Flair ® Endovascular Stent Graft IFU

Instructions for Use

B05659 Rev.3/08-14

®

Flair® EndovascularStent Graft Diagram

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INSTRUCTIONS FOR USE DEVICE DESCRIPTION

IMPLANTThe Flair® Endovascular Stent Graft (implant) is a flexible, self-expanding endoprosthesis comprised of expanded polytetrafluoroethylene (ePTFE) encapsulating a Nitinol stent framework. Nitinol is an alloy that can be processed to assume a pre-defined final configuration upon exposure to body temperature.

The Nitinol stent, including distal (outflow) and proximal (inflow) ends, is encapsulated within two layers of ePTFE. The inner lumen of the stent graft (blood contacting surface) is carbon impregnated. The ePTFE outer wall of the stent graft, which contacts the AV access graft and native vein, contains cutouts which expose the Nitinol stent.

The Flair® Endovascular Stent Graft is available in both flared (Figure 1) and straight configurations (Figure 2). The distal (outflow) end of the flared configuration devices are approximately 4 mm larger in diameter than the body section.

Figure 1. Flared configuration

Figure 2. Straight configuration

Flared devices are intended for use in lesions where the vein diameter is larger than the graft diameter, with the distal (outflow) flared end of the device to be placed in the vein. Straight devices are intended for all lesions in which the vein diameter is equivalent to or less than that of the Access graft. The Flair® Endovascular Stent Graft is available in diameters 6 mm, 7 mm, 8 mm and 9 mm and in lengths 30 mm, 40 mm, 50 mm and 70 mm. Note the 70 mm length stent graft is only available in diameters 6 mm, 7 mm and 8 mm.

DELIVERY SYSTEM (see diagram on page 2 of this booklet)Before deployment, the stent graft (A) is compressed between the inner catheter (B) and the outer catheter (C) at the distal end of the delivery system. Upon release of the stent graft by retraction of the outer catheter, the Flair® Endovascular Stent Graft expands to its pre-programmed diameter. The inner catheter connects to the back handgrip (D) via a metal tube. The coaxial outer catheter (C) connects to a Y-injection-adapter (E) with a Tuohy-Borst valve (F).

The stent graft deployment system accepts a 0.035 inch guidewire through the inner catheter lumen.

The system also features a soft, rounded tip (G) on the distal end of the inner catheter that is tapered to fit with the guidewire and the outer catheter for an atraumatic introduction.

Tightening the Tuohy-Borst valve (by turning it clockwise) prevents movement of the outer sheath relative to the inner catheter. There is also a removable safety clip (H) that prevents premature outer catheter retraction. The safety clip can be removed by pressing down on the top of the clip. In order to deploy the stent graft, the Tuohy-Borst valve must be open and the safety clip must be removed.

The delivery system has two female luer ports: one (I) at the proximal end of the handgrip, and the second (K) on top of the Y-injection-adapter. Prior to loading the deployment system over a guidewire, both ports must be flushed with sterile saline to eliminate any air bubbles that may be trapped in the inner catheter lumen and/or the stent graft lumen. When flushing the stent graft lumen via the top port, ensure that the 2-way stopcock (L) is open, and that the Tuohy-Borst valve is closed.

The Flair® Endovascular Stent Graft delivery system has a 80 cm working length, 120 cm total length, and is compatible with 9F introducer sheaths.

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X-RAY MARKERSBefore deployment, each end of the stent graft is marked by a radiopaque band. The distal end (outflow) of the stent graft (M) and the proximal end (inflow) of the stent graft (N) are marked by radiopaque marker bands on the INNER catheter of the deployment system. During stent graft deployment, the markers must remain stationary and should be used as fixed reference points. A third radiopaque markerband is incorporated into the outer catheter (O) and will move towards the handgrip during stent graft deployment, indicating the released portion of the stent graft.

STENT GRAFT SIZE SELECTIONSpecial care must be taken to ensure that the appropriate size Flair® Endovascular Stent Graft is selected.• The stent graft body diameter should be approximately 1 mm

larger than the synthetic AV access graft diameter.• Thediameteroftheangioplastyballoonforpostdilationshouldbe

equal to the stent graft body diameter. • Selectastentgraftlengththatensuresthattheentirelesioniswell

covered with the device and that the stent graft extension into the healthy vein is minimal. Allow approximately 10 mm of the stent graft to be situated beyond the stenosis into the non-diseased AV Graft and approximately 10 mm of the stent graft to extend beyond the stenosis into the non-diseased vein.

The percentage foreshortening of the stent graft during deployment at 0.5 mm oversizing is less than 8% for all sizes.

HOW SUPPLIEDThe Flair® Endovascular Stent Graft is supplied sterile (by ethylene oxide gas) unless the package has been opened or damaged. For single patient use only. Do not reuse. Do not resterilize. Store in a cool (room temperature), dry place. Protect the packaged product from direct sunlight.

INDICATION FOR USEThe Flair® Endovascular Stent Graft is indicated for use in the treatment of stenoses at the venous anastomosis of ePTFE or other synthetic arteriovenous (AV) access grafts.

CONTRAINDICATIONSThere are no known contraindications for the Flair® Endovascular Stent Graft.

WARNINGS• Thisproducthasbeendesignedforsinglepatientuseonly.Donot

reuse. Do not resterilize.• Donotexposethestentgraft totemperatureshigherthan500ºF(260ºC).ePTFEdecomposesatelevatedtemperatures,producinghighly toxic decomposition products.

• Thesterilepackaginganddevicesshouldbeinspectedpriortouse. Verify that the packaging and the device are undamaged and that the sterile barrier is intact. If damaged, do not use.

• Donotuseinpatientswithuncorrectablecoagulationdisorders.• Donotuseinpatientswithsepticemia.• Donotuseinpatientswithknownallergyorsensitivitytocontrast

media, which cannot be adequately pre-medicated.• Donotuseinpatientswithknownhypersensitivitytonickel-titanium.• DonotuseinpatientswhoseAVaccessgraftisinfected.• DonotuseinpatientswhoseAVaccessgraftshavebeenimplanted

less than 30 days.• Do not use the device in patients in which full expansion of an

appropriately sized angioplasty balloon could not be achieved during primary balloon angioplasty.

• Thedeliverycatheterisnotintendedforanyuseexceptstentgraftdeployment.

• Thestentgraft(implant)cannotberepositionedaftertotalorpartialdeployment.

• Oncepartiallyorfullydeployed,theFlair® Endovascular Stent Graft cannot be retracted or remounted onto the delivery system. Device removal after deployment can only be done with a surgical approach.

• An appropriate guidewire is required for the introduction of the stent graft delivery system into the body. The guidewire must remain in place during the introduction, manipulation and eventual removal of the deployment system.

• Afteruse,theFlair® Endovascular Stent Graft deployment system is a potential biohazard. Handle and dispose of in accordance with accepted medical practice and with applicable local, state and federal laws and regulations.

• Thesafetyandeffectivenessof thisdevice foruse in thearterialsystem have not been established.

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PRECAUTIONS• Thisdeviceshouldbeusedonlybyphysicianswhoarefamiliarwith

the complications, side effects, and hazards commonly associated with dialysis shunt revisions and endovascular procedures.

• Please note, clinical investigations regarding the safety and effectiveness of the device have been limited to implants placed within AV grafts located in the upper extremities.

• Faulty placement techniques may lead to failure in stent graftdeployment.

• Donotkinkthedeliverysystem.• Thedeliverysystemcanfunctiononlyaftertheredsafetycliphas

been pulled off and the Tuohy-Borst valve is loosened. This should not be done until the stent graft is positioned across the lesion and is ready to be deployed.

• The safety and effectiveness of this device have not been established when used around a tight bend in a looped AV graft. It is recommended to access the AV graft at the venous side of the AV graft or at the apex.

• The stent graft is anchored by the segment within the AV graftconduit and should be sized to the AV graft diameter. The flared venous segment of the stent graft is intended to address flow in the larger diameter and more elastic vein beyond the stenosis. It is not intended to provide additional device fixation.

• Carefulattentionshouldbepaidtoensurethedeviceisappropriately sized to the actual graft diameter, taking into account any change to the stated graft diameter that may have resulted from previous interventions. The appropriate length device(s) should be selected so that the stent graft extends beyond the stenosis into at least 10 mm of the non-diseased graft towards the arterial inflow and into the non-diseased vein approximately 10 mm beyond the stenosis.

• Serious complications, such as migration to the heart or lungs,have been reported when stent grafts have not been appropriately sized or when the appropriate length of placement of the proximal (inflow) end of the device (~10 mm) in the AV graft is not achieved.

• Carefulattentionoftheoperatoriswarrantedtomitigatethepotential for migration of the stent graft in the direction of flow during deployment. After deployment of approximately 15 mm of the stent graft, wait for the distal end of the stent graft to fully expand.

• Please note that devicemigrationmay occur post-discharge andhas been reported 3-10 days post-procedure.

• Duringdeploymentofthestentgraft,theentirelengthofthedelivery system should be kept as straight as possible in order to mitigate the potential for distal stent graft misplacement.

• After full stentgraftdeployment,waita fewseconds toallow forcomplete device expansion before removing the delivery system over the guidewire.

• Stentgraftdislodgementhasbeenreportedduringremovalofthedelivery system; therefore, careful attention should be paid during this portion of the procedure to prevent such occurrences.

• PostdilationofthestentgraftmustbeperformedwithaPTAballoon catheter indicated for post dilation of stents that has the same diameter as the Flair® Endovascular Stent Graft body diameter. The Flair® Endovascular Stent Graft cannot be balloon dilated beyond its stated diameter.

• TheeffectsofdirectcannulationoftheFlair® Endovascular Stent Graft have not been evaluated in a clinical study. Notify the patient that the stent graft should not be directly cannulated and that applying pressure to the implant area should be avoided.

• In caseof placement of two stent grafts (overlap), use the samedevice diameter in both cases. If a flared device is used to overlap, do not deploy the flared end inside the first stent graft. Ensure a minimum 10 mm overlap of the devices.

• The safety and effectiveness of the device if placed across an anglethatisgreaterthan90ºhavenotbeenestablished.

• Thesafetyandeffectivenessofthedeviceinpatientsinwhichitisrequired to be deployed across the antecubital fossa have not been established.

POTENTIAL COMPLICATIONS AND ADVERSE EVENTSComplicationsandAdverseEventsassociatedwiththeuseoftheFlair® Endovascular Stent Graft may include the usual complications associated with endovascular stent and stent graft placement and dialysis shunt revisions. Previously reported complications include: thrombotic occlusion, restenosis requiring reintervention, pseudoaneurysm, vessel rupture, perforation, pain, infection, hemorrhage, hematoma, arm or hand edema, steal syndrome, congestive heart failure, cerebrovascular accident and death. Stent Graft specific events that could be associated with clinical complications include stent graft misplacement, stent graft migration,

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stent graft fracture, stent graft kinking, insufficient stent graft expansion and stent graft embolism. Delivery System specific events that could be associated with clinical complications include bond joint failures, detachment of parts, incompatibility with accessory devices, premature deployment, inaccurate deployment, failure to deploy, high deployment forces, delivery system kinking, no visibility under fluoroscopy, inability to track to target location, and blood leakage from delivery system (hemostasis).

A list of all Adverse Events observed during the Flair® Endovascular Stent Graft clinical trial can be found in the chapter “Summary of Safety”(table6)oftheClinicalStudysectionofthisdocument.

MRI SafetyThe Flair® Endovascular Stent Graft was determined to be MR Conditional according to the terminology specified in the AmericanSociety for Testing and Materials (ASTM) International, Designation: F2503-08. Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment.ASTM International, 100 Barr Harbor Drive, PO Box C700, WestConshohocken,Pennsylvania,2008.

Non-clinical testing demonstrated that the Flair® Endovascular Stent Graft is MR Conditional. A patient with this implant can be scannedsafely immediately after placement under the following conditions: - Static magnetic field of 3-Tesla or 1.5-Tesla. - Spatial gradient magnetic field of 3000-Gauss/cm or less. - Maximum MR system reported whole-body-averaged specific

absorption rate (SAR) of 2-W/kg in the normal operating mode.

In non-clinical testing, the Flair® Endovascular Stent Graft produced a temperatureriseoflessthan4 °CatamaximumMRsystem-reportedwhole body averaged specific absorption rate (SAR) of 2-W/kg for 15 minutes of continuous MR scanning in a 3-Tesla MR system using a transmit/receive body coil (Signa HDx, Software 15/LX/MR, General Electric Healthcare, Milwaukee, WI). The effect of heating in the MRI environment for overlapping stent grafts or stent grafts with fractured struts is not known.

In non-clinical testing, the Flair® Endovascular Stent Graft produced a temperatureriseoflessthan3 °CatamaximumMRsystem-reportedwhole body averaged specific absorption rate (SAR) of 2-W/kg for 15 minutes of continuous MR scanning in a 1.5-Tesla MR test coil (Model 46-306600G2, General Electric Healthcare, Milwaukee, WI). The effect of heating in the MRI environment for overlapping stent grafts or stent grafts with fractured struts is not known.

MR image quality may be compromised if the area of interest is in the exact same area or relatively close to the position of the Flair® Endovascular Stent Graft. Therefore, optimization of MR imaging parameters to compensate for the presence of this implant may be necessary.

Artifact Information:Image artifact of the Flair® Endovascular Stent Graft was tested according to ASTM F2119-07 in a GE Signa HDx 3-Tesla cylindrical bore scanner (Software 15/LX/MR). Maximum artifact beyond the stent graft was 1 mm for the spin echo sequence and 5 mm for the gradient echo sequence. The lumen was obscured. Imaging parameters may need to be adjusted for artifact optimization.

It is recommended that patients with a stent graft register the MR conditions with the MedicAlert Foundation (www.medicalert.org).

SUMMARY OF CLINICAL STUDIESA total of 227 patients were treated at 16 U.S. investigational sites to evaluate the safety and effectiveness of the Flair® Endovascular Stent Graft. This study compared the Flair® Endovascular Stent Graft to balloon angioplasty in patients with stenoses at the venous anastomosis of a synthetic AV access graft. Physicians unfamiliar with the system enrolled “roll-in” patients before starting the randomized phase of the trial. A total of 37 “roll-in” patients and 190 randomized patients, 97 in the treatment arm and 93 in the control arm, were enrolled in the clinical study.

Study EndpointsTreatment Area Primary Patency (TAPP) at six months was the primary outcome used to compare the effectiveness of the study device to the PTAControl.Theprimarysafetyendpointwasevaluatedbasedontheincidence of adverse events observed within the same time interval.

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Secondary endpoints included: 1) the ability to successfully deliver the Flair® Endovascular Stent Graft, 2) procedural success 3) 2-month treatment area primary patency, 3) 2- and 6-month access circuit primary patency, 4) 2- and 6-month assisted access circuit primary patency, 5) 2- and 6-month access circuit cumulative (i.e., secondary) patency, and 6) 2- and 6-month percent stenosis of the treatment area.

Patients StudiedEligible patients had a hemodynamically significant stenosis (≥50% reduction of normal vessel diameter) accompanied by a hemodynamic, functional or clinical abnormality (defined by K/DOQI, SIR guidelines),without thrombotic occlusion, at the synthetic AV access graft-vein-anastomosis. To be included in the study, total stenosis length could not exceed 70 mm, and the entire lesion had to be located within 70 mm of the venous anastomosis. The AV access graft must have also been implanted at least 30 days and undergone at least one hemodialysis.

Patients were excluded from the study if they had had a thrombosis of the AV access graft within 7 days before the index procedure or if their access graft was infected.

MethodsPatients were prospectively randomized to treatment with the Flair® Endovascular Stent Graft or PTA. Cross-overs were not allowed.Clinical follow-up visits were conducted twomonths and sixmonthsafter the index procedure. Interim visits were conducted as clinically indicated.Quantitativeangiographywasconductedinconjunctionwiththe scheduled follow-up visits. Antiplatelet and anticoagulation therapy was at the discretion of the physician. Patients were monitored for adverse events throughout their participation in the trial.

An independent Clinical Events Committee (CEC) adjudicated alloccurrences of death, acute graft occlusion during the index procedure, cerebrovascular accident, congestive heart failure, graft dysfunction or failure, hematoma, graft or wound infection, other infection, wound complications, peripheral thromboembolism, pseudoaneurysm, pulmonary embolism, restenosis (angiographic), significant hand or arm edema, steal syndrome, subacute graft occlusion (out of lab but < 24 hours post-procedure) and thrombotic occlusion (> 24 hours post-procedure). Inaddition,theCECreviewedalladverseeventsrelatedtostudydevicefailure or malfunction. The CEC was also to review all unanticipatedadverse events; however, no such events were observed during the study.

ResultsPatientDemographicsandBaselineCharacteristicsThe randomization process resulted in 97 patients treated with the study device and 93 patients treated with balloon angioplasty as a control. Tables 1 - 4 summarize the patient demographics, medical history, AV access graft characteristics and AV access graft type for the two study groups. The 37 “roll-in” Flair® Endovascular Stent Graft patients are also noted in each table of this results section; however, the statistical comparisons and p-values are from the randomized population only.

Table 1. Patient Demographics

ROLL-IN PATIENTS RANDOMIZED PATIENTS

Flair® Device (N=37)


PTA Only (N=93) P-value

Male 37.84% (14/37) 34.02% (33/97) 38.71% (36/93) 0.548

Age of patients (yrs)

Mean±SD (N) 62.16±11.84 (37) 61.83±14.63 (97) 59.83±13.58 (93) 0.331

Range (min,max) (37.60, 84.67) (30.85, 87.37) (24.13, 90.53) --

Note: p-values are unadjusted for multiple comparisons

Table 2. Medical History





Hypertension 91.89% (34/37) 98.7% (96/97) 93.55% (87/93) 0.061

CoronaryArteryDisease 30.56% (11/36) 36.67% (33/90) 38.64% (34/88) 0.877

CongestiveHeartFailure 25.00% (9/36) 28.09% (25/89) 22.09% (19/86) 0.388

Diabetes 51.35% (19/37) 60.82% (59/97) 62.37% (58/93) 0.882

COPD 2.70% (1/37) 7.69% (7/91) 5.75% (5/87) 0.767

Hypercoagulability 0.00% (0/37) 1.10% (1/91) 0.00% (0/83) 1.000

Glomerulonephritis 5.88% (2/34) 5.56% (5/90) 3.57% (3/84) 0.721


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Table 3. AV Access Graft Location





Age of AV Graft (yrs)

Mean±SD (N) 2.15±1.83 (36) 2.19±1.89 (87) 2.65±2.14 (88)0.134

Range (min,max) (0.00, 7.26) (0.00, 10.55) (0.11, 11.98)

Location

Right 16.22% (6/37) 23.71% (23/97) 23.66% (22/93) 0.993

Left 83.78% (31/37) 76.29% (74/97) 76.34% (71/93)

Forearm 24.32% (9/37) 20.62% (20/97) 26.09% (24/92) 0.637*

Upper arm 67.57% (25/37) 75.26% (73/97) 72.83% (67/92)

Across elbow joint 13.51% (5/37) 2.06% (2/97) 1.09% (1/92)

(forearm with jump graft)

Forearm + Elbow -- 2.06% (2/97) 0.00% (0/92)

Configuration 0.624

Loop 51.35% (19/37) 43.30% (42/97) 39.78% (37/93)

Straight 48.65% (18/37) 56.70% (55/97) 60.22% (56/93)

Arterial Anastomosis 0.280

Axillary 5.41% (2/37) 2.06% (2/97) 2.15% (2/93)

Brachial 89.19% (33/37) 94.85% (92/97) 93.55% (87/93)

Radial 5.41% (2/37) 1.03% (1/97) 4.30% (4/93)

Ulnar 0.00% (0/37) 0.00% (0/97) 0.00% (0/93)

Other 0.00% (0/37) 2.06% (2/97) 0.00% (0/93)

Venous Anastomosis 0.009

Axillary 29.73% (11/37) 22.68% (22/97) 32.26% (30/93)

Basilic 51.35% (19/37) 57.73% (56/97) 54.84% (51/93)

Brachial 10.81% (4/37) 14.43% (14/97) 3.23% (3/93)

Cephalic 5.41% (2/37) 3.09% (3/97) 9.68% (9/93)

Other 2.70% (1/37) 2.06% (2/97) 0.00% (0/93)

Prior Procedure

AV Access Graft 48.57% (17/35) 58.51% (55/94) 55.56% (50/90) 0.766

Venous Anastomosis 62.86% (22/35) 68.09% (64/94) 67.42% (60/89) 1.000

VenousOutflowTract 61.76% (21/34) 44.44% (40/90) 33.72% (29/86) 0.166

* The p-value does not include category „Forearm + Elbow“ which consists of two patients who have checked both forearm and elbow.


Table 4. AV Access Graft Type





Graft Type 0.341

Tapered 15.63% (5/32) 17.50% (14/80) 12.99% (10/77) 0.509

Straight 78.13% (25/32) 66.25% (53/80) 79.22% (61/77) 0.076

Stepped 6.25% (2/32) 10.00% (8/80) 6.49% (5/77) 0.565

Other 0.00% (0/32) 6.25% (5/80) 1.30% (1/77) 0.210

Graft Size (mm) 0.373

5 0.00% (0/32) 0.00% (0/81) 0.00% (0/80) --

6 65.63% (21/32) 66.67% (54/81) 68.75% (55/80) 0.866

7 9.38% (3/32) 6.17% (5/81) 8.75% (7/80) 0.565

8 0.00% (0/32) 0.00% (0/81) 2.50% (2/80) 0.245

4/7 15.63% (5/32) 20.99% (17/81) 20.00% (16/80) 1.000

5/8 0.00% (0/32) 1.23% (1/81) 0.00% (0/80) 1.000

3/6 0.00% (0/32) 0.00% (0/81) 0.00% (0/80) --

4.5/6.5 0.00% (0/32) 1.23% (1/81) 0.00% (0/80) 1.000

Other 9.38% (3/32) 3.70% (3/81) 0.00% (0/80) 0.245


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Pre-Procedural(Baseline)AngiographicCharacteristicsTable 5 summarizes the angiographic characteristics of the test and control groups.

Table 5. Baseline Angiographic Characteristics





Lesion side

Right 16.22% (6/37) 23.71% (23/97) 23.66% (22/93) 1.000

Left 83.78% (31/37) 76.29% (74/97) 76.34% (71/93) 1.000

Lesion Length (mm)

Mean±SD (N) 32.17±11.35 (30) 35.28±13.94 (95) 37.78±12.70 (90) 0.206

Range (min,max) (13.89, 60.12) (9.86, 71.49) (9.61, 66.92)

Eccentric 0.00% (0/30) 1.04% (1/96) 0.00% (0/90) 1.000

Bend >90 degrees 0.00% (0/30) 0.00% (0/96) 0.00% (0/90) --

Thrombus 0.00% (0/30) 2.08% (2/96) 0.00% (0/90) 0.498

Tortuosity 0.00% (0/30) 0.00% (0/96) 0.00% (0/90) --

Calcification 0.00% (0/24) 0.00% (0/73) 0.00% (0/71) --

Ulcerated 0.00% (0/30) 3.13% (3/96) 4.44% (4/90) 0.714

Aneurysm 3.33% (1/30) 4.17% (4/96) 7.78% (7/90) 0.360

Intimal Flap 0.00% (0/30) 0.00% (0/96) 0.00% (0/90) --

Ectasia 0.00% (0/30) 5.21% (5/96) 3.33% (3/90) 0.722

Interpolated Reference

Vessel Diameter (mm)

Mean±SD (N) 8.38±2.25 (30) 8.28±1.54 (96) 8.71±1.72 (90) 0.069

Range (min,max) (4.99, 13.44) (5.35, 14.30) (5.87, 13.53)

MLD (mm)

Mean±SD (N) 2.56±1.27 (30) 2.37±0.88 (96) 2.32±0.80 (90) 0.655

Range (min,max) (0.75, 6.23) (0.54, 4.92) (0.00, 4.81)

% Interpolated stenosis

Mean±SD (N) 70.09%±9.94% (30) 70.93%±10.46% (96) 72.92%±8.95% (90) 0.167

Range (min,max) (51.28%, 88.89%) (49.88%, 91.84%) (42.64%, 100.00%)


Table 5 is based on angiographic core laboratory analysis except for lesion location information which is site reported, specifically, not from the core laboratory.

Patient AccountabilityA total of 13 of the 190 randomized patients missed their 6-month follow-up examination, 6 in the test group and 7 in the control group. Complianceinthetestgroupwas93.8%(91/97),andcomplianceinthe control group was 92.5% (86/93).

SUMMARY OF SAFETY

A total of 227 patients were treated at 16 U.S. investigational sites to evaluate the safety and effectiveness of the Flair® Endovascular Stent Graft. This study compared the Flair® Endovascular Stent Graft to balloon angioplasty in patients with stenoses at the venous anastomosis of a synthetic AV access graft. Physicians unfamiliar with the system enrolled “roll-in” patients before starting the randomized phase of the trial. A total of 37 “roll-in” patients and 190 randomized patients were enrolled in the clinical study. Adverse Event rates (through 210 days) for rando-mized and “roll-in” patients are presented in table 6. The statistical comparisons and p-values presented in table 6 are from the randomized population only.

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Table 6. Adverse Events through 6 Months

Adverse EventsROLL-IN PATIENTS RANDOMIZED PATIENTS




Death 2.78% (1/36) 5.26% (5/95) 5.56% (5/90) 1.000

Infection 0.00% (0/36) 6.32% (6/95) 2.22% (2/90) 0.280

Stenosis 41.67% (15/36) 40.00% (38/95) 76.67% (69/90) <0.001

Thrombotic occlusion 33.33% (12/36) 32.63% (31/95) 21.11% (19/90) 0.098

Vessel rupture 0.00% (0/36) 3.16% (3/95) 1.11% (1/90) 0.621

Pseudoaneurysm 2.78% (1/36) 5.26% (5/95) 2.22% (2/90) 0.445

Hemorrhage 0.00% (0/36) 0.00% (0/95) 0.00% (0/90) --

Hematoma 0.00% (0/36) 2.11% (2/95) 0.00% (0/90) 0.498

Significant arm or hand edema

2.78% (1/36) 3.16% (3/95) 2.22% (2/90) 1.000

Steal syndrome 2.78% (1/36) 2.11% (2/95) 1.11% (1/90) 1.000

Congestiveheartfailure 2.78% (1/36) 4.21% (4/95) 2.22% (2/90) 0.683

Cerebrovascularaccident 0.00% (0/36) 2.11% (2/95) 3.33% (3/90) 0.676

Device kinking 0.00% (0/36) 0.00% (0/95) N/A --

Device migration 0.00% (0/36) 4.21% (4/95) N/A --

Embolism 0.00% (0/36) 0.00% (0/95) N/A --

Permanent deformation of the Endoluminal Device

2.78% (1/36) 1.05% (1/95) N/A --


SUMMARY OF EFFECTIVENESSA total of 125 stent grafts were implanted in the randomized test group (49 stent grafts in the “roll-in” test group) as summarized in table 7.

Table 7. Device and Procedure Characteristics




Total Devices Used 49 125

Delivery success by Device 89.80% (44/49) 94.40% (118/125)

Patients with device implanted 37 97

0 0.00% (0/37) 0.00% (0/97) 1 72.97% (27/37) 75.26% (73/97) 2 21.62% (8/37) 21.65% (21/97) 3 5.41% (2/37) 2.06% (2/97) 4 0.00% (0/37) 1.03% (1/97)Total Length Delivered (mm) a

Mean±SD (N) 52.70±21.56 (37) 52.58±26.07 (97) Range (min,max) (30.00, 120.00) (30.00, 200.00)

Delivery success by Patient 100.00% (37/37) 98.97% (96/97)

Length of Procedure (hours) a a

Mean±SD (N) 1.13±0.53 (37) 1.08±0.56 (95)

Median 1,17 0,98

Range (min,max) (0.25, 2.42) (0.25, 3.42)Fluoroscopy time (min) a a

Mean±SD (N) 8.38±3.81 (18) 11.01±12.46 (90) Median 7,56 8,60 Range (min, max) (4.03, 18.00) (2.47, 88.30)

Primary Effectiveness Results (randomized patients)Treatment Area Primary Patency (TAPP) at six months was the primary outcome used to compare the effectiveness of the study device to the PTAControl.

Per protocol, the TAPP was defined as patency (open to blood flow) after the study index procedure until reintervention in the treatment area (within 5 mm proximal or 5 mm distal to the study device or index balloon angioplasty treated area), or thrombotic occlusion that involved the treatment area. Percutaneous or surgical treatment in areas outside the treatment area did not affect TAPP. Treatment Area Primary Patency ended when: 1) there was a reintervention in the treatment area, 2) a thrombotic occlusion involved the treatment area, 3) a surgical inter-vention excluded the treatment area from the access circuit, or 4) the AV graft was abandoned due to an inability to treat the primary lesion.

The Treatment Area Primary Patency at six months in the study device groupwas significantly higher than that observed in the PTA Controlgroup as noted in the table 8. This demonstrated superiority of the study deviceoverthePTAControlwithrespecttotreatmentareaprimarypatency.

Table 8. Treatment Area Primary Patency





Treatment Area Primary Patency

2-month 89.2% (33/37) 80.21% (77/96) 77.17% (71/92) 0.722 6-month 60.0% (21/35) 50.55% (46/91) 23.28% (20/86) <0.001

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The reasons for TAPP failures are noted in table 9.

Table 9. Treatment Area Primary Patency Failure Reasons





Two Month Treatment Area PP Failure

10.8% (4/37) 19.79% (19/96) 22.83% (21/92) 0.722

Reintervention in the treatment area

10.8% (4/37) 12.50% (12/96) 20.65% (19/92) 0.169

Thrombotic occlusion that involves treatment area

8.1% (3/37) 13.54% (13/96) 9.78% (9/92) 0.499

Surgical intervention that excludes the treatment area from the access circuit

0.0% (0/37) 5.21% (5/96) 3.26% (3/92) 0.721

AV graft abandoned due to inability to treat primary lesion

2.7% (1/37) 0.00% (0/96) 3.26% (3/92) 0.115

Six Month Treatment Area PP Failure

40.0% (14/35) 49.45% (45/91) 76.74% (66/86) <0.001

Reintervention in the treatment area

34.3% (12/35) 30.77% (28/91) 75.58% (65/86) <0.001

Thrombotic occlusion that involves treatment area

34.3% (12/35) 34.07% (31/91) 22.09% (19/86) 0.095

Surgical intervention that excludes the treatment area from the access circuit

5.7% (2/35) 18.68% (17/91) 12.79% (11/86) 0.309

AV graft abandoned due to inability to treat primary lesion

5.7% (2/35) 9.89% (9/91) 8.14% (7/86) 0.796

Figure 3 presents the Kaplan-Meier curves for freedom from treatment area loss of primary patency. Freedom from treatment area loss of primary patency was significantly better (p=0.008) in the study device group (45.8% through 210 days) than in the PTA Control (19.3%through 210 days). Empirically, the separation between the curves was observed between 60 and 90 days after the index procedures and persisted throughout the remaining follow-up time.

Figure 3. Freedom from Loss of Treatment Area Primary Patency (Randomized Patients)

Secondary Effectiveness Results:The results for the secondary study endpoints are listed in table 10.

Table 10. Secondary Effectiveness Results





Device delivery success by patient

100.00% (37/37) 98.97% (96/97) N/A N/A

*Procedural Success 94.59% (35/37) 93.81% (91/97) 73.12% (68/93) <0.001

**AccessCircuitPrimaryPatency

2-month 86.5% (32/37) 79.17% (76/96) 77.17% (71/92) 0.860

6-month 42.9% (15/35) 38.04% (35/92) 19.77% (17/86) 0.008

***AccessCircuitAssistedPrimary Patency

2-month 91.9% (34/37) 86.46% (83/96) 89.13% (82/92) 0.659

6-month 65.7% (23/35) 65.56% (59/90) 73.81% (62/84) 0.253

****AccessCircuitCumulativePatency

2-month 97.3% (36/37) 94.79% (91/96) 95.65% (88/92) 1.000

6-month 91.4% (32/35) 81.32% (74/91) 85.88% (73/85) 0.542

*****Binary Restenosis Rate of the Treatment Area

2-month 0.00% (0/27) 20.00% (16/80) 70.59% (48/68) <0.001

6-month 25.00% (7/28) 27.63% (21/76) 77.61% (52/67) <0.001


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*Procedural Success: Anatomic success (achievement of a post procedure residual stenosis < 30%

measured at the narrowest point of the lumen, as indicated by angiography) and at least one

indicator of hemodynamic or clinical success.

**Access Circuit Primary Patency: Patency (open to blood flow) following the index study

procedure until access thrombosis or an intervention of a lesion anywhere within the access

circuit (arterial anastomosis to the superior vena cava-right atrial junction). Access primary

patency ends when: 1) there was an intervention for a stenosis anywhere within the access

circuit, 2) there was an occlusion anywhere within the access circuit, or 3) there was a surgical

intervention that excluded the index stenotic area from the access circuit.

***Access Circuit Assisted Primary Patency: Patency (open to blood flow) following the index

study procedure until access thrombosis or a surgical intervention that excludes the treated

lesion from the access circuit. Percutaneous treatment(s) of either restenosis of the previous

treated lesion or a new arterial or venous outflow stenosis/occlusion, excluding access throm-

bosis, are compatible with assisted primary patency. Assisted primary patency ends when: 1)

there is an occlusion anywhere within the access circuit, or 2) there is a surgical intervention

that excludes the index stenotic area from the access circuit.

****Access Circuit Cumulative Patency (i.e., secondary patency): Patency (open to blood flow)

following the index study procedure until the access is surgically revised or abandoned because

of inability to treat the original lesion. Multiple/ repetitive treatments for occlusions that restore

patencyarecompatiblewithcumulativepatency.Cumulativepatencyendswhen:1)thereisa

surgical intervention that excludes the index stenotic area from the access circuit, or 2) the AV

access venous anastomosis is surgically revised, or 3) the AV graft is abandoned due to an

inability to treat the primary lesion.

*****Binary Restenosis Rate of the Treatment Area: Binary restenosis rates, as demonstrated

by procedural, 2 and 6-month follow-up angiograms, were calculated by the core lab.

Quantitativevesselanalysiswasperformedto identify therestenosisrateat2and6-months.

Lesions within, just proximal to or just distal to the study device or index balloon angioplasty

treatment area with a ≥50% diameter stenosis were categorized as restenotic.

Figure 4 presents the Kaplan-Meier curves for freedom from loss of

access circuit primary patency. Freedom from loss of access circuit

primary patency was 32.0% through 210 days in the study device group

and16.3%through210daysinthePTAControl(p=0.044).

Figure 4. Freedom from Loss of Access Circuit Primary Patency (Randomized Patients)


access circuit assisted primary patency. Freedom from loss of access

circuit assisted primary patency was 60.4% through 210 days in the

study device group and 72.9% through 210 days in the PTA Control

(p=0.149).

Figure 5. Freedom from Loss of Access Circuit Assisted Primary Patency (Randomized Patients)


access circuit cumulative patency. Freedom from loss of access circuit

cumulative patency was 81.7% through 210 days in the study device

groupand86.3%through210daysinthePTAControl(p=0.374).

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Figure 6. Freedom from Loss of Access Circuit Cumulative Patency (Randomized Patients)

Angiographic Results:Table 11 summarizes the angiographic characteristics of the test and control groups at six months.

Table 11. Six-Month Angiographic Evaluation





Lesion Length (mm) a a a a

Mean±SD (N) 17.54±10.22 (11) 18.02±12.54 (41) 32.12±14.32 (50)<0.001

Range (min,max) (6.70, 37.70) (4.52, 52.68) (6.96, 69.51)

Eccentric 3.57% (1/28) 0.00% (0/70) 0.00% (0/55) --

Bend >90 degrees 0.00% (0/28) 0.00% (0/70) 0.00% (0/55) --

Thrombus 3.57% (1/28) 0.00% (0/70) 0.00% (0/55) --

Tortuosity 0.00% (0/28) 0.00% (0/70) 0.00% (0/55) --

Calcification 0.00% (0/20) 0.00% (0/54) 0.00% (0/36) --

Ulcerated 0.00% (0/28) 0.00% (0/70) 0.00% (0/55) --

Aneurysm 0.00% (0/28) 4.29% (3/70) 7.27% (4/55) 0.698

Intimal Flap 0.00% (0/28) 0.00% (0/70) 0.00% (0/55) --

Ectasia 0.00% (0/28) 0.00% (0/70) 1.82% (1/55) 0.440

Interpolated Reference Vessel Diameter (mm)

Mean±SD (N) 7.35±1.44 (28) 7.59±1.19 (70) 8.36±1.71 (55) 0.004

Range (min,max) (4.76, 11.10) (4.35, 10.03) (5.47, 13.37)

MLD (mm)

Mean±SD (N) 4.63±2.00 (28) 5.10±1.49 (70) 3.32±1.46 (55) <0.001

Range (min,max) (0.00, 7.89) (0.00, 8.30) (0.00, 6.53)

% Interpolatedstenosis

Mean±SD (N) 0.35±0.27 (28) 32.07%±19.76% (70) 59.22%±19.55% (55) <0.001

Range (min,max) (0.08, 1.00) (2.01%, 100.00%) (7.13%, 100.00%)

Binary Restenosis Rate

25.00% (7/28) 27.63% (21/76) 77.61% (52/67) <0.001

Stent Graft MLD (mm)

Mean±SD (N) 5.41±1.82 (28) 5.76±1.34 (70)N/A N/A

Range (min,max) (0.00, 7.89) (0.00, 8.40)

% Interpolated stent graft stenosis

Mean±SD (N) 0.24±0.27 (28) 22.94%±18.88% (70)N/A N/A

Range (min,max) (-0.25, 1.00) (-9.97%, 100.00%)

Edge MLD (mm)

Mean±SD (N) 5.67±1.82 (28) 6.38±1.41 (70)N/A N/A

Range (min,max) (0.00, 7.87) (0.00, 9.97)

% Interpolated edge stenosis

Mean±SD (N) 0.20±0.29 (28) 14.35%±20.92%N/A N/A

Range (min,max) (-0.27, 1.00) (-26.20%, 100.00%)

Note: p-values are unadjusted for multiple comparisonsTable 11 is based on angiographic core laboratory analysis except for lesion location information which is site reported, specifically, not from the core laboratory.

Patient Death SummaryThere were eleven (11) deaths among the randomized patients, including 5 patients in the test group and 6 patients in the control group, and 1 death among the “roll-in” patients. None of these deaths were attributed to the study device.

The five (5) deaths in the study device group and one (1) death in the “roll-in” group occurred between 52 days and 197 days following the indexprocedure.Causesofdeath included: stroke (day163),MI (day60), cardiac arrest (day 101), respiratory failure (day 197), HIV compli-cations (day 52) and one (1) unknown (day 136).

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Thesix(6)deaths inthePTAControlgroupoccurredbetween45and 222daysfollowingtheindexprocedure.Causesofdeathincluded:stroke (day 45, day 59 and day 111), pulmonary edema (day 160), pericardial effusion (day 176), and complications from adenocarcinoma (day 222). Please note that the sixth death in the PTA group (day 222) was not included as an adverse event because it did not fall within the 6-month reporting period as pre-defined in the protocol (i.e., 180 ± 30 days).

Observed Device MalfunctionsThere were eleven (11) observations regarding performance of the study device reported in 8 patients. Five (5) devices were reported to be placed improperly, such that the stent-graft did not deploy where intended, requiring implantation of an additional stent graft in four cases. In addition, four (4) device migrations, three (3) of which occurred during the index procedure, and one (1) instance each of permanent device deformation and delivery system malfunction were reported.

CONCLUSIONS DRAWN FROM THE STUDY

Results of the randomized, prospective, multi-center clinical trial demonstrated that the Flair® Endovascular Stent Graft was superior to the PTA Control with respect to six-month Treatment Area PrimaryPatency (TAPP), the primary effectiveness endpoint, and no different thanthePTAControlwithrespecttosafety.

Data from the clinical trial provide a reasonable assurance that the Flair® Endovascular Stent Graft is safe and effective for the treatment of stenoses at the venous anastomosis of ePTFE or other synthetic arterio - venous (AV) access grafts when used in accordance with its labeling.

A Prospective Observational Study of the Flair® Endovascular Stent Graft Optimized Delivery System

STUDY DESIGN AND OBJECTIVESThestudy,“AProspectiveObservationalStudyoftheFlair® Endovascular Stent Graft Optimized Delivery System”, was a prospective, non- randomized, multi-center, observational study, conducted at 5 sites in the U.S. Thirty (30) subjects with clinical evidence of graft dysfunction at the synthetic AV access graft venous anastomosis were enrolled. The goal of this clinical study was to evaluate the performance of the Optimized Flair® Delivery System. The specific objectives of the study were:

Primary Objective:• Toassesstherateoftechnicalsuccessfordelivery. Technical success for delivery was defined as deployment of the

Flair® Endovascular Stent Graft to the intended location, assessed at the time of the index procedure.

Secondary Objective:• Toassessthesafetyofdelivery. Safety of delivery was defined as the absence of device- and/or

procedure-related adverse events from the time of the index procedure to 30 days post procedure. A device and/or procedure-related adverse event was defined as any undesirable clinical event that is caused by the presence or function of any part of the Optimized Delivery System or by the procedure to implant the Flair® Endovascular Stent Graft. The occurrence of such events was assessed during the procedure, at hospital discharge, and again at 30 days post-procedure.

RESULTS

Technical Success for DeliveryDuring the course of the study, thirty-four (34) attempts were made to deliver the Flair® Endovascular Stent Graft to stenoses at the venous anastomoses of thirty (30) patients. All attempts to deliver the stent graft were successful and all stent grafts were delivered to their intended location. Four (4) patients (13%) received two (2) stent grafts and the remainder received a single stent graft (87%).

• The Optimized Flair® Delivery System was effective, as the technical success rate was 100%.

Patient IMPLANT Information Card

Carry this card with you. Prior to any treatment, please show it to all medical personnel caring for you.

Manufactured by:

Bard Peripheral Vascular, Inc.aDivisionofC.R.Bard,Inc.1625 West 3rd Street Tempe, AZ 85281USATEL: 1-480-894-9515 1-800-321-4254FAX: 1-480-966-7062 1-800-440-5376www.bardpv.com

MR Conditional

This Device is classified as MR Conditional.For further details on MR compatibility, please refer to product’s IFU available on www.bardpv.com or call 1-800-562-0027.

Patient Data:Name:Address:Date of birth:

Implant Data:Product: Implant Material: Implantation site:Date of implantation:Follow up:

Hospital Data:Name:Address: Physician:Phone:

Apply “Patient/Inv. chart” sticker here

Manufactured by: Bard Peripheral Vascular, Inc. • a Division of C. R. Bard, Inc. •1625 West 3rd Street • Tempe, AZ 85281 • USA

REMOVE THESE LABELS TO COMPLETE YOUR PATIENT FILE

Patient Data: Name: Date of implantation: Implantation site: Follow up:

apply “Patient/Inv. chart” sticker here

Product Data

Manufactured by: Bard Peripheral Vascular, Inc. • a Division of C. R. Bard, Inc. •1625 West 3rd Street • Tempe, AZ 85281 • USA

apply “Patient/Inv. chart” sticker here

Product Data

Patient Data: Name: Date of implantation: Implantation site: Follow up:

15

Safety of DeliveryA total of three (3) adverse events (AEs) were reported during this study. Three (3) patients (10%) had an incident of thrombotic occlusion within the 30-day time interval. None of these were classified as serious by the investigators. In fact, two (2) of the AEs were recorded as not being related to the device and/or procedure and one (1) was recorded as an unknown relationship to thedevice.Conservatively, theone (1)AEofunknown relationship could be considered device-related. In this case, the device-related AE rate is 3.3%, which is well within the thrombotic occlusion rate experienced in the pivotal study (31/95 patients or 32.6%).

• The Optimized Flair® Delivery System was safe, as the device/ procedure-related AE rate of 3.3% was within the thrombotic occlusion rate experienced in the pivotal study (32.6%). Furthermore, there were no reports of Serious Adverse Events (SAEs), Unanticipated Adverse Device Effects (UADEs), or patient deaths.

CONCLUSIONS DRAWN FROM THE STUDYThis observational study confirms that the improvements to the delivery system do not adversely affect the safety and effectiveness of the Flair® Endovascular Stent Graft.

A Prospective, Randomized, Concurrently-Controlled Post-Approval Study of the Flair® Endovascular Stent Graft (RENOVA)

Study Design and ObjectivesThe RENOVA study is a multicenter, prospective, randomized, concurrently-controlled post-approval study evaluating the safety and effectiveness of the Flair® Endovascular Stent Graft when compared to percutaneous transluminal balloon angioplasty (PTA) alone. Onearm received only PTA (the PTA group); the second arm received PTA and a Flair® Endovascular Stent Graft(s) in the stenotic area (the Flair® Endovascular Stent Graft group). All subjects enrolled in the study were to be followed through 24 months (±30 days) post-index procedure.

Study PopulationA total of 270 patients were treated at 28 U.S. investigational sites. Subjects had a hemodynamically significant stenosis ≥50% and clinical evidence of graft dysfunction without thrombotic occlusion at the AV access graft-vein anastomosis. Total stenosis length could not exceed 70 mm, and the entire lesion had to be located within 70 mm of the venous anastomosis. Patients were excluded from the study if they had had a thrombosis of the AV access graft within 7 days before the index procedure or if their access graft was infected.

The primary objectives of this Post Approval study were to:• Demonstrate that the post intervention ACPP in the Flair®

Endovascular Stent Graft group is superior to that of the PTA group through 12 months and to estimate the patency at 24 months;

• Demonstrate that the IPF [the average number of days betweeninterventions] of the Flair® Endovascular Stent Graft group is not inferior to that of the PTA group at 12 months and to estimate the IPF at 24 months; and,

• Demonstratethatthesafety(definedasthenumberofdeviceand/or procedure related adverse events) of the Flair® Endovascular Stent Graft group is not inferior to that of the PTA group at 12 months, and to estimate the safety at 24 months.

Secondary EndpointsSecondary endpoints included: 1) The number of re-interventions to the access circuit until graft abandonment or through 12 months post-index procedure. 2) Post-Intervention Assisted Primary Patency (PAPP) at 6, 12 and 24 months. 3) Post-intervention Secondary Patency at 6, 12 and 24 months. 4) Procedural success. 5) Demonstrate the effectiveness of the BPV clinician training program assessed by the incidence of major device-related and procedure-related adverse events from the index procedure through 30-day post-procedure. 6) Evaluate Flair® Endovascular Stent Graft safety in terms of Serious Adverse Events.

16

Additional Analysis

Treatment Area Primary Patency (TAPP) at 12 and 24 months (Post-hoc analysis)

Results

Subject Accountability

Of the 270 patients enrolled, 132 received treatment with balloon angioplasty alone and 138 patients were treated with balloon angioplasty and the Flair® Endovascular Stent Graft.

74 patients died during the study period, 3 patients were lost to follow-up and 2 patients withdrew consent. 191 patients completed the study through the 24 months follow up time point.

At 12-month follow-up, examination was performed on 230 of the 270 randomized patients resulting in a compliance in the test group of 84.1% (116/138), and 86.4% (114/132) in the control group.

Patient Demographics and Baseline Characteristics

Patient Demographics and Baseline Characteristics can be found intables 12 through 16.

Table 12. Baseline Patient Demographics


PTA (N=132)

All Subjects (N=270)

P-value [1]

Patient Demographics

Sex 0.718

Male 51 (37.0%) 46 (34.8%) 97 (35.9%)

Female 87 (63.0%) 86 (65.2%) 173 (64.1%)

Age of patients (yrs) 0.935

Mean±SD (N) 63.2±13.17 (138) 63.1±12.29 (132) 63.1±12.72 (270)

Range (min, max) (26, 89) (24, 88) (24, 89)

[1] p-values for categorical variables are from a chi-square test. P-values for continuous variablesarefromaone-wayANOVAmodelwithtreatmentasafactor.

Table 13. AV Access Graft Characteristics


PTA (N=132)


P-value [1]

AV Access Graft Characteristics

Age of AV Graft (yrs) 0.777

Mean±SD (N) 1.8±2.13 (137) 1.7±2.18 (130) 1.7±2.15 (267)

Range (min, max) (0, 10) (0, 13) (0, 13)

Number of Previous Graft Revisions

0.444

Mean±SD (N) 1.8±2.39 (137) 1.6±2.47 (132) 1.7±2.43 (269)

Range (min, max) (0, 11) (0, 11) (0, 11)

Location

Right Side 39 (28.3) 35 (26.5) 74 (27.4)

Left Side 99 (71.7) 97 (73.5) 196 (72.6)

Position

Forearm 13 (9.4) 14 (10.6) 27 (10.0)

Across Antecubital 1 (0.7) 0 1 (0.4)

Upper Arm 124 (89.9) 118 (89.4) 242 (89.6)

Configuration

Loop 38 (27.7) 34 (25.8) 72 (26.8)

Straight 99 (72.3) 98 (74.2) 197 (73.2)

Arterial Anastomosis

Axillary 4 (2.9) 5 (3.8) 9 (3.3)

Brachial 129 (93.5) 124 (93.9) 253 (93.7)

Radial 4 (2.9) 2 (1.5) 6 (2.2)

Ulnar 0 1 (0.8) 1 (0.4)

Other 1 (0.7) 0 1 (0.4)

Venous Anastomosis

Axillary 62 (44.9) 57 (43.2) 119 (44.1)

Basilic 42 (30.4) 57 (43.2) 99 (36.7)

Brachial 24 (17.4) 14 (10.6) 38 (14.1)

Cephalic 7 (5.1) 4 (3.0) 11 (4.1)

Other 3 (2.2) 0 3 (1.1)

[1] p-values for categorical variables are from a chi-square test. P-values for continuous variablesarefromaone-wayANOVAmodelwithtreatmentasafactor.

17

Table 14. AV Access Graft Type


PTA (N=132)


Graft Type

Tapered 49 (35.5) 36 (27.3) 85 (31.5)

Straight 49 (35.5) 56 (42.4) 105 (38.9)

Stepped 8 (5.8) 10 (7.6) 18 (6.7)

Unknown 17 (12.3) 20 (15.2) 37 (13.7)

Other 15 (10.9) 10 (7.6) 25 (9.3)

Graft Size (mm)

6 44 (31.9) 51 (38.6) 95 (35.2)

7 26 (18.8) 21 (15.9) 47 (17.4)

8 5 (3.6) 5 (3.8) 10 (3.7)

3/6 1 (0.7) 0 1 (0.4)

4/7 47 (34.1) 43 (32.6) 90 (33.3)

5/8 1 (0.7) 0 1 (0.4)

4.5/6.5 1 (0.7) 0 1 (0.4)

Unknown 10 (7.2) 11 (8.3) 21 (7.8)

Other 3 (2.2) 1 (0.8) 4 (1.5)

Table 15. Baseline Pre-Existing Medical Conditions


PTA (N=132)


Pre-Existing Medical Conditions

None 0 (0.0%) 0 (0.0%) 0 (0.0%)

Muscular/Skeletal 80 (58.0%) 74 (56.1%) 154 (57.0%)

Digestive/Gastrointestinal 79 (57.2%) 83 (62.9%) 162 (60.0%)

Lymphatic 31 (22.5%) 29 (22.0%) 60 (22.2%)

Urinary 36 (26.1%) 35 (26.5%) 71 (26.3%)

Reproductive 26 (18.8%) 36 (27.3%) 62 (23.0%)

Steal Syndrome 4 (2.9%) 4 (3.0%) 8 (3.0%)

Psychiatric 41 (29.7%) 35 (26.5%) 76 (28.1%)

Head, Ears, Nose, Throat (HEENT) 40 (29.0%) 56 (42.4%) 96 (35.6%)

Glomerulonephritis 20 (14.5%) 22 (16.7%) 42 (15.6%)

Respiratory 60 (43.5%) 48 (36.4%) 108 (40.0%)

CHF 43 (31.2%) 43 (32.6%) 86 (31.9%)

CHD 59 (42.8%) 50 (37.9%) 109 (40.4%)

Hypertension 131 (94.9%) 124 (93.9%) 255 (94.4%)

Hypercoagulability 7 (5.1%) 5 (3.8%) 12 (4.4%)

Cerebrovascularaccident 19 (13.8%) 25 (18.9%) 44 (16.3%)

Diabetes 86 (62.3%) 85 (64.4%) 171 (63.3%)

Other 109 (79.0%) 101 (76.5%) 210 (77.8%)

Table 16. Baseline Angiographic Characteristics


PTA (N=132)


Pre-Procedural Angiographic Characteristics

Mean Lesion Length (cm) 2.174 1.980 2.079

SD 1.4843 1.4919 1.4884

Mean Stenosis (%) 69.4 69.1 69.3

SD 12.22 13.30 12.73

Table 17. Device Characteristics and Procedure Characteristics


PTA (N=132)


Device Characteristics and Procedure Characteristics

Mean Deployed Stent Graft Length 44.6 mm N/A N/A

SD 4.92

Mean Deployed Stent Graft Diameter 8.2 mm N/A N/A

SD 0.64

Number of Stent Grafts Deployed 142 N/A N/A

Number of Straight Stent Grafts 21

Number of Flared Stent Grafts 121

Total Procedure Time (min)

Mean 38.2 29.7 34.0

SD 21.15 16.23 19.35

Median 33.0 25.0 29.0

Min, Max 8, 118 7, 84 7, 118

SUMMARY OF SAFETY

A summary of all adverse events through 24 months is presented in table 18.

18

There was no significant difference between the groups for the

percentage of subjects with at least one AE: 97.0% (128/132) for

PTA and 94.2% (130/138) for Flair® Endovascular Stent Graft

(p = 0.378). The incidence of all categories of AEs was similar between

treatment groups, with the exception of stenosis requiring intervention,

which occurred significantly more frequently in the PTA group

(82.6%, 109/132) than in the Flair® Endovascular Stent Graft group

(63.0% (87/138) (p <0.001)). Table 18. Summary of All Adverse Events*


PTA (N=132)

Subjects with at least one event 130 (94.2%) 128 (97.0%)

Adverse Event Description

Cerebrovascularaccident 2 (1.4%) 6 (4.5%)

Congestiveheartfailure 9 (6.5%) 6 (4.5%)

Device kinking 0 (0.0%) 0 (0.0%)

Device migration 1 (0.7%) 1 (0.8%)**

Embolism 1 (0.7%) 0 (0.0%)

Hematoma 5 (3.6%) 1 (0.8%)

Hemorrhage 10 (7.2%) 10 (7.6%)

Infection 40 (29.0%) 42 (31.8%)

Pain 14 (10.1%) 6 (4.5%)

Perforation 1 (0.7%) 0 (0.0%)

Permanent deformation of the device 0 (0.0%) 0 (0.0%)

Pseudoaneurysm 9 (6.5%) 16 (12.1%)

Significant arm or hand edema 3 (2.2%) 3 (2.3%)

Steal syndrome 6 (4.3%) 3 (2.3%)

Stenosis requiring intervention 87 (63.0%) 109 (82.6%)

Thrombotic occlusion 60 (43.5%) 48 (36.4%)

Vessel rupture 2 (1.4%) 2 (1.5%)

Other 82 (59.4%) 83 (62.9%)

*Subjects reporting a particular event more than once are only counted once for that event.** After the index procedure (PTA), the patient experienced stenosis at the venous anastomosis,

and with the physician’s selected standard of care intervention, there was a stent migration.

PRIMARY SAFETY ENDPOINT RESULT

Safety at 12 months was a primary endpoint in the RENOVA study.

Safety was defined as the number of device and/or procedure related

adverse events. Per the study protocol, an AE was defined as device-

and/or procedure-related if the investigator classified the event as

either “unknown”, “possibly related”, or “definitely related”. The

analysis presented excludes thrombotic occlusion and stenosis

requiring intervention, as these variables were included in the

effectiveness outcomes (TAPP and ACPP). All AE’s including those

classified with device and/or procedure relatedness are presented in

table 18.

At Month 12, the number of subjects with device or procedure-related

AEs was 12 (8.7%) in the Flair® Endovascular Stent Graft group and

3 (2.3%) in the PTA group.

In the Flair® Endovascular Stent Graft group, 9 device-related AEs

were reported among 7 subjects. 9 procedure-related AEs were

reported among 8 subjects. All except one event were classified

possibly related or unknown. One device migration was classified

device and procedure related.

In the PTA group, 1 device-related AE was reported in 1 subject, and

3 procedure-related AEs were reported among 3 subjects. All events

were classified possibly related or unknown.

A Blackwelder z-test of proportions, using a non-inferiority margin of

15%, produced a p–value of <0.001. A p-value of <0.05 rejects the

null hypothesis and concludes non-inferiority. The p-value of <0.001

was smaller than the non-inferiority significance level of 0.05. Thus,

the non-inferiority of the Flair® Endovascular Stent Graft to PTA

in terms of device- and/or procedure-related adverse events was

established.

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SECONDARY SAFETY ENDPOINT RESULT

• Device- and/or Procedure-Related SAEs through 30 days: Two

device related SAEs in the Flair® Endovascular Stent Graft group

werereportedduringthe30daypost-procedureperiod.Oneevent

was reported as “thrombotic occlusion/AV graft thrombosis” and

was identified by the investigator as definitely related to the device.

The second event was reported as “thrombotic occlusion / clotted

graft”, and the investigator described relatedness to the device as

unknown. Based on the assessment of device or procedure-related

SAEs the BPV clinician training program was judged to be effective.

• Device- and/or Procedure-Related SAEs: One device and/or

procedure-related SAE was reported for one subject in the PTA

group. Nine device and/or procedure-related SAEs were reported

among eight subjects in the Flair® Endovascular Stent Graft

group. The related SAE probability at Month 12 was 5.2 (95%

CI:1.4,8.9)fortheFlair® Endovascular Stent Graft group, versus

zero probability for the PTA group. The related SAE probability at

Month24was6.1(95%CI:2.0,10.2)fortheFlair® Endovascular

Stent Graft group, versus a probability of 1.0 (95% CI: -1.0,

3.0) for the PTA group. The seeming difference in device and/or

procedure related SAE rates is not associated with a true difference

in rates of serious adverse events, but rather appears attributable

to more frequent identification of certain anticipated outcomes

as “device-related” only where an implant is present and as

“procedure-related” where an additional procedure was performed.

SUMMARY OF EFFECTIVENESS

Primary Effectiveness Endpoint Results

Table 19. Summary of Access Circuit Primary Patency


PTA (N=132) P-value [1]

AccessCircuitPrimaryPatency

12Monthrate(95%CI) 24% (0.165, 0.315) 11% (0.054, 0.167) 0.007*

24Monthrate(95%CI) 9.5% (0.029, 0.162) 5.5% (0.013, 0.097) 0.011*

Note: ‚*‘ = Denotes statistical significance at the 0.05 level.

[1]p-valueisfromaCoxregressionanalysisusingcovariateoftreatmentgrouptestingsuperi-

ority of the Flair® Endovascular Stent Graft group to that of PTA.


access circuit primary patency through 24 months.

Figure 7. Survival Curve for ACPP through Month 24

Table 20. Summary of Index of Patency Function (IPF)



Month 12

Index of Patency Function (months/intervention) ± SD

5.2 ± 4.08 4.4 ± 3.51 0.009*

Month 24

Index of Patency Function (months/intervention) ± SD

7.1 ± 7.04 5.3 ± 5.22


A non-inferiority margin of 7 days was incorporated into the calculation of the p-value. A p-value

<0.05 rejects the null hypothesis and concludes non-inferiority.

[1]p-valueisfromaBlackweldert-testtestingnon-inferiorityoftheFlair® Endovascular Stent

Graft group to that of PTA.

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Secondary Effectiveness Endpoint Results

Table 21. Summary of Secondary Effectiveness Endpoint Results


PTA (N=132)

Procedural Success Rate 112 (81.2%) 99 (75.0%)

Anatomic Success Rate 112 (81.2%) 99 (75.0%)

Hemodynamic Success Rate 138 (100.0%) 130 (98.5%)

ClinicalSuccessRate 135 (97.8%) 130 (98.5%)

EstimatedNumberofRe-Interventions[1]

12 Month Mean±SD (min, max) 1.9±2.18 (0, 10) 2.4±2.31 (0, 19)

24 Month Mean±SD (min, max) 3.4±3.52 (0, 20) 4.3±3.86 (0, 30)

Post-Intervention Assisted Primary Patency (PAPP)

12Month(95%CI) 49.7% (0.410, 0.584) 56.3% (0.474, 0.653)

24Month(95%CI) 38.4% (0.282, 0.486) 40.6% (0.312, 0.500)

Post-Intervention Secondary Patency (PSP)

12Month(95%CI) 65.3% (0.569, 0.736) 71.0% (0.629, 0.792)

24Month(95%CI) 51.8% (0.410, 0.626) 57.4% (0.481, 0.668)

[1]Fromthemonthlyrateto6months,thenumberofinterventionsto6monthsiscalculated by multiplying the rate by 6. An analogous calculation has been made for the number of interventions to 12 months and 24 months.

Note: Estimates are from a Kaplan-Meier model.

Additional Analysis

Treatment Area Primary Patency (TAPP)

Treatment Area Primary Patency (TAPP) was not one of the endpoints predefined for this post approval study. However, TAPP at 6 months was the primary effectiveness endpoint for the Flair® Endovascular Stent Graft pivotal study that supported PMA approval. The analysis of TAPP at 12 and 24 months for this post approval study is therefore presented here to further elucidate the efficacy results observed at 6 months in the pivotal study. Table 22. Treatment Area Primary Patency (TAPP)



Treatment Area Primary Patency

12Monthrate(95%CI) 47.6% (0.389, 0.564) 24.8% (0.170, 0.325) <0.001*

24Monthrate(95%CI) 26.9% (0.177, 0.360) 13.5% (0.068, 0.202) <0.001*


[1] p-value is from a Cox regression analysis using covariate of treatment group testing superiority of the Flair® Endovascular Stent Graft group to that of PTA.

Figure 8 presents the Kaplan-Meier curves for freedom from loss of treatment area primary patency through 24 months.

Figure 8. Survival Curve for TAPP through Month 24

Patient Death Summary

There were seventy-four (74) deaths among the patients, including 38 patients in the test group and 36 patients in the control group. None of these deaths were attributed to the study device.

CONCLUSIONS DRAWN FROM THE STUDY

The results from this multicenter, prospective, randomized, concur-rently-controlled Post-Approval Study demonstrate the safety and effectiveness of the Flair® Endovascular Stent Graft for the treatment of stenoses at the venous anastomosis of ePTFE or other synthetic arteriovenous (AV) through 12 months and 24 months and confirm the 6 month outcomes from the pivotal study upon which PMA approval was based.

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NOTE• Readallinstructionsforusethoroughly.• Theuseofastiffguidewireisrecommendedforstentgraftplacement.• Prophylacticantibiotictherapyshouldbeprescribedatthephysician‘s

discretion.

CLINICAL USE INFORMATION

PRECAUTION: This device should be used only by physicians who are familiar with the complications, side effects, and hazards commonly associated with dialysis shunt revisions and endovascular procedures and who have successfully completed the appropriate physician training program.

Patient and Device Selection • WARNINGS: Do not use in patients - With uncorrectable coagulation disorders - With septicemia - With known allergy or sensitivity to contrast media which

cannot be adequately pre-medicated - Whose AV Access graft is infected - Whose AV Access grafts have been implanted less than 30 days• WARNING: Do not use the device in patients in which full expansion

of an appropriately sized angioplasty balloon could not be achieved during primary balloon angioplasty.

• PRECAUTION: The safety and effectiveness of the device if placed across an angle that is greater than 90º have not been established.

• PRECAUTION: The safety and effectiveness of the device in patients in which it is required to be deployed across the antcubital fossa have not been established.

• PRECAUTION: In case the placement of two stent grafts (overlap) use the same device diameter in both cases. If a flared device is used to overlap, do not deploy the flared end inside the first stent graft. Ensure a minimum 10 mm overlap of the devices.

• Physicians should have knowledge of radiographic image inter-pretation, device selection and sizing (see page 4, Stent Graft Size Selection)

Materials Required for Device Placement• 0.035”(0.89 mm) guidewire• 9Fintroducersheath• Sterilesyringes• Contrastagent• Salinesolution• Appropriatediagnosticcathetersandaccessories• Appropriate angioplasty balloon (equal diameter to the stent graft

body diameter)

DIRECTIONS FOR USE

Preparation:

1. Access the AV graft at the venous side or at the apex. A 9F vascular introducer sheath is recommended for the implant procedure. (see figure 9)

9

2. Insert a 0.035 inch guidewire into the graft access site. Dilate the stenosis with a balloon catheter that has a rated diameter appropriate for the lesion to be treated. (see figure 10)

22

10

3. Select the Flair® Endovascular Stent Graft length required to tra- verse the stenosis. This will involve selection of an appropriate device diameter and length. Allow the stent graft to be situated beyond the stenosis into at least 10 mm of the non-diseased AV graft, and approximately 10 mm of the stent graft to extend beyond the stenosis into the non-diseased vein.

4. Carefullyremovethedeliverysystemfromitspackagingandinspect for any damage or defects. Do not use if a compromise to the sterile barrier is suspected.

Note: Do not remove the red safety clip until you are ready to deploy the stent graft.

5. Tighten the Tuohy-Borst valve on the Y-adapter (by turning it clockwise). (see figure 11)

11

6. Flush the stent graft lumen with sterile saline using a small volume (e.g., 3-cc) syringe. Attach the syringe to the luer port of the Y- adapter on top of the delivery system and apply positive pressure. Makesurethe2-waystopcockisopen.Continueuntilsalinedripsfrom the distal end of the delivery system. Close the stopcockwhen flushing is complete. Also flush saline through the inner catheter lumen via the luer port at the back of the delivery system. A larger volume syringe may be used. Flush until saline leaks from the tip of the catheter and all air is removed. (see figure 12)

12

Introduction of the Delivery System:

7. Under radiographic guidance, advance the stent graft over the guidewire across the lesion. Use the radiopaque markers to center thestentgraftacrossthelesion.Confirmtheexactpositionoftheradiopaque marker bands. It is recommended that the position of the stent graft ends (A) and (B) be marked on the monitor or that radiopaque skin markers be placed as reference points for stent graft ends. (see figure 13)

A = proximal marker band B = distal radiopaque marker band C = radiopaque marker band, moving backwards during stent

graft release

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13

Note: It is recommended to advance the delivery system past

the lesion and then pull back slightly on the entire

system prior to deployment to attain correct positioning

of the radiopaque markers and to ensure the delivery

catheter is straight.

Stent Graft Deployment:

8. Just prior to stent graft deployment, open the Tuohy-Borst valve,

then remove the red safety clip by pressing down on the top of the

grip surface the thumb, then pulling downward. (see figure 14)

14

Deploy the stent graft by pinning the back hand on the handgrip

and pulling the Y-adapter with the front hand back towards the

handgrip using a slow and steady motion. (see figure 15)

15

Pulling back the Y-adapter directly retracts the outer catheter and

exposes a corresponding portion of the stent graft. (see figure 16)

16

Precaution: Careful attention of the operator is warranted to

mitigate the potential for migration of the stent

graft in the direction of flow during deployment.

After deployment of approximately 15 mm of the

stent graft, wait for the distal end of the stent graft

to fully expand.

Note: Do not hold or kink the outer catheter of the delivery

catheter since it must be free to move during

deployment.

24

9. Full release of the stent graft is achieved when the Tuohy-Borst valve touches the handgrip. (see figure 17)

17

10. After full stent graft deployment, wait for complete device expansion before removing the delivery system over the guidewire. If resistance is felt in passing the introducer sheath, the flexible deployment system should be removed together with the introducer sheath.

11. Retract the delivery system tip by pinning the front hand on the Y- adapter and pulling back with the back hand on the handgrip until the gap between the delivery system tip and the outer catheter is closed. Tighten the Tuohy-Borst valve and remove the delivery system over the guidewire.

12. Visually confirm that the complete system has been removed. (see figure 18)

a. Inner catheterb. Distal tipc. Outer sheathd. Radiopaque marker band on outer sheathe. Distal radiopaque marker band on inner catheterf. Proximal radiopaque marker band on inner catheter

18

13. Dilate the stent graft with a balloon catheter of an inflated diameter equal to the size of the stent graft body diameter.

14. Using standard procedures, verify location and patency of the stent graft.

PATIENT IMPLANT INFORMATION CARDS • APatientIMPLANTInformationCardisprovidedinthebackofthe

IFU for your convenience. • ThePatient IMPLANT InformationCard shouldbe carefully folded

along the perforations and removed from the IFU after the completion of the procedure.

• The Patient Data, Implant Data, and Hospital Data should be carefully recorded on the card and given to the patient.

• Applyoneofthepeel-offstickersfoundintheIFUtotheindicatedareaonthePatientIMPLANTInformationCard.Thispeel-offstickercontains important information about the patient‘s stent graft implant.

• The patient should carry this cardwith them and provide to anymedical personnel caring for the patient in the future.

Post Procedure Precaution:

The effects of direct cannulation of the Flair® Endovascular Stent Graft have not been determined in a clinical study. Notify the patient that the stent graft should not be directly cannulated and that applying pressure to the implant area should be avoided.

25

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Flair® EndovascularStent Graft

C. R. BARD, INC. EXCLUDES ALL WARRANTIES, WHETHER EXPRESS OR IMPLIED, BY OPERATION OF LAW OR OTHERWISE, RELATING TO THE BARD Flair® ENDOVASCLUAR STENT GRAFT, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTIES OF MERCHANTA- BILITY OR FITNESS FOR A PARTICULAR PURPOSE.IN NO EVENT SHALL C. R. BARD, INC. BE LIABLE FOR ANY INCIDENTAL OR CONSEQUENTIAL LOSS, DAMAGE OR EXPENSE, DIRECTLY OR INDIRECTLY ARISING FROM USE OF THIS SYSTEM. C. R. BARD, INC. NEITHER ASSU- MES NOR AUTHORIZES ANY OTHER PERSON TO ASSU- ME FOR IT ANY OTHER OR ADDITIONAL LIABILITY OR RESPONSIBILITY IN CONNECTION WITH THIS SYSTEM.

Label Issue Date 08/2014In the event 3 years have elapsed between this date and pro-duct use, the user should contact Bard to see if additional product information is available.Telephone Number Inside The US: 1-800-526-4455.

Caution:Federal (U.S.A) law restricts this device to sale by or on the order of a physician.

®

27

MR Conditional

Symbols used on labeling

Keep away from sunlight

Keep dry

Caution, consult accompanying documents

Single use

Do not resterilize

Manufacturer

Date of manufacture

Contents: One sterile stent graft with delivery system.

Use by

Catalogue number

Lot number

Caution: Federal (USA) law restricts this device to sale by or on the order of a physician.

Non-Pyrogenic

Sterilized with ethylene oxide

Copyright©2014C.R.Bard,Inc.All Rights Reserved.

Bard, Flair and Flow for Life are trademarks and/or registeredtrademarksofC.R.Bard,Inc.

Flair® EndovascularStent Graft

Manufactured by:

Bard Peripheral Vascular, Inc.aDivisionofC.R.Bard,Inc.1625 West 3rd Street Tempe, AZ 85281USATEL: 1-480-894-9515 1-800-321-4254FAX: 1-480-966-7062 1-800-440-5376www.bardpv.com

B05659 Rev.3/08-14

Documents

Flair ® Endovascular Stent Graft IFU