VALIANT THORACIC STENT GRAFT SYSTEM

P100040 · Medtronic Vascular · MIH · Apr 1, 2011 · Cardiovascular

Device Facts

• Record ID: P100040
• Device Name: VALIANT THORACIC STENT GRAFT SYSTEM
• Applicant: Medtronic Vascular
• Product Code: MIH · Cardiovascular
• Decision Date: Apr 1, 2011
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Valiant® Thoracic Stent Graft with the Captivia Delivery 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 18–42 mm; and non-aneurysmal aortic proximal and distal neck lengths ≥ 20 mm.

Device Story

The Valiant Thoracic Stent Graft is a self-expanding, tubular endoprosthesis consisting of polyester graft fabric and a nitinol spring scaffold. It is delivered endoluminally via the femoral or iliac artery using the Captivia Delivery System. The system features a tip capture mechanism (FreeFlo configuration) for controlled two-stage deployment or a non-tip capture mechanism (Closed Web) for single-step deployment. The device is used by vascular surgeons in a clinical/OR setting. Upon deployment, the nitinol stent expands to conform to the aortic seal zones, providing a conduit to exclude the aneurysm from blood flow. Radiopaque markers facilitate visualization under fluoroscopy. The device is modular, allowing for multiple components to achieve sufficient coverage. By excluding the aneurysm, the device reduces the risk of rupture and aneurysm expansion, benefiting patients who are candidates for elective endovascular repair.

Clinical Evidence

Evidence includes the VALOR II prospective, multi-center, single-arm study (n=160) comparing the Valiant system to a historical Talent control group. Primary safety endpoint (all-cause mortality at 12 months) showed non-inferiority (upper 95% CI of adjusted odds ratio 1.18 < 2.25). Primary effectiveness (successful aneurysm treatment at 12 months) was 97.4% (lower 95% CI 93.4% > 80%). Secondary studies (Valiant Captivia OUS Registry, n=50; Talent Captivia Study, n=10) confirmed successful delivery and deployment of the Captivia system.

Technological Characteristics

Self-expanding tubular endoprosthesis; polyester graft fabric; nitinol wire spring scaffold; platinum-iridium radiopaque markers. Captivia Delivery System: 22, 24, 25 French outer diameter; 83 cm working length; hydrophilic coating. E-Beam sterilization (SAL 10^-6). Modular design with FreeFlo (bare spring) or Closed Web (covered spring) configurations. MR compatible at 1.5T and 3.0T.

Indications for Use

Indicated for patients 18-85 years old with fusiform or saccular aneurysms/penetrating atherosclerotic ulcers of the descending thoracic aorta. Requires appropriate iliac/femoral access, non-aneurysmal aortic diameter 18-42 mm, and proximal/distal neck lengths ≥20 mm. Contraindicated in patients with infection risk, device material allergies, connective tissue disease, or contained rupture.

Predicate Devices

• Talent Thoracic Stent Graft System (P070007)

Submission Summary (Full Text)

{0}

# Summary of Safety and Effectiveness Data

## 1.0 General Information

**Device Generic Name:**
Endovascular graft

**Device Trade Name:**
Valiant® Thoracic Stent Graft with the Captivia Delivery System

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

**Premarket Approval Application (PMA) Number:**
P100040

**Date of Panel Recommendation:**
None

**Date of Notice of Approval to the Applicant:**
April 1, 2011

## 2.0 Indications for Use

The Valiant® Thoracic Stent Graft with the Captivia Delivery 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 18–42 mm; and
- non-aneurysmal aortic proximal and distal neck lengths ≥ 20 mm.

Page 1 of 66

{1}

Page 2 of 66

# 3.0 Contraindications

The Valiant Thoracic Stent Graft with the Captivia Delivery System is contraindicated in the following clinical scenarios:

- Patients who have a condition that threatens to infect the graft.
- Patients who are sensitive to, or have allergies to, the device materials.

# 4.0 Warnings and Precautions

The warnings and precautions can be found in the Instructions for Use for the Valiant Thoracic Stent Graft with the Captivia Delivery System.

# 5.0 Device Description

## 5.1 Valiant Thoracic Stent Graft with the Captivia Delivery System

The Valiant Thoracic Stent Graft with the Captivia Delivery System is comprised of two components:

- Valiant Thoracic Stent Graft
- Captivia Delivery System

The Valiant Thoracic Stent Graft is intended to be delivered endoluminally via access through the femoral or iliac artery to the site of the lesion using the Captivia Delivery System. The stent graft is constrained by the delivery system outer sheath (graft cover) until deployed at the intended site of treatment. The pre-loaded stent graft is advanced to the diseased location over a guidewire. Upon deployment, the stent graft self-expands due to the superelastic properties of the nitinol stent. Following expansion of the device within the aorta, the proximal and distal ends of the stent 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.

### 5.1.1 Valiant Thoracic Stent Graft

The Valiant Thoracic Stent Graft is a self-expanding, tubular endoprosthesis composed of a polyester graft fabric and a spring scaffold made from nitinol wire. The metal scaffolding is composed of a series of serpentine springs stacked in a tubular configuration. The springs are sewn onto a polyester fabric with non-absorbable sutures.

Platinum-iridium radiopaque markers are sewn to the fabric to facilitate radiographic visualization of the graft material edge and the minimum overlap required when multiple stent grafts are used. The four proximal Figur8 markers, (shaped as a figure 8), and the two distal Zer0 markers, (shaped as a zero), indicate the extremities of the covered stent graft. The single Figur8 “mid-marker” indicates the minimum amount of overlap required for multiple components.

During manufacturing, the Valiant Thoracic Stent Graft is pre-loaded into a delivery system. See Figure 5-1 for a drawing of the Valiant Thoracic Stent Graft.

{2}

Figure 5-1: The Valiant Thoracic Stent Graft

# 5.1.1.1 Valiant Thoracic Stent Graft Configuration and Placement

The Valiant Thoracic Stent Graft is a modular device that accommodates the use of additional stent graft sections depending on the configuration of the anatomy where single or multiple components may be required to achieve sufficient coverage of the diseased aorta.

If the vessel diameter and condition require variable proximal and distal diameter devices, the smallest diameter stent graft should be placed first, either at the proximal or distal end of the lesion, as appropriate. The additional section is to be deployed within the primary piece following the oversizing requirements as detailed in the Instructions for Use (IFU) manual.

If the vessel diameter and condition require the same proximal and distal diameter devices, the primary section should be placed first at the proximal end of the lesion. To achieve the same final diameter with the proximal and distal sections, a tapered configuration is required for the distal section. The flare of the tapered graft permits the oversizing requirements between components.

Different end configurations are available to further accommodate anatomical dimensions. The proximal end comes in two configurations: FreeFlo or Closed Web (Figure 5-2). Devices with a FreeFlo proximal end configuration have a bare spring extending beyond the edge of the fabric at the proximal end of the stent graft and should be implanted in the most proximal position only. The Closed Web proximal end configuration, which has a covered spring at the proximal end of the stent graft, is implanted distally. The distal end configurations of the stent grafts are Closed Web or Bare Spring. The Closed Web distal end configuration has a covered spring at the distal end of the stent graft. The Bare Spring distal end configuration has a bare spring at the distal end of the stent graft that extends beyond the edge of the fabric.

Page 3 of 66

{3}

Figure 5-2: Valiant Thoracic Stent Graft End Configurations

FreeFlo Straight
(Proximal Component)

Distal Bare Spring
Straight (Distal Component)

1. Proximal End
2. Distal End
3. FreeFlo
4. Closed Web
5. Bare Spring
6. Mini Support Spring
7. Figure8 Marker
8. Zer0 Marker
9. Diameter
10. Covered Length
11. Total Length

Closed Web Straight
(Distal Component)

Closed Web Taper
(Distal Component)

NOTE: This and all other product graphics appearing in this summary are not drawn to scale, are for graphical representation only, and may appear differently under fluoroscopy.

Page 4 of 66

{4}

Page 5 of 66
12

## 5.1.2 Captivia Delivery System

The Captivia Delivery System is available in an outer diameter of 22, 24 and 25 French and consists of a single use, disposable catheter with an integrated handle to provide the user with controlled deployment. The working length of the Captivia Delivery System is 83 cm +/- 2 cm. The Captivia Delivery System (Figure 5-3) is the generic name for the following two delivery system configurations:

- The FreeFlo Stent Graft Delivery System (Tip Capture)
- The Closed Web Stent Graft Delivery System (non-Tip Capture)

## 5.1.2.1 The FreeFlo Stent Graft Delivery System

The FreeFlo Stent Graft Delivery System is used with the FreeFlo Straight configuration, the stent graft configuration that is implanted in the most proximal position. The delivery system features a tip capture mechanism from which the proximal stent graft is deployed in two stages:

(1) Deployment of the stent graft with the apices of the bare stent of the FreeFlo configuration still constrained by the tip capture mechanism; and
(2) Release of the proximal bare spring portion of the stent graft.

## 5.1.2.2 Closed Web Stent Graft Delivery System

The Closed Web Stent Graft Delivery System is used with the Closed Web Straight, Distal Bare Spring Straight, and Closed Web Tapered configuration stent grafts. Because these devices do not have a bare spring configuration at the proximal end of the stent graft, the Closed Web Delivery System does not include a tip capture mechanism. As a result, deployment using the Closed Web Delivery System is accomplished in a single step when the outer sheath is removed from the stent graft.

{5}

Page 6 of 66
/3

Figure 5-3: Captivia Delivery System
(The FreeFlo Stent Graft Delivery System on Top, Closed Web Stent Graft Delivery System on Bottom)



1. Luer Connector
2. Sideport Extension
3. Screw Gear
4. Slider/Handle
5. Trigger
6. Front Grip
7. Strain Relief
8. Graft Cover/Introducer Sheath
9. Stent Stop
10. Tip Capture Mechanism
11. RO Marker Band
12. Tapered Tip
13. Back End Lock
14. Tip Capture Release Handle
15. Clamping Ring

{6}

Page 7 of 66
14

# 6.0 Alternative Practices and Procedures

There are several other alternatives for the treatment of thoracic aortic aneurysms (TAA) including 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. The physician should fully discuss these alternatives with his/her patient to select the method that best meets expectations and lifestyle.

# 7.0 Marketing History

The Valiant Thoracic Stent Graft with the Captivia Delivery System has been commercially available for distribution outside of the United States since September 2009.

The Valiant Thoracic Stent Graft with the Captivia Delivery System has not been withdrawn from the market for any reasons related to safety or effectiveness.

# 8.0 Potential Adverse Effects of the Device on Health

Adverse events or complications associated with the use of the Valiant Thoracic Stent Graft with the Captivia Delivery System that may occur and that may require intervention include, but are not limited to, those listed in Table 8-1.

{7}

Table 8-1: Potential Adverse Effects

| • Access failure | • Endoleaks | • Procedural bleeding |
| --- | --- | --- |
| • Adynamic Ileus | • Excessive or inappropriate radiation exposure | • Prosthesis dilatation |
| • Allergic reaction (to contrast, anti-platelet therapy, stent graft material) | • Extrusion/erosion | • Prosthesis infection |
| • Amputation | • Failure to deliver the stent graft | • Prosthesis rupture |
| • Anesthetic complications | • Femoral neuropathy | • Prosthesis thrombosis |
| • Aneurysm expansion | • Fistula (including aortoenteric, arteriovenous, and lymph) | • Pseudoaneurysm |
| • Aneurysm rupture | • Gastrointestinal bleeding/complications | • Pulmonary edema |
| • Angina | • Genitourinary complications | • Pulmonary embolism |
| • Arrhythmia | • Hematoma | • Reaction to anaesthesia |
| • Arterial stenosis | • Hemorrhage/bleeding | • Renal failure |
| • Atelectasis | • Hypotension/hypertension | • Renal insufficiency |
| • Blindness | • Infection or fever | • Reoperation |
| • Bowel ischemia | • Insertion or removal difficulty | • Respiratory depression or failure |
| • Bowel necrosis | • Intercostal pain | • Sepsis |
| • Bowel obstruction | • Intramural hematoma | • Seroma |
| • Branch vessel occlusion | • Leg edema/foot edema | • Shock |
| • Breakage of the metal portion of the device | • Lymphocele | • Spinal neurological deficit |
| • Buttock claudication | • Myocardial infarction | • Stent graft migration |
| • Cardiac tamponade | • Neuropathy | • Stent graft misplacement |
| • Catheter breakage | • Occlusion – Venous or Arterial | • Stent graft occlusion |
| • Cerebrovascular accident (CVA)/Stroke | • Pain/Reaction at catheter insertion site | • Stent graft twisting or kinking |
| • Change in mental status | • Paralysis | • Transient ischemic attack (TIA) |
| • Coagulopathy | • Paraparesis | • Thrombosis |
| • Congestive heart failure | • Paraplegia | • Tissue necrosis |
| • Contrast toxicity | • Paresthesia | • Vascular ischemia |
| • Conversion to surgical repair | • Peripheral ischemia | • Vascular trauma |
| • Death | • Peripheral nerve injury | • Vascular dehiscence |
| • Deployment difficulties/ failures | • Pneumonia | • Wound dehiscence |
| • Dissection, perforation, or rupture of the aortic vessel & surrounding vasculature | • Post-implant syndrome | • Wound healing complications |
| • Embolism | • Post-procedural bleeding | • Wound infection |

Page 8 of 66

{8}

# 9.0 Summary of Preclinical Studies

## 9.1 Biocompatibility

Biocompatibility testing was conducted on materials that comprise the Valiant Thoracic Stent Graft and Captivia Delivery System in accordance with Good Laboratory Practices (21 CFR § 58), and in accordance with ISO 10993-1, and Jimurenraku No. 36 (Japan-specific biocompatibility tests as specified by Japan’s Ministry of Health, Labour, and Welfare (MHLW)).

Biocompatibility studies for the Valiant Thoracic Stent Graft were conducted based on the principles of an implant device that is in permanent contact with blood (&gt;30 days), whereas the studies for the Captivia Delivery System were based on the principles of an externally communicating device with limited contact with circulating blood (&lt;24 hr). Medtronic utilizes two separate suppliers (Supplier 1 and Supplier 2) for the Valiant Thoracic Stent Graft, both of which met the requirements as specified within the applicable standard.

Table 9-1 and Table 9-2 provide a summary of the biocompatibility test results for the Valiant Thoracic Stent Graft and the Captivia Delivery System, respectively.

Table 9-1: Summary of Biocompatibility Testing of Valiant Thoracic Stent Graft

| Test Description | Purpose | Results* (Medtronic Supplier 1) | Results* (Medtronic Supplier 2) | Results Acceptable (Y/N) |
| --- | --- | --- | --- | --- |
| Cytotoxicity, Colony Assay - MHLW | To evaluate the toxicity of the test article when exposed to Chinese Hamster Lung (V79) cells by determining the potential of the test article to inhibit colony formation in V79 cells. | The test article was not cytotoxic. There was no IC_{50} value for the test extract since toxicity was not observed. | The test article was not cytotoxic. There was no IC_{50} value for the test extract since toxicity was not observed. | Y |
| Material Mediated Pyrogen Study - USP | To evaluate the test article for the potential of inducing a pyrogenic response in rabbits. | All animals <0.5°C increase | All animals <0.5°C increase | Y |
| Bacterial Reverse Mutation - ISO | To evaluate whether the test article extract would cause mutagenic changes in the average number of revertants for Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli tester strain WP2uvrA in the presence and absence of S9 metabolic activation. | In no case was there a 2-fold or greater increase in the mean number of revertants of tester strains TA98, TA100, TA1535, TA1537, and WP2uvrA. | In no case was there a 2-fold or greater increase in the mean number of revertants of tester strains TA98, TA100, and WP2uvrA or a 3-fold or greater increase in the number of revertants of tester strains TA98, TA100, and WP2uvrA or a 3-fold or greater increase in the number of revertants of tester strains TA98, TA100, and WP2uvrA or a 3-fold or greater increase in the number of revertants of tester strains | Y |

Page 9 of 66

{9}

Page 10 of 66
17

| Test Description | Purpose | Results* (Medtronic Supplier 1) | Results* (Medtronic Supplier 2) | Results Acceptable (Y/N) |
| --- | --- | --- | --- | --- |
| | | | revertants of tester strains TA1535 and TA1537. | |
| In vitro Chromosomal Aberration - ISO | To evaluate the potential of the test article to induce chromosome aberrations, structural or numerical, in Chinese Hamster Ovary (CHO) cells in the presence or absence of an exogenous mammalian metabolic activation system. | The test article extract was not considered genotoxic to CHO cells in the presence or absence of metabolic activation. | The test article extract was not considered genotoxic to CHO cells in the presence or absence of metabolic activation. | Y |
| In vivo Mouse Micronucleus - ISO | To evaluate the potential of the test article to induce damage to the chromosomes or mitotic apparatus in mouse bone marrow cells. | No statistically significant increase in the number of MN-RETs for either test extract group. | No statistically significant increase in the number of MN-RETs for either of the test extract groups. | Y |
| Sensitization - MHLW | To evaluate the potential for the test article to cause dermal sensitization. | 1%, 10% and 100% test article extracts showed no evidence of causing sensitization. All Test Animals were graded 0. | 100%, 50% and 25% test article extracts showed no evidence of causing sensitization. All Test Animals were graded 0. | Y |
| Intracutaneous Reactivity - ISO | To evaluate the test article for potential irritation effects as a result of an intracutaneous injection in rabbits. | Difference between test and control mean scores: Sodium Chloride: 0.0 Sesame Oil: 0.0 | Difference between test and control mean scores: Sodium Chloride: 0.0 Sesame Oil: 0.0 | Y |
| Acute Systemic Toxicity - MHLW | To evaluate the test article for the potential for toxic effects after a single-dose systemic injection into mice. | There was no mortality or evidence of systemic toxicity. | There was no mortality or evidence of systemic toxicity. | Y |
| In vitro Hemolysis - MHLW | To evaluate the hemolytic activity of the test article when in contact with rabbit blood. | 1, 2, 4 hrs: all 0% | 1, 2, 4 hrs: all 0% | Y |
| In vitro Hemolysis - ASTM | To determine whether the test article causes hemolysis in vitro by direct | | Extraction Method Hemolytic Index = 0.2% | Y |

{10}

Page 11 of 66
18

| Test Description | Purpose | Results* (Medtronic Supplier 1) | Results* (Medtronic Supplier 2) | Results Acceptable (Y/N) |
| --- | --- | --- | --- | --- |
| | contact or extraction. | | Direct Contact Method Hemolytic Index = 3.3% | |
| Complement Activation, C3a - ISO | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | Concentration of C3a in the test extract was not significantly higher than the activated NHS or the negative control. | Concentration of C3a in the test extract was not statistically higher than the activated NHS control or the negative control. | Y |
| Complement Activation, SC5b-9 - ISO | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | | Concentration of SC5b-9 in the test extract was statistically higher than both the activated NHS control and the negative control. As a result, the SC5b-9 concentration of the test article was compared to historical data for the negative control and with the SC5b-9 concentration of the positive biomaterial reference control. Based on the level of activation as compared to the various controls and historical data, the test article results indicate a relatively low biological potential of activating the complement system. | Y |
| In vivo Thromboresistance - | To evaluate the potential of the test article to resist | | Test article scored similarly as | Y |

{11}

Page 12 of 66
19

| Test Description | Purpose | Results* (Medtronic Supplier 1) | Results* (Medtronic Supplier 2) | Results Acceptable (Y/N) |
| --- | --- | --- | --- | --- |
| ISO | thrombus formation. | | compared to sponsor-provided controls. Both demonstrated thromboresistance. | |
| 4-wk Subchronic Toxicity (Subcutaneous Implantation) - ISO | To determine the systemic toxicity potential of the test article following subcutaneous implantation in rats for 4 weeks. | There was no evidence of systemic toxicity from the test article.
Local macroscopic tissue reaction was not significant as compared to the negative control.
Microscopically, the test article was considered a slight irritant. Based on the nature and shape of the test article implanted, it appeared that the local reaction noted and associated clinical pathology changes were due to skin penetration and not something inherently irritating or toxic associated with the test article. | There was no evidence of systemic toxicity from the test article.
Local macroscopic tissue reaction was not significant as compared to the negative control.
Microscopic evaluation indicated the test article as a non-irritant. | Y |
| 12-wk Muscle Implantation - ISO | To evaluate the potential of the test article to induce local toxic effects after implantation in the muscle tissue of rabbits for 12 weeks. | Macroscopic reaction was not significant compared to the negative control.
Microscopically, test article was | Macroscopic reaction was not significant compared to the negative control.
Microscopically, test article was | Y |

{12}

| Test Description | Purpose | Results* (Medtronic Supplier 1) | Results* (Medtronic Supplier 2) | Results Acceptable (Y/N) |
| --- | --- | --- | --- | --- |
| | | classified as a non-irritant compared to the negative control. | classified as a slight irritant compared to the negative control. | |
| *The test lab's GLP protocol acceptance criteria changed between the time of testing at supplier 1 and supplier 2. Both studies were completed per the approved GLP protocol at the time of testing. | | | | |

Page 13 of 66
20

{13}

Table 9-2: Summary of Biocompatibility Testing of Captivia Delivery System

| Test Description | Purpose | Results | Results Acceptable (Y/N) |
| --- | --- | --- | --- |
| Cytotoxicity - MHLW | To evaluate the toxicity of the test article when exposed to Chinese Hamster Lung (V79) cells by determining the potential of the test article to inhibit colony formation in V79 cells. | The test article was not cytotoxic.
There was no IC_{50} value for the test extract since toxicity was not observed. | Y |
| Material Mediated Pyrogen Study – USP | To evaluate the test article for the potential of inducing a pyrogenic response in rabbits. | All animals <0.5°C increase. | Y |
| Maximization Sensitization – ISO | To evaluate the allergenic potential or sensitizing capacity of the test article upon exposure to guinea pigs. | All test and control animals were grade 0 (No visible change). | Y |
| Intracutaneous Reactivity – ISO | To evaluate the test article for potential irritation effects as a result of an intracutaneous injection into rabbits. | Difference between test and control mean scores: Sodium Chloride: 0.0 Sesame Oil: 0.0 | Y |
| Acute Systemic Toxicity – MHLW | To evaluate the test article for the potential for toxic effects after a single-dose systemic injection into mice. | There was no mortality or evidence of systemic toxicity. | Y |
| In vitro Hemolysis - MHLW | To evaluate the hemolytic activity of the test article when in contact with rabbit blood. | 1, 2, 4 hrs: all 0% | Y |
| Complement Activation, C3a - ISO | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | Concentration of C3a in the test extract was not statistically different than both negative control and sponsor provided control at all three time points. | Y |
| Complement Activation, SC5b-9 - ISO | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | Concentration of SC5b-9 in the test extract was lower than the negative control but similar to sponsor provided control at all three time points. | Y |
| In vivo Thromboresistance - ISO | To evaluate the potential of the test article to resist thrombus formation. | All test and sponsor provided control articles scored the same = 0 (No thrombosis). | Y |

Page 14 of 66

{14}

Page 15 of 66

# 9.2 Sterilization/Packaging/Shelf Life

The Valiant Thoracic Stent Graft with the Captivia Delivery System is a single-use device that is provided sterile to the end user. The Valiant Thoracic Stent Graft with the Captivia Delivery System is sterilized using E-Beam sterilization and is validated to demonstrate a Sterility Assurance Level (SAL) of $10^{-6}$.

Packaging performance and stability testing demonstrate that the packaging designs for the Valiant Thoracic Stent Graft with the Captivia Delivery System are sufficient to adequately protect the device and maintain the integrity of the Valiant Thoracic Stent Graft System package throughout its two-year shelf life claim.

Shelf-life testing results are presented within the *in vitro* bench test results as part of Table 9-3. Accelerated shelf-life product testing conducted on the Valiant Thoracic Stent Graft with the Captivia Delivery System supports a 2-year shelf-life claim.

# 9.3 Laboratory Studies

## Bench Testing

Medtronic conducted comprehensive preclinical, bench and analytical testing on the Valiant Thoracic Stent Graft with the Captivia Delivery System. The *in vitro* testing was intended to verify that the performance attributes of the Valiant Thoracic Stent Graft with the Captivia Delivery 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 details include results from $T=0$ (baseline) as well as results using samples accelerated aged to 2 years ($T=2$). An asterisk (*) indicates testing was performed at both $T=0$ and $T=2$. Testing verified that the Valiant Thoracic Stent Graft with the Captivia Delivery System met its product performance and design specifications.

Results obtained from *in vitro* testing provided evidence supporting the safety and effectiveness of the Valiant Thoracic Stent Graft with the Captivia Delivery System.

Table 9-3: Summary of Tests Performed related to Functionality of the Valiant Thoracic Stent Graft with the Captivia Delivery System

| Test | Test Purpose | Acceptance Criteria | Pass/Fail |
| --- | --- | --- | --- |
| Stent Graft Design Verification Testing | | | |
| Stent Graft Visual Expansion Integrity* | To evaluate any damage that occurs to the Valiant Thoracic Stent after deployment and demonstrate that the stent graft integrity meets the acceptance criteria. | No broken stents, minimum suture stitch density intact, support spring and RO markers attached, no graft tears, no graft holes larger than a diameter of 0.5 mm. | Pass |
| Stent Graft Recoil (Dimensional Verification)* | To confirm that the outer diameter of the Valiant Thoracic Stent Graft recovers within the specification after deployment, demonstrating that it meets the acceptance criteria. | The Valiant Thoracic Stent Graft must expand to a diameter that is ≥ 1 mm less than the labeled nominal diameter for aortic sections. | Pass |

* Indicates a significant difference in the average of the two test attributes.

{15}

Page 16 of 66
23

| Test | Test Purpose | Acceptance Criteria | Pass/Fail |
| --- | --- | --- | --- |
| Spring Attachment Strength* | To measure the tensile strength of the attachment of the bare and body springs to the Valiant Thoracic Stent Graft and demonstrate spring attachment strength meets the acceptance criteria. | Spring Attachment Strength LTL > 32.0 lbf (142 N) | Pass |
| Stent Graft Burst* | To determine the burst strength of the Valiant Thoracic Stent Graft and demonstrate that it meets the acceptance criteria. | Stent Graft Burst Pressure LTL ≥ 18.8 psi (130 kPa) | Pass |
| Stent Graft Crimp Strength | To determine the strength of the bond between the crimp sleeve and the stent strut used on the Valiant Thoracic Stent Graft spring and demonstrate that it meets the acceptance criteria. | Ultimate Tensile Strength LTL > 6.4 lbf (28 N) | Pass |
| Radial Force | To determine the radial force exerted by the Valiant Thoracic Stent Graft in the proximal seal zone, distal seal zone and individual body stents and demonstrate that the stent graft radial force meets the acceptance criteria. | Radial Strength ≥ 8 mmHg (1.067 kPa) | Pass |
| Stent Graft Conformability | To determine the minimum radius of curvature that the stent graft can accommodate without kinking. | Valiant Stent Graft kink radius must show improved kink resistance in a simulated thoracic anatomy compared to the Talent Thoracic Stent Graft. | Pass |
| Stent Graft Migration | To quantify the peak migration force of the stent grafts in mock blood vessels and demonstrate that the migration force meets the acceptance criteria. | Stent Graft Migration Pressure LTL ≥ 300 mmHg (40.0 kPa) | Pass |
| Stent Graft Permeability | To determine the rate of water leakage through the entire stent-graft wall, or any areas where leakage is of concern, under a pressure of 120 mmHg. | Characterization Test; Samples characterized to be <700ml/min/cm². | Results Acceptable |
| Stent Graft Joint Strength | To evaluate the joint strength between components of Endovascular Stent Graft (ESG) Systems. | Valiant Thoracic Stent Graft joint strength ≥ Talent Thoracic Stent Graft joint strength | Pass |
| Simulated Use Testing | To evaluate the performance of the Valiant Thoracic Stent Graft with the Captivia Delivery System in an anatomically representative bench top model. | The Valiant Thoracic Stent Graft with the Captivia Delivery System must exhibit the ability to reach the target treatment site, deploy the stent graft, and be withdrawn from the model. | Pass |
| Stent Graft Corrosion Testing | To evaluate the breakdown potential for the 8-peak and 5-peak chemically etched springs, as well as the support spring. | Characterization Test; Results indicate acceptable corrosion resistance. Clinical performance with the Valiant Thoracic Stent Graft indicates acceptable corrosion resistance in clinical use. | Results Acceptable |

{16}

Page 17 of 66
24

| Test | Test Purpose | Acceptance Criteria | Pass/Fail |
| --- | --- | --- | --- |
| Angulated Pulsatile Fatigue | To evaluate the device durability following 10 years simulated (400 million cycles) accelerated in vitro testing under clinically-relevant loading conditions. | Each test sample must complete 400 million cycles of pulsatile fatigue testing without a stent fracture. Graft material and suture durability characterized and compared to wear from clinically explanted specimens | Pass |
| Spring Component Fatigue | To evaluate the spring durability following 10 years simulated (400 million cycles) accelerated in vitro testing under clinically-relevant loading conditions. | Each test sample must complete 400 million test cycles of radial dilatation testing at physiologically challenging radial distension parameters without a stent fracture. | Pass |
| Overlap Radial Dilatation Fatigue | To evaluate the overlap fatigue interaction between a Valiant stent graft deployed within another Valiant Stent Graft in a vessel supported region during a 10 year simulation consisting of 400 Million cycles of accelerated in vitro testing. | Each test sample must complete 400 million test cycles of radial dilatation testing at physiologically challenging radial distension parameters without a stent fracture. Graft material and suture durability characterized and compared to wear from clinically explanted specimens. | Pass |
| Finite Element Analysis | To quantify the levels of strain of 8-peak and 5-peak springs when subjected to in vivo fatigue conditions. | Characterization Test; Fatigue safety factors characterized to be > 1 based on the endurance limit determined through endurance life testing. | Results Acceptable |
| Magnetic Resonance Compatibility | To ensure that the stent graft does not pose additional risk when the patient is subjected to a MR procedure. | 1. No additional patient risk when subjected to 1.5T & 3.0T magnetic fields.
2. Characterize image artifact created by 1.5T & 3.0T magnetic fields. | Pass |
| Delivery System Verification Testing | | | |
| Graft Cover Working Length | To determine the working length of the graft cover of the Captivia delivery system and demonstrate that it meets the acceptance criteria. | Working Length = 83 ± 2 cm | Pass |
| Tapered Tip Length | To determine the working length of the Tapered Tip of the Captivia delivery system and demonstrate that it meets the acceptance criteria. | • 22 Fr 3.8 ± 0.1 cm
• 24 Fr 4.6 ± 0.1 cm
• 25 Fr 4.6 ± 0.1 cm | Pass |
| Hydrophilic Coating Length | To determine the Hydrophilic Coating Length on the Captivia delivery system and demonstrate that it meets the acceptance criteria. | Coating Length ≥ 60 cm | Pass |
| Hydrophilic Coating Drag Force* | To determine the drag force of the hydrophilic coating on the Captivia delivery system graft cover and demonstrate that it meets the acceptance criteria. | Average drag force on coated graft cover UTL < 3.00 lbf (13.3 N) | Pass |
| Delivery System Hemostasis (with and without tip)* | To determine the ability of the Captivia Delivery System to maintain an adequate hemostatic seal and demonstrate that seal meets the acceptance criteria. | Flow Rate < 2 cc/min | Pass |

{17}

Page 18 of 66
25

| Test | Test Purpose | Acceptance Criteria | Pass/Fail |
| --- | --- | --- | --- |
| Tapered Tip Bond Strength* | To determine the tensile strength of the bond between the molded Tapered Tip and the inner member of the Captivia Delivery System and demonstrate that this bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 10.0 lbf (44.5 N) | Pass |
| Capture Fitting Tensile* | To measure the tensile strength of the connection between the Capture Fitting and the Capture Tube of the Captivia FreeFlo Delivery System and demonstrate that this connection meets the acceptance criteria. | Ultimate Tensile Strength LTL > 7.5 lbf (33 N) | Pass |
| Threaded Spindle to Tapered Tip Insert Tensile* | To measure the tensile strength of the connection between the Threaded Spindle and the Tapered Tip Insert of the Captivia FreeFlo Delivery System and demonstrate that the connection meets the acceptance criteria. | Ultimate Tensile Strength LTL > 10.0 lbf (44.5 N) | Pass |
| Tip Capture T-tube Tensile* | To measure the tensile strength of the connection between the Tip Capture T-Tube and the Capture Tube of the Captivia FreeFlo Delivery System and demonstrate that the connection meets the acceptance criteria. | Ultimate Tensile Strength LTL > 15.0 lbf (66.7 N) | Pass |
| Back End T-Tube Tensile* | To measure the tensile strength of the connection between the Back End T-Tube and the Inner Member of the Captivia Delivery System and demonstrate that the connection meets the acceptance criteria. | Ultimate Tensile Strength LTL > 10.0 lbf (44.5 N) | Pass |
| Middle Member – Flexible Stent Stop Bond Strength* | To measure the tensile strength of the bond between the Middle Member and Flexible Stent Stop of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 10.0 lbf (44.5 N) | Pass |
| Middle Member Collar to Middle Member Tensile Strength* | To measure the tensile strength of the bond between the Middle Member Collar and the Middle Member of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 8.0 lbf (36 N) | Pass |
| Middle Member to Screw Gear Interface* | To measure the force required to cause failure of the screw gear ribs that act as an interference for the middle member in the Captivia Delivery System. | Ultimate Tensile Strength LTL > 32.0 lbf (142 N) | Pass |

{18}

Page 19 of 66
26

| Test | Test Purpose | Acceptance Criteria | Pass/Fail |
| --- | --- | --- | --- |
| Graft Cover Yield Strength* | To determine the graft cover yield strength of the Captivia Delivery System and demonstrate that it meets the acceptance criteria. | Graft Cover Yield Strength LTL > Deployment Force UTL | Pass |
| Radiopaque Marker Bond Strength* | To measure the tensile strength of the bond between the Radiopaque (RO) Marker Band and the Graft Cover of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Radiopaque Marker Bond Strength LTL > 15.0 lbf (66.7 N) | Pass |
| Sideport Extension Bond Strength | To determine the bond strength of the Sideport Extension on the Captivia Delivery System and demonstrate that it meets the acceptance criteria. | Ultimate Tensile Strength LTL > 5.0 lbf (22 N) | Pass |
| Front Grip Tensile Strength* | To measure the force required to separate the Front Grip from the Screw Gear of the Captivia Delivery System and demonstrate that these components meet the acceptance criteria. | Ultimate Tensile Strength LTL > 32.0 lbf (142 N) | Pass |
| Hubcap Tensile Strength* | To measure the tensile strength of the bond between the Hubcap and T-Tube of the Captivia Delivery System and demonstrate that this bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 0.75 lbf (3.3 N) | Pass |
| Handle T-Tube Bond Strength* | To determine the ultimate tensile strength of the Handle T-Tube Assembly of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 32.0 lbf (142 N) | Pass |
| Handle T-Tube Torque Strength | To measure the torsional forces created by the friction between the Handle T-Tube and graft cover of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Ultimate Torque Strength LTL > 1.62 in-lb (18.3 N-cm) | Pass |
| End Seal – Hypotube Tensile Strength* | To measure the tensile strength of the bond between the End Seal and Hypotube of the Captivia Delivery System and demonstrate that the bond meets the acceptance criteria. | Ultimate Tensile Strength LTL > 5.0 lbf (22 N) | Pass |

Endovascular Stem/Graft System/Fertification Testing

{19}

| Test | Test Purpose | Acceptance Criteria | | Pass/Fail |
| --- | --- | --- | --- | --- |
| Crossing Profile* | To measure the outside diameter of the Captivia Delivery System and demonstrate that the crossing profile meets the acceptance criteria. | The appropriate ring gage diameter must pass over the loaded delivery system sizes per the table shown below: | | Pass |
| | | Catheter Size | Ring Gage Diameter | |
| | | 22 Fr | 22.5 Fr | |
| | | 24 Fr | 24.5 Fr | |
| | | 25 Fr | 25.5 Fr | |
| Guidewire Acceptance* | To confirm that the Captivia Delivery System is compatible with a Ø0.035" (0.89 mm) guidewire and demonstrate that the guidewire acceptance meets the acceptance criteria. | A 0.035" (0.89 mm) diameter guidewire must pass through the guidewire lumen of the Captivia Delivery System with minimal resistance. | | Pass |
| Trackability and Pushability** | To evaluate the Trackability and Pushability of the Captivia Delivery System. | The Captivia Delivery System must be advanced to and reach the target treatment site. | | Pass |
| Deployment Force* | To determine the force required to deploy the Valiant Thoracic Stent Graft from the Captivia Delivery System and demonstrate that the deployment force meets the acceptance criteria. | Deployment Force UTL < LTL of Graft Cover Yield Strength | | Pass |
| Capture Tube Retraction Force* | To determine the force required to retract the Capture Tube in the Valiant Thoracic Stent Graft with the Captivia FreeFlo Delivery System and demonstrate that the capture tube retraction force meets the acceptance criteria. | Capture Tube Retraction Force UTL < LTL of Tip Capture T-Tube Ultimate Tensile Strength | | Pass |
| * Indicates testing was performed at both T=0 and T=2
** Testing was conducted for characterization only at T=2 | | | | |

## In vivo Animal Testing

Preclinical, in vivo animal testing, using prototypes of the final device design of the Valiant Thoracic Stent Graft with the Xcelerant Delivery System, was conducted for up to six months in 16 ovine test systems to evaluate acute technical success (deployment), stent graft integrity, and histopathological response of the Valiant Thoracic Stent Graft. The results demonstrated adequate handling and visualization of the Valiant Thoracic Stent Graft with the Xcelerant Delivery System, an adequate ability to access the target anatomical location, and adequate deployment accuracy. Although, the in vivo animal testing was conducted with the prior delivery system (i.e. Xcelerant), the vast majority of the testing evaluated the stent graft which remains unchanged. Stent graft integrity and histopathological responses were acceptable. A summary of the in vivo animal testing is provided in Table 9-4.

Page 20 of 66

{20}

Table 9-4: Summary of in vivo Studies conducted using the Valiant Thoracic Stent Graft with the Xcelerant Delivery System

| Study | # of Animals | Objectives | Success Criteria | Objectives Met |
| --- | --- | --- | --- | --- |
| 30 and 60 Day Safety Study FS154 (GLP): Evaluation of the Valiant Thoracic Stent Graft with the Xcelerant Delivery System in an Ovine Model | 9 | The objectives of the study were as follows:
• Assess acute stent placement and any device related effects at the time of implant;
• Evaluate the position of the implant at the time of explant;
• Evaluate the structural integrity of the Valiant Thoracic Stent Graft at the time of explant;
• Evaluate the histology and pathology of the explants and surrounding tissue. | • Test device mean evaluation scores for each acute performance characteristic of 'average' or greater.
• Distal migration of the test devices of no more than 10 mm was considered acceptable. Position of the stent graft at implant and explant was compared using anatomical landmarks and aortograms and any change in position was documented.
• Evaluation of the structural integrity of the Valiant Thoracic Stent Graft at explant before animal termination was evaluated using angiography and/or x-rays. Success was determined by the lack of evidence of stent fractures.
• Comparable or superior histological indicators of vessel wall healing at 30 and 60 days for the Valiant Thoracic Stent Graft test devices as compared to the Talent Thoracic Stent Graft control data, including strut induced vessel wall injury, and inflammation.
• Overall quantitative morphometric analysis of tissue sections from the test device indicating similar or better vascular response than the Talent control data. | Yes |

Page 21 of 66
28

{21}

Page 22 of 66
29

| Study | # of Animals | Objectives | Success Criteria | Objectives Mat |
| --- | --- | --- | --- | --- |
| 180 Day Safety Study FS159 (GLP): Evaluation of the Valiant Thoracic Stent Graft with the Xcelerant Delivery System in an Ovine Model | 7 | The objectives of the study were as follows:
• Assess acute stent placement and any device related effects at the time of implant;
• Evaluate the position of the implant at the time of explant;
• Evaluate the structural integrity of the Valiant Thoracic Stent Graft at the time of Explant;
• Evaluate the histology and pathology of the explants and surrounding tissue. | • Test device mean evaluation scores for each acute performance characteristic of 'average' or greater.
• Distal migration of the test devices of no more than 10 mm was considered acceptable. Position of the stent graft at implant and explant was compared using anatomical landmarks and aortograms and any change in position was documented.
• Evaluation of the structural integrity of the Valiant Thoracic Stent Graft at explant before animal termination was evaluated using angiography and/or x-rays. Success was determined by the lack of evidence of stent fractures.
• Comparable or superior histological indicators of vessel wall healing at 180 days for the Valiant Thoracic Stent Graft test devices as compared to the Talent Thoracic Stent Graft control data, including strut induced vessel wall injury, and inflammation.
• Overall quantitative morphometric analysis of tissue sections from the test device indicating similar or better vascular response than the Talent control data. | Yes^{1} |
| ^{1} Please note that some degree of change in device position that may have exceeded 10 mm was noted in some cases upon angiographic measurement with respect to radiographic anatomic landmarks. However, these measurements are not necessarily reliable because of issues with parallax error that arose either from difficulties in reproducing the exact position of the animal on the table or due to some degree of animal body growth over the in-life period of the study. | | | | |

{22}

Page 23 of 66
# 10.0 Summary of Clinical Studies

The safety and effectiveness data supporting the Valiant Thoracic Stent Graft with the Captivia Delivery System included data from three multi-center studies conducted across the United States, European Union and Turkey. The aforementioned studies are summarized in Table 10-1. Please note that there were no prior feasibility studies performed using the Valiant Thoracic Stent Graft.

Table 10-1: Summary of Clinical Studies – Test Groups

| Clinical Study | Study Design | Objective | Number of Sites | Number of Subjects Enrolled |
| --- | --- | --- | --- | --- |
| VALOR II Study G050238 | Prospective, multi-center, single arm study with comparison to a historical control on the primary safety endpoint | To evaluate the safety and effectiveness of the Valiant Thoracic Stent Graft with the Xcelerant Delivery System in the United States | 24 | 160 subjects |
| Valiant Captivia OUS Registry | Post-market, non-interventional, single-arm, multicenter study | To evaluate the clinical performance of the Valiant Thoracic Stent Graft with the Captivia Delivery System in Europe and Turkey following market approval | 13 | 50 subjects |
| Talent Captivia Study G980116 | Prospective, non-randomized, multicenter study (Extension of the VALOR High Risk Arm) | To evaluate the acute clinical performance of the Talent Thoracic Stent Graft with the Captivia Delivery System | 4 | 10 subjects |

## 10.1 VALOR II Clinical Study Design

The clinical study that formed the basis for FDA’s finding that the Valiant Thoracic Stent Graft System is safe and effective for its intended use was an open-label, non-randomized, prospective, multicenter, single arm study. Medtronic conducted the VALOR II clinical study to establish a reasonable assurance of safety and effectiveness of endovascular treatment of Descending Thoracic Aneurysms (DTA) with the Valiant Thoracic Stent Graft System.

## 10.1.1 Major Design Characteristics

The VALOR II clinical study (“Valiant Test Group”) enrolled 160 subjects at 24 investigational sites across the United States under the same indications and similar study requirements as the VALOR clinical study (“Talent Control Group”). The Valiant Test Group enrolled patients diagnosed with a fusiform aneurysm and/or saccular aneurysm/penetrating atherosclerotic ulcer of the descending thoracic aorta who were considered candidates for elective surgical repair and who were low to moderate risk (SVS 0, 1, and 2) per the modified SVS/AAVS scoring system at the time of implant. A subject was

{23}

Page 24 of 66
considered officially enrolled when an access site incision was made. After enrollment, subjects are required to return for follow-up visits at 30 days, 6 months, 12 months and annually thereafter for a total of five years. Assessments at these visits include a physical examination, CT/MR, chest X-ray, and adverse event evaluation. The enrolled subjects with evaluable data were used for analysis at the completion of the 30-day, 6-month and 12-month follow-up visits.

## 10.1.1.1 Level of Masking

The Valiant Test Group was enrolled in a single-arm open-label clinical study.

## 10.1.1.2 Type of Controls

The Valiant Test Group was compared to the Talent Control Group on the primary safety endpoint (Table 10-2). The Talent Control Group, which enrolled 195 subjects, was used as the pivotal study group to evaluate the safety and effectiveness of the Talent Thoracic Stent Graft System (refer to the Summary of Safety and Effectiveness Data for the Talent Thoracic Stent Graft System (P070007) for more information).

Table 10-2: Talent Thoracic Stent Graft System Clinical Study Summary – Control Group

| Clinical Study | Study Design | Objective | Number of Sites | Number of Subjects |
| --- | --- | --- | --- | --- |
| VALOR Study G980116 | Prospective, non-randomized, multi-center study (Pivotal Test Group) | To evaluate the safety and effectiveness of the Talent Thoracic Stent Graft with the CoilTrac Delivery System in the United States | 38 | 195 subjects |

## 10.1.1.3 Duration of Study

The Talent Control Group was enrolled between March 2003 and June 2005, while the Valiant Test Group was enrolled between December 2006 and September 2009. The enrolled subjects with evaluable data were used for analyses at the completion of 30-day and 12 month follow-up visits. Long-term safety and effectiveness data on the Valiant Thoracic Stent Graft with the Xcelerant Delivery System will be collected by following enrolled subjects for a total of five years under the investigational plan.

## 10.1.1.4 Method of Allocation to Treatment Group

All subjects in the Valiant Test Group were enrolled to a single arm.

## 10.1.1.5 Treatment Arms

All subjects in the Valiant Test Group were enrolled to a single arm.

{24}

Page 25 of 66

## 10.1.2 Clinical Endpoints

The analysis included clinically relevant endpoints for patients with thoracic aortic disease. The endpoints used by Medtronic to demonstrate the safety of the device were adequate to describe the adverse events resulting from using the Valiant Thoracic Stent Graft System. Similarly, the endpoints used by Medtronic to demonstrate the effectiveness of the device were adequate to demonstrate the treatment effect.

## 10.1.2.1 Safety

The primary safety endpoint was the demonstration of non-inferiority of the Valiant Test Group relative to the Talent Control Group of all-cause mortality within 12 months.

Hypothesis testing for the primary safety endpoint consisted of a comparison of the rates of all-cause mortality within 12 months for the Valiant Test Group and the Talent Control Group using an adjusted odds ratio. The primary analysis was performed on the null hypothesis of inferiority of the Valiant Test Group relative to the Talent Control Group using the Cochran-Mantel-Haenszel (CMH) to control for SVS scores. Rejection of the null hypothesis required the upper-endpoint of the exact 1-sided 95% confidence interval of the adjusted odds ratio to be less than a non-inferiority margin of 2.25. The primary analysis set for the primary safety endpoint was the intent-to-treat¹ (ITT) population.

## 10.1.2.2 Effectiveness

The primary effectiveness endpoint was Successful Aneurysm Treatment at 12 months which was defined as the absence of both:

- Aneurysm growth of more than 5 mm at the 12-month visit relative to the 1 month visit;
- Type I and/or Type III endoleak for which a secondary procedure was performed or recommended at or before the 12 month follow-up visit.

Hypothesis testing for the primary effectiveness endpoint consisted of a comparison to a fixed value of 80%. Rejection of the null hypothesis required the lower endpoint of an exact 1-sided 95% confidence interval to be greater than 80%. The primary analysis set for the primary effectiveness endpoint was the implanted population.

## 10.1.2.3 Secondary Endpoints

The secondary endpoints included the following acute and 12-month study endpoints:

- Within 30 days: successful delivery and deployment of the stent graft; peri-operative mortality; paraplegia; paraparesis; secondary procedures due to endoleak after discharge; and one or more major adverse event(s) (MAE);

¹A subject was considered officially enrolled when an access site incision was made. This group of subjects is referred to as the intent-to-treat (ITT) population.

{25}

- Within 12 months: aneurysm-related mortality; secondary endovascular procedures due to endoleak after 30 days; conversion to open surgical repair; migration of the stent graft; loss of patency of the stent graft; aneurysm rupture; endoleak at 12 months; and one or more MAE.

Several additional descriptive statistics were calculated for complications including aortic dissection, stent graft integrity, changes in aneurysm diameter, additional secondary procedures, and stroke. Supplementary data included acute procedural data on the amount of blood loss, subjects requiring transfusion, duration of implant procedure, time in the intensive care unit, and overall hospital stay.

## 10.1.3 Success/Failure Criteria

The VALOR II US clinical study was considered successful if the null hypotheses for the tests of primary safety and effectiveness endpoints as described in Section 10.1.2.1 and Section 10.1.2.2 were rejected.

## 10.1.4 Pre-Specified Statistical Analysis Plan

### 10.1.4.1 Study Hypothesis

Analysis of the VALOR II clinical study results included hypothesis testing of the primary study endpoints and a presentation of descriptive statistics for the secondary and supplementary endpoints. The study was considered successful if the null hypotheses for the tests of primary safety and effectiveness endpoints, described in Section 10.1.2.1 and Section 10.1.2.2, were both rejected. For the primary safety endpoint and primary effectiveness endpoint, analyses based on both the ITT and implanted populations were presented. Apart from any imaging-dependent endpoints, analyses for all secondary endpoints were based on the ITT population. Only patients who received adequate imaging and were at risk for the relevant events can be included in the evaluation of the imaging-dependent endpoints.

### 10.1.4.2 Comparator

The comparator for this study was the Talent Control Group. Although conducted over different periods of time, the Valiant Test and Talent Control Groups evaluated the same treatment indications and were conducted under similar study requirements. The design of both trials addressed sources of potential bias through the use of a physician screening committee to reduce potential selection bias and a core laboratory and clinical events committee (CEC) to reduce potential assessment bias. In addition, statistical testing was employed to control for differences in baseline risk factors. Nonetheless, there are several potential concerns associated with using a historical control. First, the control is non-concurrent so there is a temporal bias of unknown size that may affect the scientific validity of the study. Second, the historical control group may include a different subject population and/or outcomes than the contemporary study. There is no guarantee that the 2 groups are comparable, even with statistical techniques such as ANOVA or Cochran-Mantel-Haenszel analysis. In addition to the above concerns, protocol deviations occurred during this study and may have also introduced bias to the data.

Page 26 of 66

{26}

Page 27 of 66

## 10.1.4.3 Methodology

This study was designed as a non-adaptive frequentist trial. The sample size was fixed by design and not adapted as a function of preliminary results.

## 10.1.4.4 Sample Size Justification

The sample size was determined based on a goal of achieving 80% statistical power at a 1-sided significance level of 5% to demonstrate the primary safety and effectiveness objectives. These calculations yielded a minimum sample size of 150 subjects to evaluate the primary safety endpoint and a minimum sample size of 100 to evaluate the primary effectiveness endpoint. Taking into consideration expected performance on the primary endpoints and an expected attrition rate, a sample size of 160 enrolled subjects was considered to be sufficient.

## 10.1.4.5 Statistical Test

Hypothesis testing for the primary safety endpoint consisted of a comparison of the rates of all-cause mortality within 12 months for the Valiant Test Group and the Talent Control Group using an adjusted odds ratio. The primary analysis was performed on the null hypothesis of inferiority of the Valiant Test Group relative to the Talent Control Group using the Cochran-Mantel-Haenszel (CMH) to control for SVS scores. Rejection of the null hypothesis required the upper-endpoint of the exact 1-sided 95% confidence interval of the adjusted odds ratio to be less than a non-inferiority margin of 2.25.

## 10.1.4.6 Method for Accommodating Missing Data

Two sensitivity analyses, a tipping-point and worst-case scenario analysis, were also performed on each of the two primary endpoints to account for the impact of non-evaluable subjects.

## 10.1.4.7 Assumptions

The primary assumption made in this study was that, within the strata represented by the SVS scores, the subjects in the Valiant Test Group and in the Talent Control Group were interchangeable. That is, the probability of a subject meeting the primary safety endpoint was, other than the treatment effect, the same in the two groups. The validity of the statistical test used for the endpoint (CMH) depends on assumption that the treatment odds ratio is constant in all of the SVS strata, but this assumption was tested and validated before performing the CMH test.

## 10.1.5 External Evaluation Groups

- **Core laboratory.** In order to provide independent verification of imaging findings, images required by protocol were sent by investigational sites to a central imaging core laboratory with processes and systems that were GMP/GCP, HIPAA, and CFR 21 Part 11 compliant and were provided within an ISO 13485 certified facility which adhered to all applicable federal regulations.

- **Screening committee.** An independent screening committee reviewed the anatomic suitability of each potential subject prior to subject enrollment into the study. The screening committee reviewed three-dimensional reconstructions of computed tomography or magnetic resonance imaging (CT/MR) scans and measurements of the thoracic aorta to assess anatomic suitability. The committee was composed of a

{27}

group of physicians with expertise and experience in the endovascular repair of thoracic aortic aneurysms.

- **Clinical Events Committee.** An independent Clinical Events Committee (CEC) adjudicated all deaths and MAEs for event type and device and procedure relatedness. The CEC was composed of a group of physicians independent of the clinical study with expertise and experience in the endovascular repair of thoracic aortic aneurysms.

- **Data monitoring committee.** An independent data monitoring committee (DMC) reviewed 30-day safety data at determined intervals during enrollment. Based on the safety data, the DMC could recommend that Medtronic Vascular continue, modify, or stop the study in accordance to previously agreed parameters. The committee was composed of three physicians with relevant training and one biostatistician, none of whom were directly involved in the conduct of the study.

## 10.1.6 Clinical Inclusion and Exclusion Criteria

Enrollment in the Valiant Test Group was limited to patients who met the following selection criteria as shown in Table 10-3.

Table 10-3: Inclusion/Exclusion Criteria for the Valiant Test Group – VALOR II

| Inclusion | Exclusion |
| --- | --- |
| 1) Subject is between the age of 18 and 85. | 1. Planned placement of the COVERED portion of the stent graft requires implant to occur in zones 0 or 1.
Landing Zones of the Thoracic Aorta |
| 2) Subject must be considered a candidate for elective surgical repair of the TAA (i.e., low to-moderate risk [categories 0, 1, and 2] per the modified SVS/AAVS scoring system at the time of implant). | 2. Subject has a thoracic aneurysm with a contained rupture. |
| 3) If subject is female of childbearing potential, she must have a negative pregnancy test within 7 days before the implant procedure. | 3. Subject has a connective tissue disease (e.g., Marfan’s syndrome, aortic medial degeneration). |
| 4) Subject has a DTA that is:
a) A fusiform aneurysm with a maximum diameter of ≥ 5 cm OR is > 2 times the diameter of the non-aneurysmal thoracic aorta;
AND/OR
b) Saccular aneurysm/penetrating atherosclerotic ulcer | 4. Subject has a mycotic aneurysm or is suspected of having systemic infection. |

Page 28 of 66

{28}

| 5) Subject's anatomy must meet all of the following anatomical criteria:
a) Subject's TAA must be ≥20 mm distal to the origin of the left common carotid artery and must be ≥20 mm proximal to the celiac artery;
b) Proximal and distal non-aneurysmal neck diameter measurements must be between 20 mm and 42 mm;
c) Proximal and distal non-aneurysmal neck must be ≥20 mm in length. | 5. Subject has received a previous stent or stent graft or previous surgical repair in the DTA. |
| --- | --- |
| 6) Thoracic aortic lesion is confirmed, at a minimum, by diagnostic contrast enhanced computerized tomography (CT) with optional 3-D reconstruction, and/or contrast enhanced magnetic resonance angiogram obtained within 4 months prior to the implant procedure. | 6. Subject requires treatment of an infrarenal aneurysm at the time of implant. |
| 7) Subject is able and willing to comply with the protocol and undergo follow-up requirements. | 7. Subject has a history of bleeding diathesis, coagulopathy, or refuses blood transfusion. |
| 8) Subject or subject's legal representative understands and has signed an informed consent approved by the sponsor and by the IRB for this study. | 8. Subject has had or plans to have a major surgical procedure within 30 days before or after the Valiant Stent Graft procedure. This does not include planned procedures that are needed for the safe and effective placement of the stent graft (i.e., carotid/subclavian transposition, carotid/subclavian bypass procedure). |
| 9) Subject has patent iliac or femoral arteries or can tolerate a vascular conduit that allows endovascular access to the aneurysmal site with the delivery system of the appropriate size device chosen for treatment. | 9. Subject has had an MI or cerebral vascular accident (CVA) within 3 months. |
| | 10. Subject is currently participating in an investigational drug or device clinical trial. |
| | 11. Subject has a known allergy or intolerance to the device components. |
| | 12. Subject has a known hypersensitivity or contraindication to anticoagulants or contrast media, which is not amenable to pre-treatment. |
| | 13. Subject has significant and/or circumferential aortic mural thrombus at either the proximal or distal attachment sites that would compromise fixation and seal of the device. |
| | 14. Subject has other medical, social, or psychological problems that, in the opinion of the investigator, preclude him or her from receiving this treatment and the procedures and evaluations pre- and post-treatment, or a limited life expectancy of less than 1 year. |

A comparison of the inclusion and exclusion criteria for the Valiant Test Group and the Talent Control Group is described in Table 10-4. These minor differences in inclusion and exclusion criteria exist to accommodate the modifications in the study designs (institution of

Page 29 of 66

{29}

a physician screening committee to assess eligibility of subjects) and to reflect current medical practices (use of conduits).

Table 10-4: Comparison of Clinical Inclusion and Exclusion Criteria – Valiant Test Group and Talent Control Group – VALOR II

| Inclusion Criteria | | Valiant Test Group |
| --- | --- | --- |
| | Subject's anatomy must meet all of the following anatomical criteria:
a. Subject's thoracic aortic aneurysm must be at least 20 mm distal to the origin of the left common carotid artery and must be at least 20 mm proximal to the celiac artery;
b. Proximal and distal non-aneurysmal neck diameter measurements must be of a range between 20 mm and 42 mm;
c. Proximal and distal non-aneurysmal neck must be 20 mm or greater in length. | Subject's anatomy must meet all of the following anatomical criteria:
a. Subject's thoracic aortic aneurysm must be at least 20 mm distal to the origin of the left common carotid artery and must be at least 20 mm proximal to the celiac artery;
b. Proximal and distal non-aneurysmal neck diameter measurements must be of a range between 18 mm and 42 mm;
c. Proximal and distal non-aneurysmal neck must be 20 mm or greater in length. |
| | Thoracic aortic lesion is confirmed, at a minimum, by diagnostic contrast enhanced computerized tomography (CT) with optional 3-D reconstruction, and/or contrast enhanced magnetic resonance angiogram obtained within four months prior to the implant procedure. | Thoracic aortic lesion is confirmed, at a minimum, by diagnostic contrast enhanced computerized tomography (CT) with optional 3-D reconstruction, and/or contrast enhanced magnetic resonance angiogram obtained within the previous three months prior to screening. |
| | Subject or subject's legal representative understands and has signed an informed consent approved by the sponsor and by the IRB for this study. | Not an inclusion criterion. |
| | Subject has patent iliac or femoral arteries or can tolerate a vascular conduit that allows endovascular access to the aneurysmal site with the delivery system of the appropriate size device chosen for treatment. | Adequacy of access vessels addressed in exclusion criteria. Use of conduits was not allowed. |
| | Exclusion Criteria | |
| | Adequacy of access vessels addressed in inclusion criteria. Use of conduits was allowed. | The subject's access vessel (as determined by the treating physician) precludes safe insertion of the delivery system. Patient requires a planned aortic conduit. |
| | Subject requires treatment of an infrarenal aneurysm at the time of implant. | Subject requires treatment of an infrarenal aneurysm at the time of implant or has had a previous surgical or endovascular treatment of an infrarenal aortic aneurysm. |
| | Subject has had a recent MI or cerebral vascular accident (CVA) (within 3 months). | Subject has had a recent (within three 3 months) cerebral vascular accident (CVA). |

## 10.1.6.1 Follow-up Schedule and Evaluations

Treatment and follow-up protocols were identical for the Valiant Test Group and Talent Control Group. Clinical assessments occur at one, six, and 12 months and annually for five years post implant at which time a physical exam and CT/MR and x-ray imaging were or will be performed. All imaging-based measures through the 12-month visit were assessed by a core laboratory. Magnetic resonance imaging was recommended in patients with impaired renal function or intolerance to contrast media.

Page 30 of 66
37

{30}

Page 31 of 66
38

## 10.1.6.2 Prospectively Defined Subgroup Evaluations

Potential differences based on lesion type were tested through a subgroup analysis of the primary safety endpoint of all-cause mortality within 12 months, in which fusiform aneurysms and saccular aneurysms/penetrating aortic ulcers were examined separately. Potential gender-based differences in treatment outcomes were also explored for both the primary safety and primary effectiveness endpoints.

## 10.1.7 Accountability of PMA Cohort

One hundred-and-sixty (160) subjects were enrolled at 24 investigational sites in the Valiant Test Group. At the time of database lock, 151 of 160 enrolled subjects were available for evaluation of the primary safety endpoint and 115 CT/MR images were available for the evaluation of primary effectiveness endpoint. Subject compliance is presented in Table 10-5. The number of data points evaluable for each endpoint is reported in the results sections. In the Talent Control Group, 195 subjects were enrolled across 38 sites with 192 being available for the evaluation of the primary safety endpoint. Additional information on the Talent Control Group patient accountability and follow-up can be found in the Summary of Safety and Effectiveness for P070007.

{31}

Table 10-5: Subject Accountability and Core Lab Imaging Compliance within 12 Months¹ – Valiant Test Group – VALOR II

| | Subject follow-up
# (%) | | | Subjects with Imaging
(at each time interval)
# (%) | | Subjects with adequate imaging to assess the
parameter
# (%) | | | | | Subject events occurring before next
visit
# | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Treatment /
Follow-up
Interval | Eligible¹ | Treatment or
Clinical
f/u | Imaging
f/u | CT/MR
Imaging | Chest
X-Ray | Max ANR
Diameter | Change in
ANR
diameter
(from 1
month) | Endoleak | Migration
(from 1
month) | Integrity | Intent
to
Treat
but
Not
Implanted | Conversion
to
Surgery | Death | Withdrawal | LTF |
| Originally
Enrolled | 160 | 100%
(160/160) | | | | | | | | | | | | | |
| Events
between
implant and 1
month follow-up visit | | | | | | | | | | | 3 | 0 | 1² | 0 | 0 |
| 1 month
(0-122 Days) | 156 | 100.0%
(156/156) | 98.7%
(154/156) | 97.4%
(152/156) | 96.8%
(151/156) | 96.2%
(150/156) | | 89.1%
(139/156) | | 95.5%
(149/156) | | | | | |
| Events
between
1 month and
6 months
follow-up visit | | | | | | | | | | | | 0 | 9 | 0 | 0 |
| 6 month
(123-336
Days)² | 147 | 75.5%
(111/147) | 93.2%
(137/147) | 92.5%
(136/147) | 77.6%
(114/147) | 89.8%
(132/147) | | 83.0%
(122/147) | 85.7%
(126/147) | 76.9%
(113/147) | | | | | |
| Events
between
6 months and
12 months
follow-up visit | | | | | | | | | | | | 0 | 7 | 0 | 0 |
| 12 month
(337-480
Days) | 133 | 87.2%
(116/133) | 91.0%
(121/133) | 87.2%
(116/133) | 84.2%
(112/133) | 86.5%
(115/133) | 85.7%
(114/133) | 75.2%
(100/133) | 78.9%
(105/133) | 82.7%
(110/133) | | | | | |

Totals 3 0 17⁴ 0 0
Death post conversion to surgery 0
Total Deaths 17

¹ The number of subjects eligible for each interval is determined by how many subjects completed a physical exam less those who converted to surgery, died, withdrew, or were lost to follow-up in the previous interval.
² "Treatment or Clinical f/u" at six months and "Events between 6 months 12 months follow-up visit" are based on the protocol-defined follow-up window. "Evaluable core lab imaging" is based on the analysis window of 123-366 days.
³ Four of 5 subjects who died within 30 days completed a physical exam at discharge and were therefore recorded as having completed the 1-month interval.
⁴ Two of 19 subjects who died within 365 days completed a physical exam prior to expiring and were therefore recorded as having completed the 12-month interval.

Page 32 of 66

{32}

# 10.1.8 Subject Population Demographics and Baseline Parameters

Table 10-6 through Table 10-8 provide the demographics, baseline medical history, and SVS risk classification of the Valiant Test Group and the Talent Control Group.

Table 10-9 through Table 10-14 provide baseline aneurysm characteristics and distribution of Valiant Thoracic Stent Grafts implanted at the initial procedure.

As shown in Table 10-6, the mean age in the Valiant Test Group was 72.2 years ± 9.1 (36-85 years) and males composed 59.4% of the study population. These and other demographic variables were similar between the Valiant Test Group and Talent Control Group.

Table 10-6: Subject Demographics – Valiant Test Group and Talent Control Group - VALOR II

| | Valiant Test Group | Talent Control Group | p-value |
| --- | --- | --- | --- |
| Age (years) | | | |
| Total Population | | | |
| n | 160 | 195 | |
| Mean ± SD | 72.2 ± 9.1 | 70.2 ± 11.1 | 0.459 |
| Median | 74.0 | 73.0 | |
| Min, max | 36, 85 | 27, 86 | |
| Sex/Gender % (m/n) | | | |
| Males | 59.4% (95/160) | 59% (115/195) | 0.769 |
| Females | 40.6% (65/160) | 41% (80/195) | |
| Race % (m/n) | | | 0.787 |
| American Indian or Alaska Native | 0% (0/160) | 0% (0/190) | |
| Asian/Native Hawaiian/Pacific Islander | 2.5% (4/160) | 1.1% (2/190) | |
| Black | 10% (16/160) | 13.2% (25/190) | |
| White | 86.3% (138/160) | 85.3% (162/190) | |
| Subject refuses to answer | 0% (0/160) | 0% (0/190) | |
| Multi-racial / other | 1.3% (2/160) | 0.5% (1/190) | |

As shown in Table 10-7, the medical history of subjects in the Valiant Test Group and Talent Control Group were similar although a number of factors contributed to a higher level of risk among the Valiant Test Group. Subjects in the Valiant Test Group have a higher rate of abdominal aortic aneurysm (AAA), prior AAA repair, carotid artery disease, percutaneous coronary intervention and hyperlipidemia while subjects in the Talent Control Group had a higher rate of gastrointestinal medical history. Additionally, a history of ascending thoracic aneurysm and the use of an abdominal aortic conduit for vascular access, both of which were exclusion criteria in the Talent Control Group, likely added to an increase in baseline risk factors for the Valiant Test Group.

Page 33 of 66
40

{33}

Table 10-7: Baseline Medical History - Valiant Test Group and Talent Control Group - VALOR II

| Medical History | Valiant Test Group
% (m/n)
(N = 160) | Talent Control Group
% (m/n)
(N = 195) | p-value |
| --- | --- | --- | --- |
| Cardiovascular | | | |
| Abdominal aortic aneurysm (AAA) | 38.8% (62/160) | 19% (37/195) | <0.001 |
| Previous AAA repair | 20.6% (33/160) | 2.1% (4/195) | <0.001 |
| Ascending thoracic aneurysm¹ | 8.1% (13/160) | | |
| Angina | 9.4% (15/160) | 14.4% (28/195) | 0.094 |
| Arrhythmia | 31.3% (50/160) | 26.7% (52/195) | 0.602 |
| Carotid artery disease | 28.1% (45/160) | 5.6% (11/195) | <0.001 |
| Congestive heart failure | 11.9% (19/160) | 8.7% (17/195) | 0.546 |
| Coronary artery disease | 44.4% (71/160) | 40.5% (79/195) | 0.928 |
| Coronary artery bypass grafting | 13.8% (22/160) | 10.3% (20/195) | 0.466 |
| Hypertension | 93.8% (150/160) | 87.2% (170/195) | 0.186 |
| Myocardial infarction | 21.3% (34/160) | 13.8% (27/195) | 0.117 |
| Percutaneous coronary intervention | 16.9% (27/160) | 5.6% (11/195) | 0.002 |
| Peripheral vascular disease | 25% (40/160) | 16.4% (32/195) | 0.091 |
| Pulmonary | | | |
| Chronic obstructive pulmonary disorder | 35% (56/160) | 36.9% (72/195) | 0.426 |
| Renal | | | |
| Renal insufficiency | 16.3% (26/160) | 17.4% (34/195) | 0.479 |
| Cerebrovascular / Neurological | | | |
| Transient ischemic attack | 11.3% (18/160) | 7.7% (15/195) | 0.471 |
| Cerebral vascular accident | 10.6% (17/160) | 9.7% (19/195) | 0.958 |
| Paraplegia | 0% (0/160) | 1% (2/195) | 0.388 |
| Paraparesis | 0.6% (1/160) | 0.5% (1/195) | 0.984 |
| Other Abnormal Body Systems | | | |
| Bleeding disorder | 2.5% (4/160) | 2.6% (5/195) | 0.994 |
| Diabetes | 21.3% (34/160) | 15.9% (31/195) | 0.426 |
| Gastrointestinal complications | 40.6% (65/160) | 53.8% (105/195) | 0.006 |
| Hyperlipidemia | 73.8% (118/160) | 43.6% (85/195) | <0.001 |
| Tobacco use in last ten years² | 44.4% (71/160) | 50.3% (98/195) | 0.333 |
| ¹ Data point was not collected in Talent Control Group.
² For Talent Control Group, subjects who answered 'Yes' to 'Tobacco Use' and whose resolution date was more than 10 years prior to implant were considered as 'No' to the question of 'Tobacco Use in the last 10 years'. | | | |

The baseline modified SVS classifications for the Valiant Test Group and Talent Control Group subjects are shown in Table 10-8. Of the 160 subjects enrolled in the Valiant Test Group, one subject (0.6%) was in SVS class 0, 17 subjects (10.6%) were in SVS class 1 and 140 subjects (87.5%) were in SVS class 2 categories. Two subjects were classified in SVS class 3 (1.3%) and constituted protocol deviations. The distribution of SVS score was statistically different between the two groups with a greater percentage of high severity scores in the Valiant Test Group.

Page 34 of 66

{34}

Table 10-8: Baseline Modified SVS/AAVS Classification - Valiant Test Group and Talent Control Group - VALOR II

| SVS/AAVS Score | Valiant Test Group
% (m/n)
(N = 160) | Talent Control Group
% (m/n)
(N = 195) | p-value |
| --- | --- | --- | --- |
| 0 | 0.6% (1/160) | 4.1% (8/195) | 0.002 |
| 1 | 10.6% (17/160) | 21% (41/195) | |
| 2 | 87.5% (140/160) | 72.8% (142/195) | |
| 3 | 1.3% (2/160) | 2.1% (4/195) | |
| 1 Modified SVS/AAVS Medical Comorbidity Grading System modified for age, hypertension, cardiac, pulmonary and renal, as described in the Valiant Test Group clinical study protocol
2 p-value is calculated using one-way ANOVA with SVS score being the dependent variable. | | | |

Table 10-9 provides the treated anatomic lesion type for both the Valiant Test Group and the Talent Control Group.

Table 10-9: Anatomic Lesion Type - Valiant Test Group and Talent Control Group - VALOR II

| Etiology | Valiant Test Group
% (m/n)
(N = 160) | Talent Control Group
% (m/n)
(N = 195) |
| --- | --- | --- |
| Thoracic Aortic Aneurysm (Fusiform) | 64.4% (103/160) | 57.4% (112/195) |
| Thoracic Aortic Aneurysm (Saccular / Penetrating ulcer) | 35.6% (57/160) | 35.9% (70/195) |
| Both | 0.0% (0/160) | 6.7% (13/195) |

Table 10-10 and Table 10-11 provide the baseline anatomical and aneurysm measurements of the Valiant Test Group and Talent Control Group.

Table 10-10: Baseline Vessel Dimensions - Core Laboratory Reported - Valiant Test Group and Talent Control Group - VALOR II

| Baseline Vessel Dimension | Valiant Test Group
% (N = 160) | Talent Control Group
% (N = 195) | p-value |
| --- | --- | --- | --- |
| Proximal Neck Diameter (mm) | | | |
| n² | 157 | 187 | |
| Mean ± SD | 32.47 ± 5.17 | 31.20 ± 4.93 | 0.074 |
| Median | 32.00 | 31.50 | |
| Min, Max | 21.0, 51.5 | 18.5, 43.5 | |
| Max Aneurysm Diameter (mm) | | | |
| n² | 160 | 187 | |
| Mean ± SD | 57.00 ± 11.03 | 55.51 ± 11.60 | 0.363 |
| Median | 56.10 | 56.00 | |
| Min, Max | 31.4, 97.7 | 26.2, 88.8 | |
| Distal Neck Diameter (mm) | | | |
| n² | 157 | 184 | |
| Mean ± SD | 31.23 ± 5.78 | 29.72 ± 5.00 | 0.050 |
| Median | 30.50 | 29.50 | |

Page 35 of 66

{35}

| Min, Max | 19.0, 51.0 | 17.0, 42.5 | |
| --- | --- | --- | --- |
| Proximal Centerline Neck Length (mm) | | | |
| n² | 157 | 187 | |
| Mean ± SD | 83.03 ± 51.05 | 80.02 ± 52.09 | 0.882 |
| Median | 80.00 | 77.90 | |
| Min, Max | 14.0, 246.5 | 10.0, 234.0 | |
| Aneurysm Length (mm) | | | |
| n² | 154 | 180 | |
| Mean ± SD | 123.25 ± 73.02 | 121.38 ± 72.69 | 0.861 |
| Median | 108.55 | 107.65 | |
| Min, Max | 17.0, 316.0 | 8.0, 297.5 | |
| Distal Neck Length (mm) | | | |
| n² | 158 | 184 | |
| Mean ± SD | 90.62 ± 58.52 | 90.00 ± 62.90 | 0.711 |
| Median | 79.05 | 73.50 | |
| Min, Max | 0.0, 285.0 | 9.0, 255.0 | |
| Right External Iliac Minimum Diameter (mm) | | | |
| n² | 120 | 122 | |
| Mean ± SD | 7.07 ± 1.96 | 6.49 ± 1.53 | 0.011 |
| Median | 7.00 | 6.50 | |
| Min, Max | 3.5, 13.5 | 2.9, 11.0 | |
| Left External Iliac Minimum Diameter (mm) | | | |
| n² | 120 | 124 | |
| Mean ± SD | 7.04 ± 1.93 | 6.59 ± 1.55 | 0.046 |
| Median | 7.00 | 6.50 | |
| Min, Max | 3.5, 13.0 | 3.3, 10.9 | |

¹ Each variable will be assessed for balance between the treatment groups. This assessment is also adjusted for SVS score of (0, 1) versus (2, 3).
² n = number of known values.

Page 36 of 66

{36}

Table 10-11: Baseline Maximum Aneurysm Diameters - Core Laboratory Reported - Valiant Test Group and Talent Control Group - VALOR II

| Diameter (mm) | Valiant Test Group
% (m/n) | Talent Control Group
% (m/n) |
| --- | --- | --- |
| 10-17 | 0.0% (0/160) | 0.0% (0/187) |
| 18-29 | 0.0% (0/160) | 0.5% (1/187) |
| 30-39 | 4.4% (7/160) | 7.5% (14/187) |
| 40-49 | 15.6% (25/160) | 20.3% (38/187) |
| 50-59 | 45.0% (72/160) | 34.8% (65/187) |
| 60-69 | 24.4% (39/160) | 24.6% (46/187) |
| 70-79 | 7.5% (12/160) | 10.2% (19/187) |
| 80-89 | 1.3% (2/160…