ZENITH ALPHA THORACIC ENDOVASCULAR GRAFT

P140016 · Cook Medical Incorporated · MIH · Sep 15, 2015 · Cardiovascular

Device Facts

• Record ID: P140016
• Device Name: ZENITH ALPHA THORACIC ENDOVASCULAR GRAFT
• Applicant: Cook Medical Incorporated
• Product Code: MIH · Cardiovascular
• Decision Date: Sep 15, 2015
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Zenith Alpha™ Thoracic Endovascular Graft is indicated for the endovascular treatment of patients with isolated lesions of the descending thoracic aorta (not including dissections) having vascular anatomy suitable for endovascular repair, including: - Iliac/femoral anatomy that is suitable for access with the required introduction systems, - Nonaneurysmal aortic segments (fixation sites) proximal and distal to the thoracic lesion: - with a length of at least 20 mm, and - with a diameter measured outer wall to outer wall of no greater than 42 mm and no less than 15 mm.

Device Story

Zenith Alpha™ Thoracic Endovascular Graft is a modular, self-expanding endovascular prosthesis used for treating descending thoracic aortic lesions (aneurysms, ulcers, BTAI). The system consists of proximal and distal components, an introduction system, and ancillary components. Components are constructed of nitinol stents sewn to polyester graft material with polyester/polypropylene sutures. The device is delivered endoluminally via femoral/iliac artery access using a pre-loaded introduction system (16-20 Fr). Upon deployment, the graft self-expands, with radial force providing fixation and sealing at the proximal and distal zones. Gold radiopaque markers facilitate visualization. The device is used by vascular surgeons in clinical settings. It provides a minimally invasive alternative to open surgical repair, potentially reducing recovery time and procedural morbidity. Clinical decision-making relies on pre-procedure imaging to ensure anatomical suitability. The device is designed to accommodate various aortic configurations through modular overlap.

Clinical Evidence

Evidence includes two prospective, nonrandomized, single-arm pivotal studies. Aneurysm/ulcer study (n=110) met primary safety (30-day freedom from MAE 96.4% vs 80.6% goal) and effectiveness (12-month device success 92.7% vs 80.7% goal) endpoints. BTAI study (n=50) showed 100% technical success and 96% device success at 30 days. Long-term follow-up (up to 5 years) and European post-market survey data support safety and performance. Adverse events included stroke, respiratory failure, and secondary interventions for endoleaks/migration.

Technological Characteristics

Modular endovascular graft; self-expanding nitinol stents; polyester graft material; braided polyester and monofilament polypropylene sutures; gold radiopaque markers. Delivery via 16-20 Fr hydrophilic-coated introduction system with rotational handle and trigger-wire release mechanism. Sterilized via ethylene oxide (SAL 10^-6). 3-year shelf life. Complies with ISO 10993-1 (biocompatibility) and ISO 25539-1 (endovascular prostheses).

Indications for Use

Indicated for endovascular treatment of isolated lesions of the descending thoracic aorta (excluding dissections) in patients with suitable vascular anatomy. Suitable anatomy requires iliac/femoral access and proximal/distal nonaneurysmal fixation sites (length ≥20 mm; diameter 15–42 mm). Contraindicated in patients with conditions threatening graft infection or known sensitivities to polyester, polypropylene, nitinol, or gold.

Reference Devices

• Zenith® TX2® TAA Endovascular Graft (P070016)
• Zenith Flex® AAA Endovascular Graft (P020018)
• Zilver® Vascular Stent (P050017)

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Endovascular Graft

Device Trade Name: Zenith Alpha™ Thoracic Endovascular Graft

Device Procode: MIH

Applicant’s Name and Address: Cook Incorporated
750 Daniels Way
P.O. Box 489
Bloomington, IN 47402-0489
USA

Date of Panel Recommendation: None

Premarket Approval (PMA)
Application Number: P140016

Date of FDA’s Notice of Approval: September 15, 2015

Priority Review: No

## II. INDICATIONS FOR USE

The Zenith Alpha™ Thoracic Endovascular Graft is indicated for the endovascular treatment of patients with isolated lesions of the descending thoracic aorta (not including dissections) having vascular anatomy suitable for endovascular repair, including:

- Iliac/femoral anatomy that is suitable for access with the required introduction systems,
- Nonaneurysmal aortic segments (fixation sites) proximal and distal to the thoracic lesion:
- with a length of at least 20 mm, and

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- with a diameter measured outer wall to outer wall of no greater than 42 mm and no less than 15 mm.

## III. CONTRAINDICATIONS

The Zenith Alpha™ Thoracic Endovascular Graft is contraindicated in:

- Patients who have a condition that threatens to infect the endovascular graft.
- Patients with known sensitivities or allergies to polyester, polypropylene, nitinol, or gold.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions are contained in the labeling (Instructions for Use).

## V. DEVICE DESCRIPTION

The Zenith Alpha™ Thoracic Endovascular Graft System is comprised of four parts:

- Proximal Component
- Distal Component
- Introduction System
- Ancillary Component

The Zenith Alpha™ Thoracic Endovascular Graft is intended to be delivered endoluminally via access through the femoral or iliac artery to the site of the lesion using the Introduction System. The endovascular graft is inserted and constrained by the introduction system's outer sheath. The pre-loaded endovascular graft is advanced to the lesion location over a guidewire. Upon deployment, the endovascular graft self-expands due to the superelastic properties of the nitinol stents. The proximal and distal ends of the proximal and distal components of the endovascular graft are intended to conform to the shape and size of the proximal and distal seal zones of the targeted lesion due to the radial force of the stents. The Zenith Alpha™ Thoracic Endovascular Graft is a modular device that accommodates the use of additional components depending on the configuration of the anatomy, where single or multiple components may be required to achieve sufficient coverage of the lesion. To provide the added coverage often needed

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during the treatment of thoracic aortic aneurysms (TAA), the distal component is overlapped with the proximal component. An ancillary component can also be used to extend graft coverage distally or extend the length of overlap between the proximal and distal components. To treat more focal aortic lesions, as are often found in blunt thoracic aortic injury (BTAI) patients and patients with ulcers, a proximal component can be used alone.

All endovascular graft components are constructed of self-expanding nitinol stents sewn to polyester graft material with braided polyester and monofilament polypropylene sutures.

# A. Proximal Component

The proximal component uses an uncovered stent at the proximal end and an internal sealing stent with fixation barbs that protrude through the graft material. All other stents are external to the graft material, except for the distal stent, which is located internal to the graft material. The proximal components (Figure 1) are available in a number of diameters and lengths and can be either nontapered or tapered. If additional graft coverage is needed proximal to the first proximal component placed, a second proximal component can be used.

Gold radiopaque markers are sewn to the luminal side of the fabric (at the location of each seal stent apex) to facilitate visualization of the edge of the graft material. The markers are located at the proximal and distal edges of the graft material; each edge contains either 5 markers (18-30 mm diameter components), 6 markers (32-38 mm diameter components), 7 markers (40-42 mm diameter components), or 8 markers (44-46 mm diameter components), corresponding to the number of stent apices.

Figure 1. Zenith Alpha™ Thoracic Endovascular Graft proximal components

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The available sizes of proximal components (nontapered and tapered) are listed in Table 1.

Table 1. Zenith Alpha™ Thoracic Endovascular Graft proximal component available sizes

| Intended Aortic Vessel Diameter (mm) | Graft Diameter (mm) | Overall Length of Nontapered Proximal Component (mm) | Overall Length of Tapered Proximal Component (mm)a | Introducer Sheath (Fr) | Introducer Sheath Outer Diameter (OD) (mm) |
| --- | --- | --- | --- | --- | --- |
| 15 | 18 | 105/127 | N/A | 16 | 6.0 |
| 16 | 18 | 105/127 | N/A | 16 | 6.0 |
| 17 | 20 | 105/127 | N/A | 16 | 6.0 |
| 18 | 22 | 105/127 | 105 | 16 | 6.0 |
| 19 | 22 | 105/127 | 105 | 16 | 6.0 |
| 20 | 24 | 105/127 | N/A | 16 | 6.0 |
| 21 | 24 | 105/127 | N/A | 16 | 6.0 |
| 22 | 26 | 105/149 | 105 | 16 | 6.0 |
| 23 | 26 | 105/149 | 105 | 16 | 6.0 |
| 24 | 28 | 109/132/155/201 | N/A | 16 | 6.0 |
| 25 | 28 | 109/132/155/201 | N/A | 16 | 6.0 |
| 26 | 30 | 109/132/155/201 | 108 | 16 | 6.0 |
| 27 | 30 | 109/132/155/201 | 108 | 16 | 6.0 |
| 28 | 32 | 109/132/155/201 | 178/201 | 18 | 7.1 |
| 29 | 32 | 109/132/155/201 | 178/201 | 18 | 7.1 |
| 30 | 34 | 113/137/161/209 | 161/209 | 18 | 7.1 |
| 31 | 36 | 113/137/161/209 | 161/209 | 18 | 7.1 |
| 32 | 36 | 113/137/161/209 | 161/209 | 18 | 7.1 |
| 33 | 38 | 117/142/167/217 | 167/217 | 18 | 7.1 |
| 34 | 38 | 117/142/167/217 | 167/217 | 18 | 7.1 |
| 35 | 40 | 117/142/167/217 | 167/217 | 20 | 7.7 |
| 36 | 40 | 117/142/167/217 | 167/217 | 20 | 7.7 |
| 37 | 42 | 121/147/173/225 | 173/225 | 20 | 7.7 |
| 38 | 42 | 121/147/173/225 | 173/225 | 20 | 7.7 |
| 39 | 44 | 125/152/179/233 | 179/233 | 20 | 7.7 |
| 40 | 46 | 125/152/179/233 | 179/233 | 20 | 7.7 |
| 41 | 46 | 125/152/179/233 | 179/233 | 20 | 7.7 |
| 42 | 46 | 125/152/179/233 | 179/233 | 20 | 7.7 |

For tapered components, the proximal diameter is listed; the distal diameter is $4\mathrm{mm}$ smaller than the proximal diameter.

# B. Distal Component

The distal component (Figure 2) is overlapped within the proximal component by at least three stents; therefore, the three most proximal stents of the distal component are located internal to the graft material to promote sealing between the proximal component and the distal component. The proximal edge of the graft is fashioned to the shape of the stent to further promote sealing. All other stents are located external to the graft material, except

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for the second most distal stent, which is located internal to the graft material, and the distal stent, which is an uncovered stent with barbs for fixation.

Gold radiopaque markers are sewn to the luminal side of the fabric (at the location of each seal stent apex) to facilitate visualization of the edge of the graft material. The markers are located at the proximal and distal edges of the graft material; each edge contains either 5 markers (28-30 mm diameter components), 6 markers (32-38 mm diameter components), 7 markers (40-42 mm diameter components), or 8 markers (44-46 mm diameter components), corresponding to the number of stent apices.

Figure 2. Zenith Alpha™ Thoracic Endovascular Graft distal component

The available sizes of distal components are listed in Table 2.

Table 2. Zenith Alpha™ Thoracic Endovascular Graft distal component available sizes

| Intended Aortic Vessel Diameter (mm) | Graft Diameter (mm) | Overall Length of Distal Component (mm) | Introducer Sheath (Fr) | Introducer Sheath Outer Diameter (OD) (mm) |
| --- | --- | --- | --- | --- |
| 24 | 28 | 160/229 | 16 | 6.0 |
| 25 | 28 | 160/229 | 16 | 6.0 |
| 26 | 30 | 160/229 | 16 | 6.0 |
| 27 | 30 | 160/229 | 16 | 6.0 |
| 28 | 32 | 160/229 | 18 | 7.1 |
| 29 | 32 | 160/229 | 18 | 7.1 |
| 30 | 34 | 142/190 | 18 | 7.1 |
| 31 | 36 | 142/190 | 18 | 7.1 |
| 32 | 36 | 142/190 | 18 | 7.1 |
| 33 | 38 | 147/197 | 18 | 7.1 |
| 34 | 38 | 147/197 | 18 | 7.1 |
| 35 | 40 | 147/197 | 20 | 7.7 |
| 36 | 40 | 147/197 | 20 | 7.7 |
| 37 | 42 | 152/204 | 20 | 7.7 |
| 38 | 42 | 152/204 | 20 | 7.7 |
| 39 | 44 | 157/211 | 20 | 7.7 |

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| Intended Aortic Vessel Diameter (mm) | Graft Diameter (mm) | Overall Length of Distal Component (mm) | Introducer Sheath (Fr) | Introducer Sheath Outer Diameter (OD) (mm) |
| --- | --- | --- | --- | --- |
| 40 | 46 | 157/211 | 20 | 7.7 |
| 41 | 46 | 157/211 | 20 | 7.7 |
| 42 | 46 | 157/211 | 20 | 7.7 |

# C. Introduction System

The Introduction System consists of a single use, disposable catheter with a rotational handle to provide the user with controlled deployment. Each Zenith Alpha™ Thoracic Endovascular Graft component is shipped preloaded onto a 16 Fr, 18 Fr, or 20 Fr Introduction System (Figure 3). All introduction systems use a rotation handle to retract the trigger-wires/release-wires and release the endovascular graft. The introduction system has a hemostatic valve and a sheath that is hydrophilically coated.

The proximal component introduction system is precurved and contains a single trigger-wire/release-wire mechanism, which attaches the proximal and distal ends of the endovascular graft to the introduction system following withdrawal of the sheath, until released by the operator. The distal component introduction system has a straight inner cannula that contains a dual trigger-wire/release-wire mechanism, which constrains the distal bare stent in a bottom cap and attaches the proximal end of the stent-graft to the introduction system, until released by the operator.

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Figure 3. Zenith Alpha™ Thoracic Endovascular Graft Introduction Systems

# D. Ancillary Component

The Zenith Alpha™ Thoracic Endovascular Graft product line includes an ancillary component that may be used to extend graft coverage distally or extend the length of overlap between components (such as between a proximal and distal component if the minimum recommended overlap length of 3 stents is not initially achieved). Note that the proximal component may be used to extend graft coverage proximally (see Section A

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for details). The ancillary component (Figure 4) is constructed of the same materials as the proximal and distal components and is deployed from a 16 Fr, 18 Fr, or 20 Fr introduction system that has a single trigger-wire/release-wire mechanism (Figure 5).

Figure 4. Zenith Alpha™ Thoracic Endovascular Graft Ancillary component

Figure 5. Zenith Alpha™ Thoracic Endovascular Graft Distal Extension Introduction System

The available sizes of distal extensions are listed in Table 3.

Table 3. Zenith Alpha™ Thoracic Endovascular Graft distal extension available sizes

| Intended Aortic Vessel Diameter (mm) | Graft Diameter (mm) | Overall Lengths of Distal Extension (mm) | Introducer Sheath (Fr) | Introducer Sheath Outer Diameter (OD) (mm) |
| --- | --- | --- | --- | --- |
| 15 | 18 | 104/148 | 16 | 6.0 |
| 16 | 18 | 104/148 | 16 | 6.0 |
| 17 | 20 | 104/148 | 16 | 6.0 |
| 18 | 22 | 104/148 | 16 | 6.0 |
| 19 | 22 | 104/148 | 16 | 6.0 |
| 20 | 24 | 104/148 | 16 | 6.0 |
| 21 | 24 | 104/148 | 16 | 6.0 |
| 22 | 26 | 104/148 | 16 | 6.0 |
| 23 | 26 | 104/148 | 16 | 6.0 |
| 24 | 28 | 108/154 | 16 | 6.0 |
| 25 | 28 | 108/154 | 16 | 6.0 |
| 26 | 30 | 108/154 | 16 | 6.0 |
| 27 | 30 | 108/154 | 16 | 6.0 |
| 28 | 32 | 108/154 | 18 | 7.1 |
| 29 | 32 | 108/154 | 18 | 7.1 |
| 30 | 34 | 112/160 | 18 | 7.1 |
| 31 | 36 | 112/160 | 18 | 7.1 |
| 32 | 36 | 112/160 | 18 | 7.1 |
| 33 | 38 | 91/141 | 18 | 7.1 |

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| Intended Aortic Vessel Diameter (mm) | Graft Diameter (mm) | Overall Lengths of Distal Extension (mm) | Introducer Sheath (Fr) | Introducer Sheath Outer Diameter (OD) (mm) |
| --- | --- | --- | --- | --- |
| 34 | 38 | 91/141 | 18 | 7.1 |
| 35 | 40 | 91/141 | 20 | 7.7 |
| 36 | 40 | 91/141 | 20 | 7.7 |
| 37 | 42 | 94/146 | 20 | 7.7 |
| 38 | 42 | 94/146 | 20 | 7.7 |
| 39 | 44 | 97/151 | 20 | 7.7 |
| 40 | 46 | 97/151 | 20 | 7.7 |
| 41 | 46 | 97/151 | 20 | 7.7 |
| 42 | 46 | 97/151 | 20 | 7.7 |

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several alternatives for treatment of isolated lesions of the descending thoracic aorta (not including dissections): endovascular repair with another endovascular graft system, open surgical repair involving implantation of a synthetic graft within the aneurysmal vessel, and medical management. Each alternative procedure has its own advantages and disadvantages. The physician should fully discuss these alternatives with the patient to select the method that best fits the patient's expectations and lifestyle.

## VII. MARKETING HISTORY

The Zenith Alpha™ Thoracic Endovascular Graft has been available outside of the United States since August 2013, when it received CE Mark for the European Union; the device is also approved in Canada (2014), Colombia (2014), Argentina (2015), Thailand (2013), Hong Kong (2014), Israel (2014), and Serbia (2014). The Zenith Alpha™ Thoracic Endovascular Graft has not been withdrawn from any market due to reasons related to safety or effectiveness.

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# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (i.e., complications) associated with the use of the device.

- Amputation
- Anesthetic complications and subsequent related problems (e.g., aspiration)
- Aneurysm enlargement
- Aneurysm rupture and death
- Aortic damage, including perforation, dissection (e.g., retrograde dissection), bleeding, rupture, and death
- Aortic valve damage
- Aortobronchial fistula
- Aortoesophageal 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 related problems (e.g., arrhythmia, tamponade, myocardial infarction, congestive heart failure, hypotension, hypertension, angina)
- Claudication (e.g., buttock, lower limb)
- Death
- Edema
- Embolization (micro and macro) with transient or permanent ischemia or infarction
- Endoleak

- Endoprosthesis: improper component placement; incomplete and/or difficult component insertion, deployment (e.g., access failure), or removal; catheter breakage; component migration and/or separation; suture break; occlusion; infection; stent fracture; graft material wear; component twist/kink; dilatation; erosion; puncture; perigraft flow; barb separation; corrosion
- Excessive or inappropriate radiation exposure
- Femoral neuropathy
- Fever, localized inflammation, and/or post-implant syndrome
- Genitourinary complications and subsequent related problems (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection)
- Hepatic failure
- Impotence
- Infection of the aneurysm, device, or access site, including abscess formation, transient fever, and pain
- Lymphatic complications and subsequent related problems (e.g., lymph fistula, lymphocele)
- Neurologic local or systemic complications and subsequent related problems (e.g., stroke, transient ischemic attack, paraplegia, paraparesis/spinal cord shock, paralysis, paresthesia, peripheral nerve injury, blindness, change in mental status)

- Occlusion of coronary arteries
- Pulmonary embolism
- Pulmonary/respiratory complications and subsequent attendant problems (e.g., pneumonia, respiratory failure, prolonged intubation, atelectasis)
- Renal complications and subsequent related problems (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- Surgical conversion to open repair
- Vascular access site complications (e.g., infection, pain, hematoma, pseudoaneurysm, arteriovenous fistula)
- Vascular spasm or vascular trauma (e.g., iliofemoral vessel dissection, intramural hematoma, bleeding, rupture, death)
- Vessel damage, (e.g., arterial stenosis)
- Wound complications and subsequent related problems (e.g., dehiscence, infection, tissue necrosis)

For the specific adverse events that occurred in the clinical studies, please see Section X below.

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# IX. SUMMARY OF PRECLINICAL STUDIES

The following preclinical studies were performed on the Zenith Alpha™ Thoracic Endovascular Graft and Introduction System:

A. Biocompatibility
B. Sterilization, Packaging, and Shelf Life
C. Nonclinical Bench Testing
D. Animal Studies

The introduction system (not the endovascular graft components) was modified following completion of enrollment in the pivotal clinical studies described in Section X.

Specifically, the introduction system was modified to include the rotation handle and Captor® sleeve shown in Figure 3. Accordingly, additional preclinical studies were conducted to evaluate performance of the modified introduction system, as noted below. The modified introduction system was also assessed in a subset of patients treated during continued access (refer to Section XI, Part B) as well as during a European post-market survey (refer to Section XI, Part C).

# A. Biocompatibility

Biocompatibility of all materials (polyester graft material, nitinol stents, polyester sutures, polypropylene sutures, and gold radiopaque markers) used in the Zenith Alpha™ Thoracic Endovascular Graft implant was assessed by testing specified in ISO 10993-1, Biological Evaluation of Medical Devices, including cytotoxicity, sensitization, skin irritation or intracutaneous reactivity, acute systemic toxicity, pyrogenicity, genotoxicity and mutagenicity, hemocompatibility, subchronic toxicity, and reaction toward implantation, as summarized in Table 4. Testing for carcinogenicity was considered unnecessary due to the similarities of the materials used in the Zenith Alpha™ Thoracic Endovascular Graft to other implantable devices with a significant history of long-term biocompatibility.

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Table 4. Summary of biocompatibility testing for the materials used in the Zenith Alpha™ Thoracic Endovascular Graft

| Test Type | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Cytotoxicity: ISO Elution Method (1X MEM Extract) | Determine whether extracts would cause cytotoxicity | The device/material shall not show more than 50% lysis (grade 2, mild cell lysis) | Pass |
| ISO Maximization Sensitization Study (Extract) | Evaluate the potential for delayed dermal contact for sensitization | The device/material shall show no evidence of causing delayed dermal contact sensitization | Pass |
| ISO Intracutaneous Study (Extract) | Determine whether extracts would cause local dermal irritant or toxic effects | The device/material shall not exhibit significant irritation | Pass |
| USP and ISO Acute Systemic Toxicity (Extracts) | Determine whether extracts would cause acute systemic toxicity | The device/material shall show no evidence of significant systemic toxicity | Pass |
| Subchronic Systemic Toxicity Study (in rats following subcutaneous implant) | Determine whether extracts would cause subchronic systemic toxicity | The device/material shall show no evidence of significant systemic toxicity | Pass |
| ISO Muscle Implantation Study | Evaluate the potential for irritation or toxicity in muscle tissue | The device/material shall not cause significant irritation | Pass |
| Genotoxicity: Bacterial Reverse Mutation Study (Extract) | Evaluate whether extracts cause mutagenic changes in bacteria | The device/material shall not cause mutagenic changes | Pass |
| Genotoxicity: In Vitro Chromosomal Aberration Study in Mammalian Cells (Extract) | Determine whether extracts would show genotoxicity in mammalian cells | The device/material shall show no evidence of genotoxicity in mammalian cells | Pass |
| Genotoxicity: Mouse Peripheral Blood Micronucleus Study (Extract) | Determine whether extracts would show genotoxicity in mouse peripheral blood cells | The device/material shall show no evidence of genotoxicity in mouse peripheral blood cells | Pass |
| Hemocompatibility: ASTM In Vitro Hemolysis (Extract) | Determine whether extracts would cause hemolysis in vitro | The device/material shall be considered nonhemolytic | Pass |
| Hemocompatibility: ASTM Partial Thromboplastin Time (Extract) | Evaluate whether extracts cause changes in the clotting time of human plasma | The device/material shall not significantly affect clotting time | Acceptable |
| Hemocompatibility: C3a Complement Activation Assay (Extract) | Evaluate the potential for activating the complement system | The device/material shall not exhibit significant complement activation | Pass |
| Hemocompatibility: SC5b-9 Complement Activation Assay (Extract) | Evaluate the potential for activating the complement system | The device/material shall not exhibit significant complement activation | Pass |

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The blood-contacting components of the Zenith Alpha™ Thoracic Endovascular Graft introduction system, with the exception of the gray positioner and bottom cap used in both the original and modified introduction systems, are the same as the components used in the introduction systems of the Zenith® TX2® TAA Endovascular Graft (TX2) (P070016) or the Zenith Flex® AAA Endovascular Graft (AAA) (P020018), which have established biocompatibility. Biocompatibility testing for the materials used with the TX2 and AAA devices was assessed by testing specified in ISO 10993-1, Biological Evaluation of Medical Devices, including cytotoxicity, sensitization, skin irritation or intracutaneous reactivity, acute systemic toxicity, and hemocompatibility.

The base materials for the gray positioner (polyvinyl chloride) and bottom cap (nylon) are the same as those used in the introduction systems of the Zenith® TX2® TAA Endovascular Graft or the Zenith Flex® AAA Endovascular Graft; however, the specific formulations have been slightly modified. Therefore, additional biocompatibility testing was considered necessary for these materials; results of testing are summarized in Tables 5 and 6.

Table 5. Results of biocompatibility testing of the gray positioner material

| Test Type | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Cytotoxicity: ISO Elution Method – 1X MEM Extract | Determine whether extracts would cause cytotoxicity | The device/material shall not show more than 50% lysis (grade 2, mild cell lysis) | Pass |
| Sensitization: ISO Maximization Sensitization Study – Extract (NaCl and sesame oil) | Evaluate the potential for delayed dermal contact for sensitization | The device/material shall show no evidence of causing delayed dermal contact sensitization | Pass |
| Intracutaneous reactivity: ISO Intracutaneous Study – Extract (NaCl and sesame oil) | Determine whether extracts would cause local dermal irritant or toxic effects | The device/material shall not exhibit significant irritation | Pass |
| Acute systemic toxicity: USP and ISO Systemic Toxicity Study – Extract (NaCl and sesame oil) | Determine whether extracts would cause acute systemic toxicity | The device/material shall show no evidence of significant systemic toxicity | Pass |
| Hemocompatibility: In Vitro Hemolysis – Modified ASTM-Extraction Method (NaCl) | Determine whether extracts would cause hemolysis in vitro | The device/material shall be considered nonhemolytic | Pass |

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Table 6. Results of biocompatibility testing of the bottom cap material

| Test Type | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Cytotoxicity: ISO Elution Method – 1X MEM Extract | Determine whether extracts would cause cytotoxicity | The device/material shall not show more than 50% lysis (grade 2, mild cell lysis) | Pass |
| Sensitization: Murine Local Lymph Node Assay – Extract (NaCl and DMSO) | Determine whether extracts would cause an increase in proliferation of lymphocytes within mouse lymph nodes | The device/material shall show no evidence of causing sensitization | Pass |
| Intracutaneous reactivity: ISO Intracutaneous Study – Extract (sesame oil) | Determine whether extracts would cause local dermal irritant or toxic effects | The device/material shall not exhibit significant irritation | Pass |
| Acute systemic toxicity: ISO Systemic Toxicity Study – Extract (NaCl and sesame oil) | Determine whether extracts would cause acute systemic toxicity | The device/material shall show no evidence of significant systemic toxicity | Pass |
| Hemocompatibility: ASTM Hemolysis – Direct Contact and Extract (CMS-PBS) | Determine whether test article or test article extract would cause hemolysis in vitro | The device/material shall be considered nonhemolytic | Pass |

Results of these tests support the biocompatibility of the Zenith Alpha™ Thoracic Endovascular Graft. Based upon the previous history of the clinical use of the components and the results of the aforementioned tests, biocompatibility of the Zenith Alpha™ Thoracic Endovascular Graft was reasonably demonstrated.

# B. Sterilization, Packaging, and Shelf Life

The Zenith Alpha™ Thoracic Endovascular Graft is sterilized using an ethylene oxide (EtO) sterilization process to achieve a minimum sterility assurance level (SAL) of $10^{-6}$ . Packaging, performance, and stability testing demonstrate that the packaging designs for the Zenith Alpha™ Thoracic Endovascular Graft including the modified introduction system are sufficient to adequately protect the device and maintain the integrity of the Zenith Alpha™ Thoracic Endovascular Graft package throughout its 3-year shelf life claim.

Shelf life testing results for 3-year time accelerated aged devices are presented with the in vitro bench testing results in Tables 7 through 9 (asterisk indicates test was also performed for shelf life testing). Accelerated shelf life product testing conducted on the Zenith Alpha™ Thoracic Endovascular Graft including the modified introduction system supports a 3-year shelf life claim.

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# C. Bench Testing

A testing plan for the Zenith Alpha™ Thoracic Endovascular Graft was developed to provide an assessment of device deployability, clinical/mechanical function, and integrity. The specific laboratory (in vitro) tests that were considered in assessing the Zenith Alpha™ Thoracic Endovascular Graft included tests listed in the testing standard ISO 25539-1, Cardiovascular implants – Endovascular devices – Part 1: Endovascular prostheses.

The following tables provide a summary of the laboratory (in vitro) testing results for the complete assembly (Table 7), introduction system (Table 8), and endovascular graft (Table 9). Except as noted in Table 8, all complete assembly testing and introduction system testing was performed on the modified introduction system. These test results verified that the Zenith Alpha™ Thoracic Endovascular Graft met product performance and design specifications.

Table 7. Complete assembly testing

| Test Method | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Force to Deploy* | Evaluate force necessary to deploy endovascular prosthesis | Sheath withdrawal < 100 N and trigger-wire/release-wire pull force < 45 N during alternate release sequence | Pass |
| Profile/ Diameter Test* | Determine maximum diameter of loaded introduction system | Because this test is for characterization only, there are no acceptance criteria | N/A |
| Visibility* | Evaluate visibility of endovascular system during simulated use | 100% success for the following visibility parameters: • Visualization of the proximal tip • Visualization of the tip of the sheath • Visualize all stents and radiopaque markers • Visualization of the overlap zone | Pass |

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| Test Method | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Simulated Use* | Evaluate performance of endovascular system during simulated use | 100% success for the following deployment parameters: ·Successful flush through Captor® valve assembly and inner cannula with saline/heparin solution ·Verification of placement of Captor® sleeve ·Activation of hydrophilic coating ·Advancement of device over wire guide and through anatomical model ·Sheath pullback ·Proximal bare stent remains attached to the delivery system during repositioning (proximal component only) ·Distal bare stent remains attached to the delivery system during repositioning (distal component only) ·Operation of rotating handle to release the distal trigger-wires ·Operation of rotating handle to release the proximal trigger-wires ·Successful retraction of telescoping handle (distal component only) ·Successful deployment of distal bare stent (distal component only) ·Graft expansion into model ·Graft positioning ·Subassembly removal from graft and sheath ·Sheath removal from model ·Operation of Captor® valve/Captor® sleeve ·After withdrawal of grey positioner, the hemostatic valve remains in place | Pass |

*Test also performed for shelf life testing on time-accelerated aged devices.

Table 8. Introduction system testing

| Test Method | Purpose | Acceptance Criteria | Result |
| --- | --- | --- | --- |
| Bond Strength* | Evaluate tensile strength of introduction system bonds | Tensile strength ·≥4 N for UAT/wirea ·≥5 N for suturea ·>23 N for handle/positioner, cap/positioner, and tip/cannula ·≥26.88 N for captor body/VRTS ·>72 N for pin vise/cannula ·≥45 N for wire/bushing ·>77 N for sheath/valve | Pass |
| Torsional Bond Strength* | Evaluate torsional bond strength of introduction system bonds | Torsional strength >0.068 Nm for pin vise/cannula, handle/cannula hub, handle/positioner, cap/positioner and tip/cannula | Pass |

*Test also performed for shelf life testing on time-accelerated aged devices.

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*Same for original and modified introduction systems; was not retested for modified system.

Table 9. Endovascular graft testing

| Test Method | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Circumferential Tensile Strength | Evaluate circumferential strength of graft material | Strength must be ≥ 2.1 N/mm | Pass |
| Corrosion | Evaluate susceptibility of metallic components of prosthesis to corrosion | Breakdown potential statistically greater than or equal to that of a currently approved endovascular graft | Pass |
| Dimensional Verification* | Evaluate diameters and lengths of deployed endovascular prosthesis | ·Outside diameter ± 5% of nominal outside diameter ·Length ± 5% of specified length | Pass |
| Seam Strength | Evaluate tensile strength of graft material seam | Strength must be ≥ 2.1 N/mm | Pass |
| Fatigue & Durability (pulsatile) | Evaluate pulsatile fatigue and durability of implant under intended conditions of use | Aneurysm/ulcer indication No stent fractures after the completion of 400 million pulsatile fatigue cycles BTAI indication No stent fractures that affect structural integrity after the completion of 400 million pulsatile fatigue cycles | Pass |
| Fatigue & Durability (longitudinal) | Evaluate longitudinal fatigue and durability of implant under intended conditions of use | Proximal sealing stent Following 400 million cycles: ·No more than 3 (total) and 2 consecutive pairs of barb failures ·No more than 4 consecutive stent-to-graft attachment site failures ·No stent failures Distal bare stent Following 400 million cycles: ·No more than 4 consecutive barb failures ·No more than 2consecutive stent-to-graft attachment site failures ·No stent failures | Pass |
| Flex/Kink | Evaluate minimum kink radius prosthesis can accommodate | Calculated maximum kink radius ≤ 20 mm | Pass |
| Integral Water Permeability | Evaluate rate of water leakage through endovascular prosthesis, including overlap | Rate of leakage < 362 ml/cm2/min | Pass |
| Longitudinal Tensile Strength | Evaluate longitudinal strength of graft material | Strength > 100 N | Pass |

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| Test Method | Purpose | Acceptance Criterion | Result |
| --- | --- | --- | --- |
| Migration Resistance | Evaluate force required to displace prosthesis | Minimum pull-out force > 8.14 N | Pass |
| MRI Testing | Evaluate magnetic field interactions between implant and MR system | •Deflection angle < 45 degrees •No torque •Heating < 5.7 °C •Artifact assessed for characterization | Pass |
| Pull Test for Modular Components | Evaluate force required to separate modular components | Same as for the previously approved device (Zenith TX2 TAA Endovascular Graft), this test is for characterization only, as the forces acting to cause component separation in the thoracic aorta have not been definitively characterized, such that there are no established acceptance criteria. | N/A with respect to an established acceptance criterion; force was comparable to that for the previously approved device |
| Radial Force/Hoop Strength | Evaluate force exerted by self-expanding implant | Minimum and maximum forces: •Smin≥2.3 N and Smax≤19.1 N for internal sealing stents •Smin>0 N and Smax≤10.6 N for external stents •Smin>0 N and Smax≤8.2 N for bare stents | Pass |
| Stent-free Surface Area | Calculate the stent-free area percentages for the bare stent configurations | Because this test is for characterization only, there are no acceptance criteria | N/A |
| Strength of Stent-to-graft Attachment* | Evaluate strength of suture attachment between graft and stent | Attachment strength: •>0 N for internal stents •>0.81 N for proximal sealing stents •>1.26 N for external stents •>1.63 N for distal bare stents | Pass |
| Stress/Strain Analysis (FEA) | To evaluate maximum and minimum stresses and strains on the stents when subjected to in vivo pulsatile load conditions | Fatigue factor of safety > 1.0 | Pass |
| | To evaluate maximum and minimum stresses and strains on the barbs when subjected to in vivo longitudinal loading conditions | Fatigue factor of safety > 1.0 | Pass |
| Wall Thickness | Evaluate graft material thickness | Wall thickness must be within 0.127 mm ± 0.025 mm | Pass |
| Water Permeability | Evaluate rate of water leakage through graft material | Rate of leakage < 362 ml/cm2/min | Pass |

*Test also performed for shelf life testing on time-accelerated aged devices.

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# D. Animal Studies

The Zenith Alpha™ Thoracic Endovascular Graft is the same basic design as the Zenith® TX2® TAA Endovascular Graft, a cylindrical endovascular prosthesis with self-expanding stents sewn to graft material. Moreover, the Zenith® Alpha™ Thoracic Endovascular Graft is constructed of the same base raw nitinol, polyester, and polypropylene materials as are used in the Zilver® Vascular Stent (P050017), the Zenith Flex® AAA Endovascular Graft (P020018), and the Zenith® TX2® TAA Endovascular Graft (P070016). These devices have undergone animal testing and shown acceptable histopathological response. Additionally, these devices have shown acceptable biocompatible and have a history of safe clinical use in humans. Therefore, animal studies specific to the Zenith Alpha™ Thoracic Endovascular Graft were considered not necessary.

# X. SUMMARY OF THE PIVOTAL CLINICAL STUDIES

The Zenith Alpha™ Thoracic Endovascular Graft is indicated for the endovascular treatment of patients with isolated lesions of the descending thoracic aorta (not including dissections) having vascular anatomy suitable for endovascular repair.

The Zenith Alpha™ Thoracic Endovascular Graft has been the subject of several documented clinical evaluations, including two pivotal studies (one international) that evaluated the safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft in patients with thoracic aneurysm/ulcer and blunt thoracic aortic injury (BTAI), as summarized in Table 10. Additional clinical evaluations (see Section XI) include a continued access study for the aneurysm/ulcer indication and a European post-market survey to further confirm performance of a user interface modification to the introduction system (rotation handle).

Table 10. Summary of primary pivotal studies

| Pivotal Study | Study Design | Objective | Number of Sites with Enrollment | Number of Subjects |
| --- | --- | --- | --- | --- |
| Aneurysm/ Ulcer | Prospective, nonrandomized, single-arm, multinational (US, Japan, Germany, England, Sweden) study | To evaluate safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft for the treatment of patients with aneurysms/ulcers of the descending thoracic aorta. | 23 | 110 |
| Zilver® Vascular Stent (P050017) | Inclusion of 100 patients with Aneurysm/ulcer | To evaluate safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft for the treatment of patients with aneurysms/ulcers of the descending thoracic aorta. | 23 | 110 |
| Zenith® Flex® AAA Endovascular Graft (P020018) | Inclusion of 100 patients with Aneurysm/ulcer | To evaluate safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft for the treatment of patients with aneurysms/ulcers of the descending thoracic aorta. | 23 | 110 |

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| Pivotal Study | Study Design | Objective | Number of Sites with Enrollment | Number of Subjects |
| --- | --- | --- | --- | --- |
| BTAI | Prospective, nonrandomized, noncomparative, single-arm, US multicenter study | To evaluate safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft for the treatment of blunt traumatic aortic injury. | 17 | 50 |

# ANEURYSM/ULCER PIVOTAL STUDY

# A. Study Design

The Zenith Alpha™ Thoracic Endovascular Graft pivotal study was a prospective, nonrandomized, single-arm, multinational study that was conducted to evaluate the safety and effectiveness of the Zenith Alpha™ Thoracic Endovascular Graft for the treatment of patients with aneurysms/ulcers of the descending thoracic aorta. Patients were treated between March 17, 2010 (first US enrollment on October 1, 2010) and January 16, 2013. The database for this PMA reflected data collected on 110 subjects under G100079 through April 7, 2015. There were 23 investigational sites, including centers in the US (51 patients at 14 sites), Japan (43 patients at 3 sites), Germany (13 patients at 4 sites), Sweden (3 patients at 1 site), and England (1 patient at 1 site). The presenting anatomy, based on core laboratory analysis of pre-procedure imaging, was a thoracic aneurysm in $81.8\%$ (90/110) of patients and a thoracic ulcer in $18.2\%$ (20/110) of patients.

The pivotal study endpoints were established based on performance goals derived from the pivotal study of the previous device, the Zenith® TX2® TAA Endovascular Graft. Similar inclusion/exclusion criteria were used between the two studies. A post hoc analysis was performed comparing demographic, comorbid, and baseline anatomical characteristics between the present study and the previous Zenith® TX2® TAA Endovascular Graft study used to derive the performance goals for hypothesis testing. Of the few variables that were found to be different between studies, none appeared to be relevant with respect to assessing the safety and effectiveness endpoints, thus confirming that comparing to performance goals derived from the previous study remained appropriate.

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# 1. Clinical Inclusion and Exclusion Criteria

Enrollment in the pivotal study for the aneurysm/ulcer indication was limited to subjects who met the following inclusion criteria:

- Descending thoracic aneurysm with diameter $\geq 5.0$ cm
- Descending thoracic aneurysm with a history of growth $\geq 5$ mm per year
- Descending thoracic degenerative or atherosclerotic ulcer $\geq 10$ mm in depth and $20\mathrm{mm}$ in diameter

Subjects were not permitted to enroll in the pivotal study if they met any of the following:

## General Exclusion Criteria

- Less than 18 years of age (20 years in Japan)
- Life expectancy less than 2 years
- Pregnant or breastfeeding or planning on becoming pregnant within 60 months
- Unwilling to comply with the follow-up schedule
- Inability or refusal to give informed consent
- Less than 30 days beyond primary endpoint for other investigative drug or device study

## Medical Exclusion Criteria

- Receiving home oxygen therapy
- $\mathrm{FEV}_1 &lt; 1$ liter
- Left ventricular ejection fraction &lt; 20%
- New York Heart Association Classification 4
- Myocardial infarction within the last 3 months
- Stroke within the last 3 months
- Diagnosed or suspected congenital degenerative collagen disease (for example, Marfan’s or Ehlers-Danlos syndrome)
- Systemic infection (e.g., sepsis)
- Bleeding diathesis, uncorrectable coagulopathy, or refuses blood transfusion
- Allergy to polyester, polypropylene, nitinol, or gold
- Untreatable reaction to contrast, which in the opinion of the investigator, cannot be adequately premedicated
- Symptomatic carotid disease warranting intervention, which will not be

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performed prior to TAA repair

- Mycotic aneurysm, leaking/ruptured aneurysm, impending rupture, aortobronchial fistula, aortoesophageal fistula, or traumatic injury
- Surgical or endovascular AAA repair within 30 days before or after TAA repair
- Previous placement of a thoracic endovascular graft
- Aortic dissection
- Prior open repair involving the descending thoracic aorta including supra-renal aorta and/or arch (prior elephant trunk procedure is acceptable if &gt;30 days post-procedure)
- Interventional and/or open surgical procedures (unrelated to TAA repair) within 30 days before or after TAA repair

# Anatomical Exclusion Criteria

- Treatment length (i.e., aneurysm/ulcer length including fixation sites) along greater curvature:
&gt; 127 mm for 18 to 24 mm diameter grafts
&gt; 149 mm for 26 mm diameter grafts
&gt; 355 mm for 28 to 32 mm diameter grafts (nontapered and tapered)
&gt; 324 mm for 34 and 36 mm diameter grafts (nontapered)
&gt; 363 mm for 34 and 36 mm diameter grafts (tapered)
&gt; 339 mm for 38 and 40 mm diameter grafts (nontapered)
&gt; 332 mm for 38 and 40 mm diameter grafts (tapered)
&gt; 354 mm for 42 mm diameter grafts (nontapered)
&gt; 347 mm for 42 mm diameter grafts (tapered)
&gt; 369 mm for 44 and 46 mm diameter grafts (nontapered)
&gt; 355 mm for 44 mm diameter grafts (tapered)
&gt; 362 mm for 46 mm diameter grafts (tapered)

- Proximal neck length measuring &lt; 20 mm between the left common carotid artery and aneurysm (covering the subclavian artery is acceptable except in patients with LIMA bypass, anomalous vertebral artery off of the arch in the region of the subclavian artery, or dominant vertebral artery off of the subclavian artery)
- Distal neck length measuring &lt; 20 mm between the celiac artery and the aneurysm
- Aortic arch radius &lt; 20 mm (if device is deployed in arch)

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- Proximal neck diameter, measured outer wall to outer wall on a sectional image or multiplanar reconstruction (CT), $&lt; 15 \mathrm{~mm}$ or $&gt;42 \mathrm{~mm}$
- Distal neck diameter, measured outer wall to outer wall on a sectional image or multiplanar reconstruction (CT), $&lt; 15 \mathrm{~mm}$ or $&gt;42 \mathrm{~mm}$ (estimate from more proximal segment if diaphragm makes identification of the outer wall difficult)
- Tortuosity, calcification, occlusive disease, or arterial diameter, measured inner wall to inner wall on a sectional image, that is not conducive to placement of the introducer sheath (16 Fr for 18 to $30\mathrm{mm}$ diameter grafts, 18 Fr for 32 to $38\mathrm{mm}$ diameter grafts, or 20 Fr for 40 to $46\mathrm{mm}$ diameter grafts) – use of an access conduit is acceptable
- Prohibitive calcification, occlusive disease, or tortuosity of intended fixation sites
- Circumferential thrombus in region of intended fixation sites
- Inverted funnel-shaped proximal neck with $&gt;10\%$ increase in diameter over length of neck
- Funnel-shaped distal neck with $&gt;10\%$ increase in diameter over length of neck
- Inability to preserve the left common carotid artery and celiac artery
- Aneurysm or angulation in the distal thoracic aorta that would preclude advancement of the introduction system

# 2. Follow-up Schedule

The study follow-up schedule (Table 11) consisted of both clinical and imaging (CT and X-ray) assessments at post-procedure (pre-discharge), 30 days, 6 months, 12 months, and yearly thereafter through 5 years.

Table 11. Study follow-up schedule

| Study Schedule | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | Pre-op | Intra-op | Post-procedure | 30-Day | 6-Month | 12-Month | 24-Monthd |
| Clinical exam | X | | X | X | X | X | X |
| Blood tests | X | | X | X | X | X | X |
| CT scan | Xa | | | Xc | Xc | Xc | Xc |
| Thoracic x-ray | | | | X | X | X | X |
| Angiography | Xb | X | | | | | |

aIt is recommended that imaging be performed within 6 months before the procedure.
bRequired only to resolve any uncertainties in anatomical measurements necessary for graft sizing.
$^{\mathrm{c}}$ MR imaging may be used for those patients experiencing renal failure or who are otherwise unable to undergo contrast-enhanced CT scan, with TEE being an additional option in the event of suboptimal MR imaging.

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$^{\mathrm{d}}$ Yearly thereafter through 5 years.

An independent core laboratory analyzed all patient imaging. An independent clinical events committee (CEC) adjudicated all major adverse events (MAEs), including all patient deaths; additionally the CEC also adjudicated core laboratory reports of migration and device integrity loss. An independent data safety monitoring board (DSMB) monitored the clinical trial according to an established safety monitoring plan.

# 3. Clinical Endpoints

The primary safety endpoint was 30-day freedom from major adverse events (MAEs), and the performance goal was 80.6%. MAEs were defined as the following: all-cause death; Q-wave myocardial infarction; cardiac event involving arrest, resuscitation, or balloon pump; ventilation &gt; 72 hours or reintubation; pulmonary event requiring tracheostomy or chest tube; renal failure requiring permanent dialysis, hemofiltration, or kidney transplant in a patient with a normal pre-procedure serum creatinine level; bowel resection; stroke; paralysis; amputation involving more than the toes; aneurysm or vessel leak requiring reoperation; deep vein thrombosis requiring surgical or lytic therapy; pulmonary embolism involving hemodynamic instability or surgery; coagulopathy requiring surgery; or wound complication requiring return to the operating room.

The safety hypothesis of the study was that the freedom from MAEs at 30 days met the performance goal of 80.6%. The performance goal was said to have been met provided that the null hypothesis is rejected in favor of the alternative with a one-tailed exact binomial test at the 0.025 level. Given that πMAE (30) is the probability that a randomly selected patient experienced freedom from MAE at 30 days, the null and alternative hypotheses were as follows.

The primary effectiveness endpoint was 12-month device success, and the performance goal was 80.7%. Device success at 12 months was defined as: technical success, with none of the following at 12 months:

- Type I or type III endoleaks requiring re-intervention
- Aneurysm rupture or conversion to open surgical repair
- Aneurysm enlargement greater than 5 mm

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When technical success was achieved, the physician accessed the aneurysm site and deployed the Zenith Alpha™ Thoracic Endovascular Graft at the intended location. The endovascular graft must be patent at the time of deployment completion as evidenced by intraoperative angiography.

The effectiveness hypothesis of the study was that device success at 12 months met the performance goal of 80.7%. The performance goal was said to have been met provided that the null hypothesis is rejected in favor of the alternative with a one-tailed exact binomial test at the 0.025 level. Given that πDS(12) is the probability that a randomly selected patient experienced device success at 12 months, the null and alternative hypotheses were as follows.

## Pre-specified Statistical Analysis Plan

Null Hypothesis: The 30-day freedom from MAE for patients treated with the Zenith Alpha™ Thoracic Endovascular Graft does not meet the performance goal (80.6%).

$$
\mathrm{H}0: \pi \mathrm{MAE}(30) \leq 80.6\%
$$

Alternate Hypothesis: The 30-day freedom from MAE for patients treated with the Zenith Alpha™ Thoracic Endovascular Graft meets the performance goal (80.6%).

$$
\mathrm{HA}: \pi \mathrm{MAE}(30) &gt; 80.6\%
$$

Therefore, the null hypothesis will be rejected in favor of the alternative provided that no more than 13 of the 110 enrolled subjects experienced a major adverse event within 30 days.

Null Hypothesis: The 12-month device success for patients treated with the Zenith Alpha™ Thoracic Endovascular Graft does not meet the performance goal (80.7%).

$$
\mathrm{H}0: \pi \mathrm{DS}(12) \leq 80.7\%
$$

Alternate Hypothesis: The 12-month device success for patients treated with the Zenith Alpha™ Thoracic Endovascular Graft meets the performance goal (80.7%).

$$
\mathrm{HA}: \pi \mathrm{DS}(12) &gt; 80.7\%
$$

Therefore, the null hypothesis will be rejected in favor of the alternative provided that no more than 12 of the 110 enrolled subjects experience a device failure within 12 months. This corresponds to 89.1% device success. The actual number of patients who can

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experience an event may be less since the sample size of 110 was augmented to include subjects who may become lost to follow-up.

The statistical analysis plan used for the Zenith Alpha™ Thoracic Endovascular Graft clinical study was prospectively defined. Taking into account expected attrition, and a goal of achieving at least 80% statistical power at a one-sided significance level of 2.5%, a sample size of 110 enrolled subjects was considered to be sufficient using a margin of 10%. The safety and effectiveness endpoints were said to be met if the null hypothesis was rejected in favor of the alternate hypothesis using a one-tailed exact binomial test for each endpoint.

## Success/Failure Criteria

The Zenith Alpha™ Thoracic Endovascular Graft clinical study was considered a success if both the primary safety and primary effectiveness endpoints were met. These endpoints were assessed by demonstrating accordance to a prespecified performance goal, sufficient to reject the null hypotheses in regards to freedom from MAE at 30 days and device success at 12 months. The analyses required that the performance goals, which were chosen based on the 30-day freedom from MAE rate and the 12-month device success for subjects treated with the currently approved Zenith® TX2® TAA Endovascular Graft, be met.

## B. Accountability of PMA Cohort

At the time of the database lock, of 110 subjects enrolled in the PMA study, 90% (99/110) were eligible for follow-up at 12 months (Table 12). All subjects were evaluable for the primary safety endpoint (freedom from MAE at 30 days). All eligible subjects were also evaluable for the primary effectiveness endpoint (12-month device success) based on a component of the composite measure having been assessed at the time of the procedure, consistent with the performance goal development. Two patients, although enrolled in the study, did not receive the device due to an inability to advance/gain access to the target treatment site. Although the primary safety and effectiveness endpoints were evaluated at 30 days and 12 months, respectively, data presented herein include longer-term follow-up that was available at the time of the data lock (April 7, 2015). Table 12 reports the percent of follow-up data available through 4 years.

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Table 12. Follow-up availability

| Follow-up Visit | Patients Eligible for Follow-up | Percent of Data Availablea | | | | Adequate Imaging to Assess the Parameterb | | | | Events Occurring Before Next Interval | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Patients with Data for that Visit | CTc | X-ray | Patients with Follow-up Pendingd | Size Increase | Endoleak | Migration | Fracture | Death | Conversion | LTF/WTHD | Not Due for Next Visit |
| Operative | 110 | 110/110 (100%) | NA | NA | 0 | NA | NA | NA | NA | 0 | 0 | 0 | 0 |
| 30-day | 110e | 106/110 (96.4%) | 105/108 (97.2%) | 98/108 (90.7%) | 0 | 105/108 (97.2%) | 102/108 (94.4%) | NA | 105/108 (97.2%) | 3 | 0 | 0 | 2e |
| 6-month | 105 | 99/105 (94.3%) | 97/105 (92.4%) | 92/105 (87.6%) | 0 | 96/105 (91.4%) | 91/105 (86.7%) | 94/105 (89.5%) | 98/105 (93.3%) | 2 | 0 | 4 | 0 |
| 12-month | 99 | 91/99 (91.9%) | 92/99 (92.9%) | 84/99 (84.8%) | 0 | 92/99 (92.9%) | 83/99 (83.8%) | 92/99 (92.9%) | 92/99 (92.9%) | 7 | 1 | 2 | 0 |
| 2-year | 89 | 78/89 (87.6%) | 79/89 (88.8%) | 75/89 (84.3%) | 8 | 77/89 (86.5%) | 73/89 (82.0%) | 77/89 (86.5%) | 77/89 (86.5%) | 3 | 0 | 7 | 45 |
| 3-year | 34 | 23/34 (67.6%) | 20/34 (58.8%) | 18/34 (52.9%) | 11 | 17/34 (50.0%) | 15/34 (44.1%) | 17/34 (50.0%) | 17/34 (50.0%) | 0 | 0 | 0 | 26 |
| 4-year | 8 | 6/8 (75.0%) | 6/8 (75.0%) | 6/8 (75.0%) | 2 | 6/8 (75.0%) | 6/8 (75.0%) | 6/8 (75.0%) | 6/8 (75.0%) | 0 | 0 | 0 | 8 |

NA - Not assessed.
LTF/WTHD - Lost-to-follow-up and withdrawn.
aSite-submitted data.
bBased on core laboratory analysis.
cIncludes MRI or TEE imaging (which is allowed per protocol) when the patient is unable to receive contrast medium due to renal failure.
Patients still within follow-up window, but data not yet available.
Two patients did not receive the device at the time of the implant procedure and therefore only 30-day clinical follow-up was applicable before the patients exited the study, with no further follow-up due thereafter.

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# C. Study Population Demographics and Baseline Parameters

The tables below present the demographics, comorbidities, American Society of Anesthesiologists (ASA) Physical Status Classification, Society of Vascular Surgery/International Society of Cardiovascular Surgery (SVS-ISCVS) risk score classification, the type of lesion, and the baseline anatomic characteristics of the study population. The majority of subjects were male $(58.2\%)$ with a mean age of 72.2 years. The most common medical conditions noted at the pre-procedure visit were hypertension, hypercholesterolemia, smoking, history of aneurysm, chronic obstructive pulmonary disease (COPD), and peripheral vascular disease. Subjects were most commonly classified as ASA II $(55.5\%)$ , followed by ASA III $(26.4\%)$ and ASA IV $10\%$ . The SVS-ISCVS classification was used to further characterize vascular morbidity. These comorbidities mirror the population with aneurysms and ulcers of the descending thoracic aorta (DTA). The demographics and characteristics are presented in Table 13.

Table 13. Demographics and patient characteristics

| Demographic | Mean ± SD (n, range) or Percent Patients (number/total number) |
| --- | --- |
| Age (years) | |
| All patients | 72.2 ± 9.8 (n=110, 42 – 92) |
| Male | 70.7 ± 9.9 (n=64, 42 – 85) |
| Female | 74.3 ± 9.4 (n=46, 44 – 92) |
| Gender | |
| Male | 58.2% (64/110) |
| Female | 41.8% (46/110) |
| Ethnicity | |
| White | 53.6% (59/110) |
| Hispanic or Latino | 0 |
| Black or African American | 8.2% (9/110) |
| American Indian or Alaska Native | 0 |
| Asian | 38.2% (42/110) |
| Native Hawaiian or other Pacific Islander | 0 |
| Other | 0 |
| Height (in) | 65.3 ± 4.5 (n=110, 55.1 – 75.2) |
| Weight (lbs) | 161.7 ± 44.3 (n=110, 79.2 – 330.0) |
| Body mass index | 26.5 ± 6.0 (n=110, 16.4 – 50.0) |

The medical history and comorbid medical conditions for the patient cohort are presented in Table 14.

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Table 14. Pre-existing comorbid medical conditions

| Medical History | Percent Patients (number/total number) |
| --- | --- |
| Cardiovascular | |
| Myocardial infarction (MI) | 12.7% (14/110) |
| Angioplasty/stent | 10.0% (11/110) |
| Cardiac or thoracic surgery | 16.4% (18/110) |
| Prior diagnosis of symptomatic congestive heart failure (CHF) | 10.0% (11/110) |
| Angina | 16.4% (18/110) |
| Prior diagnosis of arrhythmia | 23.6% (26/110) |
| Hypertension | 88.2% (97/110) |
| Coronary artery bypass graft | 11.8% (13/110) |
| Vascular | |
| Thromboembolic event | 0.9% (1/110) |
| Peripheral vascular disease | 21.8% (24/110) |
| Symptomatic carotid disease warranting intervention | 1.8% (2/110) |
| Any aneurysm (other than the study lesion) | 45.5% (50/110) |
| Thoracic aortic aneurysm | 2.7% (3/110) |
| Abdominal aortic aneurysm | 26.4% (29/110) |
| Other aneurysm* | 16.4% (18/110) |
| Degenerative or atherosclerotic ulcer (other than the study lesion) | 0.9% (1/110) |
| Any dissection | 9.1% (10/110)b |
| Thoracic aortic dissection | 6.4% (7/110)c |
| Abdominal aortic dissection | 0 |
| Other dissectiond | 2.7% (3/110) |
| Thoracic trauma | 3.6% (4/110)e |
| Aortobronchial fistula | 0.9% (1/110) |
| Aortoesophageal fistula | 0 |
| Bleeding diathesis or uncorrectable coagulopathy | 0 |
| Endarterectomy | 1.8% (2/110) |
| Diagnosed or suspected congenital degenerative collagen disease | 0 |
| Pulmonary | |
| Chronic obstructive pulmonary disease (COPD) | 25.5% (28/110) |
| Home oxygen | 1.8% (2/110) |
| Renal | |
| Chronic renal failure | 10.0% (11/110) |
| Hemodialysis | 1.8% (2/110) |
| Chronic peritoneal dialysis | 0 |
| Endocrine | |
| Diabetes | 19.1% (21/110) |
| Hypercholesterolemia | 73.6% (81/110) |
| Infectious disease | |
| Systemic infection | 0 |
| Gastrointestinal | |
| Gastrointestinal disease | 34.5% (38/110) |
| Hepatobiliary | |
| Liver disease | 12.7% (14/110) |
| Neoplasms | |
| Cancer | 24.5% (27/110) |
| Neurologic | |
| Stroke | 10.9% (12/110) |
| Substance use | |
| Past or current smoker | 71.8% (79/110) |
| Allergies | |
| Allergies | 41.8% (46/110) |

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aThe "other" aneurysm category includes patients with aneurysms in different locations (i.e., not descending thoracic or abdominal aorta) and patients with aneurysms in multiple locations.
bAll patients had a history of aortic dissection but at the time of enrollment had no radiographic evidence of aortic dissection.
cThe treated aneurysm/ulcer was located in the same aortic segment as the previously diagnosed dissection in four patients.
dThe "other" dissection category includes patients with dissection in different locations (i.e., not descending thoracic or abdominal aorta) and patients with dissections in multiple locations.
eAll patients had a history $(&gt;1$ year) of traumatic thoracic injury.

Table 15 reports the ASA classification.

Table 15. ASA physical status classification

| ASA Classification | Percent Patients (number/total number) |
| --- | --- |
| Healthy patient (1) | 8.2% (9/110) |
| Mild systemic disease (2) | 55.5% (61/110) |
| Severe systemic disease (3) | 26.4% (29/110) |
| Incapacitating systemic disease (4) | 10.0% (11/110) |
| Moribund patient (5) | 0 |

Table 16 reports the SVS-ISCVS risk score.

Table 16. SVS-ISCVS risk score classification

| SVS-ISCVS Category | Percent Patients (number/total number) |
| --- | --- |
| Diabetes risk score | |
| 0 | 83.6% (92/110) |
| 1 | 5.5% (6/110) |
| 2 | 9.1% (10/110) |
| 3 | 1.8% (2/110) |
| 4 | 0 |
| Smoking risk score | |
| 0 | 47.3% (52/110) |
| 1 | 30.0% (33/110) |
| 2 | 13.6% (15/110) |
| 3 | 9.1% (10/110) |
| Hypertension risk score | |
| 0 | 11.8% (13/110) |
| 1 | 29.1% (32/110) |
| 2 | 31.8% (35/110) |
| 3 | 27.3% (30/110) |
| Hyperlipidemia risk score | |
| 0 | 26.4% (29/110) |
| 1 | 17.3% (19/110) |
| 2 | 1.8% (2/110) |
| 3 | 54.5% (60/110) |

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| SVS-ISCVS Category | Percent Patients (number/total number) |
| --- | --- |
| Cardiac status risk score | |
| 0 | 70.0% (77/110) |
| 1 | 18.2% (20/110) |
| 2 | 11.8% (13/110) |
| 3 | 0 |
| Carotid disease risk score | |
| 0 | 84.5% (93/110) |
| 1 | 13.6% (15/110) |
| 2 | 0.9% (1/110) |
| 3 | 0.9% (1/110) |
| Renal status risk score | |
| 0 | 87.3% (96/110) |
| 1 | 10.9% (12/110) |
| 2 | 0 |
| 3 | 1.8% (2/110) |
| Pulmonary status risk score | |
| 0 | 66.4% (73/110) |
| 1 | 26.4% (29/110) |
| 2 | 6.4% (7/110) |
| 3 | 0.9% (1/110) |
| Total SVS/ISCVS risk score | 5.9 ± 2.6 (n=110, 1-14) |

The majority of subjects $(81.8\%)$ had fusiform aneurysms and the remaining $18.2\%$ had penetrating atherosclerotic ulcers. Table 17 reports the presenting morphology.

Table 17. Presenting morphology type per the core laboratory

| Morphology | Percent Patients (number/total number) |
| --- | --- |
| Aneurysm | 81.8% (90/110) |
| Ulcer | 18.2% (20/110) |

The main baseline anatomical measurements were as follows: mean proximal neck diameter at the left common carotid artery (LCCA) was $34.0 \pm 3.0 \mathrm{~mm}$ , mean proximal neck length was $94.7 \pm 57.8 \mathrm{~mm}$ , mean maximum aneurysm diameter was $60.9 \pm 11.4 \mathrm{~mm}$ , mean distal neck diameter was $31.0 \pm 5.1 \mathrm{~mm}$ , and mean aneurysm length was $113.5 \pm 63.0 \mathrm{~mm}$ . The mean ulcer depth was $14.1 \pm 3.7 \mathrm{~mm}$ and the mean ulcer length was $34.8 \pm 20.3 \mathrm{~mm}$ . Table 18 reports presenting anatomical dimensions of the aneurysm/ulcer, the proximal and distal aortic necks, and the right and left iliac arteries.

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Table 18. Presenting anatomical dimensions reported per the core laboratory

| Measure | Mean ± SD (n, range) |
| --- | --- |
| Aneurysm dimensions | |
| Major diameter (mm) | 60.9 ± 11.4 (n=90, 41 – 99) |
| Minor diameter (mm) | 51.7 ± 11.1 (n=90, 30 – 92) |
| Length (mm) | 113.5 ± 63.0 (n=90, 25.4 – 324.0) |
| Ulcer dimensions | |
| Ulcer depth (mm) | 14.1 ± 3.7 (n=20, 8 – 25) |
| Length (mm) | 34.8 ± 20.3 (n=20, 11.0 – 85.7) |
| Proximal neck diameter | |
| Left common carotid artery | |
| Major (mm) | 34.0 ± 3.0 (n=110, 24 – 42) |
| Minor (mm) | 31.1 ± 3.5 (n=110, 18 – 39) |
| 20 mm distal to left common carotid artery | |
| Major (mm) | 33.3 ± 4.3 (n=110, 22 – 54) |
| Minor (mm) | 30.6 ± 4.3 (n=110, 20 – 49) |
| Distal neck diameter | |
| 20 mm proximal to celiac artery | |
| Major (mm) | 31.0 ± 5.1 (n=110, 20 – 48) |
| Minor (mm) | 28.9 ± 4.7 (n=110, 19 – 42) |
| Celiac artery | |
| Major (mm) | 29.5 ± 4.4 (n=110, 20 – 44) |
| Minor (mm) | 27.3 ± 3.8 (n=110, 19 – 38) |
| Proximal neck length | |
| Left common carotid artery to distal part of neck (mm) | 94.7 ± 57.8 (n=110, 14.4 – 276.7) |
| Distal neck length | |
| Celiac artery to proximal part of neck (mm) | 105.2 ± 63.2 (n=110, 5.6 – 268.5) |
| Right iliac artery diameter | |
| Narrowest segment (mm) | 6.7 ± 1.6 (n=105, 3 – 10)a |
| Left iliac artery diameter | |
| Narrowest segment (mm) | 6.9 ± 1.8 (n=104, 0 – 11)a |

aCT imaging was not always adequate for measurement of the iliac arteries.

Table 19 reports the distribution in aneurysm diameter/ulcer depth.

Table 19. Distribution in range of maximum aneurysm diameter or ulcer depth per the core laboratory

| Type | Size Rangea | Percent Patients (number/total number) |
| --- | --- | --- |
| Aneurysm | 40 mm – < 50 mm | 8.9% (8/90) |
| | 50 mm – < 60 mm | 40.0% (36/90) |
| | 60 mm – < 70 mm | 36.7% (33/90) |
| | 70 mm – < 80 mm | 6.7% (6/90) |
| | 80 mm – < 90 mm | 4.4% (4/90) |
| | 90 mm – < 100 mm | 3.3% (3/90) |

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| Type | Size Rangea | Percent Patients (number/total number) |
| --- | --- | --- |
| Ulcer | < 20 mm | 95.0% (19/20) |
| | 20 mm – < 30 mm | 5.0% (1/20) |
| | 30 mm – < 40 mm | 0 |
| | 40 mm – < 50 mm | 0 |
| | 50 mm – < 60 mm | 0 |
| | 60 mm – < 70 mm | 0 |
| | 70 mm – < 80 mm | 0 |

${}^{a}$ Diameter for aneurysms and depth for ulcers.

Table 20 provides the distribution in location of the aneurysm/ulcer.

Table 20. Location of the primary aneurysm/ulcer as determined by the core laboratory

| Location | Percent Patients (number/total number) | | |
| --- | --- | --- | --- |
| | Aneurysm Patients | Ulcer Patients | All Patients |
| Location in the descending thoracic aorta | | | |
| Proximal | 26.7% (24/90) | 50.0% (10/20) | 30.9% (34/110) |
| Middle | 53.3% (48/90) | 30.0% (6/20) | 49.1% (54/110) |
| Distal | 20.0% (18/90) | 20.0% (4/20) | 20.0% (22/110) |

# D. Procedural Information

The majority (71.8%) of procedures were performed under general anesthesia, followed by local anesthesia in 21.8% of procedures. Vascular access was gained via femoral artery cutdown in 62.7% of subjects, percutaneously in 36.4% of subjects, and by using a conduit in 0.9% of subjects. The mean procedure time was $99.4 \pm 53.6$ minutes (range 31-362 minutes) and the mean procedural blood loss was $121.8 \pm 137.7$ ml. The mean anesthesia time was $162.7 \pm 61.4$ minutes and the mean fluoroscopy time was $20.0 \pm 20.1$ minutes.

Adjunctive techniques for spinal cord protection to prevent paraplegia were performed in $40.0\%$ of subjects (72.7% were cerebral spinal fluid (CSF) drainage), and induced hypotension to ease deployment was performed in $7.3\%$ of subjects. The left subclavian artery (LSA) was covered completely in $13\%$ of subjects. No LCCA to LSA bypass or LSA transposition were performed.

The access method used to insert the Zenith Alpha™ Thoracic Endovascular Graft is presented in Table 21. Three types of methods were used: percutaneous (direct needle puncture of the access vessel), cutdown (surgical exposure of the access vessel), and conduit (surgical technique used to bypass prohibitive access vessels). For the

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percutaneous access method, the procedure time was $88.8 \pm 44.7$ minutes, blood loss was $128.5 \pm 136.4$ cc, and incidence of access site complications was $7.3\%$ . For the cutdown/conduit access method, the procedure time was $105.4 \pm 57.6$ minutes, blood loss was $118.0 \pm 139.3$ cc, and incidence of access site complications was $5.7\%$ . These data support the use of either method of access for the device.

Table 21. Access method used to insert the endovascular graft

| Type | Percent Patients (number/total number) | | |
| --- | --- | --- | --- |
| | Aneurysm Patients | Ulcer Patients | All Patients |
| Percutaneous | 31.1% (28/90) | 60.0% (12/20) | 36.4% (40/110) |
| Cutdown | 67.8% (61/90) | 40.0% (8/20) | 62.7% (69/110) |
| Conduit | 1.1% (1/90) | 0 | 0.9% (1/110) |

The location of the graft components relative to an identified site is provided as percent of subjects in Table 22.

Table 22. Graft location per core laboratory

| Location | Percent Patients (number/total number) | | |
| --- | --- | --- | --- |
| | Aneurysm Patients | Ulcer Patients | All Patients |
| Proximal aspect of graft | | | |
| Above LCCA | 0 | 0 | 0 |
| Below LCCA, above LSA | 9.1% (8/88) | 30.0% (6/20) | 13.0% (14/108) |
| Below LSA | 83.0% (73/88) | 60.0% (12/20) | 78.7% (85/108) |
| Unable to assessa | 8.0% (7/88) | 10.0% (2/20) | 8.3% (9/108) |
| Distal aspect of graft | | | |
| Above celiac artery | 95.5% (84/88) | 90.0% (18/20) | 94.4% (102/108) |
| Below celiac artery | 0 | 0 | 0 |
| Unable to assessa | 4.5% (4/88) | 10.0% (2/20) | 5.6% (6/108) |

LCCA = left common carotid artery; LSA = left subclavian artery.
${}^{a}$ All patients had post-procedure angiography but not all imaging was adequate for core laboratory review.

Two patients required axillary-axillary bypasses prior to the index procedure (both from a Japanese site). Additional procedures performed after graft deployment included use of a vessel closure device in 26 patients, LCCA stent placement in one patient, LSA stent placement in one patient, LSA coil embolization in five patients, femoral endarterectomy in two patients, thromboendarterectomy and patch right femoral in one patient, iliac artery stent placement in three patients, and chimney stent to maintain blood flow to the

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LCCA and LSA coil embolization in one patient. Table 23 reports additional procedures performed either before or after graft implantation.

Table 23. Additional procedures

| Procedure | Percent Patients (number/total number) | |
| --- | --- | --- |
| | Before Graft Deployment | After Graft Deployment |
| Left carotid artery stent | 0 | 0.9% (1/110) |
| Left subclavian artery stent | 0 | 0.9% (1/110) |
| Iliac artery angioplasty | 0.9% (1/110) | 0 |
| Iliac artery stent | 0 | 2.7% (3/110) |
| Vessel closure device | 0 | 23.6% (26/110) |
| Other | 1.8% (2/110)a | 8.2% (9/110)b |

aTwo patients from Japan (1040051 and 1040069) underwent axillary-axillary bypass prior to the index procedure.
bTwo patients (1030005 and 1030044) underwent right femoral endarterectomy after the index procedure. One patient (0465997) underwent thromboendarterectomy and patch right femoral after the index procedure. Five patients (1040023, 1040033, 1040039, 1040051, and 1040069) underwent coil embolization of the left subclavian artery after the index procedure. One patient (1040080) had a chimney stent placed to maintain blood flow to the left common carotid artery and coil embolization of the left subclavian artery after the index procedure.

The device was successfully implanted in $98.2\%$ of subjects (two patients did not receive the device due to the inability to insert/advance the introduction system) and all subjects $(100\%)$ survived the endovascular procedure. Overall, the procedural results were as expected for the treatment of patients with aneurysms or ulcers of the DTA.

# Clinical Utility Measures

The mean hospital stay after endovascular treatment was 7 days (range 1-185 days). One patient remained in the hospital 185 days due to a stroke the day of the procedure and was discharged to a long-term care facility. The mean stay in the intensive care unit (ICU) was $2.3 \pm 8.9$ days, and the mean days to ambulation was $1.6 \pm 1.5$ days. The clinical utility results are presented in Table 24.

Table 24. Clinical utility measures

| Clinical Utility Measure | Mean ± SD (n, range)a | | |
| --- | --- | --- | --- |
| | Aneurysm | Ulcer | All patients |
| Duration of ICU stay (days) | 2.6 ± 9.9 (n=88, 0 - 91) | 0.8 ± 0.6 (n=20, 0 - 2) | 2.3 ± 8.9 (n=108, 0 - 91) |
| Days to resumption of oral fluid intake | 0.4 ± 0.6 (n=89, 0 - 3) | 0.5 ± 0.8 (n=20, 0 - 3) | 0.4 ± 0.6 (n=109, 0 - 3) |

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| Clinical Utility Measure | Mean ± SD (n, range)a | | |
| --- | --- | --- | --- |
| | Aneurysm | Ulcer | All patients |
| Days to resumption of regular diet | 1.3 ± 1.1 (n=89, 0 - 6) | 1.5 ± 3.1 (n=19, 0 - 14) | 1.3 ± 1.6 (n=108, 0 - 14) |
| Days to resumption of bowel function | 2.3 ± 1.5 (n=70, 0 - 8) | 2.0 ± 2.1 (n=15, 0 - 8) | 2.3 ± 1.6 (n=85, 0 - 8) |
| Days to ambulation | 1.6 ± 1.3 (n=88, 0 - 9) | 1.8 ± 2.2 (n=20, 0 - 10) | 1.6 ± 1.5 (n=108, 0 - 10) |
| Days to hospital discharge | 7.4 ± 19.6 (n=90, 1 - 185) | 5.0 ± 5.3 (n=20, 1 - 19) | 7.0 ± 17.8 (n=110, 1 - 185) |

aNot all clinical utility measures were assessed for all 110 patients.

# Devices Implanted

Table 25 shows the percent of patients who received each type of Zenith Alpha™ Thoracic Endovascular Graft component (proximal, distal, or distal extension) during the initial implant procedure. Also included is the graft diameter range implanted for each component type. Although available for use in the aneurysm/ulcer study, graft diameters ranging from $18\mathrm{mm}$ to $26\mathrm{mm}$ were used only in the BTAI study.

Table 25. Stent-graft component type deployed

| Type | Percent Patients (number/total number)a | | | Graft Diameter Range (All Patients) |
| --- | --- | --- | --- | --- |
| | Aneurysm Patients | Ulcer Patients | All patients | |
| Proximal component (nontapered or tapered) | 100% (88/88) | 100% (20/20) | 100% (108/108) | 28 to 46 mm |
| Distal component | 37.5% (33/88) | 0 | 30.6% (33/108) | 32 to 46 mm |
| Ancillary component | 27.3% (24/88)b | 5.0% (1/20) | 23.1% (25/108) | |
| Additional proximal component | 13.6% (12/88) | 5.0% (1/20) | 12.0% (13/108) | 28 to 46 mm |
| Distal extension | 14.8% (13/88)c | 0 | 12.0% (13/108) | |

aTwo aneurysm patients did not receive a device as the introduction system could not be successfully advanced; therefore, the denominator is 108, not 110.
bOne patient received both an additional proximal component and a distal extension.
cIncludes 12 patients who received 1 distal extension, and 1 patient who received 2 distal extensions.

Table 26 further summarizes the total number of components placed during the initial implant procedure.

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Table 26. Total number of components placed during the initial implant procedure

| Main Body Design | Percent Patients (number/total number)a | Percent Patients (number/total number) | | | |
| --- | --- | --- | --- | --- | --- |
| | | | 1 | 2 | 3 |
| One-piece (proximal only) | Aneurysm Patients | 62.5% (55/88) | 69.1% (38/55) | 29.1% (16/55) | 1.8% (1/55) |
| | Ulcer Patients | 100% (20/20) | 95.0% (19/20) | 5.0% (1/20) | 0 |
| | All Patients | 69.4% (75/108) | 76.0% (57/75) | 22.7% (17/75) | 1.3% (1/75) |
| Two-piece (proximal and distal) | Aneurysm Patients | 37.5% (33/88) | N/A | 78.8% (26/33) | 21.2% (7/33) |
| | Ulcer Patients | N/A | N/A | N/A | N/A |
| | All Patients | 30.6% (33/108) | N/A | 78.8% (26/33) | 21.2% (7/33) |

aTwo aneurysm patients did not receive a device as the introduction system could not be successfully advanced; therefore, the denominator is 108, not 110.

Table 27 reports the sizes (diameters and lengths) of the nontapered proximal components used during the initial implant procedure.

Table 27. Diameters and lengths of nontapered proximal component (ZTLP-P) sizes used

| Diameter (mm) | Length (mm) | n |
| --- | --- | --- |
| 28 | 132 | 2 |
| | 155 | 2 |
| 30 | 132 | 8 |
| | 155 | 2 |
| 32 | 132 | 7 |
| | 155 | 4 |
| | 201 | 5 |
| 34 | 137 | 3 |
| | 161 | 6 |
| | 209 | 2 |
| 36 | 137 | 10 |
| | 161 | 6 |
| | 209 | 1 |
| 38 | 142 | 7 |
| | 167 | 3 |
| | 217 | 6 |
| 40 | 142 | 2 |
| | 167 | 3 |
| | 217 | 1 |
| 42 | 121 | 3 |
| | 173 | 4 |
| 44 | 125 | 2 |
| | 233 | 1 |
| 46 | 179 | 4 |

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Table 28 reports the sizes (diameters and lengths) of the tapered proximal components used during the initial implant procedure.

Table 28. Diameters and lengths of tapered proximal component (ZTLP-PT) sizes used

| Diameter (mm) | Length (mm) | n |
| --- | --- | --- |
| 34 | 161 | 4 |
| | 209 | 1 |
| 36 | 161 | 7 |
| | 209 | 4 |
| 38 | 167 | 1 |
| | 217 | 3 |
| 42 | 173 | 5 |
| 44 | 179 | 1 |
| 46 | 179 | 1 |

Table 29 reports the sizes (diameters and lengths) of the distal components used during the initial implant procedure.

Table 29. Diameters and lengths of distal component (ZTLP-D) sizes used

| Diameter (mm) | Length (mm) | n |
| --- | --- | --- |
| 32 | 160 | 4 |
| | 229 | 1 |
| 34 | 142 | 2 |
| | 190 | 1 |
| 36 | 142 | 3 |
| | 190 | 1 |
| 38 | 147 | 4 |
| | 197 | 5 |
| 40 | 147 | 1 |
| 42 | 152 | 6 |
| 44 | 157 | 3 |
| 46 | 157 | 2 |

Table 30 reports the size (diameters and lengths) of the ancillary components used during the initial implant procedure.

Table 30. Diameters and lengths of ancillary component sizes used

| Diameter (mm) | Length (mm) |…