1
`AneuRxrM Stent Graft System
`
`Instructions for Use
`
`IMPORTANT!
`Do not attempt to use the AneuRx Stent Graft System before completely reading and
`understanding the infonnation contained in this booklet.
`
`Carefully inspect all product packaging for damage or defects prior to use. Do not use
`product if any sign of damage or breach of the sterile barrier is observed.
`
`These devices are supplied STERILE for single use only. After use, dispose of the Delivery
`Catheters in accordance with hospital, administrative and/or government policy. Do not
`resterilize.
`The AneuRx Deployment Handle is supplied non-sterile. The Deployment Handle must be
`sterilized prior to first use using steam sterilization under vacuum. The Deployment Handle
`may be resterilized and reused as described in the Deployment Handle Instructions for Use.
`• Caution: Federal (U.S.) Law restricts this device to sale by or on the order of a physician.
`
`q
`
`)
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`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 1 of 41
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`

`

`TABLE OF CONTENTS
`1. DEVICE DESCRIPTION _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1
`1
`2. IND/CATIONS
`1
`3. CONTRAINDICATIONS
`2
`4. WARNINGSANDPRECAUTIONS
`2
`4.1 GENERAL (in order of severity)
`4.2 PATIENT SELECTION, TREATMENT, AND FOLLOW-UP (in order ofseverity)
`4.3 HOW SUPPLIED
`4.4 MAGNETIC RESONANCE IMAGING (MRI) SAFETY
`4.5 IMPLANTATION PROCEDURES
`5. ADVERSE EVENTS
`5.1 OBSERVED ADVERSE EVENTS
`5.2 POTENTIAL ADVERSE EVENTS
`5.3 ADVERSE EVENT REPORTING
`6. CLINICAL STUDIES
`6.1 PRIMARY ENDPOINTS
`6.2 SECONDARY ENDPOINTS
`6.3 PATIENTS STUDIED
`6.4 METHODS
`6.5 RESULTS
`7. PATIENT SELECTION AND TREATMENT
`7.1 INDIVIDUALIZATION OF TREATMENT
`7.2 SPECIFIC PATIENT POPULATIONS
`8. PATIENT COUNSELING INFORMATION
`9. HOW SUPPLIED
`JO. CLINICIAN USE INFORMATION
`10.1 PHYSICIAN TRAINING PROGRAM
`10.2 INSPECTION PRIOR TO USE
`10.3 MATERIALS REQUIRED (NOT INCLUDED IN STENT GRAFT SYSTEM
`PACKAGING) _ _ _ _ _ _ _ _ _ __..,.. _ _ _ _ _ _ _ _ _ _ _ _ _ _ 19
`10.4 MATERIALS RECOMMENDED (NOT INCLUDED IN STENT GRAFT SYSTEM
`PACKAGING) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ l9
`19
`10.5 MRI INFORMATION
`10.6 PREPARATION OF THE ANEURX STENT GRAFT SYSTEM
`
`2
`
`3
`3
`
`3
`4
`
`4
`
`6
`
`6
`
`7
`
`7
`
`7
`
`7
`
`8
`
`11
`15
`15
`
`16
`16
`
`17
`18
`18
`
`18
`
`20
`
`)
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`)
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`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 2 of 41
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`

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`10.7 DELIVERY PROCEDURE (BIFURCATED STENT GRAFT) _ _ _ _ _ _ _ _ 20
`22
`10.8 DEPLOYMENT PROCEDURE (BIFURCATED STENT GRAFT)
`10.9 DELIVERY CATHETER REMOVAL PROCEDURE (BIFURCATED STENT GRAFT) 23
`10.10 ILIAC STENT GRAFT DEPLOYMENT _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 23
`10.ll DELIVERY, DEPLOYMENT, AND CATHETER REMOVAL PROCEDURE (ILIAC
`STENT GRAFT) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 24
`11. PATIENT INFORMATION _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 25
`12. EXPLANATION OF SYMBOLS _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 26
`13. DISCLAIMER OF WARRANTY _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 26
`
`)
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`)
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`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 3 of 41
`
`

`

`•
`
`•
`
`1. DEVICE DESCRIPTION
`The AneuRx Stent Graft System is designed to treat infrarenal abdominal aortic ar aorto-iliac
`aneurysms using an endovascular approach. When placed within the aneurysm, the AneuRx
`Stent Graft provides a permanent, alternative conduit for blood flow within the patient's
`vasculature by excluding the aneurysmal sac from blood flow and pressure. The AneuRx
`Stent Graft System provides an alternative treatment choice in lieu of major open surgery.
`The Medtronic AneuRx Stent Graft System includes:
`a Stent Graft (either Bifurcated Stent Graft, Iliac Stent Graft, Iliac Extender Cuff Stent
`•
`Graft or Aortic Extender Cuff Stent Graft) that is modular and fully stented along its
`length;
`a pre-loaded (with a Stent Graft), sterile Delivery Catheter;
`a reusable, non-sterile Deployment Handle (supplied separately); and
`radiopaque markers imbedded in the Stent Graft proximally and distally; the markers are
`visualized under fluoroscopy.
`The AneuRx Stent Graft System is constructed from self-expanding nickel-titanium (Nitinol)
`alloy stent rings and woven polyester graft tubes. Each stent ring is a series of diamond(cid:173)
`shaped segments connected side-to-side in the circumferential direction to form a ring. The
`diamond-shaped segments are laser cut from a single piece of Nitinol tubing.
`The Stent Graft is loaded inside a Delivery Catheter which facilitates the placement of the
`Stent Graft via the arterial vasculature (e.g., femoral arteries). Using fluoroscopic guidance,
`the Delivery Catheter is properly positioned within the patient's vasculature and the Stent
`Graft is deployed from the Delivery Catheter using the AneuRx Deployment Handle. The
`Deployment Handle aids in the retraction of the graft cover on the Delivery Catheter, exposing
`the Stent Graft to aortic vasculature.
`
`•
`
`•
`
`2. INDICATIONS
`The AneuRx Stent Graft System is indicated for the endovascular treatment of infrarenal
`abdominal aortic or aorto-iliac aneurysms having:
`adequate iliac/femoral access;
`•
`infrarenal non-aneurysmal neck length of at least 1 cm at the proximal and distal ends of
`the aneurysm and a vessel diameter I 0-20% smaller than the labeled device diameter;
`• morphology suitable for endovascular repair;
`one of the following:
`•
`a diameter> 5 cm;
`a diameter of 4-5 cm and has increased in size by 0.5 cm in the last 6 months; or
`twice the diameter of the normal infrarenal aorta.
`
`3. CONTRAINDICATIONS
`There are no known contraindications currently associated with this device.
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 4 of 41
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`

`

`4. WARNINGS AND PRECAUTIONS
`(See also Individualization of Treatment)
`4.1 GENERAL
`• Do not attempt to use the AneuRx Stent Graft System before completely reading and
`understanding the information contained in this booklet.
`• This device should only be used by physicians and teams trained in vascular interventional
`techniques, including training in the use of the device. Specific training expectations are
`described in Section 10.1 PHYSICIAN TRAINING PROGRAM.
`• Do not use the AneuRx Stent Graft in patients unable to undergo the necessary
`preoperative and postoperative imaging and implantation studies as described in Section
`10.6 PREPARATION OF THE ANEURX STENT GRAFT SYSTEM.
`• The results of the clinical studies indicated that patients who experience an unsuccessful
`endovascular repair attempt, and as a result undergo conversion to surgical Abdominal
`Aortic Aneurysm (AAA) repair, are likely to have increased complications arising from
`both procedures (i.e., cardiac complications, fever, infection, musculoskeletal
`complications, neurological complications, pulmonary complications, vascular disease,
`vessel dissection, wound healing issues, and mortality; reference Section 5. ADVERSE
`EVENTS for specific information on adverse event categories).
`• The long-term performance of the graft has not been established. Patients should be
`regularly monitored for leaks and aneurysm growth.
`• The safety and effectiveness of the AneuRx Stent Graft System for the treatment of
`abdominal aortic aneurysms has not been evaluated in patients:
`• with aneurysms pending rupture
`• with connective tissue disorder
`• with hypercoagulability
`■ with mesenteric artery occlusive disease
`■ with ilio-femoral, thoracic, or inflammatory aneurysms
`• with juxtarenal AAA
`• with pararenal AAA
`• with suprarenal or thorocoabdominal aneurysms
`• who are morbidly obese
`• pregnant or nursing
`less than 18 years old
`•
`■ with less than one-year life expectancy.
`• Always have a vascular surgery team available at institutions performing endovascular
`grafting in the event that conversion to open surgical repair is required.
`
`4.2 PATIENT SELECTION, TREATMENT, AND FOLLOW-UP
`• Do not use this device in patients having an active systemic infection.
`• Do not use this device in patients with sensitivities or allergies to the device materials.
`The materials include: polyethylene-terephthalete (PET), nickel, titanium, tantalum,
`stainless steel, polyetheresterblock-copolymer (Hytrel), polyetherblockamide (Pebax),
`polyetheretherketone (PEEK), platinum, ethyl cyanoacrylate, poly (methyl methacrylate),
`and hydroquinone.
`• The results of the clinical study indicate that women treated with this device may have a
`higher mortality rate as compared to their male counterparts.
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 5 of 41
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`

`

`I
`
`• The use of this device requires administration of radiographic agents. Patients with
`preexisting renal insufficiency may have an increased risk of renal failure postoperatively.
`• Proper use of this device requires accurate fluoroscopic imaging. This device is not
`recommended for patients whose weight exceeds 350 lbs (150 kg) or whose weight may
`impede accurate fluoroscopic imaging.
`• Conversion to standard surgical repair should be considered for patients experiencing an
`increase in the size of their AAA.
`• The results of the clinical study indicate that subjects experiencing reduced blood flow
`through the graft limbs and/or leaks may be required to undergo secondary interventions
`or minor surgical procedures.
`• All patients should be monitored closely and checked periodically for aneurysmal size
`increase or occlusion of vessels in the treatment area. Patients who experience perigraft
`flow should undergo imaging studies more frequently.
`
`4.3 HOW SUPPLIED
`• For single use only. AneuRx Stent Graft Delivery Catheters are disposable; do not reuse.
`Note product "Use Before" date.
`• Never attempt to resterilize an AneuRx Stent Graft or Delivery Catheter. Resterilization
`may adversely affect the proper mechanical function of the AneuRx Stent Graft and could
`result in patient injury and/or conversion to an open surgical procedure.
`• Always inspect the device and packaging to verify that no damage has occurred as a result
`of shipping and that the sterile barrier has not been compromised. If damage occurs, do
`not use the product and return the device to Medtronic AneuRx.
`
`4.4 MAGNETIC RESONANCE IMAGING (MRI) SAFETY
`MRJ may be used on the graft only under specific conditions. See Section I 0.5 MRI
`INFORMATION for details.
`
`4.5 IMPLANTATION PROCEDURES
`• Do not bend or kink the Delivery Catheter because it may cause the AneuRx Stent Graft to
`improperly deploy.
`• Do not deploy the AneuRx Stent Graft in a location that will occlude arteries necessary to
`supply blood flow to organs or extremities.
`• Always use fluoroscopic guidance to advance the Delivery Catheter. Do not use excessive
`force to advance or withdraw the Delivery Catheter when resistance is encountered.
`Exercise particular care in areas of stenosis, intravascular thrombosis, or in calcified or
`tortuous vessels.
`• Always monitor the implant procedure under fluoroscopy to detect kinking or alignment
`problems with the AneuRx Stent Graft components. If the Delivery Catheter kinks during
`insertion, do not attempt to deploy the AneuRx Stent Graft. Remove the system and insert
`a new Delivery Catheter.
`Inadequate anchoring may result in increased risk of leakage into the aneurysm or
`•
`migration of the Stent Graft.
`• Do not retract the cover of the AneuRx Stent Graft Delivery Catheter before placing the
`Delivery Catheter in the proper anatomical location. The AneuRx Stent Graft cannot be
`replaced or drawn back into the Delivery Catheter, even if the Stent Graft is only partially
`deployed.
`Improper placement may result in leakage or occlusion, necessitating surgical removal of
`the device.
`
`•
`
`)
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 6 of 41
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`

`

`I
`
`5. ADVERSE EVENTS
`5.1 OBSERVED ADVERSE EVENTS
`A prospective, multi-center clinical investigation comparing the AneuRx Stent Graft System
`to conventional open surgery provides the basis of the observed adverse event rates. A total of
`four-hundred-sixteen ( 416) subjects were enrolled in the Stent Graft arm of the study; sixty(cid:173)
`six (66) patients were enrolled in the Surgical Control arm of the study.
`A total of 1105 devices (Bifurcated Stent Grafts, Iliac Stent Grafts, Iliac Extender Cuff Stent
`Grafts, and the Aortic Extender Cuff Stent Grafts). were successfully delivered and deployed
`in 405 patients. The cumulative follow-up was 498 years with a mean follow-up of 1.2 years
`(range Oto 2.1 years).
`
`)
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`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 7 of 41
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`Table 5.1 Adverse Events
`
`Early ~30 Days
`Stent Graft
`(n/N)
`(7/416)
`
`2%
`
`%
`
`Early ~30 Days
`Control
`(n/N)
`
`%
`
`0%
`
`(0/66)
`
`0.2%
`4%
`
`2%
`
`(1/416)
`(18/416)
`(7/416)
`
`0%
`
`3%
`
`6%
`
`(0/66)
`
`(2/66)
`
`(4/66)
`
`1%
`
`4%
`
`0%
`
`2%
`
`4%
`
`0%
`
`5%
`
`0%
`
`8%
`
`0%
`
`14%
`
`(0/66)
`
`(3/66)
`
`(0/66)
`
`(5/66)8
`
`(0/66)
`(9/66)' 0
`
`(1/66)
`
`Late > 30 Days
`Stent Graft
`(n/N)
`(416)7
`
`5%
`
`%
`
`0.2% (1/416)
`0.2% (1/416)
`0.7% (3/416)
`<)% (2/416)
`
`1%
`
`(4/416)
`
`0.2% (l/416)
`<l % (2/416)9
`(3/416)
`
`1%
`
`1%
`
`(5/416)
`
`I
`
`Late >30 Days
`Control
`(n/N)
`
`%
`
`9%
`
`(6/66)
`
`0%
`
`0%
`
`0%
`
`(0/66)
`
`(0/66)
`(0/66)
`
`0%
`
`0%
`
`0%
`
`5%
`
`0%
`
`0%
`
`0%
`
`(0/66)
`
`(0/66)
`
`(0/66)
`(3/66)9
`(0/66)
`(0/66)
`
`(0/66)
`(0/66)
`
`(5/416)
`(17/416)
`(0/416)
`(7/416)8
`(15/416)
`(4/416) 10
`3%
`Vascular Occlusion (includes thrombosis and thromboembolism)
`0.5% (2/416)
`2%
`(8/416)
`2%
`0.5% (2/416)
`0%
`(0/66)
`0%
`(0/416)
`0%
`Venous
`1 Includes: hematuria, brachia! and femoral hematomas, elevated PT/INR, groin hemorrhage, retroperitoneal
`bleed, urethral bleeding
`2 Includes: scrotal and foreskin edema, lower extremity swelling
`3 Includes: delayed wound healing, lymphatic leak, seroma
`4 Includes: bilateral pleural effusions, shortness of breath, respiratory failure/arrest, atelectasis, pneumonia
`5 Includes: renal insufficiency/failure, dialysis, elevated creatinine
`6 Includes: angiodyplasia of stomach, bowel ischemia, ileus, constipation, nausea/vomiting, ulcers, rectal
`bleeding, cholcystitis, diarrhea, bowel obstruction, GI bleed, small bowel mesentery bleed, sigmoid colon
`necrosis
`7 Four (1%, 4/416) late deaths (>30 days post-procedure) occurred that were classified as device related. One
`(~1%, 1/416) death had an unknown cause at the time of the data analysis. One death was undetermined but
`possibly occurred by cerebral embolism. One death was due to renal failure and pulmonary complications. One
`death was due to neurological complications.
`8 p = 0.015
`9 p=0.02
`0 p = 0.002
`'
`
`Adverse Event
`
`Deaths
`Other Adverse Events
`AAA Rupture
`
`Bleeding'
`Cardiac Failure/Infarction
`Edema2
`Wound Healing Complications3
`Impotence
`Pulmonary Complications4
`Renal Failure5
`Gastrointestinal Complications6
`
`Arterial
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 8 of 41
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`5.2 POTENTIAL ADVERSE EVENTS
`Adverse events (in alphabetical order) which may be associated with the use of the device, the
`implant procedure or the attendant equipment and supplies (reference Table 5.1) include:
`• Cardiac failure/infarction
`• Thromboemolism
`• Graft or native arterial occlusion
`• Venous thrombosis and edema
`• Ruptured vessel/aneurysm
`• Gastrointestinal complications
`Impotence
`•
`• Renal failure
`• Pulmonary/respiratory complications
`• Central or peripheral nervous system impairment
`• Wound infection or hematoma
`• Device failures due to:
`Migration
`
`Dilation
`Endoleak
`
`Rupture
`Erosion with fistula or pseudo-aneurysm
`
`5.3 ADVERSE EVENT REPORTING
`Any adverse event ( clinical incident) involving the AneuRx Stent Graft System should be
`reported to Medtronic AneuRx immediately. To report an incident, call (800) 465-5533.
`
`)
`
`_)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 9 of 41
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`

`

`6. CLINICAL STUDIES
`A total of four-hundred-sixteen ( 416) patients were treated at 13 U.S. investigational centers
`in the Evaluation of the Safety and Efficacy of the AneuRx Stent Graft System in the
`Treatment of Abdominal Aortic Aneurysms (AAA). The study was a nonrandomized,
`prospective, multicenter clinical investigation designed to evaluate the safety and efficacy of
`the AneuRx Stent Graft System in the treatment of infrarenal abdominal aortic or aorto-iliac
`aneurysms.
`
`6.1 PRIMARY ENDPOINTS
`The prospective, controlled, clinical trial was designed to compare endovascular repair of
`abdominal aortic aneurysms to conventional open surgical repair of abdominal aortic
`aneurysms in terms of safety, procedural parameters and hospital activities. The primary
`endpoints used for the trial included:
`• Delivery Success/Deployment Success
`• Stent Graft Migration
`• Aneurysm Exclusion
`• Stent Graft Patency
`• Device Integrity
`• Morbidity and Mortality
`• Aneurysm Rupture
`• Expansion of the AAA by >5mm
`• Conversion to Surgical Repair
`• Additional Procedure Required
`
`6.2 SECONDARY ENDPOINTS
`The secondary treatment endpoints were defined as all endpoints outside the primary
`endpoints that can be compared to the Surgical Control Group. The secondary endpoints
`include:
`• Duration of Surgical Procedure
`• Amount of Blood Loss
`• Number of Patients Requiring Blood Transfusion
`• Time to Endotracheal Extubation
`• Time to Unassisted Ambulation
`• Time to Resumption of Normal Diet
`• Time in ICU
`• Hospital Length of Stay (LOS)
`
`6.3 PATIENTS STUDIED
`Patients were enrolled into two groups: the Surgical Control Group and the Stent Graft
`Treatment Group. All patients enrolled in the clinical trial were candidates for open surgical
`repair of an infrarenal aortic or aorto-iliac aneurysm fitting one of the following descriptions:
`aneurysm > 5cm in diameter
`•
`aneurysm 4-5cm in diameter and has increased in size by 0.5cm in last 6 months
`•
`aneurysm is twice the diameter of the normal infrarenal aorta
`•
`aneurysm is saccular.
`•
`Additionally, patients enrolled in the Stent Graft Treatment Group were required to have
`adequate iliac/femoral access and an infrarenal non-aneurysmal neck of at least I cm.
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 10 of 41
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`6.4 METHODS
`Patients enrolled in the Surgical Control Group underwent open surgical repair of their
`aneurysm by replacement with a prosthetic graft. Patients enrolled in the Stent Graft
`Treatment Group were implanted with an AneuRx Bifurcated Stent Graft and an AneuRx Iliac
`Stent Graft. Iliac and/or Aortic Extender Cuff Stent Grafts were used, as needed, in specific
`cases.
`The Stent Graft Treatment Group and Surgical Control Group underwent baseline Spiral CT
`evaluation. The Stent Graft Treatment Group had IVUS immediately pre- and post-placement
`as well as post treatment Spiral CT evaluation. The numbers presented in the following
`summaries are based on core lab evaluations of the Spiral CTs.
`Surgical Control Group patients and Stent Graft Treatment Group patients were followed at
`the same postoperative intervals: pre-discharge, I month, 6 months, and 12 months. All
`patients treated were included in the intent-to-treat analysis.
`
`)
`
`)
`
`8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 11 of 41
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`

`

`I
`
`Table 6.1 Patient Demographics
`
`Demographic
`
`Stent Graft
`(N = 416) 1
`73 (45-93)
`
`Control
`<N = 66)
`69 (49-85)
`
`Age (years)
`
`Alcoholism
`
`Angina pectoris
`
`Cancer
`
`3%
`
`18%
`
`26%
`
`14%
`
`24%
`
`2%
`
`12%
`
`10% (n=415)
`
`11%
`89%
`11%
`
`64%
`
`0%
`
`33%
`
`4%
`
`18%
`
`20% (n=415)
`
`26%
`
`45% (n=415)
`
`3%
`
`12%
`
`8%
`
`0%
`
`4% (n=413)
`
`86% (n=414)
`
`5%
`
`23%
`
`26%
`
`12%
`
`36%
`
`6%
`
`9%
`
`14%
`
`15%
`85%
`8%
`
`56%
`
`2%
`
`24%
`
`3%
`
`18%
`
`24%
`
`14%
`
`53%
`
`2%
`
`3%
`
`3%
`
`0%
`
`6%
`
`82%
`
`Cerebrovascular disease
`Chronic obstructive pulmonary disease2
`
`Chronic renal failure
`
`Diabetes
`
`Family history of aneurysm disease
`Gender
`Female
`Male
`History of CV A (n=49)
`
`Hypertension
`
`Immunodeficiency
`
`Myocardial infarction prior to last 6 months
`
`Myocardial infarction within previous 6 months
`
`Obesity
`
`Peripheral vascular disease
`Previous surgery in affected area3
`
`Prior coronary intervention procedure
`
`Radiation of the affected area
`Symptomatic cardiac arrhythmia4
`
`Symptomatic congestive heart failure
`
`Systemic infection - current
`
`Thromboembolic events
`
`Tobacco use
`Unless otherwise noted, N = 416
`p = 0.037
`p = 0.027
`p = 0.029
`
`2
`3
`4
`
`9
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 12 of 41
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`

`

`I
`
`)
`
`)
`
`Table 6.2 Aneurysm Diameter Distribution
`
`Stent Graft
`
`Control
`
`Neck
`N=346
`%
`4.
`
`n
`16
`32
`5
`
`Aneu~·sm
`N=3 0
`%
`0
`0
`I.
`
`Neck
`N=47
`
`Aneu53sm
`N= 3
`
`%
`0
`
`%
`4.3
`
`n
`0
`
`5
`
`Table 6.3 Aneurysm Length Distribution
`
`Stent Graft
`
`Control
`
`Aneu;]'.sm
`N=3 3
`%
`0.9
`0.
`l.5
`.4
`5.7
`12.3
`17.
`21.
`38.4
`
`Ane!!Zsm
`N- 4
`%
`0
`
`2
`
`Diameter Range
`
`mm
`mm
`mm
`mm
`mm
`mm
`mm
`
`Length Range
`
`mm
`mm
`mm
`mm
`mm
`mm
`mm
`
`10
`
`7'-l
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 13 of 41
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`

`

`6.5 RESULTS
`The safety and effectiveness results are presented in the tables below.
`
`Principal Safety Results
`The time intervals capture the events between the follow up time periods. Denominators that
`are < 416 reflect patients that were successfully treated with the Stent Graft, measures that are
`determined by cine, and the actual readable images sent to the corelab by the investigational
`sites. The denominators are determinable measures based on the image quality.
`
`Five of 415 (1.2%) patients underwent open surgical repair (conversion) due to iliac access
`difficulty or due to the unsuccessful delivery, deployment or positioning of at least one of the
`stent graft components. One patient (0.2%) refused placement of an Extender Cuff for
`treatment of endoleak and instead opted for open surgical repair. Two patients (0.5%) were
`converted to open surgical repair following rupture of the AAA.
`
`Patients with technical success underwent an additional procedure(s): 19 patients for
`Extender Cuff placement due to endoleak, with or without migration, and 8 for non-patent
`endovascular grafts.
`
`Safety Measures and
`other Clinical Events
`Aneurysm Rupture
`Conversion to Surgical
`Repair
`Additional Procedure
`Required
`
`Table 6.4 Principal Safety Results (N=416)
`Pre-discharge to one year
`Pre-discharge to six
`months
`1/405 (0.2%)
`7/415 (1.7%)
`
`1/405 (0.2%)
`8/415(1.9%)
`
`16/405 (3.9%)
`
`27/405 (6.7%)
`
`)
`
`II
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 14 of 41
`
`

`

`I
`
`Principal Effectiveness Results
`416 patients were enrolled in the study. Denominators that are < 416 reflect a subset of the
`patients implanted with a Stent Graft and with readable images sent to the corelab by the
`investigational sites.
`
`Efficacy
`Measures
`Delivery Success/
`Deployment
`Success
`Stent Graft
`Migration
`Aneurysm non-
`Exclusion
`( evidence of
`endoleak)
`Stent Graft
`Patency
`Device Integrity'
`I. Stent graft
`fractures
`
`Table 6.5 Principal Effectiveness Results
`Pre-discharge
`Pre-discharge
`6 months
`N=416
`N=l89
`N=189
`405/415 (97.6%)
`- -
`- -
`
`1 year
`N=189
`- -
`
`Baseline
`
`Baseline
`
`3/173 (1.7%)
`
`3/187 (1.6%)
`
`165/354 (46.6%)
`
`74/169 (43.8%)
`
`38/162 (24.0%)
`
`30/172(17.4%)
`
`352/352 (100%)
`
`167/168 (99.4%)
`
`156/162 (96.3%)
`
`166/171 (97.1%)
`
`1. 0/383 (0%)
`
`I. 0/137 (0%)
`
`I. 0/113 (0%)
`
`1.
`
`0/133 (0%)
`
`)
`
`)
`
`2. Kinking
`and/or
`twisting
`Morbidity and
`Contained in Section 5. ADVERSE EVENTS
`Mortality
`1No patient with a device kink or twist had nonpatency, migration, or required additional procedures for
`correction.
`
`2. 3/174 (1.7%)
`
`2. 5/188 (2.6%)
`
`2. 14/351 (3.9%) 2. l 1/186 (5.9%)
`
`12
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 15 of 41
`
`

`

`Type
`
`eno
`b F II
`T bl 6 6 A neurvsm E xoans1on ,v
`a e
`0 OW-UD
`6 months
`Pre-discharge
`Pre-discharge
`N=158
`N=158
`N=416
`4/147--z (2.7%)
`Baseline
`Baseline
`Expansion of the
`evaluation
`evaluation
`AAAbv>5mm
`416 patients were enrolled m the study. Denominators that are < 416 reflect the number of patients implanted
`with a Stent Graft and the actual readable images sent to the corelab by the investigational sites. The
`denominators are determinable measures based on the image quality. One patient suffered an Ml after enrollment
`and prior to implantation.
`2 Patients required to have both predischarge and 6 month data for determination. 11 patients
`did not have both values.
`Table 6. 7 Aneurysm Growth in the Presence of Endoleaks at 12 months (N = 172)
`Decreased2 Unknown3
`Enlarged 1 Unchanged
`Location
`
`1 year
`N=158
`6/158 (3.8%)
`
`Proximal
`Attachment Site
`Distal Attachment
`Site
`Junctional
`(modular)
`Collateral
`
`Unknown
`
`Total
`
`0
`
`0
`
`0
`
`1
`
`1
`
`2
`
`1
`
`2
`
`2
`
`15
`
`6
`
`26
`
`Defined as size change of>5 mm.
`2 Defined as size change of <5 mm.
`3 No data or no conclusion regarding aneurysm size changes.
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`1
`
`0
`
`1
`
`2
`
`)
`
`13
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 16 of 41
`
`

`

`Table 6.8 Secondary Outcome: Surgical Control vs. Stent Graft
`Stent Graft
`Surgical
`Mean (range) Difference [95% CI]
`Control
`Mean (ranee)
`293 (125-623)
`N=65
`
`Endpoint
`
`Duration of Anesthesia
`(min) 1
`
`Duration of Procedure (min/
`
`Blood Loss (cc/
`
`Patients Requiring Blood
`Transfusion (% )2
`
`Days to Endotracheal
`Extubation2
`
`Days to Unassisted
`Ambulation2
`
`Days to Resumption of
`Normal Diet2
`
`Days in ICU2
`
`Hospital Le~th of Stay
`(LOS, days)
`
`I
`2
`
`p < 0.002
`p<0.001
`
`210 (90-498)
`N=65
`
`1617 (200-
`8000)
`
`N=65
`
`55
`N=65
`
`1.3
`N=60
`
`3.6
`
`N=65
`
`4.9
`N=60
`
`3.5 (0-72)
`N=66
`
`9.3 (3-72)
`
`N=50
`
`255 (110-814)
`N=415
`174(71-680)
`N=415
`
`544 (0-3500)
`N=410
`
`24
`
`N=4IO
`
`0.2
`
`N=374
`
`1.4
`
`N=392
`
`1.3
`
`N=389
`0.9 (0-83)
`N=396
`
`38[14,62]
`
`36 [16, 56]
`
`1073 [886,1261]
`
`31 [18, 44]
`
`1.1 [0.6, 1.5]
`
`2.2 [1.8, 2.5]
`
`3.6 [3.2, 3.9]
`
`2.5 [1. 1, 3.9]
`
`3.4 (0.8-84)
`
`5.9 [4.3, 7.6]
`
`N=406
`
`Cause
`
`AAA Rupture
`
`b p
`a e . mere:ent C
`onvers1ons. »v rimarv C a use of Failure
`T bl 6 9 E
`6 months
`1 month
`Before 30
`During
`days
`procedure
`1
`0
`
`0
`
`0
`
`Leak: Collateral
`Vessels Filling
`Aneurysm
`Unsuccessful vessel
`access or device
`malposition
`Total
`
`0
`
`4
`
`4
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`I
`
`2
`
`14
`
`1 year
`
`I
`
`0
`
`0
`
`1
`
`)
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 17 of 41
`
`

`

`(
`
`Cause
`
`A.AA Rupmrc
`
`b P.
`T
`I 610F:I
`•, cctlvc
`ab c
`C .onvcrs10ns, iv nmanr
`C ause o f F ·1
`•a1 urc
`During
`Before 30
`1 month
`6 months
`procedure
`days
`0
`()
`
`u
`
`0
`
`Leak: Collateral
`Vessels Filling
`Aneurysm
`Unsuccessful vessel
`access or device
`~osition
`Total
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`I
`
`0
`
`I
`
`0
`
`()
`
`0
`
`1 year
`
`0
`
`0
`
`0
`
`0
`
`~
`
`7. PATIENT SELECTION AND TREATMENT
`
`7.1 INDIVIDUALIZATION OF TREATMENT
`(SEE WARNINGS AND PRECAUTIONS)
`Medtronic AneuRx recommends that the AncuRx Stent Graft diameter be at least 2mm larger
`than the aortic diameter and 1 mm larger than the iliac diameter (I 0-20% oversizing). The
`length of the AneuRx Stent Graft should be suf1icicnt to reach from just inferior to the most
`caudal major renal artery to non-aneurysmal tissue in the common iliac artery. All lengths and
`diameters of the devices necessa1y to complete tlH~ procedure should be available to the
`operator_
`The risks and benefits previously dcscrihcd in Section 6. CLINICAL STUDIES should be
`carefully considered for each patieul before use of the AneuRx Stent Graft System. Patient
`selection factors to be assess should include:
`
`• patient's age and life expectancy (reference 4. WARNTNGS AND PRECAUTIONS)
`• co-rr~orbiditit.:s (e.g., cardiac, pulmonary or renal insufficiency prior to surgery, morbid
`obesity etc.)
`• patient's morphologic suitability for cndovascular repair
`•
`the risk of aneurysm rupture balanced against the risk of treatment with the J\.neuR.x Stent
`Graft System
`The final treatment decision is at the di scretion of the physician and patient.
`
`l S
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 18 of 41
`
`

`

`7.2 SPECIFIC PATIENT POPULATIONS
`The safety and effectiveness of the AneuRx Stent Graft System for the treatment of abdominal
`aortic aneurysms has not been evaluated in patients:
`• with aneurysms pending rupture
`• with connective tissue disorder
`• with hypercoagulability
`• with mesenteric artery occlusive disease
`• with ilio-femoral, thoracic, or inflammatory aneurysms
`• with juxtarenal AAA
`• with pararenal AAA
`• with suprarenal or thorocoabdominal aneurysms
`• who are morbidly obese
`• pregnant or nursing
`less than 18 years old
`•
`• with less than one-year life expectancy
`
`•
`
`•
`
`•
`
`8. PATIENT COUNSELING INFORMATION
`The physician should consider the following points when counseling the patient about this
`device:
`• differences between endovascular repair and surgical repair
`risks related to open surgical repair
`•
`risks related to endovascular repair
`•
`• open surgical repair is considered the gold standard for AAA repair
`• ~ndoyascular repair is a new option with potential advantages related to its minimally
`mvas1ve approach
`it is possible that subsequent endovascular or open surgical repair of the aneurysm may be
`reqmred
`!he lqng term effe~tivenes_s of en~ovascular repair has not been established; annual
`·
`1magmg and surveillance 1s required
`details contained in the Patient Information Booklet regarding risks occurring after
`implantation of the device, e.g., cardiac complications, neurological complications, etc.
`results of the clinical study indicate that women treated with this device may have a higher
`mortality rate as compared to their male counterparts
`
`•
`
`Medtronic AneuRx recommends that the physician disclose to the patient (in written form) all
`risks associated with treatment using the AneuRx Stent Graft System.
`
`16
`
`)
`
`)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 19 of 41
`
`

`

`9. HOW SUPPLIED
`The AneuRx Stent Graft components are available in the following lengths and diameters:
`S
`Table 9.1 P d
`'fi
`ro uct ioec1 1cations
`Catheter Diameter
`Expanded Stent
`(outer)
`Graft Length
`
`Catheter Length
`(working length)
`
`20mm/12mm
`22mm/13mm
`24mm/14mm
`26mm/15mm
`28mm/16mm
`20mm/12mm
`22mm/13mm
`24mm/14mm
`26mm/15mm
`28mm/16mm
`
`Expanded Stent
`Graft Diameters
`AneuRx Bifurcated Stent Graft and Delivery Catheter
`21 Fr.
`13 .5cm
`21 Fr.
`13.5cm
`21 Fr.
`13 .5cm
`21 Fr.
`13 .5cm
`21 Fr.
`13.5cm
`21 Fr.
`16.5cm
`21 Fr.
`16.5cm
`21 Fr.
`16.5cm
`21 Fr.
`16.5cm
`21 Fr.
`16.5cm
`AneuRx Iliac Stent Graft and Delivery Catheter
`16 Fr.
`8.5cm
`16 Fr.
`8.5cm
`16 Fr.
`8.5cm
`16 Fr.
`8.5cm
`16 Fr.
`8.5cm
`16 Fr.
`11.5cm
`16 Fr.
`11.5cm
`16 Fr.
`11.5cm
`16 Fr.
`11.5cm
`16 Fr.
`l 1.5cm
`AneuRx Iliac Extender Cuff Stent Graft and Delivery Catheter
`55cm
`16 Fr.
`5.5cm
`12cm
`55cm
`16 Fr.
`5.5cm
`13cm
`55cm
`16 Fr.
`5.5cm
`14cm
`55cm
`16 Fr.
`5.5cm
`15cm
`55cm
`16 Fr.
`5.5cm
`16cm
`AneuRx Aortic Extender Cuff Stent Graft and Delivery Catheter
`55cm
`21 Fr.
`3.75cm
`20mm
`55cm
`21 Fr.
`3.75cm
`22mm
`55cm
`21 Fr.
`3.75cm
`24mm
`21 Fr.
`55cm
`3.75cm
`26mm
`55cm
`21 Fr.
`3.75cm
`28mm
`
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`55cm
`
`12mm
`13mm
`14mm
`15mm
`16mm
`12mm
`13mm
`14mm
`15mm
`16mm
`
`)
`
`17
`
`Edwards Lifesciences Corporation, et al. Exhibit 1019, p. 20 of 41
`
`

`

`STERJLE : Each AneuRx Stent Graft (Bifurcated, Iliac, Iliac and Aortic Extender Cuff) is
`individually packaged inside of a Delivery Catheter. The Delivery Catheters are sterilized
`using gamma radiation and are supplied sterile for single use only.
`Do not reuse or attempt to resterilize.
`Do not use if package is opened or damaged.
`NON-STERILE: The AneuRx Deployment Handle is supplied non-sterile and must be
`sterilized prior to first use using steam sterilization under vacuum. The Deployment Handle
`may be resterilized and reused as described in the Deployment Handle Instructions For Use.
`CONTENTS:
`One (1) AneuRx Stent Graft and Delivery Catheter
`One ( 1) envelope containing patient materials and tracking information
`One (1) Instructions for Use Manual
`
`STORAGE: Store at room temperature.
`
`10. CLINICIAN USE INFORMATION
`
`)
`
`10.1 PHYSICIAN TRAINING PROGRAM
`CAUTION: Physicians performing the AneuRx Stent Graft procedure must be trained
`in vascular interventional procedures and are required to have successfully completed
`additional training and certification by Medtronic AneuRx in the use of the AneuRx
`Stent Graft System.
`The recommended skill/knowledge requirements for physicians using the AneuR.x Stent Graft
`System are outlined below.
`Patient selection:
`• knowledge of the natural history of abdominal aortic aneurys