TALENT THORACIC STENT GRAFT SYSTEM

P070007 · Medtronic Vascular · MIH · Jun 5, 2008 · Cardiovascular

Device Facts

• Record ID: P070007
• Device Name: TALENT THORACIC STENT GRAFT SYSTEM
• Applicant: Medtronic Vascular
• Product Code: MIH · Cardiovascular
• Decision Date: Jun 5, 2008
• Decision: APWD
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Talent™ Thoracic Stent Graft System is intended for the endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta in patients having appropriate anatomy, including: Iliac/femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories; Non-aneurysmal aortic diameter in the range of 18 – 42mm; and Non-aneurysmal aortic proximal and distal neck lengths ≥ 20mm.

Device Story

The Talent™ Thoracic Stent Graft System is a modular endovascular device used to treat descending thoracic aortic aneurysms. It consists of self-expanding nitinol springs covered by a polyester woven graft, pre-loaded into the CoilTrac delivery system. The system is inserted endoluminally via the femoral or iliac artery by a physician. The device is tracked through the vasculature to the target site, where it is deployed to exclude the aneurysm from blood flow. Multiple modular sections (main sections and extensions) can be combined to match patient anatomy. Radiopaque markers on the graft assist in visualization and alignment under fluoroscopy. By excluding the aneurysm, the device reduces the risk of rupture and aneurysm-related mortality. Clinical outcomes are monitored via CT/MR imaging to assess for endoleaks, migration, or aneurysm growth. The device is intended for use in a clinical setting, typically by vascular surgeons or interventionalists.

Clinical Evidence

The VALOR Pivotal Study was a multi-center, non-randomized study of 195 subjects. Primary safety endpoint: All-Cause Mortality at 12 months (16.1% vs 29.8% literature control). Primary effectiveness endpoint: Successful Aneurysm Treatment at 12 months (89.2% vs 80% performance goal). Secondary endpoints included MAEs, aneurysm-related mortality, and secondary procedures. 30-day MAE rate was 41.0% for the test group vs 84.4% for the retrospective open surgery comparator. Clinical data at 2 years continues to support safety and effectiveness.

Technological Characteristics

Modular system comprising self-expanding nitinol springs and polyester woven graft. Features include FreeFlo, Bare Spring, and closed/open web end configurations. Delivery system uses 0.035" guidewire, 22-25Fr crossing profile. Materials tested per ISO 10993-1. MRI-conditional at 1.5T and 3.0T. Sterilized with 100% Ethylene Oxide.

Indications for Use

Indicated for patients with fusiform aneurysms, saccular aneurysms, or penetrating ulcers of the descending thoracic aorta. Requires appropriate iliac/femoral access, non-aneurysmal aortic diameter 18–42mm, and proximal/distal neck lengths ≥20mm. Contraindicated in patients with conditions threatening graft infection or sensitivities/allergies to device materials.

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: Talent™ Thoracic Stent Graft System

Applicant Name and Address: Medtronic Vascular
3576 Unocal Place
Santa Rosa, CA 95403
USA

Premarket Approval Application (PMA) Number: P070007

Date of Panel Recommendation: None

Date of Notice of Approval to Applicant: June 5, 2008

Expedited: Not Applicable

## II. INDICATION FOR USE

The Talent™ Thoracic Stent Graft System is intended for the endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta in patients having appropriate anatomy, including:

- Iliac/femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories;
- Non-aneurysmal aortic diameter in the range of 18 – 42mm; and
- Non-aneurysmal aortic proximal and distal neck lengths ≥ 20mm.

## III. CONTRAINDICATIONS

The Talent™ Thoracic Stent Graft is contraindicated in:

- Patients who have a condition that threatens to infect the graft.
- Patients with sensitivities or allergies to the device materials.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Talent™ Thoracic Stent Graft System labeling (Instructions for Use).

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# V. DEVICE DESCRIPTION

## Talent™ Thoracic Stent Graft System

The Talent™ Thoracic Stent Graft is pre-loaded into the CoilTrac Delivery System. The loaded delivery system is inserted endoluminally via the femoral or iliac artery and tracked through the patient’s vasculature to deliver the stent graft to the target site.

## Talent™ Thoracic Stent Graft

The Talent™ Thoracic Stent Graft is composed of a series of shaped, self-expanding nitinol springs to form a stent. The self-expanding nitinol stent is covered by a polyester woven graft. The graft material is sewn to the stent. Radiopaque markers are sewn to the graft to help visualize and identify the edge of the graft material, stent graft alignment, and the minimum overlap required when multiple stent grafts are used.

The Talent™ Thoracic Stent Graft System is a modular device system that accommodates the use of multiple stent graft sections. Depending on the patient’s anatomy, single or multiple stent grafts may be required to achieve coverage and exclude the target lesion. The Talent™ Thoracic Stent Graft offers multiple graft configurations in order to support optimum matching of the device(s) to individual patient anatomies. Different proximal and distal end configurations accommodate patient anatomy and allow graft mating. Figure 1 illustrates the various stent graft end configurations, and Table 1 summarizes the features of various modular stent graft component sections.

Figure 1: Talent™ Thoracic Stent Graft End Configurations

Table 1: Talent™ Thoracic Stent Graft Component Summary

| Component | Proximal End Configuration | Distal End Configuration | Total Length | Covered Length | Available Diameters | Straight or Tapered Tube |
| --- | --- | --- | --- | --- | --- | --- |
| Proximal Main Section | FreeFlo (>22mm)
Bare Spring (22mm) | Closed Web | 130mm | 112-116mm | 22mm – 46mm | Straight Tube |
| Distal Main Section | Open Web | Closed Web | 130mm | 110-114mm | 26mm – 46mm | Tapered Tube |
| Proximal Extension | FreeFlo | Open Web | 80-90mm | 46-54mm | 26mm – 46mm | Straight Tube |
| Distal Extension | Open Web | Bare Spring | 80-90mm | 46-54mm | 26mm – 46mm | Straight Tube |

## Selection of Stent Grafts

Stent graft sizing, component selection, required overlap between components, and order of component deployment is provided in the Instructions for Use (IFU).

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# Proximal Main Section

The proximal main section has an uncovered nitinol spring as the proximal end configuration, which allows for trans-vessel flow. Proximal main stent grafts with a proximal diameter greater than 22mm have a mini-support spring to aid in sealing. The proximal end configuration in which an uncovered nitinol spring and mini-support spring are present is called the ‘FreeFlo’ configuration. The proximal end configuration in which an uncovered nitinol spring is present without a mini-support spring is called a ‘Bare Spring’ configuration. The distal end of the stent graft has a closed web configuration.

Figure 2: Talent™ Thoracic Main Section

# Distal Main Section

Distal main sections are typically used to increase the length of coverage of the treated vessel when the proximal main section is inadequate in length to exclude the aneurysm. The distal main section utilizes a proximal configuration in which the outline of the most proximal spring is covered with fabric leaving a “tulip” effect, called open web. The distal configuration is a closed web configuration.

Figure 3: Talent™ Thoracic Distal Main Section

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# Proximal Extension

Proximal extensions are intended to be used when the proximal end of a previously implanted stent graft requires extension to fully exclude the target lesion, or to treat proximal Type I endoleaks. The proximal extension is deployed within the proximal end of the previously implanted stent graft. The proximal end of the stent graft has a FreeFlo configuration, which allows for trans-vessel flow. The distal end of the stent graft has an open web configuration.

Figure 4: Talent™ Thoracic Proximal Extension

# Distal Extension

Distal extensions are intended to be used when the distal end of a previously implanted stent graft requires extension to fully exclude the target lesion, or to treat distal Type I endoleaks. The distal extension is deployed in the distal end of the previously implanted stent graft and extends distally. The proximal end has an open web configuration. The distal configuration has a bare spring extending beyond the edge of the fabric, which allows for trans-vessel flow.

Figure 5: Talent™ Thoracic Distal Extension

# CoilTrac Delivery System

The CoilTrac Thoracic Delivery System is composed of an inner catheter with a tapered tip, a push rod shaft with spring and cup plunger, and a graft cover. The inner catheter allows tracking of the system over a 0.035" guidewire, the push rod shaft with spring and cup plunger is the deployment platform, and the graft cover is for graft containment and deployment. The

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nose of the system is a flexible tapered tip. The graft cover has a hemostasis valve at the proximal section and a radiopaque marker band at the distal end. The radiopaque marker indicates the edge of the sheath under fluoroscopy. The crossing profile of the delivery catheter is 22, 24, or 25Fr, depending upon the size of the stent graft chosen. See Figure 6.

Figure 6: CoilTracDelivery System

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the treatment of thoracic aortic aneurysms (TAA): endovascular repair using another endovascular grafting system; surgical implantation of a synthetic graft within the aneurysmal vessel; and medical management. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

# VII. MARKETING HISTORY

Currently, the Talent™ Thoracic Stent Graft System is available in over 50 regions, including: the European Union; Asia; Africa; the Middle East; Latin America; Australia; and New Zealand. The device has not been withdrawn from the market for any reason related to safety or effectiveness.

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VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

The potential adverse effects (e.g., complications) that may occur and/or require intervention with the use of this device include, but are not limited to:

- Amputation
- Aneurysm Enlargement
- Balloon rupture
- Breakage of the metal portion of the device
- Cardiac Failure/Infarction
- Change in mental status
- Conversion to open surgery
- Death
- Deployment difficulties
- Edema
- Embolization
- Endoleak
- Erectile Dysfunction
- Erosion with fistula or pseudoaneurysm
- Failure to deploy
- Gastrointestinal complications, including: adynamic ileus, bowel (ileus, transient ischemic, infarction, necrosis)
- Graft twisting and/or kinking
- Hemorrhage/Bleeding
- Inaccurate placement
- Infection and fever
- Insertion and removal difficulties
- Intercostal pain
- Neurological complications, including: spinal cord ischemia with paraplegia; paraparesis and/or paresthesia; Cerebral Vascular Accidents (CVA); Transient Ischemic Attacks (TIA); neuropathy; and blindness
- Prosthetic thrombosis
- Pulmonary complications
- Renal failure
- Rupture of graft material
- Ruptured vessel/aneurysm sac enlargement
- Stent graft migration
- Vascular complications, including: thrombosis; thromboembolism; occlusion (arterial and venous); vessel dissection¹ or perforation; collateral vessel occlusion; vascular ischemia; tissue necrosis; and amputation
- Wound healing complications.

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

¹ Aortic dissection is an infrequent but recognized risk of endovascular repair. In the first 10 years of clinical experience (outside the U.S. (OUS) - commercial and U.S. - investigational), there were 39 reported events of retrograde dissection in patients. Of the 39 reported events, 33 patients had a pre-existing aortic dissection

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# IX. SUMMARY OF PRECLINICAL STUDIES

## A. Biocompatibility

Toxicology and biocompatibility testing was conducted for materials in the Talent™ Thoracic Stent Graft System. Testing was conducted in accordance with Good Laboratory Practices (21 CFR §58) and ANSI/AAMI/ISO 10993-1: 2003 Biological Evaluation of Medical Devices. The Talent™ Thoracic Stent Graft was classified per ISO 10993-1 Biological Evaluation of Medical Devices as an implant device in permanent contact (> 30 days) with blood. The CoilTrac (Thoracic) Delivery System was classified as an externally communicating device in limited contact (< 24 hours) with circulating blood.

Table 2 summarizes the test results for the Talent™ Thoracic Stent Graft. Table 3 summarizes the test results for the CoilTrac (Thoracic) Delivery System. All the results of the toxicology and biocompatibility testing were acceptable.

Table 2: Summary of Biocompatibility Testing – Talent™ Thoracic Stent Graft

| Test Name | Purpose | Results | Pass/Fail |
| --- | --- | --- | --- |
| Cytotoxicity: Colony Assay | Evaluate effect of leaching substances on colony formation (Chinese Hamster Lung Cell) | Average colony formation (% of controls): 91-109% | Pass |
| MHLW Maximization Sensitization | Determine test article potential to cause delayed dermal sensitization (Guinea Pig) | 1%, 10% and 100% test article extracts showed no evidence of causing sensitization. All test animals were graded 0 | Pass |
| ISO Irritation/Intracutaneous Toxicity | Determine local dermal irritant effects of leachables extracted from the test article (Rabbit) | Difference between test and control scores:
Saline: 0.0
Sesame Oil: 0.0 | Pass |
| MHLW Systemic Toxicity | Determine potential of leachables extracted from the test article to cause acute systemic toxicity (Mouse (strain Crl:CF-1BR)) | No evidence of mortality or systemic toxicity | Pass |
| 4-wk Sub-Chronic Toxicity (Subcutaneous Implantation) | Evaluate potential sub-chronic toxicity (Rat) | No evidence of systemic toxicity
Local Macroscopic tissue reaction not significant compared to the negative control
Microscopically considered a slight irritant | Acceptable |
| Genotoxicity: Bacterial Reverse Mutation Study (AMES) | Determine whether extract causes mutagenic changes in the test strains in the presence or absence of S9 metabolic activation (Salmonella typhimurium strains TA98, TA 100, TA1535, and TA1537; Esherichia coli strain WP2uvrA) | No case of ≥ 2-fold increase in mean # of revertants | Pass |

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| Test Name | Purpose | Results | Pass/Fail |
| --- | --- | --- | --- |
| Genotoxicity: in vitro
Chromosomal Aberration | Determine whether the test extract causes genotoxicity in the presence and absence of S9 metabolic activation. (Chinese Hamster Ovary cells) | Test extracts were concluded to be negative for the induction of structural chromosome aberrations in Chinese Hamster Ovary Cells: $\chi^2 = 0.5$ and 1.2 | Pass |
| Genotoxicity: Mouse Peripheral Blood Micronucleus | Evaluate test extract potential to cause genotoxic changes in the chromosomes or the mitotic apparatus of murine polychromatic erythrocytes (Mouse (strain Crl:CD-1(ICR) BR)) | No statistically significant increase in the # of MN-RETs for each test group | Pass |
| 12 week ISO Muscle Implantation | Evaluate evidence of irritation or toxicity, post-implantation (Rabbit) | Macroscopic Score: 0.0 = ‘Not Significant’
Microscopic Score: 4.4 = ‘Slight Irritant’ | Acceptable |
| Hemocompatibility: MHLW in vitro Hemolysis | Evaluate if test article extract causes hemolysis (Rabbit) | • 1 hr & 2 hrs: 0%
• 4 hrs: 1.1% | Pass |
| C3a Complement Activation Assay | Ensure that the potential extractables did not activate the complement system (Extract: Normal Human Serum (NHS)) | C3a concentration not significantly higher than the controls | Pass |
| Partial Thromboplastin Time Assay | Detect material mediated effects on the intrinsic coagulation pathway (Extract: Human Citrated Plasma) | Shortened clotting time compared to negative control | Acceptable |
| in vivo Thromboresistance | Evaluate the potential of the test device to resist thrombus formation when placed in the vasculature (Dog) | Grade 1, 2 & 2.
Test article was thromboresistant. (Note: Test Article = finished device) | Pass |
| USP Pyrogen Study | Determine if the test solution induced a pyrogenic response (Rabbit) | Initial test: 1 rabbit was 0.6° above baseline temperature
Retest: 1 rabbit of the 8 total had an increase of 0.5°C or above.
Total rise for all 8 rabbits was 1.3°C | Pass |

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Table 3: Summary of Biocompatibility Testing – Talent™ Thoracic CoilTrac Delivery System

| Test Name | Purpose | Results | Pass/Fail |
| --- | --- | --- | --- |
| Cytotoxicity: Colony Assay | Evaluate effect of leaching substances on colony formation (Chinese Hamster Lung Cell) | Average colony formation (% of controls): 91-110% | Pass |
| MHLW Maximization Sensitization | Determine test article potential to cause delayed dermal sensitization (Guinea Pig) | 0.1%, 1% and 10% Test Article Extracts showed no evidence of causing sensitization. All Test Animals were graded 0 | Pass |
| ISO Irritation/Intracutaneous Toxicity | Determine local dermal irritant effects of leachables extracted from the test article (Rabbit) | Difference between test and control scores: Saline: 0.0 Sesame Oil: 0.0 | Pass |
| MHLW Systemic Toxicity | Determine potential of leachables extracted from the test article to cause acute systemic toxicity (Mouse (strain Crl: CF-1 BR)) | No evidence of mortality or systemic toxicity | Pass |
| Hemocompatibility: MHLW in vitro Hemolysis | Evaluate if test article extract causes hemolysis (Rabbit) | • 1 hr & 2 hrs = 0%
• 4 hrs = 1.3% | Pass |
| C3a Complement Activation Assay | Ensure that the potential extractables did not activate the complement system (Extract: Normal Human Serum (NHS)) | C3a concentration not significantly higher than the negative control | Pass |
| Partial Thromboplastin Time Assay | Detect material mediated effects on the intrinsic coagulation pathway (Extract: Human Citrated Plasma) | Shortened clotting time compared to negative control. | Acceptable |
| In vivo Thromboresistance | Evaluate the potential of the test device to resist thrombus formation when placed in the vasculature (Dog) | Grade 1, 2 & 2. Test article was thromboresistant. (Note: Test Article = finished device) | Pass |
| USP Pyrogen Study | Determine if the test solution induced a pyrogenic response (Rabbit) | All animals < 0.5° C increase. | Pass |

## B. Product Testing

Medtronic conducted comprehensive pre-clinical, bench and analytical testing on the Talent™ Thoracic Stent Graft System. The in vitro testing was intended to verify that the performance attributes of the Talent™ Thoracic Stent Graft System are sufficient to minimize adverse events under anticipated clinical conditions. This testing included both the stent graft and the delivery system. All testing was conducted in accordance with national and international standards and guidance documents.

The testing detailed in Table 4 verified that the Talent™ Thoracic Stent Graft System (implant and delivery system) met its product performance and design specifications. Results obtained from in vitro testing provided evidence supporting the safety and effectiveness of the Talent™ Thoracic Stent Graft System.

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Table 4: Summary of Testing of Talent™ Thoracic Stent Graft System

| Test | Specification / Acceptance Criteria | Summary Test Results |
| --- | --- | --- |
| Stent Graft Visual Integrity | • No broken stents
• 5-13 sutures/cm density (springs)
• Loose sutures are allowable if they continue to attach the stent and/or RO marker to the graft material.
• No graft holes or tears
• Support springs may contain deformation if the spring remains attached to the graft material | All samples met the acceptance criteria. |
| Spring Radial Force | Characterization study | The mean forces were found to be 1.38 lbf, 1.48 lbf and 1.12 lbf for the 32mm, 40mm and 46mm springs respectively. This testing demonstrates the ability of the Talent™ Stent Graft to exert an outwardly positive radial force on the graft, allowing the Talent™ Stent Grafts to expand and maintain an open lumen and provide sealing in a variety of patient anatomies. |
| Stent Graft Dimensional Verification | Diameter ≥ nominal diameter - 1 mm | All samples met the acceptance criteria. |
| Stent Graft Conformability | The stent graft kink radius must accommodate a 90° bend without kinking | All samples met the acceptance criteria. |
| Stent Graft Migration Resistance | Characterization study | This testing characterizes the proximal pullout force of the main device following deployment in a mock aorta. The mean peak force required to displace the proximal section of the stent graft was 1228.18 gf. Based upon these results, component migration appears unlikely. |
| Stent Graft Joint Strength | Characterization study | This testing characterizes the ability of the modular components of the Talent™ Stent Graft System to resist separation. The mean peak force required to displace a Distal Main section from a Proximal Main section was 190.54 gf. |
| Spring Attachment Strength | Characterization study | This testing quantified the attachment strength of the Talent™ Stent Graft springs to the graft material. The strength ranged from 22.98 to 44.86 lbf for bare springs and from 52.13 to 89.69 lbf for body springs. |
| Crimp Strength | Crimp strength must be greater than 5.25 lbf for 32mm, 6.03 lbf for 40mm and 6.05 lbf for 46mm. | All samples met the acceptance criteria. |

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| Test | Specification / Acceptance Criteria | Summary Test Results |
| --- | --- | --- |
| Nitinol Alloy Material and Surface Analysis | **Property-Requirement**

**Chemical Composition**
Nickel: 55.9% reference
Titanium: Balance
Carbon: <0.05%
Oxygen: <0.05%
Any single trace element: <0.05%
Total trace elements (Other than Ni, Ti, C, and O): <0.4%

**Transformation Property**
A_{s} temperature: -15 +/- 5°C

**Mechanical Properties**
UTS (ksi): 206 – 246 ksi
Elongation (%): 4% min | All samples met the acceptance criteria. |
| Surface Analysis | Must be smooth and uniform in color with no blotches, spotting or pinholes | All samples met the acceptance criteria. |
| Potentiodynamic Polarization Corrosion | Characterization Test | This testing evaluated, per ASTM F2129, the general resistance of springs to pitting in the simulated clinical conditions. The test results indicate that the stent springs used in the Talent^{TM} Thoracic Stent Grafts have a high resistance to localized corrosion under simulated in-vivo conditions. |
| MRI | The presence of the stent graft must not pose an additional unacceptable risk to patients when subjected to 1.5T and 3.0T magnetic fields. | All samples met the acceptance criteria. The device has therefore been determined to be MRI-conditional. |
| Graft Component Tensile Strength | Characterization study | Graft component tensile strength testing was conducted to characterize the tensile strength of the graft material. The mean tensile strength of material was 55.19 lbf. |
| Stent Graft Permeability | Characterization study | This testing characterizes the rate of water flow through the Talent^{TM} Thoracic Stent Graft under a pressure of 120 mm Hg. The mean rate of leakage per unit area was calculated as 487.17 ml/min/cm^{2}. The water permeability observed is consistent with the water permeability of polyester materials used in endovascular and vascular applications. |
| Stent Graft Burst | Stent graft burst pressure LTL ≥ 18.8 psi | All samples met the acceptance criteria. |

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| Test | Specification / Acceptance Criteria | Summary Test Results |
| --- | --- | --- |
| Finite Element Analysis | Characterization study | Finite element analysis was used to determine the location and magnitude of the maximum strains in the Nitinol wire frame as a function of radial compression when subjected to catheter loading and an in vivo pulsatile loading environment. The peak strains at simulated catheter loading were determined to be below the yield strain of the Nitinol springs. Maximum strain locations and values determined from the simulated in vivo pulsatile loading were subsequently used as a reference in appropriate in vitro testing including pulsatile fatigue testing. |
| Whole Spring Fatigue | No fractures over 400 million cycles of clinically relevant loading conditions. | All samples met the acceptance criteria. |
| Graft Material and Seam Fatigue Testing | No unacceptable (based on individual sample evaluation) seam damage, suture propagation, or suture-hole elongation over 400 million cycles of clinically relevant loading conditions. | All samples met the acceptance criteria. |
| Whole Device Fatigue Testing | Must demonstrate structural integrity over 400 million cycles.
No structural failures of the device that would compromise spring to graft attachment or patency.
No graft material failure as a result of interaction of stent-graft components with each other. | All samples met the acceptance criteria. |
| Delivery Catheter Tensile Bond Strength Tests | Varies depending upon specific test. Acceptance criteria ranged from 5.0 lbf to 35 lbf. | All samples met the acceptance criteria. |
| Delivery Catheter Torsional Bond Strength Tests | Ultimate Torsional Strength > 1.62 lb·in | All samples met the acceptance criteria. |
| Sheath Marker Visualization | Characterization study | The radiopacity of the introducer sheath (graft cover) radiopaque marker was evaluated in ovine models under fluoroscopy. |
| Graft Cover Tensile Strength | Yield Strength LTL > Deployment Force UTL | All samples met the acceptance criteria. |
| Delivery System Hemostasis | Water leakage flow rate < 2 ml/min | All samples met the acceptance criteria. |

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| Test | Specification / Acceptance Criteria | Summary Test Results |
| --- | --- | --- |
| Trackability / Pushability | Characterization study | Trackability/pushability testing was conducted to characterize the force required to track the delivery system over a guidewire through a tortuous path. The mean force required for pushability and trackability of the delivery systems under worse case scenarios (largest diameter and longest length stent grafts) ranged from 1260.90 gf to 1906.47 gf. |
| Guidewire Acceptance | Delivery system must pass 0.035" diameter guidewire with minimal resistance and without damaging the delivery system or guidewire. | All samples met the acceptance criteria |
| Deployment Force | Deployment Force UTL must be less than Sheath to Hub Bond Strength LTL and Graft Cover Yield Strength LTL | All samples met the acceptance criteria |
| Delivery System Torquability | Characterization study | Delivery system torquability testing was conducted to characterize the torque (rotational) response of the stent graft system within simulated vasculature. |
| Delivery System Kink Radius | Characterization study | Delivery system kink radius testing was conducted to characterize the delivery system kink radius by determining the minimum radius of curvature to forcefully produce a kink. For the worst case (largest diameter stent with largest diameter delivery system) the mean radius to create a kink was observed to be 10.25cm. |
| Crossing Profile | The maximum outer diameter must be less than 1 Fr size over the nominal size. | All samples met the acceptance criteria |
| Working Length | Working length must be 90 ± 1cm | All samples met the acceptance criteria |

## C. Animal Studies

Three primary animal studies were conducted in the development of the Talent™ Thoracic Stent Graft System. One study was performed in a canine model and two in a swine model. All devices were of dimensions consistent with human clinical use. Two studies [swine (n=15) and canine (n=5)] evaluated smaller diameter devices implanted in the infra-renal aorta. The third study [(swine (n=5)] evaluated large diameter devices implanted in the thoracic aorta. Based on the results of the pre-clinical testing presented in this model, the Talent™ Thoracic Stent Graft System is capable of being successfully delivered and deployed in the animal aorta, maintaining integrity and vessel patency, and does not instigate unacceptable mechanical damage or immune response to the vessel. These studies are summarized in the Table 6 below.

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Table 5. Summary of non-clinical in vivo studies

| Study | Animal Model | Purpose | Results and Interpretation |
| --- | --- | --- | --- |
| Talent™
Stent Study | Porcine
(15 animals) | Stent Graft
System ability to be placed in a living animal aorta and the ability of the implant to maintain patency and apposition to the vessel wall | Technical Success (15 animals)
Successful implants at the target location.

Device Associated Events: Integrity, Patency Migration (7 animals)
Springs and graft material intact, maintained integrity.
Patent lumens with no evidence of thrombus in stent graft.

Histopathology (7 animals)
Device well tolerated (63 days – 251 days), as evidenced by patent lumen and lack of significant chronic inflammatory response.
Neo-intimal formation in process. |
| A Safety and Efficacy Study
Evaluating the World Medical Endoluminal Stent-graft in the Thoracic Aorta of Swine | Porcine
(5 animals) | Acute and chronic performance and biocompatibility
12-weeks in a porcine vascular model.
Histological analysis | Technical Success (5 animals)
Deployment: Successful implants at the target location.

Device Associated Events: Integrity, Patency Migration (4 animals)
Devices maintained integrity with no evidence of spring or graft material failure.
Patent lumens with no evidence of significant occlusions.
Excellent proximal and distal device fixation with native vessel wall, with no evidence of migration.
Appropriate aortic blood flow.

Histopathology (4 animals)
Gross pathology normal and similar to adjacent tissue.
Lack of significant inflammatory response.
Cellular infiltration into luminal surface for neo-intimal formation.
Tissue growth consistent with healing response leading to formation of a stable neo-intimal lining. |
| Pre-Clinical Study
Evaluating the World Medical Endoluminal Stent Graft in a Canine Model | Canine
(5 animals) | Acute and chronic performance and biocompatibility at 12 weeks in a canine vascular model.
Histological analysis was also performed | Technical Success (5 animals)
Deployment: successfully at the target location for all five (5) animals.

Device Associated Events: Integrity, Patency Migration. (5 animals)
Devices maintained integrity with no evidence of spring or graft material failure.
Grafts widely patent at the time of removal.

Histopathology (5 animals)
All animals tolerated the implant procedures well.
Gross pathology normal and similar to adjacent tissue.
Lack of significant inflammatory response.
Cellular infiltration into luminal surface for neo-intimal formation.
Tissue growth consistent with normal healing response leading to formation of a stable neo-intimal lining. |

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# D. Packaging, Shelf Life Testing, and Sterilization

The Talent™ Thoracic Stent Graft is a single-use device that is provided sterile. Sterilization is accomplished using 100% Ethylene Oxide. The sterilization process, equipment, and facility were found to be acceptable and a Sterility Assurance Level (SAL) of 10⁻⁶ was achieved. Product and package stability testing of the Talent™ Abdominal Stent Graft was performed and validated for a 2-year shelf life.

# X. SUMMARY OF CLINICAL STUDIES

Medtronic performed a clinical study to establish a reasonable assurance of safety and effectiveness of endovascular treatment of descending thoracic aortic aneurysms with the Talent™ Thoracic Stent Graft System for the endovascular repair of fusiform aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta in patients having appropriate anatomy in the U.S. under an investigational device exemption (IDE) study. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.

## A. Study Design

The VALOR Pivotal Study (VALOR Test Group) was a multi-center, non-randomized clinical study conducted within the U.S. to evaluate the safety and effectiveness of the Talent™ Thoracic Stent Graft System when used in the treatment of subjects with descending thoracic aortic aneurysms (fusiform aneurysms and saccular aneurysms/penetrating ulcers).

For the VALOR Test Group, 38 sites enrolled a total of 195 subjects. In the VALOR Test Group, analysis of the primary endpoints used follow-up visits at 1, 6 and 12 months after the implant procedure and annually for a total of 5 years from the date of the initial implant. Clinical sites sent CT/MR and chest X-ray (CXR) images to an independent Core Laboratory to provide an assessment of patient data through one year post implantation. All major adverse events (MAEs) were adjudicated by an independent Clinical Events Committee (CEC) for device and procedure relatedness.

The primary safety endpoint was All-Cause Mortality at one year. The All-Cause Mortality rate of TAA repair with the Talent™ Thoracic Stent Graft was to be compared to the literature All-Cause Mortality rate for open surgical TAA repair, within one year of the initial procedure (29.8%). In addition, safety outcomes for the Talent™ Thoracic Stent Graft were compared to the retrospective surgical comparator group described below.

### Original Literature Control

The original literature control compared the All-Cause Mortality rate of TAA repair of the Talent™ Thoracic Stent Graft with the literature All-Cause Mortality rate for open surgical TAA repair, within one year of the initial procedure. Based on the adequacy of information regarding disease etiology, length of follow-up information and definition of events, three articles were chosen, from which 608 subjects had atherosclerotic lesions that accurately fit the VALOR Test Group’s intended patient population of descending thoracic aortic aneurysms. Of the 608 patients, the number of patients surviving at 12 months was estimated from the 12 month rates given in the Kaplan-

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Meier curves included in each article. Using this method, 181 patients were estimated to have died within one year, establishing an All-Cause Mortality rate of 29.8%.

## Retrospective Open Surgery Group (Comparator Group)

After the original VALOR Trial was conducted, additional retrospective open surgical data were gathered from selected surgical centers to serve as a comparator for Acute Procedural Outcomes and Acute Adverse Events, as well as to further compare early and 12-Month Mortality and Aneurysm-Related Mortality. This Retrospective Open Surgery Group included 189 subjects from 3 centers who matched selected inclusion/exclusion criteria of the VALOR study. The VALOR Test and Retrospective Open Surgery Groups included surgical candidates diagnosed with a thoracic aortic aneurysm of degenerative etiology. The VALOR Test Group candidates were of low to moderate risk (Society of Vascular Surgery (SVS) risk levels 0, 1, and 2).

The primary effectiveness endpoint, Successful Aneurysm Treatment², was compared to a fixed rate of 80%, the lowest success rate consistent with the results from the control population described below. The effectiveness measure of 80% had also been used for the previously approved thoracic endograft.

## Effectiveness Control

The control population for the primary effectiveness endpoint was derived from the 21 subjects who had reached 1 year of follow-up from both the high risk and low risk feasibility studies at the time.

## B. Subject Accountability and Follow-up

For the VALOR Test Group, 38 sites enrolled a total of 195 subjects. One (1) subject had technical failure and did not receive a stent graft and therefore did not have any imaging follow-up. Four (4) subjects died and one (1) withdrew from the study before the 1-month visit.

There were 189 subjects eligible for clinical and imaging follow-up at 1-month follow-up interval. Of these 189 subjects, 80.4% (152/189) had a clinical follow-up. Please note; three (3) additional subjects who were not eligible for clinical follow-up had imaging follow-up within the expanded time windows (as footnoted within Table 6 below).

At the 6-month follow-up interval, 173 subjects were eligible for clinical and imaging follow-up. Of these, 74.0% (128/173) had clinical follow-up and 73.8% (127/173) had imaging follow-up. CT imaging was performed on 68.2% (118/173) subjects.

At the 12-month follow-up interval, 157 subjects were eligible for clinical and imaging follow-up. Of these, 71.3% (112/157) had clinical follow-up and 90.4% (142/157) had imaging

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follow-up. CT imaging was performed on 82.8% (130/157) subjects. Detailed subject accountability for 1, 6, and 12 months is provided in Table 6.

Table 6: Subject and Imaging Accountability Table– VALOR Test Group Only

| Treatment / Follow-up Interval | Patient follow-up | Patients with imaging performed at time interval (Core Lab) | Patients with adequate imaging to assess the parameter | Patient events occurring before next visit^{2} |
| --- | --- | --- | --- | --- |
| Eligible | Clinical Follow-up^{3} | Imaging Follow-up^{3} | CT Imaging^{3} | KUB Imaging^{3} | Aneurysm size increase^{3} | Endoleak^{2} | Migration^{4} | Integrity^{3} | Technical Failure | Conversion to Surgery | Death | Withdrawal | Lost to Follow-up |
| Originally Enrolled | 195 | | | | | | | | | 1 | | | |
| Events after implant but before 1-month visit | | | | | | | | | | | 0 | 4 | 1 |
| Events at 1-month visit | 189 | 152 | 192 | 184 | 189 | | 174 | 182 | 161 | | | | |
| Events after 1-month visit but before 6-month visit | | | | | | | | | | | 0 | 14 | 2 |
| Events at 6-month visit | 173 | 128 | 127 | 118 | 114 | 117 | 112 | 117 | 93 | | | | |
| Events after 6-month visit but before 12-month visit | | | | | | | | | | | 1 | 13 | 1 |
| Events at 12-month visit | 157 | 112 | 142 | 130 | 125 | 129 | 123 | 129 | 97 | | | | |

1 - Data analysis sample size varies for each of the timepoints above and in following tables. This variability is due to patient availability for follow-up, as well as, quantity and quality of images available from specific timepoints for evaluation. For example, the number and quality of images available for evaluation of endoleak at 6 months is different than the number and quality of images available at 12 months due to variation in the number of image exams performed, the number of images provided from the clinical site to the Core Lab, and/or the number of images with acceptable evaluation quality.

2 - Protocol-defined time windows were used for clinical follow-up and patient events:
- 1-month: 16 days to 44 days
- 6 month: 153 days to 213 days
- 12-month: 335 days to 395 days

3 - Expanded time windows were used for Imaging follow-up and assessment of imaging-dependant parameters:
- 1-month: 0 days to 122 days
- 6 month: 153 days to 213 days
- 12-month: 335 days to 480 days for CT, Endoleak and Aneurysm size increase
- 335 days to 760 days for X-ray and Integrity.

4 - Number of subjects evaluable for migration assessment were based on CT performed in windows and Slice interval and thickness &lt;5mm for 10mm evaluation.

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# C. Demographics and Baseline Medical History

Tables 7 through 10 provide the demographics of the VALOR Test Group subjects and the Retrospective Open Surgery Group.

Table 7: Subject Demographics: VALOR Test Group vs. Retrospective Open Surgery Group

| | VALOR Test Group | Retrospective Open Surgery | p-value |
| --- | --- | --- | --- |
| Total Population Age | | | |
| N | 195 | 189 | |
| Mean ± SD (years) | 70.2 ± 11.1 | 69.6 ± 9.1 | 0.528 |
| Median | 73.0 | 71.0 | |
| Min-Max | 27 - 86 | 27 - 85 | |
| Male Age | | | |
| N | 115 | 99 | |
| Mean ± SD (years) | 69.3 ± 11.7 | 69.9 ± 8.5 | 0.680 |
| Median | 72.0 | 71.0 | |
| Min-Max | 27 - 85 | 40 - 84 | |
| Female Age | | | |
| N | 80 | 90 | |
| Mean ± SD (years) | 71.6 ± 10.1 | 69.3 ± 9.8 | 0.130 |
| Median | 74.0 | 71.0 | |
| Min-Max | 38 - 86 | 27 - 85 | |
| Gender | | | |
| Males | 59.0% (115) | 52.4% (99) | 0.218 |
| Females | 41.0% (80) | 47.6% (90) | |
| Ethnicity | | | |
| White, non-Hispanic | 83.1% (162) | 93.7% (177) | 0.007 |
| Black- non-Hispanic | 12.8% (25) | 5.8% (11) | |
| Hispanic (White or Black) | 2.6% (5) | 0.5% (1) | |
| Asian/Pacific Islander | 1.0% (2) | 0% (0) | |
| Native American | 0% (0) | 0% (0) | |
| Other | 0.5% (1)¹ | 0% (0) | |
| 1 - One subject had Ethnicity specified as “None given.” | | | |

Table 8: Subject Anatomic Lesion Type for VALOR Test Group

| Thoracic Lesion² | VALOR Test Group - N (%) |
| --- | --- |
| Fusiform | 112 (57.4%) |
| Saccular/Penetrating Ulcer | 70 (35.9%) |
| Both | 13 (6.7%) |
| 1- The Retrospective Open Surgery Group did not provide patient level data for the anatomic lesion type treated. | |

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Table 9: Baseline Medical History: VALOR Test Group vs. Retrospective Open Surgery Group

| Body System / Condition | VALOR Test Group % (m/n) N = 195 | Retrospective Open Surgery % (m/n) N = 189 | p-value |
| --- | --- | --- | --- |
| Cardiovascular | | | |
| Angina | 14.4% (28/195) | 22.8% (26/114) | 0.064 |
| Arrhythmias | 26.7% (52/195) | 20.3% (37/182) | 0.182 |
| Carotid artery disease | 5.6% (11/195) | Not Available | N/A |
| Congestive heart failure (CHF) | 8.7% (17/195) | 11.2% (21/187) | 0.495 |
| Coronary artery bypass grafting (CABG) | 10.3% (20/195) | 13.3% (25/188) | 0.428 |
| Coronary artery disease (CAD) | 40.5% (79/195) | 49.2% (91/185) | 0.099 |
| Hypertension | 87.2% (170/195) | 88.8% (166/187) | 0.641 |
| Myocardial infarction (MI) | 13.8% (27/195) | 20.9% (39/187) | 0.079 |
| Percutaneous coronary intervention (PCI) | 5.6% (11/195) | Not Available | N/A |
| Peripheral vascular disease (PVD) | 16.4% (32/195) | 37.4% (70/187) | <0.001 |
| Symptomatic thoracic aortic aneurysm | 26.2% (51/195) | Not Available | N/A |
| Abdominal Aortic Aneurysm (AAA) | 19.0% (37/195) | 37.0% (70/189) | <0.001 |
| Abdominal Aortic Aneurysm Repair | 2.1% (4/195) | 27.5% (52/189) | <0.001 |
| Gastrointestinal conditions | 53.8% (105/195) | Not Available | N/A |
| Renal insufficiency | 17.4% (34/195) | 16.0% (30/187) | 0.784 |
| Musculoskeletal conditions | 53.8% (105/195) | Not Available | N/A |
| Neurological | | | |
| Cerebral vascular accident (CVA) | 9.7% (19/195) | 13.4% (25/186) | 0.267 |
| Paraplegia | 1.0% (2/195) | 0.5% (1/186) | 1.000 |
| Paraparesis | 0.5% (1/195) | Not Available | N/A |
| Transient ischemic attack (TIA) | 7.7% (15/195) | Not Available | N/A |
| Pulmonary | | | |
| Chronic obstructive pulmonary disease | 36.9% (72/195) | 42.6% (80/188) | 0.296 |
| Tobacco use | 76.9% (150/195) | 75.9% (142/187) | 0.904 |
| Other abnormal body systems | | | |
| Hyperlipidemia | 43.6% (85/195) | Not Available | N/A |
| Diabetes | 15.9% (31/195) | 8.6% | 0.030 |
| Bleeding disorders | 2.6% (5/195) | Not Available | N/A |
| 1 - m = number in category, n = number of known values | | | |

Table 10: Baseline Modified SVS Classification: VALOR Test Group

| | n | SVS 0 % (m) | SVS 1 % (m) | SVS 2 % (m) | SVS 3 % (m) |
| --- | --- | --- | --- | --- | --- |
| Modified SVS^{1} | 195 | 4.1% (8) | 21.0% (41) | 72.8% (142) | 2.1% (4) |
| 1 - SVS Medical Co-Morbidity Grading System for SV3 Modified for Age (>85), Uncontrolled Hypertension and Cardiac MI within 6 months with no intervention. | | | | | |

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# D. Baseline Aneurysm Data

Table 11 lists the initial aneurysm diameter sizes treated. Table 12 lists the baseline dimensions of the vessels treated.

Table 11: Baseline Maximum Aneurysm Diameters: VALOR Test Group vs. Retrospective Open Surgery Group

| Aneurysm Diameter (mm) | VALOR Test Group | | Retrospective Open Surgery %(m/n) | p-value Site-Reported VALOR vs. Retrospective Open Surgery4 |
| --- | --- | --- | --- | --- |
| | Site-Reported % (m/n) | Core Lab Reported % (m/n) | | |
| 10-17 | 0% (0/188) | 0% (0/187) | 0% (0/189) | <0.001 |
| 18-29 | 0% (0/188) | 0.5% (1/187) | 0% (0/189) | |
| 30-39 | 4.3% (8/188) | 7.5% (14/187) | 0% (0/189) | |
| 40-49 | 10.6% (20/188) | 20.3% (38/187) | 0.5% (1/189) | |
| 50-59 | 34.6% (65/188) | 34.8% (65/187) | 13.8% (26/189) | |
| 60-69 | 33.5% (63/188) | 24.6% (46/187) | 40.7% (77/189) | |
| 70-79 | 12.2% (23/188) | 10.2% (19/187) | 24.3% (46/189) | |
| 80-89 | 3.2% (6/188) | 2.1% (4/187) | 16.9% (32/189) | |
| 90-99 | 1.1% (2/188) | 0% (0/187) | 0.5% (1/189) | |
| 100-109 | 0.5% (1/188) | 0% (0/187) | 1.6% (3/189) | |
| 110-119 | 0% (0/188) | 0% (0/187) | 0.5% (1/189) | |
| 120+ | 0% (0/188) | 0% (0/187) | 1.1% (2/189) | |
| 1 - Denominator is 188 subjects with site reported data.
2 - Denominator is 187 subjects with evaluable scans.
3 - This p-value represents a Monte Carlo estimate of the p-value for the exact Mantel-Haenszel Chi-Square test for trend, based on 100,000 Monte Carlo repetitions. | | | | |

Table 12: Baseline Vessel Dimensions (Core Lab Reported): VALOR Test Group Only

| Vessel Dimensions (mm) | n1 | Mean ± SD | Median | Min | Max |
| --- | --- | --- | --- | --- | --- |
| Proximal neck diameter | 187 | 31.2 ± 4.9 | 31.5 | 18.5 | 43.5 |
| Aneurysm diameter | 187 | 55.5 ± 11.6 | 56.0 | 26.2 | 88.8 |
| Distal neck diameter | 184 | 29.7 ± 5.0 | 29.5 | 17.0 | 42.5 |
| Proximal neck length | 187 | 80.0 ± 52.1 | 77.9 | 10.0 | 234.0 |
| Aneurysm length | 180 | 121.4 ± 72.7 | 107.7 | 8.0 | 297.5 |
| Distal neck length | 184 | 90.0 ± 62.9 | 73.5 | 9.0 | 255.0 |
| Right external iliac minimum diameter | 122 | 6.5 ± 1.5 | 6.5 | 2.9 | 11.0 |
| Left external iliac minimum diameter | 124 | 6.6 ± 1.5 | 6.5 | 3.3 | 10.9 |
| 1- Denominators are n specified from readable scans. | | | | | |

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# E. Baseline Devices Implanted Data

Table 13 provides details on the number of devices implanted per subject for the VALOR Test Group.

Table 13: Number of Talent™ Thoracic Devices Implanted at Initial Procedure

| Devices Implanted | |
| --- | --- |
| Number per subject | % (m)^{1} |
| 0 | 0.5% (1) |
| 1 | 19.5% (38) |
| 2 | 28.7% (56) |
| 3 | 24.6% (48) |
| 4 | 17.4% (34) |
| 5 | 7.2% (14) |
| 6 | 1.5% (3) |
| 7+ | 0.5% (1) |
| 1- m= number of subjects implanted & percentages based on total number of enrolled subjects (N=195) | |

Table 14 cross-tabulates the 194 subjects in the VALOR Test Group who had Talent™ Stent Grafts implanted by the number of main sections and the number of extensions. For example, 38 subjects had a single main section implanted and no extensions, and 5 subjects had one main section and one extension. Similarly, 51 subjects had two main sections and no extensions and 6 had two main sections and one extension.

Table 14: Number of Main Sections and Number of Extensions Implanted at Initial Procedure: VALOR Test Group Only

| m (%)^{1} | Number of Extensions | | | | |
| --- | --- | --- | --- | --- | --- |
| | | 0 | 1 | 2 | Total |
| Number of Main Sections | 1 | 38 (19.59%) | 5 (2.58%) | 1 (0.52%) | 44 (22.68%) |
| | 2 | 51 (26.29%) | 6 (3.09%) | 5 (2.58%) | 62 (31.96%) |
| | 3 | 41 (21.13%) | 11 (5.67%) | 2 (1.03%) | 54 (27.84%) |
| | 4 | 18 (9.28%) | 6 (3.09%) | 0 (0.00%) | 24 (12.37%) |
| | 5 | 6 (3.09%) | 1 (0.52%) | 0 (0.00%) | 7 (3.61%) |
| | 6 | 2 (1.03%) | 1 (0.52%) | 0 (0.00%) | 3 (1.55%) |
| | Total | 156 (80.41%) | 30 (15.46%) | 8 (4.12%) | 194 (100.00%) |
| 1 – m = number of subjects with tabulated number of main sections and extensions. Percentages based on total number of implanted subjects (N=194) | | | | | |

Table 15 provides details on the components (proximal main devices, proximal extension devices, distal main devices, and distal extension devices) implanted per subject for the VALOR Test Group.

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Table 15: Talent™ Thoracic Stent Graft Devices Implanted

| Diameter (mm) | Stent Graft Modular Component (Number Implanted) | | | |
| --- | --- | --- | --- | --- |
| | Proximal Main % (m)¹ | Proximal Extension % (m)¹ | Distal Extension % (m)¹ | |
| 22 | 0.5% (1) | | | |
| 24 | 1.4% (3) | | | |
| 26 | 1.9% (4) | 0.0% (0) | 0.0% (0) | |
| 28 | 2.8% (6) | 0.0% (0) | 12.0% (3) | |
| 30 | 3.8% (8) | 4.8% (1) | 4.0% (1) | |
| 32 | 8.1% (17) | 14.3% (3) | 8.0% (2) | |
| 34 | 11.4% (24) | 4.8% (1) | 16.0% (4) | |
| 36 | 16.1% (34) | 14.3% (3) | 8.0% (2) | |
| 38 | 19.4% (41) | 19.0% (4) | 16.0% (4) | |
| 40 | 11.4% (24) | 4.8% (1) | 12.0% (3) | |
| 42 | 10.9% (23) | 4.8% (1) | 8.0% (2) | |
| 44 | 5.2% (11) | 9.5% (2) | 8.0% (2) | |
| 46 | 7.1% (15) | 23.8% (5) | 8.0% (2) | |
| Total Catalog Devices Implanted | 211 | 21 | 25 | |
| 1 - m = number of subjects implanted with specific type of device within each diameter category & denominator is the total number of the specific type of device implanted. | | | | |

## F. Safety Results

### Primary Safety Endpoints

#### All-Cause Mortality at One Year: VALOR Test Group vs. Original Literature Control

The primary safety endpoint was All-Cause Mortality at 12 months. Based on the test of superiority of the All-Cause Mortality rate in the Test Group to that of the original literature control group with an All-Cause Mortality rate of 181 of 608 subjects, or 29.8% (H₀: P_TestArm ≥ P_SurgicalGroup versus Hₐ: P_TestArm &lt; P_SurgicalGroup), the VALOR Test Group subjects met the pre-specified performance goal of 29.8%. The primary safety endpoint of the VALOR Study was met. Through one year, subjects who received the Talent™ Thoracic Stent Graft experienced an All-Cause Mortality rate of 16.1% and the subjects who underwent open surgery experienced a rate of 29.8%.

#### All-Cause Mortality at 30 days and 12 months: VALOR Test Group vs. Retrospective Open Surgery Group

Table 16 describes the 30-day mortality rates for the VALOR Test Group as compared to the Retrospective Open Surgery Group. The VALOR Test Group experienced a lower rate of early mortality (2% vs. 8%). An analysis of freedom from All-Cause Mortality was performed, and a Kaplan-Meier plot of subject freedom from All-Cause Mortality is provided in Table 17 and Figure 7.

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Table 16: All-Cause Mortality at 30 Days and 12 months

| | VALOR Test Group % (m/n) | Retrospective Open Surgery % (m/n) | 95% Exact Confidence Interval of Difference^{1,2} |
| --- | --- | --- | --- |
| All-cause mortality at 30 days | 2.1% (4/195) | 7.9% (15/189) | (-10.9%, -1.3%) |
| All-cause mortality at 12 months | 16.1% (31/192) | 20.6% (39/189)^{3} | (-12.4%, -3.4%) |
| 1 - Confidence level was not adjusted for multiplicity. Confidence interval for difference (VALOR Test Group – Retrospective Open Surgery group) in percentage was calculated by the exact method.
2 - Difference represents the (% of patients with mortality from any cause within the period in the population treated with the test device) - (% of patients with mortality from any cause within the period in the population treated with open surgery).
3 - Of the 39 deaths, this data includes both information from the reporting centers and queries of the National Social Security Death Index database. | | | |

Figure 7: KM Plot of All Cause Mortality at 30 Days and 12 Months: VALOR Test Group vs. Retrospective Open Surgery Group

Table 17: Details of Kaplan-Meier Plot of Freedom from All Cause Mortality at 30 Days and 12 Months: VALOR Test Group vs. Retrospective Open Surgery Group

| | VALOR Test Group | | | Retrospective Open Surgery | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Treatment to 30 days | 31 days to 182 days | 183 days to 365 days | Treatment to 30 days | 31 days to 182 days | 183 days to 365 days |
| No. at Risk | 195 | 190 | 176 | 189 | 174 | 157 |
| No. of Events | 4 | 13 | 14 | 15 | 17 | 7 |
| No. Censored | 1 | 1 | 1 | 0 | 0 | 1 |
| Kaplan-Meier Estimate | 0.980 | 0.912 | 0.839 | 0.921 | 0.831 | 0.794 |

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# Secondary Safety Endpoints

## Major Adverse Events (MAE) at 30 days for VALOR Test Group vs. Retrospective Open Surgery Group

Adverse events were categorized by severity in the VALOR Trial and in the Retrospective Open Surgery Group using the following definitions. A Major Adverse Event (MAE) was defined as the occurrence of any of the following:

- Death:
- due to complications of the procedure, including bleeding, vascular repair, transfusion reaction, or conversion to open surgical TAA repair
- within 30 days of the baseline implant or surgical procedure
- Respiratory complications (atelectasis / pneumonia, pulmonary embolism, pulmonary edema, respiratory failure)
- Renal complications (renal failure, renal insufficiency)
- Cardiac: MI, unstable angina, new arrhythmia, exacerbation of congestive heart failure (CHF)
- Neurological: new CVA / embolic events, paraplegia / paraparesis
- Aneurysm rupture
- Gastrointestinal: bowel ischemia
- Major bleeding complication (procedural or post-procedural), coagulopathy
- Vascular complications.

Comparisons of the 30-day MAEs for the Talent™ Thoracic subjects versus the retrospective Open Surgical Group are further summarized in Figure 8 and Tables 18 through 20 below.

Table 18: Summary of MAEs for VALOR Test Group vs. Retrospective Open Surgery Group (30 days)

| Category | VALOR Test Group | | Retrospective Open Surgery | | 95% Exact Confidence Interval of Difference^{1,2} |
| --- | --- | --- | --- | --- | --- |
| | Major Adverse Events 0-30 days % (m/n) N=195 | | Major Adverse Events 0-30 days % (m/n) N=189^{1} | | |
| Any MAE | 41.0% | (80/195) | 84.4% | (151/179) | (-51.9%, -34.2%) |
| Respiratory complications | 13.3% | (26/195) | 46.9% | (84/179) | (-42.2%, -24.6%) |
| Renal complications | 6.2% | (12/195) | 29.1% | (52/179) | (-30.6%, -15.3%) |
| Cardiac complications | 12.3% | (24/195) | 44.7% | (80/179) | (-41.0%, -23.5%) |
| Neurological complications | 11.8% | (23/195) | 20.1% | (36/179) | (-16.0%, -0.7%) |
| GI complications | 1.0% | (2/195) | 0.6% | (1/179) | (-2.1%, 3.2%) |
| Bleeding complications | 15.4% | (30/195) | 48.0% | (86/179) | (-41.7%, -23.4%) |
| Vascular complications | 21.0% | (41/195) | 12.3% | (22/179) | (1.1%, 16.5%) |
| Target Lesion Aneurysm Rupture | 0.0% | (0/195) | 0.6% | (1/179) | (-3.1%, 1.4%) |
| 1 - 10 subjects were followed for less than 16 days without MAE so they were eliminated from the analysis.
2 - Confidence level was not adjusted for multiplicity. Confidence interval for difference (VALOR Test Group – Retrospective Open Surgery Group) in percentage was calculated by the exact method.
3 - Difference represents the (% of patients free from MAEs within 30 days in the population treated with the test device) - (% of patients free from MAEs within 30 days in the population treated with open surgery). | | | | | |

{24}

One or more MAEs were reported in 80 of the 195 VALOR Test Group subjects available for evaluation, resulting in a probability of freedom from MAEs of 59%. In the Retrospective Open Surgery group, 151 of the 179 subjects had one or more MAEs, resulting in a freedom from MAE rate of 15.6% in this group.

Table 19: Freedom from MAEs at 30 days: VALOR Test Group vs. Retrospective Open Surgery Group

| Parameter | VALOR Test Group | Retrospective Open Surgery | 95% Exact Confidence Interval of Difference^{1,2} |
| --- | --- | --- | --- |
| Number of subjects at start | 195 | 179 | |
| Number of subjects with one or more events | 80 | 151 | |
| Probability of freedom from event | 59.0% | 15.6% | (34.2%, 51.9%) |
| 1 - Confidence level was not adjusted for multiplicity. Confidence interval for difference (VALOR Test Group – Retrospective Open Surgery Group) in percentage was calculated by the exact method.
2 - Difference represents the (% of patients free from MAEs within 30 days in the population treated with the test device) - (% of patients free from MAEs within 30 days in the population treated with open surgery). | | | |

Figure 8: Kaplan-Meier Plot of Freedom from MAEs at 30 Days: VALOR Test Group vs. Retrospective Open Surgery Group

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Table 20: Details of Kaplan-Meier Plot of Freedom from MAEs at 30 Days for VALOR Test Group vs. Retrospective Open Surgery Group

| | VALOR Test Group | | | Retrospective Open Surgery | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Treatment to 5 days | 6 days to 15 days | 16 days to 30 days | Treatment to 5 days | 6 days to 15 days | 16 days to 30 days |
| No. at Risk | 195 | 122 | 118 | 189 | 47 | 29 |
| No. of Events | 73 | 4 | 3 | 141 | 9 | 1 |
| No. Censored | 0 | 0 | 1 | 1 | 9 | 0 |
| Kaplan-Meier Estimate | 0625 | 0.605 | 0.590 | 0.254 | 0.203 | 0.196 |

## Serious Major Adverse Events at 30 days and 12 months: VALOR Test Group

VALOR MAEs were further stratified into more clinically severe events: Serious Major Adverse Events (Serious MAEs). These Serious MAEs were fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, caused persistent or significant disability/incapacity, or resulted in a congenital anomaly/birth defect. MAEs were reviewed by the CEC and adjudicated as either device- and/or procedure-related as per the study protocol. A MAE that was identified as a Serious Adverse Event (SAE) by the clinical Investigator was defined as a Serious MAE. During the VALOR Study, 59 of 195 evaluable subjects had one or more Serious Major Adverse Events within 30 days, giving a rate of Serious MAEs within 30 days of 30.3% (95% CI 23.9-37.2%). Eighty-two (82) of 192 evaluable subjects had one or more Serious MAEs within 12 months, providing a Serious MAE rate of 42.7% (95% CI 35.6-50.0%). These data are further summarized in Figure 9 and Tables 21 through 23.

Table 21: Summary of Serious MAEs from VALOR Test Group Only

| Category | 0-30 days % (m) N=195 | | 0-30 days 95% Exact CI | 0-365 days % (m) N=192 | | 0-365 days 95% Exact CI |
| --- | --- | --- | --- | --- | --- | --- |
| | Serious Major Adverse Events | | | Serious Major Adverse Events | | |
| Any Serious MAE | 30.3% | (59/195) | (23.9%, 37.2%) | 42.7% | (82/192) | (35.6%, 50.0%) |
| Respiratory complications | 6.7% | (13/195) | (3.6%, 11.1%) | 15.1% | (29/192) | (10.4%, 21.0%) |
| Renal complications | 3.6% | (7/195) | (1.5%, 7.3%) | 6.8% | (13/192) | (3.7%, 11.3%) |
| Cardiac complications | 5.1% | (10/195) | (2.5%, 9.2%) | 12.0% | (23/192) | (7.7%, 17.4%) |
| Neurological complications | 9.7% | (19/195) | (6.0%, 14.8%) | 13.5% | (26/192) | (9.0%, 19.2%) |
| GI complications | 0.5% | (1/195) | (0.0%, 2.8%) | 1.0% | (2/192) | (0.1%, 3.7%) |
| Bleeding complications | 13.3% | (26/195) | (8.9%, 18.9%) | 14.6% | (28/192) | (9.9%, 20.4%) |
| Vascular complications | 9.2% | (18/195) | (5.6%, 14.2%) | 10.4% | (20/192) | (6.5%, 15.6%) |
| Target Lesion Aneurysm Rupture | 0.0% | (0/195) | (0.0%, 1.9%) | 0.5% | (1/192) | (0.0%, 2.9%) |
| 1 - Confidence level was not adjusted for multiplicity. Confidence interval for the percentage was calculated by the exact (binomial) method. | | | | | | |

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Table 22: Freedom from Serious MAEs at 30 days and 12-months - VALOR Test Group

| Parameter | Talent™ Thoracic | |
| --- | --- | --- |
| | Serious MAE at 30 days | Serious MAE at 12-months |
| Number of subjects at start | 195 | 192^{1} |
| Number of subjects with one or more events | 59 | 82 |
| Probability of freedom from event | 69.7% | 57.3% |
| Exact 95% confidence interval for freedom from event^{2} | (62.7%, 76.1%) | (49.1%, 63.4%) |
| 1 -192 subjects followed for the required time frame.
2 - Confidence level was not adjusted for multiplicity. Confidence interval for the percentage was calculated by the exact (binomial) method. | | |

Figure 9: Kaplan-Meier Plot of Freedom from Serious MAEs: VALOR Test Group Only

Table 23: Details of Kaplan-Meier Plot of Freedom from Serious MAEs: VALOR Test Group Only

| | VALOR Test Group | | |
| --- | --- | --- | --- |
| | Treatment to 30 days | 31 days to 182 days | 183 days to 365 days |
| No. at Risk | 195 | 135 | 118 |
| No. of Events | 59 | 13 | 10 |
| No. Censored | 1 | 4 | 5 |
| Kaplan-Meier Estimate | 0.697 | 0.629 | 0.575 |

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# Aneurysm-Related Mortality

Table 24 provides Aneurysm-Related Mortality information for the VALOR Test and Retrospective Open Surgery Groups. A Kaplan-Meier plot of subject freedom from Aneurysm-Related Mortality is provided in Figure 10, and an analysis of freedom from Aneurysm-Related Mortality was provided in Table 25.

Table 24: Aneurysm-Related Mortality at 12 Months: VALOR Test Group vs. Retrospective Open Surgery

| | VALOR Test Group^{1} % (m/n) | Retrospective Open Surgery^{2} % (m/n) | 95% Exact Confidence Interval of Difference^{3,4} |
| --- | --- | --- | --- |
| Aneurysm-Related Mortality at 12 Months | 3.1% (6/192) | 11.6% (22/189) | (-14.2%, -2.9%) |
| 1 - Aneurysm-related mortality was defined as any death within 30 days from initial implantation or occurring as a consequence of an aneurysm rupture, a conversion to open repair, or any other secondary endovascular procedure relative to the aneurysm that was treated by the Talent™ Thoracic Stent Graft System as evidenced by CT, angiography or direct observation at surgery or autopsy. Excluded are aneurysms in anatomic areas other than the targeted segment treated by the Talent™ Thoracic Stent Graft System.
2 - The definition for Aneurysm Related Mortality for the Retrospective Open Surgery Group was any death within 30 days from the surgical procedure or any death caused by re-intervention of the targeted aortic segment, or by complications related to the graft or the procedure (e.g., graft infections, rupture, pseudoaneurysm, aorto-eophageal fistula, aorto-bronchial fistula).
3 - Confidence level was not adjusted for multiplicity. Confidence interval for difference (VALOR Test Group – Retrospective Open Surgery Group) in percentage was calculated by the exact method.
4 - Difference represents the (% of patients with aneurysm-related mortality within 12 months in the population treated with the test device) - (% of patients with aneurysm-related mortality within 12 months in the population treated with open surgery). | | | |

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Figure 10: Kaplan-Meier Plot of Freedom from Aneurysm-Related Mortality: VALOR Test Group vs. Retrospective Open Surgery Group


Table 25: Details of Kaplan-Meier Plot of Freedom from Aneurysm-Related Mortality at 12 Months: VALOR Test Group vs. Retrospective Open Surgery Group

| | VALOR Test Group | | | Retrospective Open Surgery | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Treatment to 30 days | 31 days to 182 days | 183 days to 365 days | Treatment to 30 days | 31 days to 182 days | 183 days to 365 days |
| No. at Risk | 195 | 190 | 176 | 189 | 174 | 157 |
| No. of Events | 4 | 1 | 1 | 15 | 7 | 0 |
| No. Censored | 1 | 13 | 14 | 0 | 10 | 8 |
| Kaplan-Meier Estimate | 0.980 | 0.974 | 0.969 | 0.921 | 0.883 | 0.883 |

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# G. Effectiveness Results

## Primary Effectiveness Endpoint: Aneurysm-Related Mortality at 12 Months

The primary effectiveness endpoint, which was Successful Aneurysm Treatment, was met. This endpoint was a composite endpoint defined by:

- no aneurysm growth greater than 5 mm at the 12-month follow-up visit when compared to the 1-month follow-up visit as assessed by the Core Lab (after the initial Talent™ Thoracic Stent Graft implant); and
- absence of a Type I endoleak as assessed by the Core Lab for which a secondary procedure was performed before, at or as a result of the 12-month follow-up visit.

The rate of Successful Aneurysm Treatment in the VALOR Test Group, 89.2%, was higher than the 80% comparator (which was based on earlier feasibility studies). As shown in Table 26, the Talent™ Thoracic Stent Graft achieved a successful aneurysm treatment rate of 89.2%. Table 27 provides details regarding subjects who have failed the successful aneurysm treatment endpoint.

Table 26: Successful Aneurysm Treatment: VALOR Test Group

| Primary Effectiveness Endpoint | % (m / n) [95% CI] | 95% Exact Confidence Interval |
| --- | --- | --- |
| Successful Aneurysm Treatment at 12 months | 89.2% (116/130)^{1} | [82.6% – 94.0%] |
| 1 - Eligible subjects for Successful Aneurysm Treatment required images depicting a one and twelve month aneurysm size, or had a Type I endoleak which required endovascular repair to be included in the analysis. Twenty-nine (29) subjects were missing a 12 month image at the Core Lab and were excluded from this analysis.
2 - Confidence level was not adjusted for multiplicity. Confidence interval for the percentage was calculated by the exact (binomial) method. | | |

Table 27: Summary of Subjects with Primary Effectiveness Failure: VALOR Test Group

| Subjects with Primary Effectiveness Failure | n |
| --- | --- |
| Aneurysm growth > 5mm | 10^{1} |
| Type I endoleak requiring re-intervention | 3 |
| Aneurysm growth > 5mm and Type I endoleak requiring re-intervention | 1^{2} |
| 1 - Of the 10 subjects, four (4) had secondary procedures. Of the remaining six (6) subjects, one (1) patient died of cardiac arrest at approximately 24 months, and one died of cirrhosis at 14 months.
2- This subject is alive at 24 months. | |

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# Other Effectiveness Data

Table 28 summarizes the other secondary endpoints from the VALOR Test Group.

Table 28: Other Effectiveness Data for VALOR Test Group

| Secondary Endpoint | Incidences % (m / n) | | 95% Exact CI^{1} |
| --- | --- | --- | --- |
| Successful deployment and delivery of the stent graft at implantation | 99.5% | (194/195)^{2} | (97.2%, 100.0%) |
| Secondary procedures due to endoleak at 30 days | 0.0% | (0/194) | (0.0%, 1.9%) |
| Conversion to open surgical repair within 12 months post-implantation | 0.5% | (1/192)^{3} | (0.0%, 2.9%) |
| Aneurysm rupture within 12 months post-implantation | 0.5% | (1/192)^{4} | (0.0%, 2.9%) |
| Stent graft migration between 1 and 12 months | 3.9% | (4/103)^{5} | (1.1%, 9.6%) |
| Proximal stent graft migration > 10 mm proximally | 0.0% | (0/103) | (0.0%, 3.5%) |
| Proximal stent graft migration > 10 mm distally | 1.9% | (2/103) | (0.2%, 6.8%) |
| Distal stent graft migration > 10 mm proximally | 1.9% | (2/103) | (0.2%, 6.8%) |
| Distal stent graft migration > 10 mm distally | 0.0% | (0/103) | (0.0%, 3.5%) |
| All endoleaks at 12 months (Core Lab reported) | 12.2% | (15/123) | (7.0%, 19.3%) |
| Type I | 4.9% | (6/123)^{6} | (1.8%, 10.3%) |
| Type II | 4.9% | (6/123)^{7} | (1.8%, 10.3%) |
| Type III | 0.0% | (0/123) | (0.0%, 3.0%) |
| Type IV | 0.0% | (0/123) | (0.0%, 3.0%) |
| Unknown | 2.4% | (3/123) | (0.5%, 7.0%) |
| Secondary procedures due to endoleak between 31 days and 365 days | 6.5% | (12/186)^{8} | (3.4%, 11.0%) |
| Loss of patency of the stent graft at 12 months | 0% | (0/107) | (0.0%, 3.4%) |
| Loss of stent graft integrity at 12 months^{9} | 2.1% | (2/97)^{10} | (0.3%, 7.3%) |
| Change in maximum aneurysm diameter from 1 month image | | | |
| Increase > 5 mm | 8.5% | (11/129) | (4.3%, 14.7%) |
| Stable | 67.4% | (87/129) | (58.6%, 75.4%) |
| Decrease > 5 mm | 24.0% | (31/129) | (16.9%, 32.3%) |
| 1 - Confidence level was not adjusted for multiplicity. Confidence interval for the percentage was calculated by the exact (binomial) method.
2 - One (1) subject did not receive a stent graft due to extensive disease and heavy calcification of the iliac arteries.
3 - One (1) subject was converted to surgery. The stent graft was explanted 9 months post initial procedure due to an apparent infection in the stented segment of the aorta.
4 - One (1) subject experienced aneurysm rupture at the distal thoracic aorta, at the stent graft seal zone. Review of CT scans by the Core Lab revealed patient had a thoraco-abdominal aneurysm rather than an isolated descending thoracic aneurysm as well as an inadequate distal landing zone.
5 - Migration is defined as proximal or distal movement of the stent graft (>10mm) relative to fixed anatomic landmarks. The 1-month CTA/MRA was used as the baseline for this determination.
• Two (2) subjects had no MAEs due to their device migration.
• One (1) subject underwent a secondary procedure at Day 273. Two additional proximal main devices were implanted to resolve migration and cover a pseudoaneurysm. Repair was successful
• One (1) subject had no MAEs due to their device migration. Subject underwent a planned AAA open repair at approximately 2 months and expired at approximately 14 months from cirrhosis. | | | |

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| Secondary Endpoint | Incidences % (m / n) | 95% Exact CI^{1} |
| --- | --- | --- |
| 6 - None of the six (6) subjects with Type I endoleak underwent secondary procedure within 12 months | | |
| 7 - One (1) of the six (6) subjects with Type II endoleak underwent a secondary procedure at 140 days | | |
| 8 - The 12 subjects who received a secondary endovascular procedure are characterized as follows, all secondary repairs were successful:
• Two (2) patients had endoleaks detected at day 6 and 35, with secondary procedures at Day 84 and 186, respectively. Proximal mains were placed to correct Type I endoleaks (proximal).
• One (1) patient had endoleak detected at day 55, with secondary procedure at Day 334. Proximal extension was placed to correct Type I endoleak (proximal).
• Four (4) patients had endoleak detected at days 22, 29, 33 and 38, with secondary procedures at Day 140, 203, 116 and 253, respectively. Distal extensions were placed to correct three Type I endoleaks (distal) and one Type II endoleak.
• One (1) patient had endoleak detected at day 8, with secondary procedure at Day 113. Distal mains were placed to correct a Type III endoleak.
• Three (3) patients had endoleaks detected at day 19, 27 and 32, with secondary procedures at Day 56, 49 and 42, respectively. Proximal and distal mains were placed to correct one Type I (distal) endoleak and two Type I (proximal) endoleaks.
• One (1) patient had endoleak detected at day 155, with secondary procedure at Day 246. Proximal and Distal extensions were placed to correct a Type I (proximal) endoleak. | | |
| 9 - Loss of stent graft integrity is defined as the absence of stent fractures and/or graft fabric defects. | | |
| 10 - Of the two (2) subjects with loss of stent graft integrity, one was due to a nitinol spring fracture and the second was a connecting bar fracture. Neither subject had any adverse event related to these fractures. Both subjects are alive at 24 months. | | |

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# H. Supplemental Acute Procedural Data

Table 29 provides the Acute Procedural Data for VALOR Test Group and Retrospective Open Surgery Group. The VALOR Test Group showed reduced blood loss, reduced need for transfusions, as well as shorter ICU and hospital stays when compared to open surgery.

Table 29: Supplementary Acute Procedural Data

| Parameter | VALOR Test Group | Retrospective Open Surgery | 95% Confidence Interval of Difference |
| --- | --- | --- | --- |
| Subjects requiring blood transfusion (%) | 22.7% (44/194) | 93.7% (164/175) | (-77.5%, -63.5%) |
| Blood loss during procedure (ml) (mean ± SD)^{1} | 371.2 ± 514.4 | 3054.9 ± 1702.4 | (-2961.1, -2406.2) |
| Duration of implant procedure (min) (mean ± SD)^{2} | 154.2 ± 76.0 | 303.3 ± 97.6 | (-166.9, -131.3) |
| Time in Intensive Care Unit (hours) for all assessable subjects (mean ± SD)^{3} | 46.8 ± 114.3 | 185.3 ± 204.7 | |
| Overall hospital stay (days) (mean ± SD)^{4} | 6.4 ± 11.5 | 16.7 ± 15.0 | (-12.9, -7.5) |
| 1 - 189 VALOR Test Group subjects and 57 Retrospective Open Surgery subjects had known data for this parameter.
2 - 194 VALOR Test Group subjects and 178 Retrospective Open Surgery had known data for this parameter.
3 - 193 VALOR Test Group subjects and 168 Retrospective Open Surgery had known data for this parameter.
4 - 195 VALOR Test Group subjects and 186 Retrospective Open Surgery had known data for this parameter.
5 - Confidence level was not adjusted for multiplicity. Confidence intervals for difference (VALOR Test Group-Retrospective Open Surgery group) in means were calculated using a t-distribution. Confidence intervals for difference (VALOR Test Group-Retrospective Open Surgery group) in percentages were calculated by the exact method. Confidence interval for Time in ICU is not calculated due to a large number of ties in the data (i.e. large number of “0 hours” reported in the Test Group).
6 - For Duration of Procedure and Overall Hospital Stay, difference represents the (mean of specific acute procedural parameter in the population treated with the test device) - (mean of specific acute procedural parameter in the population undergoing open surgical repair). For Patients Requiring Blood Transfusion, difference represents the (% of patients with the specific acute procedural parameter for the population treated with the test device) - (% of patients with the specific acute procedural parameter for the population undergoing open surgical repair). | | | |

# I. Evaluation of Gender Bias

To more carefully evaluate the possible gender-based differences in outcome of treatment with the Talent™ Thoracic Stent Graft, a gender subset analysis was performed on safety and effectiveness outcomes within the VALOR Test Group. Female and male subjects had very similar all-cause mortality at 12 months (the Primary Safety Endpoint): 15.2% and 16.8%, respectively, for an overall rate of 16.1%. Successful aneurysm treatment at 12 months (the Primary Effectiveness Endpoint) was 98.2% in females and 82.4% in males for an overall rate of 89.2%. These findings indicate a nearly equal safety outcome for males and females and a higher successful aneurysm treatment rate for female subjects. Additional analyses of the performance of this device in female patients will be conducted as part of a post-approval study.

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# J. VALOR Test Group Results by Lesion Type

The VALOR Test Group consisted of subjects with the following three groups of lesion types:

- Subjects with fusiform thoracic aneurysms
- Subjects with saccular aneurysms and/or penetrating ulcers
- Subjects with multiple types of lesions (fusiform thoracic aneurysms and saccular and/or penetrating ulcers).

Demographic and lesion characteristics, as well as safety and effectiveness endpoint analysis by lesion type, are provided below in Tables 30 through 36. Although the safety and effectiveness results of each of the separate lesion types support the poolability of the data, this information is provided for completeness sake and for physician reference.

## Subject Demographics and Lesion Characteristics

Table 30: Subject Demographics by Lesion Type – VALOR Test Group Only

| | Fusiform | Saccular/Penetrating Ulcer | Multiple Lesion |
| --- | --- | --- | --- |
| Age for Total Population | | | |
| N | 112 | 70 | 13 |
| Mean ± SD (years) | 71.7 ± 9.2 | 68.0 ± 13.4 | 69.4 ± 11.9 |
| Median | 74.0 | 72.0 | 74.0 |
| Min-Max | 39 – 86 | 27 – 85 | 46 – 85 |
| Male | | | |
| N | 63 | 44 | 8 |
| Mean ± SD (years) | 70.7 ± 8.9 | 67.8 ± 14.6 | 67.1 ± 13.9 |
| Median | 73.0 | 72.0 | 72.5 |
| Min-Max | 50 – 85 | 27 – 85 | 46 – 85 |
| Female | | | |
| N | 49 | 26 | 5 |
| Mean ± SD (years) | 73.1 ± 9.3 | 68.5 ± 11.5 | 73.0 ± 7.8 |
| Median | 75.0 | 70.5 | 75.0 |
| Min-Max | 39 – 86 | 38 – 82 | 64 – 84 |
| Gender | | | |
| Males | 56.3% (63) | 62.9% (44) | 61.5% (8) |
| Females | 43.8% (49) | 37.1% (26) | 38.5% (5) |
| Ethnicity | | | |
| White, non-Hispanic | 84.8% (95) | 81.4% (57) | 76.9% (10) |
| Black- non-Hispanic | 12.5% (14) | 12.9% (9) | 15.4% (2) |
| Hispanic (White or Black) | 1.8% (2) | 2.9% (2) | 7.7% (1) |
| Asian/Pacific Islander | 0% (0) | 2.9% (2) | 0% (0) |
| Native American | 0% (0) | 0% (0) | 0% (0) |
| Other | 0.9% (1)¹ | 0% (0) | 0% (0) |
| 1- One subject declined providing ethnicity | | | |

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Table 31: Baseline Vessel Dimensions by Lesion Type: VALOR Test Group Only (Core Lab Reported¹)

| Vessel Dimension | n | Mean ± SD | Median | Min | Max |
| --- | --- | --- | --- | --- | --- |
| Proximal Neck Diameter (mm) | | | | | |
| Fusiform | 107 | 32.1 ± 4.7 | 32.5 | 19.0 | 43.5 |
| Saccular/Penetrating Ulcer | 67 | 29.8 ± 5.2 | 30.5 | 18.5 | 43.5 |
| Multiple Lesion | 13 | 31.0 ± 4.1 | 30.0 | 25.0 | 37.7 |
| Max Aneurysm Diameter (mm) | | | | | |
| Fusiform | 107 | 60.3 ± 9.1 | 59.0 | 43.5 | 88.8 |
| Saccular/Penetrating Ulcer | 68 | 48.0 ± 11.9 | 44.8 | 26.2 | 79.8 |
| Multiple Lesion | 12 | 55.7 ± 7.1 | 55.7 | 44.4 | 71.3 |
| Distal Neck Diameter (mm) | | | | | |
| Fusiform | 104 | 31.0 ± 4.8 | 30.8 | 18.5 | 42.0 |
| Saccular/Penetrating Ulcer | 67 | 27.9 ± 4.9 | 27.5 | 17.0 | 42.5 |
| Multiple Lesion | 13 | 28.4 ± 4.5 | 26.4 | 22.0 | 38.0 |
| Proximal Neck Length (mm) | | | | | |
| Fusiform | 107 | 82.4 ± 50.9 | 78.0 | 12.9 | 234.0 |
| Saccular/Penetrating Ulcer | 67 | 76.2 ± 56.0 | 70.0 | 10.0 | 214.0 |
| Multiple Lesion | 13 | 79.9 ± 42.2 | 78.9 | 18.0 | 149.0 |
| Aneurysm Length (mm) | | | | | |
| Fusiform | 101 | 145.7 ± 71.6 | 157.9 | 30.0 | 297.5 |
| Saccular/Penetrating Ulcer | 66 | 86.8 ± 63.6 | 63.0 | 8.0 | 258.9 |
| Multiple Lesion | 13 | 107.7 ± 49.5 | 99.0 | 34.0 | 186.0 |
| Distal Neck Length (mm) | | | | | |
| Fusiform | 104 | 74.1 ± 51.9 | 62.2 | 10.9 | 225.0 |
| Saccular/Penetrating Ulcer | 67 | 114.5 ± 71.3 | 105.0 | 9.0 | 255.0 |
| Multiple Lesion | 13 | 90.7 ± 60.7 | 66.7 | 11.9 | 180.8 |
| Right External Iliac Min Diameter (mm) | | | | | |
| Fusiform | 71 | 6.5 ± 1.6 | 6.3 | 3.5 | 11.0 |
| Saccular/Penetrating Ulcer | 43 | 6.7 ± 1.5 | 6.5 | 2.9 | 9.7 |
| Multiple Lesion | 8 | 5.5 ± 1.5 | 5.4 | 4.0 | 7.9 |
| Left External Iliac Min Diameter (mm) | | | | | |
| Fusiform | 71 | 6.7 ± 1.5 | 6.5 | 4.0 | 10.9 |
| Saccular/Penetrating Ulcer | 45 | 6.5 ± 1.5 | 6.5 | 3.3 | 9.6 |
| Multiple Lesion | 8 | 5.8 ± 1.5 | 6.1 | 3.4 | 8.0 |
| 1- Denominators are n specified from readable scans. | | | | | |

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Table 32: Baseline Vessel Shape by Lesion Type (Core Lab Reported1) – VALOR Test Group Only

| Vessel Shape | Fusiform % (m/n) | Saccular/Penetrating Ulcer % (m/n) | Multiple Lesion % (m/n) |
| --- | --- | --- | --- |
| Proximal Neck Shape | | | |
| Parallel | 14.0% (15/107) | 41.8% (28/67) | 30.8% (4/13) |
| Funnel | 22.4% (24/107) | 22.4% (15/67) | 23.1% (3/13) |
| Inverted Funnel | 63.6% (68/107) | 35.8% (24/67) | 46.2% (6/13) |
| Distal Neck Shape | | | |
| Parallel | 27.9% (29/104) | 49.3% (33/67) | 46.2% (6/13) |
| Funnel | 54.8% (57/104) | 37.3% (25/67) | 38.5% (5/13) |
| Inverted Funnel | 17.3% (18/104) | 13.4% (9/67) | 15.4% (2/13) |
| 1- Denominators are n specified for readable scans | | | |

Primary and Secondary Safety and Effectiveness Endpoint Analysis by Lesion Type

Table 33: Primary Safety Endpoint: All Cause Mortality by Lesion Type – VALOR Test Group Only

| Lesion Type | % (m/n) [95% CI]¹ |
| --- | --- |
| Fusiform | 15.6% (17/109) [9.4%-23.8%] |
| Saccular/Penetrating Ulcer | 15.7% (11/70) [8.1%-26.4%] |
| Multiple Lesion |…