0.82
0.05 | 118
5
97
0.96
0.02 | 49
12
45
0.82
0.05 |
| Permanent
dialysis or
transplant | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
0
4
1.00
0.00 | 70
0
4
1.00
0.00 | 156
0
41
1.00
0.00 | 66
0
17
1.00
0.00 | 119
0
102
1.00
0.00 | 53
0
55
1.00
0.00 |
| Bowel resection | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
3
4
0.98
0.01 | 70
1
4
0.99
0.01 | 153
5
38
0.97
0.01 | 65
1
17
0.99
0.01 | 117
5
98
0.97
0.01 | 52
1
54
0.99
0.01 |
| Stroke | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
4
3
0.98
0.01 | 70
6
1
0.91
0.03 | 153
5
38
0.97
0.01 | 63
7
13
0.90
0.04 | 117
6
98
0.95
0.02 | 50
7
48
0.90
0.04 |
| Paraplegia | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
2
3
0.99
0.01 | 70
4
3
0.94
0.03 | 155
2
39
0.99
0.01 | 63
4
13
0.94
0.03 | 119
2
100
0.99
0.01 | 53
4
51
0.94
0.03 |
| PE involving
hemodynamic
instability or
surgery | Number at risk¹
Cumulative events
Cumulative
censored²
Kaplan-Meier est.³
Standard error | 160
0
4
1.00
0.00 | 70
0
4
1.00
0.00 | 156
0
41
1.00
0.00 | 66
0
17
1.00
0.00 | 119
0
102
1.00
0.00 | 53
0
55
1.00
0.00 |
| Aneurysm or
vessel leak
requiring
re-operation | Number at risk¹
Cumulative events
Cumulative
censored² | 160
0
4
1.00 | 70
1
4
0.99 | 156
0
41
1.00 | 65
1
17
0.99 | 119
0
102
1.00 | 52
1
54
0.99 |

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| Event | Parameter | 30 days | | 365 days | | 730 days | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Endo | Open | Endo | Open | Endo | Open |
| | Kaplan-Meier est.³
Standard error | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 | 0.01 |
| Amputation involving more than toes | Number at risk¹ | 160 | 70 | 156 | 66 | 119 | 53 |
| | Cumulative events | 0 | 0 | 0 | 1 | 0 | 1 |
| | Cumulative censored² | 4 | 4 | 41 | 16 | 102 | 54 |
| | Kaplan-Meier est.³
Standard error | 1.00 | 1.00 | 1.00 | 0.98 | 1.00 | 0.98 |
| | | 0.00 | 0.00 | 0.00 | 0.02 | 0.00 | 0.02 |
| Deep vein thrombosis requiring surgery or lytic therapy | Number at risk¹ | 160 | 70 | 156 | 66 | 119 | 53 |
| | Cumulative events | 0 | 0 | 1 | 0 | 1 | 0 |
| | Cumulative censored² | 4 | 4 | 40 | 17 | 101 | 55 |
| | Kaplan-Meier est.³
Standard error | 1.00 | 1.00 | 0.99 | 1.00 | 0.99 | 1.00 |
| | | 0.00 | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 |
| Coagulopathy requiring surgery | Number at risk¹ | 160 | 70 | 156 | 65 | 119 | 52 |
| | Cumulative events | 0 | 1 | 0 | 1 | 0 | 1 |
| | Cumulative censored² | 4 | 4 | 41 | 17 | 102 | 55 |
| | Kaplan-Meier est.³
Standard error | 1.00 | 0.99 | 1.00 | 0.99 | 1.00 | 0.99 |
| | | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 | 0.01 |
| Wound complication requiring return to OR | Number at risk¹ | 160 | 70 | 156 | 66 | 117 | 53 |
| | Cumulative events | 0 | 0 | 2 | 0 | 2 | 0 |
| | Cumulative censored² | 4 | 4 | 41 | 17 | 100 | 55 |
| | Kaplan-Meier est.³
Standard error | 1.00 | 1.00 | 0.99 | 1.00 | 0.99 | 1.00 |
| | | 0.00 | 0.00 | 0.01 | 0.00 | 0.01 | 0.00 |

*Subset of events pre-selected from list in Table 15 prior to start of the study by the physician steering committee.
¹ Number of patients at risk at the beginning of the interval
² Total censored patients up to and including the specific interval
³ Made at end of interval

## G. Effectiveness Results

### Freedom from Rupture

The primary effectiveness hypothesis was based on 30-day rupture-free survival (i.e., freedom from rupture), which was non-inferior (p&lt;0.01) in the endovascular treatment group compared to the open surgical control group (100% vs. 100%). Because there were no ruptures in either group, the planned analysis (Blackwelder) could not be performed, and an alternate analysis (exact non-inferiority test) was necessary to generate the p value. Freedom from rupture was 100% in both groups through 365 days post-procedure. Freedom from rupture is 100% in both groups through 730 days post-procedure, with follow-up on-going.

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# Freedom from Device Events

The results from Kaplan-Meier analysis for freedom from any of the following device events are illustrated in Figure 15 and presented in Table 17: technical failure; loss of patency; rupture; secondary intervention; conversion; stent fracture; Type I or III endoleak; or migration. Freedom from any device event was 94.9% at 30 days and 90.1% at 365 days. Freedom from any device event at 730 days is 89.1%, with follow-up on-going.

Figure 15. Freedom from Device Events

Table 17. Kaplan-Meier Estimate for Freedom from Device Events

| Days | Kaplan-Meier Estimate | Standard Error | Lower 95% Confidence Limit | Upper 95% Confidence Limit | Cumulative Events | Cumulative Censored | Patients Remaining |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 30 | 0.949 | 0.0176 | 0.914 | 0.983 | 8 | 14 | 138 |
| 365 | 0.901 | 0.0254 | 0.851 | 0.951 | 14 | 55 | 91 |
| 730 | 0.891 | 0.0271 | n/a | n/a | 15 | 105 | 40 |

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# Change in Size

Table 18 reports the percent of patients with an increase (&gt;5 mm), decrease (&gt;5 mm), or no change (≤5 mm) in aneurysm diameter or ulcer depth at each follow-up timepoint subsequent to pre-discharge (baseline) based on the results from core lab analysis. In total, 9 patients (7 aneurysm, 2 ulcer) experienced an increase in size within 12 months, with no new cases of growth identified at the 24-month follow-up, which remains on-going.

Table 18. Percent of Endovascular Treatment Patients with an Increase, Decrease, or No Change in Aneurysm/Ulcer Size Based on Core Lab Analysis

| Timepoint | Combined % (n) | Aneurysm % (n) | Ulcer % (n) |
| --- | --- | --- | --- |
| 30-day | | | |
| Increase (>5 mm) | 0.8% (1/121)^{1} | 1.0% (1/105) | 0% (0/16) |
| Decrease (>5 mm) | 6.6% (8/121) | 5.7% (6/105) | 12.5% (2/16) |
| No change (≤5 mm) | 92.6% (112/121) | 93.3% (98/105) | 87.5% (14/16) |
| 6-month | | | |
| Increase (>5 mm) | 3.4% (4/117)^{2} | 3.1% (3/98) | 5.3% (1/19) |
| Decrease (>5 mm) | 33.3% (39/117) | 33.7% (33/98) | 31.6% (6/19) |
| No change (≤5 mm) | 63.2% (74/117) | 63.3% (62/98) | 63.2% (12/19) |
| 12-month | | | |
| Increase (>5 mm) | 7.1% (8/112)^{3} | 7.2% (7/97) | 6.7% (1/15) |
| Decrease (>5 mm) | 48.2% (54/112) | 50.5% (49/97) | 33.3% (5/15) |
| No change (≤5 mm) | 44.6% (50/112) | 42.3% (41/97) | 60% (9/15) |
| 24-month | | | |
| Increase (>5 mm) | 1.8% (1/56)^{4} | 0% (0/49) | 14.3% (1/7) |
| Decrease (>5 mm) | 53.6% (30/56) | 57.1% (28/49) | 28.6% (2/7) |
| No change (≤5 mm) | 44.6% (25/56) | 42.9% (21/49) | 57.1% (4/7) |

1 This aneurysm patient is also counted as an increase at 6 and 12 months, was without detectable endoleak or evidence of graft infection, and was found to have a decrease in size at the 24-month follow-up (without secondary intervention).

2 Includes three new patients (2 aneurysm, 1 ulcer). Both aneurysm patients are also counted as an increase at 12 months. One aneurysm patient had no detectable endoleak or evidence of graft infection and was found to have no change in size at 24 months (without secondary intervention). The other aneurysm patient also had no detectable endoleak or evidence of graft infection, but had an aortic neck diameter at the location of actual graft placement that does not meet the recommended oversizing of at least 10% as well as an inverted funnel-shaped proximal neck and a funnel-shaped distal neck. This same patient also underwent two secondary interventions for aneurysm growth and expired within 30 days of the later secondary intervention (after removal of ventilator support following a stroke). The ulcer patient, who was noted to have a Type II endoleak at pre-discharge, was found to have no change in size at 12 months and 24 months (without secondary intervention).

3 Includes five new patients (4 aneurysm, 1 ulcer). In three of the aneurysm patients, each of which are awaiting further follow-up, there was no detectable endoleak or evidence of graft infection, but the aortic neck diameter at the location of actual graft placement does not meet the recommended oversizing of at least 10%, and there was also an inverted funnel-shaped proximal aortic neck and a funnel-shaped distal aortic neck. The other new aneurysm patient was noted to have a distal Type I endoleak, underwent two secondary interventions, and is awaiting further follow-up. In the new ulcer patient, who also exhibited growth at 24 months, there was no detectable endoleak or evidence of graft infection, but the aortic neck diameter at the location of actual graft placement does not meet the recommended oversizing of at least 10%.

4 This ulcer patient was first noted to have growth at 12 months, as discussed in note '3'.

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# Endoleak

Table 19 reports the percent of patients with endoleak (by type) at each follow-up timepoint based on the results from core lab analysis.

Table 19. Percent of Endovascular Treatment Patients with Endoleak (New and Persistent) Based on Core Lab Analysis

| Type | Timepoint | | | | |
| --- | --- | --- | --- | --- | --- |
| | Pre-discharge | 30-day | 6-month | 12-month | 24-month |
| Any (new only) | 12.6% (17/135) | 1.6% (2/126)^{a,b} | 0% (0/114) | 1.0% (1/103)^{c} | 0% (0/57) |
| Any (new and persistent) | 12.6% (17/135) | 4.8% (6/126) | 2.6% (3/114) | 3.9% (4/103) | 1.8% (1/57) |
| Multiple | 0% (0/135) | 0% (0/126) | 0% (0/114) | 0% (0/103) | 0% (0/57) |
| Proximal Type I | 0% (0/135) | 0% (0/126) | 0% (0/114) | 0% (0/103) | 0% (0/57) |
| Distal Type I | 0.7% (1/135) | 0.8% (1/126) | 0.9% (1/114) | 0% (0/103) | 0% (0/57) |
| Type IIa | 1.5% (2/135) | 0.8% (1/126)^{a} | 0% (0/114) | 0% (0/103) | 0% (0/57) |
| Type IIb | 5.9% (8/135) | 2.4% (3/126) | 1.8% (2/114) | 1.9% (2/103) | 1.8% (1/57) |
| Type III | 1.5% (2/135) | 0.8% (1/126)^{b} | 0% (0/114) | 1.0% (1/103)^{b} | 0% (0/57) |
| Type IV | 1.5% (2/135) | 0% (0/126) | 0% (0/114) | 0% (0/103) | 0% (0/57) |
| Unknown | 1.5% (2/135) | 0% (0/126) | 0% (0/114) | 1.0% (1/103)^{c} | 0% (0/57) |

aType IIa in one patient who did not undergo endoleak assessment at pre-discharge.
bNon-junctional Type III endoleak in one patient that was not evident at pre-discharge or 6-months, is not associated with aneurysm growth, has not required reintervention, and is awaiting further follow-up.
cUnknown Type endoleak, but in a patient who previously had a Type IIb endoleak at pre-discharge and no endoleak at 30 days or 6 months.

# Migration

Table 20 reports the percent of patients with core lab-identified and CEC-confirmed migration (&gt;10 mm) at each follow-up timepoint (date of first occurrence). There have been no patients with clinically significant migration (i.e., migration resulting in endoleak, growth, or requiring secondary intervention).

Table 20. Percent of Patients with CEC-Confirmed Migration (Date of First Occurrence)

| Item | 30-day | 6-month | 12-month | 24-month |
| --- | --- | --- | --- | --- |
| Migration (>10 mm) | 0% (0/111) | 0.9% (1/112)* | 1.9% (2/106)* | 1.8% (1/55)* |

*Includes two cases of caudal migration of the proximal graft and two cases of cranial migration of the distal graft. All patients have an aortic neck diameter at the location of actual graft placement that does not meet the recommended oversizing of at least 10%. Additionally, three also have placement of the pertinent barbed stent in a neck that is either an acutely angled segment or in an area of thrombus.

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# Device Integrity

Table 21 reports the percent of patients with device integrity findings at each follow-up timepoint based on the results from core lab analysis. One patient was noted to have a device integrity finding: entanglement of neighboring struts of the distal bare stent, which has not been associated with migration, endoleak, or the need for secondary intervention.

Table 21. Percent of Endovascular Treatment Patients with Device Integrity Findings by Core Lab

| Finding | Timepoint | | | | |
| --- | --- | --- | --- | --- | --- |
| | Pre-discharge | 30-day | 6-month | 12-month | 24-month |
| Stent fracture | 0% (0/152) | 0% (0/136) | 0% (0/127) | 0% (0/123) | 0% (0/63) |
| Barb separation | 0% (0/152) | 0% (0/136) | 0% (0/127) | 0% (0/123) | 0% (0/63) |
| Stent-to-graft separation | 0% (0/152) | 0% (0/136) | 0% (0/127) | 0% (0/123) | 0% (0/63) |
| Component separation | 0% (0/152) | 0% (0/136) | 0% (0/127) | 0% (0/123) | 0% (0/63) |
| Other | 0.7% (1/152)^{1} | 0% (0/136) | 0% (0/127) | 0.8% (1/123)^{1} | 0% (0/63) |

1 Entanglement of neighboring struts of distal bare stent; same patient at pre-discharge and 12 months; finding not associated with migration, endoleak, or the need for secondary intervention.

# Kink, Compression, and Patency

Table 22 reports the results from core lab assessment for endovascular graft kink (evidence of reduced graft diameter or narrowing of lumen in the presence of acute aortic angulation), compression (evidence of reduced graft diameter or narrowing of the lumen in the absence of aortic angulation), and loss of patency. Three patients were noted to have a kink at one or more timepoints and two patients were noted to have compression at one or more timepoints. None required a secondary intervention.

Table 22. Endovascular Graft Kink, Compression, and Loss of Patency by Core Lab Analysis

| Finding | Timepoint | | | | |
| --- | --- | --- | --- | --- | --- |
| | Pre-discharge | 30-day | 6-month | 12-month | 24-month |
| Kink | 1.9% (3/155) | 0.7% (1/139) | 0.8% (1/127) | 1.6% (2/123) | 0% (0/63) |
| Compression | 1.4% (2/142)^{a} | 0.8% (1/124)^{a} | 0.9% (1/117)^{a} | 0.9% (1/108)^{a} | 2.1% (1/47)^{a} |
| Loss of patency | 0% (0/138) | 0% (0/126) | 0% (0/114) | 0% (0/103) | 0% (0/57) |

a Concentric constriction of one mid-body stent of the device not associated with tortuosity or flow limitation with expansion of the stents above and below the compressed segment -- this should be distinguished from the phenomena of endovascular graft collapse described in literature for other (non-Zenith) grafts.

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# Re-interventions

Seven (4.4%) endovascular treatment patients (6 aneurysm, 1 ulcer) and four (5.7%) open surgical control patients (2 aneurysm, 2 ulcer) underwent at least one re-intervention within 365 days subsequent to the initial aneurysm/ulcer repair procedure. The reasons for re-intervention are reported in Table 23. There have been no conversions to open surgical repair in the endovascular treatment group.

Table 23. Reasons for Secondary Intervention

| Reason | Endovascular | | | Open Surgical | | |
| --- | --- | --- | --- | --- | --- | --- |
| | 0-30 days | 31-365 days | 366-730 days | 0-30 days | 31-365 days | 366-730 days |
| Aneurysm rupture | 0 | 0 | 0 | 0 | 0 | 0 |
| Component separation | 0 | 0 | 0 | n/a | n/a | 0 |
| Symptoms | 0 | 0 | 0 | 1^{f} | 0 | 0 |
| Occlusion | 0 | 0 | 0 | 0 | 0 | 0 |
| Device stenosis | 0 | 0 | 0 | n/a | n/a | n/a |
| Device kink | 0 | 0 | 0 | n/a | n/a | n/a |
| Device migration | 0 | 0 | 0 | n/a | n/a | n/a |
| Infection | 0 | 0 | 0 | 0 | 0 | 0 |
| Endoleak | 3 | 2^{a} | 0 | | | |
| Proximal Type I | 1^{b} | 0 | 0 | | | |
| Distal Type I | 1^{c} | 2^{a} | 0 | | | |
| Type IIa | 0 | 0 | 0 | n/a | n/a | n/a |
| Type IIb | 0 | 0 | 0 | | | |
| Type III | 1^{d} | 0 | 0 | | | |
| Type IV | 0 | 0 | 0 | | | |
| Unknown | 0 | 0 | 0 | | | |
| Other | 0 | 3^{e} | 1^{i} | 3^{f,g} | 1^{h} | 0 |

n/a – not applicable
a One aneurysm patient with two interventions for a distal Type I endoleak – bare stent placement and stent placement/coil embolization/distal extension placement.
b Aneurysm patient treated with proximal main body extension placement.
c Aneurysm patient treated with molding balloon angioplasty and distal extension placement
d Aneurysm patient underwent angiogram to rule out endoleak.
e Includes one ulcer patient with iliac artery occlusion, treated with femoral-femoral bypass; one aneurysm patient with growth, treated with distal extension placement in overlap and distal end of graft; and one aneurysm patient who developed a pseudoaneurysm at follow-up, treated with proximal extension placement.
f One ulcer patient with multiple reasons of symptoms and other (continued bleeding), treated with re-exploration and hemostatic sealing agents.
g Includes one aneurysm patient with intrapleural hematoma, treated with exploratory thoracotomy and evacuation; one ulcer patient with bleeding and tamponade, treated with intercostal vessel ligation.
h One aneurysm patient who developed an aorto-esophageal fistula at follow-up, treated with custom endograft placement.
i One aneurysm patient with growth, treated with placement of additional endovascular graft components, who also underwent secondary intervention for growth at 31-365 days, as discussed in note ‘e’.

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# H. Clinical Utility

Another secondary hypothesis was superior clinical utility in the endovascular treatment group compared to the open surgical control group. All clinical utility measures were superior in the endovascular treatment group compared to the open surgical control group ($p&lt;0.01$), as reported in Table 24.

Table 24. Clinical Utility Measures

| Measure | Endovascular | Open Surgical | Diff (95% CI)^{1} | p value^{2} |
| --- | --- | --- | --- | --- |
| Number of blood transfusions | 0.3 ± 1.0 (160) | 1.7 ± 1.9 (70) | -1.4 (-1.9, -0.9) | <0.01 |
| Duration of intubation (hrs) | 2.8 ± 4.6 (147) | 53.1 ± 85.4 (66) | -50 (-71, -29) | <0.01 |
| Duration of ICU stay (days) | 2.2 ± 6.2 (153) | 9.4 ± 16.9 (70) | -7.2 (-11, -3.1) | <0.01 |
| Days to ambulation | 1.6 ± 2.5 (148) | 5.5 ± 5.6 (63) | -3.9 (-5.4, -2.5) | <0.01 |
| Days to resumption of oral fluid intake | 0.7 ± 1.9 (155) | 4.0 ± 5.6 (60) | -3.3 (-4.8, -1.8) | <0.01 |
| Days to resumption of regular diet | 1.9 ± 2.7 (156) | 5.2 ± 3.7 (58) | -3.3 (-4.4, -2.3) | <0.01 |
| Days to resumption of bowel function | 2.9 ± 2.3 (94) | 5.5 ± 3.3 (61) | -2.6 (-3.6, -1.7) | <0.01 |
| Days to hospital discharge | 5.0 ± 8.6 (159) | 16.1 ± 18.7 (70) | -11 (-16, -6.4) | <0.01 |

¹ Confidence interval on difference in means utilized the T-distribution and is unadjusted for multiplicity.
² $p$ values are unadjusted for multiplicity.

# I. Evaluation of Gender Bias

The distribution in gender was not significantly different between study groups, yet, in order to more carefully evaluate possible gender-based differences in outcome of treatment with the Zenith TX2® TAA Endovascular Graft, a gender subset analysis was performed on outcomes related to safety and effectiveness. Specifically, the percent of patients with severe morbid events within 30 days and the Kaplan-Meier freedom from device events within 12 months were evaluated.

The analysis showed that the percent of female patients experiencing severe morbid events within 30 days was 2.2% (1/45) in the endovascular treatment group and 28.6% (8/28) in the open surgical control group. Kaplan-Meier freedom from device events at 12 months was 86% for female patients in the endovascular treatment group. The results, as described above, show that the benefits of TAA therapy, in terms of freedom from severe morbidity and freedom from device events, in the female patient subset are consistent with the results of the overall pivotal analysis; additional analyses of the performance of this device in female patients will be conducted as part of the a post-approval study.

# J. Evaluation of Ulcer Patients

Separate analyses were provided for ulcer patients treated during the primary study. A total of 12 institutions enrolled 23 endovascular treatment patients with descending thoracic ulcers. At 12 months, 22 of these patients were eligible for follow-up. Twenty-one (95%) had clinical follow-up and 20 (91%) had CT imaging.

The 30-day and 365-day all-cause mortality survival estimates were 100% for the ulcer patients. The 30-day mean total morbidity score was $0.6 \pm 1.0$ for ulcer patients, as compared to $1.3 \pm 3.0$ for the ulcer and aneurysm patients combined. No ulcer patients experienced a

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severe morbid event within 30 days of treatment. The 365-day survival estimate of freedom from severe morbid events was 91.1% in this group.

No device integrity issues, migrations, ruptures or conversions were reported for ulcer patients through 730 days. There were no reports of device kink, compression, or loss of patency. Two (2) patients experienced an increase in ulcer depth &gt;5 mm at one or more timepoints; one patient appears to have stabilized. Two patients had an endoleak at pre-discharge; both had resolution without intervention by the time of the 30-day follow-up. One patient had a reported Type III endoleak at the 12-month follow-up; however, the source of the leak is unknown as this patient had a one-piece device placed with no additional components.

The results from the separate analyses show that the results for ul…