MEDTRONIC VASCULAR ENDURANT STENT GRAFT SYSTEM

P100021 · Medtronic Vascular · MIH · Dec 16, 2010 · Cardiovascular

Device Facts

• Record ID: P100021
• Device Name: MEDTRONIC VASCULAR ENDURANT STENT GRAFT SYSTEM
• Applicant: Medtronic Vascular
• Product Code: MIH · Cardiovascular
• Decision Date: Dec 16, 2010
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The Endurant Stent Graft System is indicated for the endovascular treatment of infrarenal abdominal aortic or aorto-iliac aneurysms in subjects with the following characteristics: Adequate iliac/femoral access that is compatible with vascular access techniques, devices and/or accessories Proximal neck length of ≥ 10 mm Infrarenal neck angulation of ≤ 60° Distal fixation length of ≥ 15 mm Aortic neck diameters with a range of 19-32 mm Iliac diameters with a range of 8-25 mm Morphology suitable for aneurysm repair

Device Story

Endurant Stent Graft System treats infrarenal abdominal aortic/aorto-iliac aneurysms via endovascular repair. System includes modular nitinol/polyester stent grafts (bifurcated, contralateral limb, iliac/aortic extensions) and disposable delivery systems (aortic/iliac). Physician inserts components via femoral arteries using fluoroscopic guidance; stent graft self-expands to seal aneurysm proximally/distally, excluding it from blood flow. Radiopaque markers facilitate placement. Device benefits include minimally invasive aneurysm exclusion, reducing rupture risk. Clinical decision-making relies on pre-operative CT/MRA imaging to confirm anatomical suitability (neck length, angulation, diameters). Post-procedure, providers monitor aneurysm size, endoleaks, and device integrity via serial imaging.

Clinical Evidence

Prospective, non-randomized, multi-center study (n=150) with historical control (Talent, n=166). Primary safety: 96.0% MAE-free at 30 days (Endurant) vs 89.2% (Talent). Primary effectiveness: 97.5% successful aneurysm treatment at 12 months. Secondary outcomes: 0% Type I/III endoleaks, 0% migration, 96.8% patency at 12 months. No conversions to open surgery. Bench testing verified 400 million cycle fatigue durability.

Technological Characteristics

Modular stent graft: nitinol stents (laser-cut suprarenal, wire-formed body) sewn to polyester fabric with polyester/UHMWPE sutures. Radiopaque platinum markers. Delivery system: 14-20F, hydrophilic coating, fluoroscopic guidance. Sterilization: E-Beam (SAL 10^-6). 2-year shelf life. No software/algorithm.

Indications for Use

Indicated for endovascular treatment of infrarenal abdominal aortic or aorto-iliac aneurysms in patients ≥ 18 years with adequate iliac/femoral access, proximal neck length ≥ 10 mm, infrarenal neck angulation ≤ 60°, distal fixation length ≥ 15 mm, aortic neck diameters 19-32 mm, and iliac diameters 8-25 mm. Contraindicated in patients with infection, allergy to device materials, or conditions precluding elective repair.

Reference Devices

• Talent Abdominal Stent Graft System (P070027)

Submission Summary (Full Text)

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# Summary of Safety and Effectiveness Data

## I. General Information

**Device Generic Name:**
Endovascular graft

**Device Trade Name:**
Endurant® Stent Graft System

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

**Premarket Approval Application (PMA) Number:**
P100021

**Date of Panel Recommendation:**
None

**Date of Notice of Approval to the Applicant:**
December 16, 2010

## II. Indications for Use

The Endurant Stent Graft System is indicated for the endovascular treatment of infrarenal abdominal aortic or aorto-iliac aneurysms in subjects with the following characteristics:

- Adequate iliac/femoral access that is compatible with vascular access techniques, devices and/or accessories
- Proximal neck length of ≥ 10 mm
- Infrarenal neck angulation of ≤ 60°
- Distal fixation length of ≥ 15 mm
- Aortic neck diameters with a range of 19-32 mm
- Iliac diameters with a range of 8-25 mm
- Morphology suitable for aneurysm repair

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# III. Contraindications

The Endurant Stent Graft System is contraindicated in:

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

# IV. Warnings and Precautions

Please see the warnings and precautions in the labeling (Instructions for Use).

# V. Device Description

## A. General Endurant Stent Graft System Description

The Endurant Stent Graft System is comprised of two key components: an implantable stent graft (Endurant Stent Graft) and a disposable delivery system (Endurant Delivery System). The pre-loaded stent graft is advanced to the aneurysm location over a guidewire. Upon retraction of the graft cover, the stent graft self expands to the indicated vessel diameter. During deployment and expansion, the stent graft is intended to form proximal and distal seal zones above and below the aneurysm location.

The Endurant Stent Graft System is modular and consists of four stent graft component configurations:

- Bifurcated (aorto-iliac) Component
- Contralateral Limb Component
- Iliac Extension Component
- Aortic Extension Component

Each component is introduced separately into the patient’s vascular system. After the placement of the bifurcated and contralateral limb components, aortic and limb extension components may be introduced separately into the vessel and are mated *in vivo* to the components already *in situ*. All components are composed of nitinol metal stents sewn to a fabric graft. The suprarenal stents with anchor pins on the proximal end are laser cut from a nitinol tube. The wire formed stents are sewn to the polyester graft fabric using a polyester suture, whereas the suprarenal stents are sewn to the graft fabric using an ultra high molecular weight polyethylene suture. This suture is designed to aid in better stent to graft attachment strength, thus providing a more durable proximal attachment. Radiopaque markers, constructed of platinum, are sewn onto the stent graft to aid in visualization of the stent graft under fluoroscopy and to facilitate accurate placement of the device. Refer to Figure 1 for an overview of stent graft components.

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The stent graft is designed to be placed in the native vessel such that the unconstrained stent graft diameter is larger than the diameter of the native vessel into which it is to be placed. This “oversizing” helps to exclude the aneurysm from aortic blood flow and to ensure the stent graft is held in place. The amount of oversizing required is dependent on the diameter of the native vessel.

Figure 1: Endurant Stent Graft Configurations
Note: Graphic representation is not shown to scale

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# B. Bifurcated Stent Graft Component

The bifurcated stent graft component (refer to Figure 2) is the primary component which is inserted into the patient’s aorta. The proximal section of the bifurcated stent graft component is deployed into the proximal neck and upper section of the aneurysm. The stent graft bifurcates into two smaller tubes: an ipsilateral iliac limb and a short contralateral leg.

The bifurcated component is available in proximal diameters ranging between 23 and 36 mm, with covered lengths ranging between 124 and 166 mm.

Figure 2: Endurant Bifurcated Stent Graft Component

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# C. Contralateral Limb Component

The contralateral limb component is deployed once the bifurcated component has been implanted, providing a conduit for blood flow into the contralateral iliac artery (refer to Figure 3). The proximal end of the contralateral limb component is deployed within the short contralateral leg of the bifurcated stent graft component. The contralateral limb component is available in distal diameters ranging between 10 and 28 mm, with covered lengths between 82 and 124 mm.

The proximal diameter is 16 mm for all sizes of contralateral limbs and is the same for all sizes, thus ensuring that this component can dock with all available bifurcated stent graft configurations.

Figure 3: Endurant Contralateral Limb Component

# D. Iliac Extension Component

In cases where additional distal length of the stent graft is needed, iliac extension components are available (refer to Figure 4). The iliac extension component is available in distal/proximal diameters ranging between 10 and 28 mm, with a covered length of 82 mm.

Figure 4: Endurant Iliac Extension Component

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# E. Aortic Extension Component

In cases where additional proximal length of the stent graft is needed, the aortic extension component is available. The aortic extension component (refer to Figure 5) is available in distal/proximal diameters ranging between 23 and 36 mm, with covered lengths of 49 mm or 70 mm.

Figure 5: Endurant Aortic Extension Component

# F. Endurant Delivery System

The Endurant Delivery System, which constrains the Endurant Stent Graft, facilitates the placement of the stent graft via the arterial vasculature (e.g., femoral arteries). Using fluoroscopic guidance, the delivery system is properly positioned within the patient’s vasculature and the stent graft is deployed. There are two kinds of Endurant Delivery Systems: the Endurant Aortic Delivery System and the Endurant Iliac Delivery System. The Endurant Aortic Delivery System delivers the Endurant stent graft components containing anchor pins (i.e. bifurcated and aortic extension) and has a tip capture mechanism and a thumb wheel. The Endurant Iliac Delivery System delivers Endurant stent graft components that do not have anchor pins (i.e. contralateral limb and iliac extensions). The Iliac Delivery System does not contain a tip capture mechanism or a thumb wheel.

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# G. Endurant Aortic Delivery System

The Endurant Aortic Delivery System is available in an outer diameter of 18 and 20 French. The working length of the Endurant Aortic Delivery System is 57cm +/- 2 cm and the total length is 120 +/- 3 cm.

A pictorial representation of the Endurant Aortic Delivery system is provided in the figure below (refer to Figure 6).

Figure 6: Endurant Aortic Delivery System

| # | Components | # | Components |
| --- | --- | --- | --- |
| 1 | Tip Capture Assembly | 8 | Trigger |
| 2 | Graft Cover | 9 | Front Grip |
| 3 | RO Marker Band | 10 | Stent Stop |
| 4 | Rear Handle | 11 | Back End T-Tube |
| 5 | Screw Gear | 12 | Thumb Wheel |
| 6 | Strain Relief | | |
| 7 | Slider | | |

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# H. Endurant Iliac Delivery System

The Endurant Iliac Delivery System is available in an outer diameter of 14, 16 and 18 French. The working length of the Endurant Iliac Delivery System is 57cm +/- 2 cm and the total length is 109 +/- 3 cm.

A pictorial representation of the Endurant Iliac Delivery system is provided in the figure below (refer to Figure 7).

Figure 7: Endurant Iliac Delivery System

# VI. Alternative Practices and Procedures

There are several other alternatives for the treatment of abdominal aortic aneurysms (AAA): 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.

# VII. Marketing History

The current version of the Endurant Stent Graft System has been commercially available since March 2010 outside the United States. The Endurant Stent Graft System has not been withdrawn from any market for reasons related to safety or effectiveness.

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# VIII. Potential Adverse Effects of the Device on Health

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

- Amputation
- Anesthetic complications and subsequent attendant problems (e.g. aspiration)
- Aneurysm enlargement
- Aneurysm rupture and death
- Aortic damage, including perforation, dissection, bleeding, rupture and death
- Arterial or venous thrombosis and/or pseudoaneurysm
- Arteriovenous fistula
- Bleeding, hematoma or coagulopathy
- Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis)
- Cardiac complications and subsequent attendant problems (e.g. arrhythmia, myocardial infarction, congestive heart failure, hypotension, hypertension)
- Claudication (e.g., buttock, lower limb)
- Death
- Edema
- Embolization (micro and macro) with transient or permanent ischemia or infarction
- Endoleak
- Fever and localized inflammation
- Genitourinary complications and subsequent attendant problems (e.g., ischemia, erosion, fistula, incontinence, hematuria, infection)
- Hepatic failure
- Impotence
- Infection of the aneurysm, device access site, including abscess formation, transient fever and pain
- Lymphatic complications and subsequent attendant problems (e.g., lymph fistula)
- Neurologic local or systemic complications and subsequent attendant problems (e.g., confusion, stroke, transient ischemic attack, paraplegia, paraparesis, paralysis)
- Occlusion of device or native vessel
- Pulmonary complications and subsequent attendant problems
- Renal complications and subsequent attendant problems (e.g., artery occlusion, contrast toxicity, insufficiency, failure)
- Stent graft: improper component placement; incomplete component deployment; component migration; suture break; occlusion; infection; stent fracture; graft twisting and/or kinking; insertion and removal difficulties; graft material wear; dilatation; erosion; puncture and perigraft flow
- Surgical conversion to open repair
- Vascular access site complications, including infection, pain, hematoma, pseudoaneurysm, arteriovenous fistula, dissection.
- Vascular spasm or vascular trauma (e.g., iliofemoral vessel dissection, bleeding, rupture, death)
- Vessel damage
- Wound complications and subsequent attendant problems (e.g., dehiscence, infection, hematoma, seroma, cellulitis)

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# IX. Summary of Preclinical Studies

# A. Biocompatibility

Biocompatibility testing was conducted on the Endurant Stent Graft and the Endurant Delivery System to ensure that the finished device is safe and biocompatible. Testing was performed 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)). The Endurant Stent Graft was categorized as an implant device with permanent blood contact (>30 days). The Endurant Delivery System was categorized as an external communicating device in limited contact with circulating blood (<24 hours). All testing performed met the requirements as specified within the applicable standard.

Table 1: Summary of Biocompatibility Testing - Endurant Stent Graft

| Test | Purpose | Results | Acceptance Criteria Met (Y/N) |
| --- | --- | --- | --- |
| MHLW Cytotoxicity, Colony Assay | 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 IC50value for the test extract since toxicity was not observed. | Yes |
| ISO MEM Elution, Cytotoxicity | To determine whether leachables extracted from the test material would cause cytotoxicity when exposed to L-929 mouse fibroblast cells. | Test article extract: Grade 0 (no reactivity) | Yes |
| ISO Maximization Sensitization | To evaluate the allergenic potential or sensitizing capacity of the test article upon exposure to guinea pigs. | All test animals were grade 0 (no visible change) resulting in 0% sensitized. | Yes |
| MHLW Maximization Sensitization | To evaluate the potential for the test article to cause dermal sensitization. | Test Extract Concentrations (100%, 50%, and 25%): All test animals were grade 0. | Yes |
| ISO Intracutaneous Reactivity | To evaluate the test article for potential irritation effects as a result of an intracutaneous injection in New Zealand White rabbits. | Difference between test article and corresponding control: Saline: 0.0 Cottonseed Oil: 0.0 | Yes |
| MHLW Acute Systemic Toxicity | To evaluate the test article for the potential for toxic effects after a single-dose systemic injection into mice. | Test animals did not exhibit greater biological reaction than the corresponding negative control group. | Yes |
| Material Mediated Pyrogen Study | To evaluate the test article for the potential of inducing a pyrogenic response in rabbits. | Temperature increases: 0.0°C, 0.0°C, and 0.0°C. | Yes |
| 4-wk Sub-Chronic Toxicity Study following Subcutaneous Implantation | To determine the subchronic toxicity potential of the test article following subcutaneous implantation in rats for 4 weeks. | Test animals did not demonstrate any differences that were attributed to the test article when compared to control animals. Bioreactivity Rating = 1.9 (mild reaction) | Yes |
| In-vitro Reverse Mutation Assay S. typhimurium and E. coli | To evaluate the potential of the test article to induce reverse mutation in histidine (his to his') and tryptophan (tryp' to tryp') genes in S. typhimurium and E. coli, respectively. | A statistically significant increase in the number of revertant colonies was not observed with the test article. | Yes |
| In-vitro Chromosomal Aberration | 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. | A statistically significant increase in the number of structural chromosomal aberrations was not observed with the test article. | Yes |

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| Test | Purpose | Results | Acceptance Criteria Met (Y/N) |
| --- | --- | --- | --- |
| In-vivo Rodent Bone Marrow Micronucleus Assay | To evaluate the potential of the test article to induce damage to the chromosomes or mitotic apparatus in mouse bone marrow cells. | A statistically significant increase in the number of micronucleated PCEs was not observed with the test article. | Yes |
| 12-week ISO Muscle Implantation | To evaluate the potential of the test article to induce local toxic effects after implantation in the muscle tissue of 3 rabbits for 12 weeks. | Test implant sites did not demonstrate any significant difference as compared to the control implant sites. Bioreactivity Rating = 1.5 (no reaction) | Yes |
| MHLW in-vitro Hemolysis | To evaluate the hemolytic activity of the test article when in contact with rabbit blood. | % Hemolysis for test extracts: 1 hour: 0.11% 2 hours: 0.00% 4 hours: 0.00% | Yes |
| ISO Unactivated Partial Thromboplastin Time Assay | To measure the effect of the test article on the clotting time of human plasma. | Average clotting time of the test article was not significantly decreased or increased compared to both negative controls. | Yes |
| Complement Activation Assay, C3a and SC5b-9 | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | Concentration of C3a and SC5b-9 in the test extract was not significantly greater compared to both negative and plasma controls. | Yes |
| ISO in-vitro Hemocompatibility Assay | To show that the test article did not adversely affect selected hematological parameters of human blood. The hematological parameters tested were complete blood count including platelets, hematocrit, and erythrocyte indices. | No statistically significant difference between the test extract and both negative controls in any of the hematological parameters challenged. | Yes |
| In-vivo Thrombogenicity | To evaluate the potential of the test article to resist thrombus formation when placed in the vasculature of sheep. | Animal 660: Score 1 (minimal thrombosis) Animal 656: Score 0 (no thrombosis) Animal 653: Score 1 (minimal thrombosis) | Yes |

Table 2: Summary of Biocompatibility Testing – Endurant Delivery System

| Test Performed | Purpose | Results | Acceptance Criteria Met (Y/N) |
| --- | --- | --- | --- |
| MHLW Cytotoxicity, Colony Assay | 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 | No significant difference in colony formation between the neat (100%) concentration of test extract compared to the negative control. | Yes |
| ISO Maximization Sensitization | To evaluate the allergenic potential or sensitizing capacity of the test article upon exposure to guinea pigs | All test animals were grade 0 (no visible change) resulting in 0% sensitized. | Yes |
| ISO Intracutaneous Reactivity | To evaluate the test article for potential irritation effects as a result of an intracutaneous injection into New Zealand White rabbits | Difference between test article and corresponding control: Saline: 0.0 Cottonseed Oil: 0.0 | Yes |
| MHLW Acute Systemic Toxicity | To evaluate the test article for the potential for toxic effects after a single-dose systemic injection into mice | Test animals did not exhibit greater biological reaction than the corresponding negative control group. | Yes |
| Material Mediated Pyrogen Study | To evaluate the test article for the potential of inducing a pyrogenic response in rabbits | Temperature increases: 0.1°C, 0.0°C, and 0.0°C. | Yes |

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| Test Performed | Purpose | Results | Acceptance Criteria Met (Y/N) |
| --- | --- | --- | --- |
| MHLW in-vitro Hemolysis | To evaluate the hemolytic activity of the test article when in contact with rabbit blood | % Hemolysis for test extracts:
1 hour: 0.11%
2 hours: 0.00%
4 hours: 0.00% | Yes |
| ISO Unactivated Partial Thromboplastin Time Assay | To measure the effect of the test article on the clotting time of human plasma. | Average clotting time of the test article was not significantly decreased or increased compared to both negative controls. | Yes |
| Complement Activation Assay, C3a and SC5b-9 | To measure complement activation in human plasma as a result of exposure of the plasma to the test article. | Concentration of C3a and SC5b-9 in the test extract was not significantly greater compared to both negative and plasma controls. | Yes |
| ISO in-vitro Hemocompatibility Assay | To show that the test article did not adversely affect selected hematological parameters of human blood. The hematological parameters tested were complete blood count including platelets, hematocrit, and erythrocyte indices. | No statistically significant difference between the test extract and both negative controls in any of the hematological parameters challenged. | Yes |
| In-vivo Thrombogenicity | To evaluate the potential of the test article to resist thrombus formation when placed in the vasculature of sheep. | Animal 660:
Score 1 (minimal thrombosis)
Animal 656:
Score 0 (no thrombosis)
Animal 653:
Score 1 (minimal thrombosis) | Yes |

## B. Sterilization, Packaging and Shelf Life

The Endurant Stent Graft System is a single-use device that is provided sterile to the end user. The Endurant Stent Graft 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 Endurant Stent Graft System are sufficient to adequately protect the device and maintain the integrity of the Endurant Stent Graft System package throughout its 2-year shelf-life claim.

Shelf-life testing results are presented alongside the in-vitro bench test results as part of Table 3. Accelerated shelf-life product testing conducted on the Endurant Stent Graft supports a 2-year shelf-life claim.

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# C. Laboratory Studies

## Bench Testing

Medtronic conducted comprehensive preclinical, bench and analytical testing on the Endurant Stent Graft System. The *in vitro* testing was intended to verify that the performance attributes of the Endurant 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 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 Endurant Stent Graft System (implant and delivery systems) met its product performance and design specifications.

Results obtained from *in vitro* testing provided evidence supporting the safety and effectiveness of the Endurant Stent Graft System.

Table 3: Endurant Stent Graft System Testing

| In Vitro Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Stent Graft Design Verification testing | | | |
| Stent Graft Dimensional Verification * | Confirm that the outer diameter and covered length of the Endurant Stent Graft recovers within the specification after deployment from the Endurant Delivery System | • Diameter Tolerances (except 10.0 mm) = ± 1.0 mm
• 10.0 mm Diameter Tolerance = +1.0/-0.5 mm
• Covered length Tolerances = +5.0/- 10.0 mm | PASS |
| Stent Graft Visual Expansion Integrity * | Evaluate any damage that occurs to the Endurant Stent Graft after deployment from the Endurant Delivery System | • No broken stents and no visual stent deformation.
• Loose sutures are allowable if they maintain stent or RO marker attachment to the graft material with a minimum allowable density of 5 sutures/cm.
• Graft hole diameter < 0.50 mm | PASS |
| Suprarenal Stent Inspection * | Determine whether the suprarenal stents of the Endurant Bifurcated Stent Graft maintain visual and dimensional integrity after deployment from the Endurant Delivery System | • No anchor pin dimensional changes
• No cracks, broken stents, gouges or indentations of the suprarenal stent | PASS |
| Stent Graft Migration Force | Measure the peak tensile securement force of active fixation anchor pins of the Endurant Stent Graft. The peak tensile securement force is indicative of the stent graft’s ability *in vivo* to resist (oppose) distal migration | • 23mm Endurant Migration resistance force > 6.72 N
• 25mm Endurant Migration resistance force > 8.10 N
• 28mm Endurant Migration resistance force > 10.45 N
• 32mm Endurant Migration resistance force > 13.12 N
• 36mm Endurant Migration resistance force > 17.13 N | PASS |
| Endurant Stent Graft Migration Resistance Characterization Using Bovine Aorta | Characterize the Endurant Stent Graft migration resistance in simulated clinical conditions utilizing harvested bovine aorta | Since this test is for characterization only, there are no acceptance criteria. | NA |
| Graft Longitudinal Tensile Strength* | Determine the longitudinal tensile strength of the graft fabric of the Endurant Stent Graft | • Lower tolerance limit (LTL) > upper tolerance limit (UTL) of the Deployment Force
• LTL > UTL Migration Resistance Force | PASS |

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| In Vitro Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Stent Graft Seal Evaluation | Compare the proximal seal performance of the Endurant and Talent Stent Grafts | Seal performance of Endurant > seal performance of Talent | PASS |
| Stent Graft Joint Strength | Measure the joint strength between modular components of the Endurant Stent Graft | - Joint Strength between Bifurcated Stub Leg and Contralateral Limb > 3.3 N
- Joint Strength between a 28mm Iliac Limb and 28mm Iliac Extension > 5.73 N
- Joint Strength between a 10mm Iliac Limb and 10mm Iliac Extension > 0.92 N | PASS |
| Stent Attachment Tensile Strength | Measure the tensile strength of the stent attachment to the stent graft of the Endurant Stent Graft | **For Proximal Stent:**
Stent Attachment Strength > Deployment Force

**For Body Stent:**
Stent Attachment Strength > 33.36 N &
Stent Attachment Strength > 50% of Deployment Force | PASS |
| Stent Graft Permeability | Determine the rate of water leakage through the entire stent-graft wall | UTL < 700 ml/min/cm² @ 120 mmHg | PASS |
| Aortic Body and Limb Flexibility * | Characterize the degree of flow occlusion occurring in the aortic body when placed at an aortic neck angle of 75° and in aortic limbs when placed at an angle of 90° of the Endurant Stent Graft | **Aortic Body Flexibility:** LTL Suprarenal Cross-sectional Area at 75° > 50.00% Area at 0°

**Iliac Limb Flexibility:** LTL Cross-sectional Area at 90° > 50.00% Area at 0° | PASS |
| Stent Crimp Strength | Measure the crimp connecting sleeve tensile strength of the stent rings of the Endurant Stent Graft | Ultimate Tensile Strength > 8.90 N | PASS |
| Stent Radial Force | Measure the radial force exerted by the suprarenal and proximal stents (“fixation zone”) of the Endurant Stent Graft | Endurant Proximal Fixation Zone Radial Force (N/mm) > 0 N/mm | PASS |
| Finite Element Analysis | Quantify the maximum fatigue strains occurring in the nitinol stents under crimp strain and in vivo loading conditions. Furthermore, use fatigue life data to present estimates of fatigue safety factors. | The safety factors based on the endurance limit should be > 1. The endurance limit was based upon experimentally measured estimates of nitinol fatigue life at 100 million cycles. | PASS |
| Stent Radial Fatigue | Evaluate the fatigue performance of the Endurant stent graft during a 10 year simulation consisting of 400 million cycles of accelerated in vitro testing in a compliant conduit | Each test sample must complete 400 million test cycles of radial dilatation testing at physiologically challenging radial distension parameters without a stent fracture | PASS |
| Whole Device Pulsatile Fatigue | Evaluate the fatigue wear characteristics of the Endurant Stent Graft System in the unsupported vessel region during a 10 year simulation consisting of 400 million cycles of accelerated in vitro testing. | 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 |
| Angulated Longitudinal Fatigue | Evaluate the long-term durability of the Endurant stent graft when subjected to cyclic longitudinal deformations during a 10 year simulation | Each test sample must complete 400 million cycles of longitudinal fatigue testing without a stent fracture. Graft material and suture durability characterized and compared to wear from clinically explanted specimens. | PASS |
| Anchor Pin Asymmetric Fatigue | Evaluate the fatigue performance of the Endurant suprarenal anchor pins during a 10 year simulation consisting of 400 million cycles of accelerated in vitro testing. | Each test sample must complete 400 million test cycles within test specification without a test fracture or an abnormality | PASS |

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| In Vitro Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Angulated Neck Fatigue | Evaluate the long-term durability of the Endurant Stent Graft when deployed within an angulated neck | Each test sample must complete 400 million cycles of fatigue testing without separation of the suprarenal stent from the stent graft body or stent fractures. Graft material and suture durability characterized and compared to wear from clinically explanted specimens. | PASS |
| Overlap Fatigue | Evaluate the fatigue performance of two overlapping Endurant stent grafts during a 10 year simulation consisting of 400 million cycles of accelerated in vitro testing in a compliant conduit. | 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 |
| Stent Graft Corrosion Testing | Evaluate the corrosion resistance properties of Endurant nitinol laser-cut and wire formed stents. | The stent breakdown potential shall not be lower than the in vivo biologically relevant rest potential. | PASS |
| Delivery System Verification Testing | | | |
| Delivery System Hemostasis – Before and After Tip Removal* | Determine the ability of the End Seal Plug, Backend T-tube, and valves of the Endurant Delivery System to maintain an adequate hemostatic seal before and after tip removal | Flow rate < 2 cc/min | PASS |
| Taper Tip to Inner Member Bond Tensile* | Measure the tensile strength of the Taper Tip to Inner Member bond of the Endurant Delivery System | LTL > 66.72 N
LTL > UTL Tip Advancement Force | PASS |
| Sleeve/Taper Tip Bond Strength (Aortic Delivery System) * | Measure the tensile strength of the Over-Molded Taper Tip to Sleeve bond of the Endurant Delivery System | LTL > 66.72 N
LTL > UTL Tip Advancement Force | PASS |
| Spindle/ Spindle tube Bond Strength (Aortic Delivery System) | Measure the tensile joint strength of the Spindle to Spindle Hypotube of the Endurant Delivery System | LTL > 66.72 N
LTL > UTL Deployment Force
LTL > UTL Tip Advancement Force | PASS |
| Spindletube/Middle Member Bond Strength (Aortic Delivery System) * | Determine the tensile force required to break the Middle Member - Spindle Hypotube bond of the Endurant Delivery System | LTL > 66.72 N
LTL > UTL Deployment Force
LTL > UTL Tip Advancement Force | PASS |
| Handle/T-Tube Bond Strength * | Determine the ultimate tensile strength of the T-Tube Assembly of the Endurant Delivery System | LTL > 66.72 N
LTL > UTL Deployment Force | PASS |
| Backend T-Tube Bond Strength * | Measure the tensile strength of the Inner Member to Back-End T-Tube bond of the Endurant Stent Delivery System | LTL > 66.72 N
LTL > UTL Tip Advancement Force (Aortic only) | PASS |
| Graft Cover Tensile Strength *
(PEBAX, Vestamid and Joint section) | For the Endurant Delivery System Graft Cover Tubing Assembly, this test determined the unrecovered strain at specified proof loads for the PEBAX and Vestamid / PEBAX joint sections and the load at yield (offset 0.8%) of the Vestamid section. | Graft cover tensile strength > greater of pre-determined proof load or deployment force. | PASS |
| Handle T-Tube Torsion Strength * | Evaluate the torsional strength of the handle T-Tube assembly bond between the graft cover tubing and the handle T-Tube of the Endurant Delivery System | For 18 Fr Endurant Delivery Systems:
Torsion Bond Strength LTL > 0.23 N-m

For 20 Fr Endurant Delivery Systems:
Torsion Bond Strength LTL > 0.37 N-m | PASS |

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| In Vitro Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Spindle Hypotube to Middle Member Torsion Strength (Aortic Delivery System) * | Measure the torque force required to break the bond between the Spindle Hypotube and Middle Member of the Endurant Delivery System | LTL Torsion Bond Strength > 0.15 N-m | PASS |
| Backend T-Tube Torque – Inner Member Torque Strength * | Measure the torque force required to break the bond between the backend T-Tube and Inner Member on the Endurant Delivery System | LTL Torsion Bond Strength > 0.04 N-m | PASS |
| Spindle Hypotube Torque-Tensile (Aortic Delivery System) * | Measure the tensile force required to break the skip-cut portion of the Spindle Hypotube of the Endurant Delivery System after each Spindle Hypotube has withstood 540° of torque. | - LTL Spindle Hypotube Tensile Strength > UTL Tip Advancement Force
- LTL Spindle Hypotube Tensile Strength >66.72 N
- LTL Spindle Hypotube Tensile Strength > UTL Deployment Force | PASS |
| Middle Member Lock Tensile Strength * | Measure tensile strength of the bond between the Middle Member Locks and Middle Member of the Endurant Delivery System | - LTL Tensile Strength > UTL Tip Advancement Force
- LTL Tensile Strength > 66.72 N
- LTL Tensile Strength > UTL Deployment Force | PASS |
| RO Marker Band Tensile Strength * | Measure the tensile strength of the bond between the radiopaque marker band and the graft cover on the Endurant Delivery System | - LTL Tensile Strength > 33.36 N
- LTL Tensile Strength > ½ of UTL Deployment Force | PASS |
| T-Tube Hubcap Bond Strength * | Measure the tensile strength of the bond between the hubcap and handle T-Tube of the Endurant Delivery System | LTL Tensile Strength > 2.22 N | PASS |
| Endseal to Hypotube Bond Tensile Strength* | Measure the tensile strength of the bond between the End Seal and Hypotube of the Endurant Delivery System | LTL Tensile Strength > 2.22 N | PASS |
| Forward Wheel Wall Torque Strength * | Measure the forward torque force at the wall of the rear grip required to separate the wheel from the screwwgear of the Endurant Stent Graft System with Design Improvements | LTL > 0.62 N-m | PASS |
| Working and Total Length * | Determine the working and total lengths of the Endurant Delivery System | - Working Length: 57 ± 2 cm
- Total Length: Aortic delivery system: 120 ± 3 cm
Iliac delivery system: 109 ± 3 cm | PASS |
| Crossing Profile * | Determine the outside diameter of the Endurant Delivery System | The appropriate ring gage must pass over the loaded delivery system without any damage to the delivery system. | PASS |
| Guidewire Acceptance* | Confirm that the Endurant Delivery System is compatible with a 0.035" guidewire | The delivery system must pass a 0.035" guidewire with ≤100 gF of resistance | PASS |
| Deployment Force * | Determine the force to deploy the Endurant Stent Graft System within a simulated vasculature model | Deployment Force < Graft Cover Material's Yield Strength | PASS |
| Delivery System Lubricity (Hydrophilic Coating Presence) * | Determine the presence of hydrophilic coating on the Endurant Delivery System | Hydrophilic coating must be present on the graft cover | PASS |
| Trackability * | Evaluate the trackability of the Endurant Stent Graft System | The system must be able to track through simulated tortuous anatomies to reach the placement location | PASS |
| Pushability * | Evaluate the pushability of the Endurant Stent Graft System | The system must be able to be pushed through simulated tortuous anatomies to reach the placement location | PASS |

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| In Vitro Test | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Torquability * | Characterize the torquability of the Endurant Stent Graft System. | Since this test is for characterization only, there are no acceptance criteria | NA |
| Flex/Kink * | Evaluate the ability of the Endurant Stent Graft System to withstand flex/kink | The delivery system must resist kinking such that the stent graft can be deployed at the intended placement location | PASS |
| Graft Cover Torque* | Evaluate the graft cover torque capability of the Endurant Delivery System | The graft cover joint (PEBAX to Vestamid) must withstand torque forces during gate alignment such that stent graft deployment occurs successfully | PASS |
| Release of Anchor Pins (AP) (Aortic Delivery System) * | Determine the ability of the Endurant Stent Graft System to provide proper and timely release of the anchor pins in a simulated use model | All suprarenal apices must remain within the sleeve until the backend thumbwheel is advanced. The stent graft must successfully deploy. | PASS |
| Deployment Accuracy (Aortic Delivery System) * | Characterize the deployment accuracy of the Endurant Stent Graft System. | Since this test is for characterization only, there are no acceptance criteria. | NA |
| Ability to Withdraw (Aortic Delivery System) * | Determine the ability to withdraw the Endurant Delivery System post stent graft deployment | The operator must recapture the spindle and tapered tip, and the delivery system must be withdrawn, intact, from the simulated use model after stent graft deployment | PASS |
| Tip Advancement Force (Aortic Delivery System) * | Measure the force required to advance the tapered tip and deploy the anchor pins of the Endurant Stent Graft System | UTL < 88.96 N | PASS |
| Spindle Advancement | Measure the rate of release of the modified spindle used in the Endurant Aortic Stent Graft System | Kaplan-Meier survival statistically better than control, for rate of spindle release from the suprarenal stent. | PASS |
| Stent Graft Length vs. Diameter | Assess the length of the deployed Endurant Stent Graft as a function of diameter | UTL Actual Length – Deployed Length ≤ ±10% Actual Length | PASS |

* Indicates tests performed at T=0 (baseline) and T=2 (accelerated aged shelf-life)

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# In vivo Animal Testing

Preclinical in vivo animal testing, using prototypes of the final device design, was conducted in 27 animals to evaluate acute technical success (deployment), stent graft integrity, and histopathological response of the Endurant Stent Graft System in ovine models for up to 6 months. The prototype design and the final device design are similar enough for the animal study results to be applicable to the final Endurant design. The results demonstrated the ability to access the target anatomical location, adequate handling and visualization of the delivery system and implant, and deployment accuracy. Stent graft integrity and histopathological response were acceptable. The results support the safety and expected performance of the Endurant Stent Graft System. A summary of the in-vivo animal testing is provided in Table 4.

Table 4: Summary of Endurant In-Vivo Studies

| Study | # of Animals | Objectives | Success Criteria | Objectives Met?¹ |
| --- | --- | --- | --- | --- |
| Acute Evaluation of Medtronic Vascular’s Endurant Stent Graft System in an Ovine Model | 6 | Evaluate the following performance characteristics:
• Trackability/Flexibility of Endurant Delivery System
• Pushability/Kink resistance of Endurant Delivery System
• Torquability of Endurant Delivery System (Aortic Delivery System - for bifurcated and aortic cuff devices)
• Guidewire compatibility/Delivery system movement over the wire
• Crossing ability
• Deployment
• Visibility of system under fluoroscopy for both Endurant Stent Graft and Delivery System
• Accuracy of placement of Endurant Stent Graft
• Tip advancement of Endurant Aortic Delivery System
• Delivery system retraction and withdrawal
• Functional hemostasis of delivery system (back bleed)
• Post procedural inspection
• Ease of use | Successful completion of this study was defined as mean evaluation scores for each performance characteristic of component of the test device as being 'average' (rating "3") or greater. | Yes |
| Evaluation of Medtronic Vascular’s Endurant Abdominal Stent Graft System’s Bail Out Procedures in an Ovine Model | 2 | In the event the sleeve holding the apices of the proximal bare spring and anchor pins of the device is not able to be removed because of a delivery system failure, a bail-out procedure to effectively retract the system is necessary. The purpose of this study is to evaluate the acute performance of the Endurant Stent Graft System in the event of device failure. The capacity of the prosthesis to be effectively removed without significant damage will be investigated. | As this was an evaluation of a specific procedure for the Endurant Delivery System, no specific success criteria were established. | Yes |

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| Study | # of Animals | Objectives | Success Criteria | Objectives Met?¹ |
| --- | --- | --- | --- | --- |
| Evaluation of Medtronic Vascular’s Endurant Abdominal Stent Graft System in an Ovine Model (30-Day Safety Study) | 7 | • Assess acute stent graft placement and any device related effects at the time of implant.
• Evaluation of the position of the implant at the time of explant
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the time of explant
• Evaluation of histology and pathology of explants and surrounding tissue | • Distal migration of the test devices of no more than 10 mm will be considered acceptable. Position of the stent graft at implant and explant will be compared using anatomical landmarks, aortagrams and intravascular ultrasound (IVUS) and any change in position will be documented.
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the explant procedure, before animal termination, will be evaluated using angiography, IVUS and/or x-ray. Success will be determined by the lack of evidence of stent fractures.
• Comparable or superior histological indicators of vessel wall healing at 30 days for Endurant Abdominal Stent Graft test devices as compared to the Talent Abdominal 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 response than the Talent control data. | Yes |
| Evaluation of Medtronic Vascular’s Endurant Abdominal Stent Graft System in an Ovine Model (90-Day Safety Study) | 6 | • Assess acute stent graft placement and any device related effects at the time of implant.
• Evaluation of the position of the implant at the time of explant
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the time of explant
• Evaluation of histology and pathology of explants and surrounding tissue | • Distal migration of the test devices of no more than 10 mm will be considered acceptable. Position of the stent graft at implant and explant will be compared using anatomical landmarks, aortagrams and intravascular ultrasound (IVUS) and any change in position will be documented.
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the explant procedure, before animal termination, will be evaluated using angiography, IVUS and/or x-ray. Success will be determined by the lack of evidence of stent fractures.
• Comparable or superior histological indicators of vessel wall healing at 90 days for Endurant Abdominal Stent Graft test devices as compared to the Talent Abdominal 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 response than the Talent control data. | Yes |

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| Study | # of Animals | Objectives | Success Criteria | Objectives Met?¹ |
| --- | --- | --- | --- | --- |
| Evaluation of Medtronic CardioVascular’s Endurant Stent Graft System in an Ovine Model (180-Day Safety Study) | 6 | • Assess acute stent graft placement and any device related effects at the time of implant.
• Evaluation of the position of the implant at the time of explant
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the time of explant
• Evaluation of histology and pathology of explants and surrounding tissue | • Ability to deliver and deploy all stent grafts to the intended location.
• Distal migration of the test devices of no more than 10 mm will be considered acceptable. Position of the stent graft at implant and explant will be compared using anatomical landmarks, aortagrams and intravascular ultrasound (IVUS) and any change in position will be documented.
• Evaluation of the structural integrity of the Endurant Abdominal Stent Graft at the explant procedure, before animal termination, will be evaluated using angiography, IVUS and/or x-ray. Success will be determined by the lack of evidence of stent fractures.
• Comparable or superior histological indicators of vessel wall healing at 180 days for Endurant Abdominal Stent Graft test devices as compared to the Talent Abdominal Stent Graft control data, including strut induced vessel wall injury, inflammation, thrombus, endothelialization, and neointimal formation.
• Overall quantitative morphometric analysis of tissue sections from the test device indicating similar or better response than the Talent control data. | Yes |

¹ Please note that some degree of change in device position that may have exceeded 10 mm was noted in some cases upon radiographic or IVUS measurement with respect to either the control device or 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 weight gain over the in-life period of the study.

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# X. Summary of Clinical Studies

The Endurant Stent Graft System US Clinical Study (G070208; also referenced as the Endurant Stent Graft System US IDE) information summarized below includes the clinical safety and effectiveness data. Data on 150 subjects were available at 30-days post-index procedure and data on 129 subjects were available at 12-months post index procedure. The 30-day and 1-year data set was provided to support the marketing application of the Endurant Stent Graft System. The aforementioned trial is summarized in Table 5. The trial under which the historical control data were captured is summarized in Table 6.

Table 5: Endurant Stent Graft System Clinical Study Summary – Test Group

| Clinical Study | Study Design | Objective | Number of Sites | Number of Subjects (enrolled) |
| --- | --- | --- | --- | --- |
| Endurant Stent Graft System Clinical Study | Prospective, non-randomized, multi-center study with a historical control | Evaluate the safety and effectiveness of the Endurant Stent Graft System | 26 | 150 subjects |

Table 6: Talent Abdominal Stent Graft System Clinical Study Summary - Historical Control

| Clinical Study | Study Design | Objective | Number of Sites | Number of Subjects (enrolled) |
| --- | --- | --- | --- | --- |
| Talent Abdominal Stent Graft System Pivotal Clinical Study | Prospective, non-randomized, multi-center stud; study was used as a historical control for Endurant US Clinical Study | Evaluate the safety and effectiveness of the Talent Abdominal Stent Graft System | 13 | 166 subjects |

# A. Clinical Study Design

The Endurant Stent Graft System data presented as part of P100021 formed the basis for FDA’s finding that the System is safe and effective for its intended use. A total of 150 patients were enrolled in the bifurcated study arm of the US Study. An independent core lab reviewed CT scans and abdominal x-rays to assess aneurysm changes, device position and integrity, and endoleaks.

The objective of the Endurant Stent Graft System US Clinical Study was to evaluate the safety and effectiveness of the Endurant Stent Graft System in the treatment of infrarenal abdominal aortic and aortoiliac aneurysms.

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# 1.0 Major Design Characteristics of the Endurant Stent Graft System US Clinical Study

The US Clinical Study was an open label, non-randomized design. The Endurant Stent Graft System bifurcated arm (n = 150) was compared to a historical control, namely the Talent AAA Stent Graft System, a prior generation endovascular abdominal aortic aneurysm stent graft system. The Talent Control group (n = 166) was the pivotal cohort in the study of the Talent Abdominal Stent Graft (refer to the Summary of Safety and Effectiveness Data (SSED) for the Talent Abdominal Stent Graft System (P070027) for more information), where enrollment occurred at 13 sites between February 2002 and April 2003. The determination of the safety and effectiveness of Endurant Stent Graft System was based on the data collected in the first year post-implant. Additionally, Medtronic will continue to follow the patients enrolled in the US Clinical Study for a total of 5 years under the same clinical protocol.

# 2.0 Clinical Endpoints of the Endurant Stent Graft System US Clinical Study

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

# 2.1 Safety

The primary safety endpoint for this analysis was the proportion of patients free from a Major Adverse Event (MAE) within 30 days of the index procedure (based on a composite MAE rate), compared to the Talent Control Group. Other secondary endpoints and analyses include all-cause mortality through 1 and 12 months, aneurysm-related mortality (ARM) through 12 months, and adverse events. All Major Adverse Events (MAEs) were adjudicated by an independent clinical events committee and study safety was monitored by a data safety monitoring committee. Follow-up visits were conducted at 1 month, 6 months, and 12 months to support the marketing application, and subjects will continue to be followed annually thereafter, for a total of 5 years from the index procedure.

# 2.2 Effectiveness

The primary effectiveness endpoint for this analysis was successful aneurysm treatment at one year. Successful aneurysm treatment was an endpoint that included successful delivery and deployment, aneurysm growth, endoleaks, stent graft occlusion, conversion to surgery, rupture and migration. Imaging-based events were assessed by an independent core laboratory. The primary effectiveness endpoints were compared to the Talent Control Group. Other secondary endpoints and analyses included each of the components of the composite endpoint and technical observations, defined as an observed effect or malfunction of the stent graft which is not related to any adverse event, through 12 months. Follow-up visits were conducted at 1 month, 6 months, and 12 months to support the marketing application and subjects will continue to be followed annually thereafter, for a total of 5 years from the index procedure.

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# 2.3 Success/Failure Criteria

The Endurant Stent Graft System US Clinical Study was considered a success if both primary safety and effectiveness study objectives were met. These objectives were assessed by demonstrating non-inferiority of the Endurant Test Group to the Talent Control Group in regards to freedom from MAEs at 30 days and successful aneurysm treatment at 12 months following the index procedure, where non-inferiority was pre-specified with a quantifiable margin of 10%.

# 2.4 Pre-Specified Statistical Analysis Plan

The statistical analysis plan utilized for the Endurant Stent Graft System study was prospectively defined. Taking into consideration the Talent study results, expected attrition, and a goal of achieving at least a minimum of 80% statistical power at a one-sided significance level of 5%, a sample size of 150 enrolled subjects was considered to be sufficient using a 10% non-inferiority margin. The difference in outcomes was determined utilizing a propensity score method (stratification). The primary safety hypothesis was defined as the proportion of subjects free from the occurrence of a MAE within 1 month (Day 0 - Day 30) of the implantation of the Endurant Stent Graft. For statistical comparison of the primary safety endpoint between the Endurant and the Talent Control group, a non-inferiority hypothesis was tested. The primary effectiveness endpoint was an endpoint defined as the proportion of subjects who had a successful aneurysm treatment as evaluated at the time of the index procedure and at 12 months. For statistical comparison of the primary effectiveness endpoint between the Endurant and the Talent Control group, a non-inferiority hypothesis was tested. Results presented here are based on analysis using available data. A sensitivity analysis on the intent-to-treat population, including all patients enrolled, was performed using multiple imputation methods.

# 2.5 External Evaluation Groups

- **Core Laboratory.** In order to provide independent verification of imaging findings, images required by protocol were sent by the sites to a central imaging core laboratory with processes and systems that are GMP/GCP, HIPAA, and CFR 21 Part 11 compliant and are provided within an ISO 13485 certified facility which adheres to all applicable federal regulations.
- **Clinical Events Committee.** An independent Clinical Events Committee (CEC) adjudicated all deaths and MAEs for event type and device and procedure relatedness. Members included interventional cardiologists, vascular surgeons, cardiothoracic surgeons, and interventional radiologists who had no conflicts of interest related to the study sponsor or the study investigators.
- **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 have recommended that Medtronic Vascular continue, modify, or stop the study in accordance to previously agreed parameters. The committee was composed of physicians with relevant training and one biostatistician who were not directly involved in the conduct of the study.

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# 3.0 Study Design

Medtronic compared the Endurant Stent Graft System to the Talent Stent Graft System as part of the primary safety and effectiveness endpoint utilizing hypotheses. This study design generated valid scientific evidence by comparing the test group to an endovascular control group. This design provided the following advantages:

- the test and control subject populations were both treated by endovascular repair;
- both safety and effectiveness endpoints can be compared directly; and
- study entry criteria were comparable.

It is important to note that there are considerations associated with using a historical control, such as the Talent Stent Graft Control. Talent subjects were enrolled between 2002 and 2003, whereas Endurant subjects were enrolled between 2008 and 2009. Between the time that the two studies were conducted, the therapy has evolved and physicians became more experienced with the endovascular repair (EVAR) procedure. Also, unobserved differential characteristics between two cohorts cannot be adjusted. However, both populations were treated for abdominal aortic aneurysms and the results from the Talent Stent Graft Control group provide a valid control to compare with the Endurant Stent Graft System.

Since the initial enrollment, no significant changes were made to the Endurant Stent Graft System US Clinical Study design.

# 3.1 Clinical Inclusion and Exclusion Criteria

Enrollment in the Endurant Stent Graft System US Clinical Study was limited to patients who met the following selection criteria as shown in Table 7.

Table 7: Endurant Stent Graft System Inclusion and Exclusion Criteria

| Inclusion | Exclusion |
| --- | --- |
| Subject is ≥ 18 years old. | Subject has a life expectancy ≤ 1 year |
| Subject (or Subject’s legal representative) understands and voluntarily has signed and dated an Informed Consent document approved by the Sponsor and by the Institutional Review Board | Subject is participating in another investigational drug or device study and has not completed the follow-up required for that study at least 1 month prior to signing the consent form in this study |
| Subject is able and willing to comply with the protocol and undergo follow-up requirements | Subject is a female of childbearing potential in whom pregnancy cannot be excluded. A pregnancy test with negative results is required at the time of screening |
| Subject is a suitable candidate for elective surgical repair of AAA by as evaluated by American Society of Anesthesiologists (ASA) Physical Status Classification System I, II, or III | Subject has an aneurysm that is:
a. Suprarenal.
b. Isolated ilio-femoral.
c. Mycotic.
d. Inflammatory
e. Pseudoaneurysm |
| Subject has an abdominal aortic or aortoiliac aneurysm characterized by one or more of the following:
a. Aneurysm is > 5cm in diameter (diameter measured is perpendicular to the line of flow).
b. Aneurysm is 4 - 5 cm in diameter and has increased in size ≥ 0.5 cm within the last 6 months | Subject has an untreated thoracic aneurysm > 4.5 cm in diameter |

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| Inclusion | Exclusion |
| --- | --- |
| Subject meets all the following anatomical criteria as demonstrated on contrast enhanced CT or MRA imaging:
a. Suprarenal angle ≤ 45 degrees (angle between the proximal neck and the suprarenal aorta).
b. Infrarenal angulation ≤ 60 degrees (angle between the proximal neck and the aneurysm).
c. Infrarenal aneurismal neck length with at least 10 mm of non-aneurismal aorta, immediately inferior to the most inferior major renal artery | Subject requires emergent aneurysm treatment, e.g., trauma or rupture |
| Subject has vascular dimensions, e.g., aortic and iliac diameters, lengths from renal arteries to iliac bifurcation and hypogastric arteries, in the range of sizes available for the Endurant Stent Graft and within the sizing recommendations | Subject has an aneurysm that involves the part of the aorta at the ostia of the renal arteries |
| Subject has a proximal aortic neck diameter ≥ 19 mm and ≤ 32 mm | Subject has a history of bleeding diathesis or coagulopathy |
| The distal fixation center of the iliac arteries must have a diameter ≥ 8 mm and ≤25 mm bilateral | Subject has had or plans to have an unrelated major surgical or interventional procedure within 1 month before or after implantation of the Endurant Stent Graft |
| Subject has documented imaging evidence of at least 1 patent iliac and 1 femoral artery, or can tolerate a vascular conduit that allows introduction of the device | Subject has had a myocardial infarction (MI) or cerebral vascular accident (CVA) within 3 months prior to implantation of the Endurant Stent Graft |
| Subject has distal non-aneurysmal iliac (cylindrical) fixation length ≥ 15 mm bilaterally | Subject has a reversed conical neck defined as a > 4 mm distal increase over a 10 mm length |
| | Subject has a known allergy or intolerance to the device components |
| | Subject has a known hypersensitivity or contraindication to anticoagulants, antiplatelets, or contrast media, which is not amenable to pre-treatment |
| | Subject has significant (> 25% of vessel circumference of aortic neck and iliac artery, and/or > 50% of the length of the iliac artery) aortic mural thrombus at either the proximal or distal attachment centers that would compromise fixation and seal of the device bilaterally |
| | Subject has ectatic iliac arteries requiring bilateral exclusion of hypogastric blood flow |
| | Subject whose arterial access site is not anticipated to accommodate the diameter of the Endurant Stent Graft Delivery System (14F-20F) due to size or tortuosity |
| | Subject is morbidly obese (body mass index ≥ 40 kg/m2) or has other documented clinical conditions that severely inhibit radiographic visualization of the aorta |
| | Subject has active infection at the time of the index procedure documented by pain, fever, drainage, positive culture and/or leukocytosis (WBC > 11,000 mm3) that is treated with antimicrobial agents (nonprophylactic) |
| | Subject has congenital degenerative collagen disease, e.g., Marfan’s Syndrome |
| | Subject has a creatinine > 2.00 mg/dl (or > 182 μmol/L) |
| | Subject is on dialysis |

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Two different scoring systems were used to describe the comorbid state of patients (SVS in Talent and ASA in Endurant); however, a common grading system was applied to both study groups to provide a valid comparison (Modified SVS/AAVS Medical Co-morbidity Grading System). There are some differences in anatomical criteria based on device-specific stent graft sizes. Exclusion criteria in the Endurant Test Group included restrictions to ensure subject safety, such as exclusion of emergency aneurysm treatment, allergies to device, and elevated creatinine. More detailed or specific criteria were included in the Endurant study due to the advancement of the management of the disease. Since the Talent clinical study began in 2002, recommendations for EVAR and AAA management have evolved. Main differences between Endurant and Talent Inclusion/Exclusion Criteria are detailed in Table 8.

Table 8: Summary of Endurant vs. Talent Inclusion/Exclusion Criteria

| Endurant | Talent |
| --- | --- |
| Inclusion Criteria | |
| Baseline Risk Factors | |
| ASA Physical Status Classification I, II and III | SVS/ISCVS category 0, 1 and 2 |
| Anatomical Characteristics | |
| • AAA >5 cm in diameter or is 4-5 cm but increased in size ≥0.5 cm within last 6 months
• Proximal AAA neck length ≥10 mm
• Suprarenal ≤45 and infrarenal ≤60 degrees
• Proximal aortic neck diameter ≥19 mm and ≤32 mm
• Iliac diameters ≥8 mm and ≤25 mm | • AAA >4 cm in diameter or 1.5 times larger than native aorta or symptomatic
• Proximal AAA neck length ≥5 mm*
• Infrarenal ≤60 degrees
• Proximal aortic neck diameter ≥14 mm and ≤32 mm
• Iliac diameters ≥8 mm and ≤18 mm
• Renal arteries ≥9 cm from aortic bifurcation |
| Exclusion Criteria | |
| Baseline Risk Factors | |
| • Untreated thoracic aneurysm > 4.5 cm diameter
• Emergent aneurysm treatment (trauma, rupture)
• Known allergy to device component
• Creatinine ≥2.0 mg/dl (182μmol/L)
• On dialysis | SVS/ISCVS category 3 or unsuitable for elective surgical repair |
| Anatomical Characteristics | |
| • Aneurysm that involves the part of the aorta at the ostia of the renal arteries
• Reversed conical neck > 4mm distal increase over 10 mm length.
• Significant aortic mural thrombus that would compromise distal fixation and seal of device.
• Morbidly obese body mass index ≥40kg/m² or other clinical conditions that inhibit radiographic visualization of aorta | • One or more patent subrenal arteries with potential retrograde flow after stent grafting.
• Dominant patent internal mammary artery, occluded or stenotic celiac and superior mesenteric artery. Lesion that cannot be crossed with guidewire.
• No distal vascular bed (one vessel lower extremity run-off required) |

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*Although the inclusion criteria for proximal AAA neck length was ≥ 5 mm in the Talent clinical study, Medtronic decided to indicate as part of the Talent Stent Graft System marketing application a proximal AAA neck length of ≥ 10 mm.

## 3.2 Treatment and Follow-Up Schedule:

The Endurant Stent Graft System was used in the endovascular treatment of abdominal aortic or aortoiliac aneurysms. The following follow-up scheme was required for both Endurant and Talent:

1. 1 month following the index procedure;
2. 6 months following the index procedure;
3. 12 months following the index procedure; and
4. annually thereafter, for a total of 5 years from the index procedure.

At each visit, abdominal X-ray and CT with and without contrast medium were required. Alternative imaging modalities such as Color Duplex Ultrasound, Magnetic Resonance Imaging were recommended in patients with impaired renal function or intolerance to contrast media.

## B. Patient Accountability, Follow-up, Demographic and Baseline Information

This section contains information on patient accountability and follow-up as well as the demographic and baseline parameters for the Endurant Stent Graft System US Clinical Study.

## 1.0 Patient Accountability, Follow-up

For the Endurant Test Group, 150 subjects were enrolled across 26 sites. Detailed subject accountability and follow-up are presented in Table 9. The numbers found in Table 9 as well as subsequent sections represent those patients that had data available to assess the relevant parameters. In the Talent Control Group, 166 subjects were enrolled across 13 sites, with 100% (162/162) of available subjects receiving clinical follow-up and 98.8% (160/162) receiving imaging follow-up at one month. At 12 months, 97.2% (138/142) had clinical follow-up and 93.0% (132/142) had imaging follow-up. Additional information on the Talent Control Group patient accountability and follow-up can be found in the Summary of Safety and Effectiveness for P070027.

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Table 9: Subject and Imaging Accountability – Endurant Test Group¹

| Interval (Analysis Window) | Subject follow-up | | | Subjects with imaging performed (Core Lab) | | Subjects with adequate imaging to assess the parameter (Core Lab) | | | | Subject events occurring before next visit | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Eligible | Clinical Follow-up | Imaging Follow-up | CT/MRA Imaging | KUB Imaging | Aneurysm size increase | Endoleak | Migration | Technical Observation | No Implant | Conversion to Surgery | Death | Withdrawal | Lost to Follow-up | Not Due for Next Visit |
| Originally Enrolled | 150 | | | | | | | | | 0 | | | | | |
| Events after implant but before a 1 Month visit | | | | | | | | | | | 0 | 0 | 0 | 0 | 0 |
| 1 Month (Day 1-90) | 150 | 149 (99%) | 149 (99%) | 147 (98%) | 124 (83%) | | 143 (95%) | | 149 (99%) | | | | | | |
| Events after 1 Month visit but before a 6 Month visit | | | | | | | | | | | 0 | 2 | 0 | 0 | 0 |
| 6 Month (Day 91-304) | 148 | 143 (97%) | 138 (93%) | 135 (91%) | 134 (91%) | 132 (89%) | 129 (87%) | 132 (89%) | 138 (93%) | | | | | | |
| Events after 6 Month visit but before a 12 Month visit | | | | | | | | | | | 0 | 4 | 0 | 0 | 12 |
| 12 Month (≥ Day 305²) | 132 | 128 (97%) | 129 (98%) | 128 (97%) | 125 (95%) | 127 (96%) | 123 (93%) | 125 (95%) | 129 (98%) | | | | | | |
| ¹ Data analysis sample size varies for each of the timepoints above and in the following tables. This variability is due to subject 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 Technical observations assessed by imaging include stent-graft kinking, stent-graft twisting, stent-graft wireform fracture, suprarenal bare stent fracture, anchor pin fracture, and stent-graft stenosis.
³ In cases where 12 month imaging follow-up data were not available, subsequent imaging follow-up data were used. | | | | | | | | | | | | | | | |

## C. Study Population Demographics and Baseline Parameters

The demographics between the Endurant Test Group and Talent Control Group were comparable. The sex/gender distribution was similar between the two study groups and consistent with studies of other devices for the treatment of Abdominal Aortic Aneurysms. The baseline medical histories of the Endurant test group and Talent control group were sufficiently similar to allow comparison of device safety and effectiveness, with high prevalence of hypertension, chronic obstructive pulmonary disease and tobacco use in the past 10 years in both study groups. The significant difference between Endurant and Talent in baseline PVD was not considered sufficient to invalidate the comparison. The baseline SVS/AAVS risk classifications were similar with over 80% subjects with SVS 2 or above in both study groups.

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Table 10 through Table 12 provides the demographics, baseline medical history and SVS risk classification of the Endurant Test Group and the Talent Control Group. Table 13 and Table 14 provide baseline aneurysm characteristics and distribution of aneurysm diameters for both the Endurant and Talent groups.

Table 10: Subject Demographics

| Parameter | Statistics/Category | Endurant Test Group (N=150) | Talent Control Group (N=166) | p-Value^{1} |
| --- | --- | --- | --- | --- |
| Age (years) | | | | |
| | Mean ± SD | 73.1 ± 8.0 | 74.1 ± 7.5 | 0.255 |
| | Median | 73.0 | 76.0 | |
| | Min, max | 52, 88 | 51, 89 | |
| Sex/Gender % (m/n) | | | | |
| | Male | 91.3% (137/150) | 91.6% (152/166) | > 0.999 |
| Race % (m/n) | | | | |
| | White | 98.7% (148/150) | 92.8% (154/166) | 0.013 |
| | Non-white | 1.3% (2/150) | 7.2% (12/166) | |
| ^{1}p-values were based on t-tests for continuous variables and Fisher’s Exact test for categorical variables. | | | | |

Table 11: Baseline Medical History

| Body System / Condition | Endurant Test Group % (m/n) | Talent Control Group % (m/n) | p-Value^{1} |
| --- | --- | --- | --- |
| Cardiovascular | | | |
| Angina | 18.0% (27/150) | 16.9% (28/166) | 0.882 |
| Arrhythmia | 39.3% (59/150) | 44.0% (73/166) | 0.426 |
| Congestive heart failure | 16.0% (24/150) | 28.3% (47/166) | 0.010 |
| Hypertension | 86.7% (130/150) | 83.7% (139/166) | 0.528 |
| Myocardial infarction | 30.0% (45/150) | 38.6% (64/166) | 0.124 |
| Peripheral vascular disease | 22.7% (34/150) | 46.4% (77/166) | < 0.001 |
| Renal | | | |
| Renal insufficiency | 28.7% (43/150) | 33.1% (55/166) | 0.397 |
| Other abnormal body systems | | | |
| Chronic obstructive pulmonary disease | 35.3% (53/150) | 39.2% (65/166) | 0.488 |
| Diabetes | 26.7% (40/150) | 15.7% (26/166) | 0.019 |
| Tobacco use in the last 10 years | 44.0% (66/150) | 44.6% (74/166) | > 0.999 |
| ^{1}p-values were based on Fisher’s Exact Test | | | |

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Table 12: Baseline Modified SVS Classification

| SVS/AAVS Classification | Endurant Test Group % (m/n) | Talent Control Group % (m/n) | p-Value^{1} |
| --- | --- | --- | --- |
| SVS 0 | 0.0% (0/150) | 0.6% (1/166) | 0.802 |
| SVS 1 | 16.0% (24/150) | 15.7% (26/166) | |
| SVS 2 | 54.7% (82/150) | 55.4% (92/166) | |
| SVS 3 | 29.3% (44/150) | 28.3% (47/166) | |
| 1 p-value was based on the Cochran-Mantel-Haenzel test for mean score differences in SVS classification | | | |

Table 13 and Table 14 provide the baseline aneurysm and anatomical measurements of the Endurant Test Group and Talent Control Group.

Table 13: Baseline Aneurysm Characteristics (Corelab Reported)

| Dimension | Statistics | Endurant Test Group | Talent Control Group | p-Value^{2} |
| --- | --- | --- | --- | --- |
| Maximum aneurysm diameter (mm) | n^{1} | 150 | 156 | |
| | Mean ± SD | 55.9 ± 8.7 | 55.0 ± 9.3 | 0.359 |
| | Median | 54 | 53 | |
| | Min, Max | 39, 103 | 38, 88 | |
| Proximal neck diameter (mm) | n^{1} | 150 | 156 | |
| | Mean ± SD | 23.5 ± 3.0 | 25.3 ± 3.6 | < 0.001 |
| | Median | 23 | 26 | |
| | Min, Max | 17, 31 | 16, 32 | |
| Right iliac diameter (mm) | n^{1} | 148 | 148 | |
| | Mean ± SD | 14.2 ± 4.2 | 14.5 ± 3.6 | 0.447 |
| | Median | 14 | 14 | |
| | Min, Max | 9, 48 | 7, 39 | |
| Left iliac diameter (mm) | n^{1} | 150 | 153 | |
| | Mean ± SD | 13.9 ± 3.1 | 14.3 ± 3.8 | 0.347 |
| | Median | 14 | 14 | |
| | Min, Max | 8, 24 | 8, 38 | |
| Proximal neck length (mm) | n^{1} | 150 | 154 | |
| | Mean ± SD | 31.0 ± 14.3 | 22.9 ± 12.5 | <0.001 |

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Table 14: Distribution of Aneurysm Diameters (Core lab reported)

| Dimension | Statistics | Endurant Test Group | Talent Control Group | p-Value² |
| --- | --- | --- | --- | --- |
| | Median | 29 | 21 | |
| | Min, Max | 5³, 74 | 3, 75 | |
| Infrarenal neck angle (°) | n¹ | 150 | 127 | |
| | Mean ± SD | 35.2 ± 13.7 | 30.5 ± 15.8 | 0.009 |
| | Median | 34 | 30 | |
| | Min, Max | 5, 73 | 0, 72 | |
| Suprarenal neck angle (°) | n¹ | 150 | NA | |
| | Mean ± SD | 16.0 ± 10.3 | NA | NA |
| | Median | 14 | NA | |
| | Min, Max | 2, 58 | NA | |
| ¹ Number of subjects with readable scans.
² p-Values were based on a two-sample t-test
³ Based on Core Lab measurements, two (2) subjects had proximal neck length measurements <10 mm and were outside the margin of error; however, the site reported measurements were >10 mm. | | | | |
| | Statistics/ Category | Endurant Test Group | Talent Control Group |
| --- | --- | --- | --- |
| Maximum Aneurysm Diameter %(m/n)¹ | < 30 mm | 0.0% (0/150) | 0.0% (0/156) |
| | 30 mm - < 40 mm | 0.7% (1/150) | 1.3% (2/156) |
| | 40 mm - < 50 mm | 16.0% (24/150) | 26.3% (41/156) |
| | 50 mm - < 60 mm | 63.3% (95/150) | 44.2% (69/156) |
| | 60 mm - < 70 mm | 13.3% (20/150) | 20.5% (32/156) |
| | 70 mm - < 80 mm | 4.0% (6/150) | 5.8% (9/156) |
| | 80 mm - < 90 mm | 1.3% (2/150) | 1.9% (3/156) |
| | 90 mm - < 100 mm | 0.7% (1/150) | 0.0% (0/156) |
| | 100 mm - < 110 mm | 0.7% (1/150) | 0.0% (0/156) |
| | ≥ 110 mm | 0.0% (0/150) | 0.0% (0/156) |
| Aneurysm Diameter % (m/n) < 50 mm | | 16.7% (25/150) | 27.6% (43/156) |
| Aneurysm Diameter % (m/n) ≥ 50mm | | 83.3% (125/150) | 72.4% (113/156) |
| ¹ n = number of subjects with readable scans. | | | |

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# 2.0 Devices Implanted

Table 15 below provides a breakdown of the number of Endurant Stent Graft devices implanted at the index procedure per subject.

Table 15: Total Number of Devices Implanted at Initial Procedure

| Number of Devices Implanted on a Subject | Endurant Test Group (%m/n)^{1} |
| --- | --- |
| 1 | 0.7% (1/150) |
| 2 | 40.0% (60/150) |
| 3 | 30.0% (45/150) |
| 4 | 25.3% (38/150) |
| 5 | 3.3% (5/150) |
| 6 | 0.7% (1/150) |
| ≥ 7 | 0.0% (0/150) |
| ^{1} Denominator includes all subjects who received the test device. | |

# 2.1 Device Implanted by Type at Index Procedure

All 150 Endurant subjects received a main bifurcated device and all but one (1) subject received a contralateral limb device. Forty-five (45) subjects received aortic or iliac limb extension(s). Since multiple stent graft configurations may be used in a single subject, the number of total devices implanted exceeded the number of subjects enrolled. There was limited use of aortic extensions in the US clinical study. However, it is important to note that the design of the proximal section of the aortic extension component (i.e., the suprarenal stent and the seal stent) is identical to the design of the proximal section of the bifurcated component; therefore, the performance of the two components is expected to be comparable.

Table 16: Devices Implants by Type at Index Procedure

| Device Type | Endurant Test Group (%m/n)^{1} |
| --- | --- |
| Main Bifurcated | 100.0% (150/150) |
| Contralateral Limb | 99.3% (149/150) |
| Extension - any type | 30.0% (45/150) |
| Extension – iliac | 28.7% (43/150) |
| Extension – aorta | 2.0% (3/150) |
| ^{1} Denominator includes all subjects who received the test device. A subject may receive multiple device types. | |

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## 2.2 Sizes of Devices Implanted

Table 17 below shows the distribution of sizes of the bifurcated stent graft used in the Endurant US Clinical Study.

Table 17: Devices Implanted by Size at Index Procedure

| Stent Graft Proximal Diameter
(Main Bifurcated, mm) | Endurant
% (m/n)^{1} |
| --- | --- |
| 23 | 10.7% (16/150) |
| 25 | 26.0% (39/150) |
| 28 | 36.7% (55/150) |
| 32 | 22.0% (33/150) |
| 36 | 4.7% (7/150) |
| 1 Denominator includes all subjects who received the main bifurcated test device. | |

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# D. Safety and Effectiveness Results

Table 18 presents the key outcomes of the Endurant US IDE Clinical Trial; detailed analyses may be found in the following sections.

Table 18: Summary of Key Outcomes

| | Total Number of Patients Reaching Follow-up | | Aneurysm Rupture | | Conversion to Surgical Repair | | Death | | Aneurysm Related Mortality^{1} | | Major Adverse Event | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | T N | C N | T N | C N | T N | C N | T N (%) | C N (%) | T N (%) | C N (%) | T N (%) | C N (%) |
| Intra-operative | 150 | 166 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a^{2} | n/a^{2} |
| ≤ 30 Days | 150 | 166 | 0 | 0 | 0 | 0 | 0 (0%) | 3 (2%) | 0 (0%) | 3 (2%) | 6 (4%) | 18 (11%) |
| > 30 Days to 12 Months | 150 | 157 | 0 | 0 | 0 | 0 | 6 (4%) | 10 (7%) | 0 (0%) | 3 (2%) | 11 (7%) | 13 (8%) |
| Total Patients | 150 | 166 | 0 | 0 | 0 | 0 | 6 | 13 | 0 | 3 | 15^{3} | 30^{3} |
| Kaplan-Meier Summaries | |…