BARD LIFESTENT VASCULAR STENT SYSTEM

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION Device Generic Name: Peripheral Stent System Device Trade Name: Bard® LifeStent® Vascular Stent System Device Procode: NIP Applicant's Name and Address: Bard Peripheral Vascular, Inc. 1625 West 3rd Street Tempe, AZ 85281-1740 USA Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P070014/S037 Date of FDA Notice of Approval: May 31, 2016 The original PMA (P070014) was approved on February 13, 2009 and is indicated to improve luminal diameter in the treatment of symptomatic de novo or restenotic lesions up to 160 mm in length in the native superficial femoral artery (SFA) and/or proximal popliteal artery with reference vessel diameters ranging from 4.0 – 6.5 mm. The SSED to support the indication is available on the CDRH website (http://www.accessdata.fda.gov/cdrh_docs/pdf/P070014b.pdf) and is incorporated by reference here. These indications for use were expanded on December 23, 2010 (P070014/S010) to include lesions up to 240 mm in length. The SSED to support the indication is available on the CDRH website (http://www.accessdata.fda.gov/cdrh_docs/pdf/P070014S010B.pdf). The current supplement was submitted to expand the indication for the device to include treatment of lesions in the mid and distal popliteal artery. ## II. INDICATIONS FOR USE The Bard® LifeStent® Vascular Stent System is intended to improve luminal diameter in the treatment of symptomatic de novo or restenotic lesions up to 240 mm in length in the native superficial femoral artery (SFA) and popliteal artery with reference vessel diameters ranging from 4.0 – 6.5 mm. ## III. CONTRAINDICATIONS The LifeStent® Vascular Stent System is contraindicated for use in: - Patients with a known hypersensitivity to nitinol (nickel, titanium), and tantalum. - Patients who cannot receive recommended anti-platelet and/or anti-coagulation P070014/S037: FDA Summary of Safety and Effectiveness Data Page 1 {1} therapy. - Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or stent delivery system. #### **IV. WARNINGS AND PRECAUTIONS** See WARNINGS AND PRECAUTIONS in the LifeStent® Vascular Stent System labeling (Instructions for Use). #### **V. DEVICE DESCRIPTION** The Bard® LifeStent® Vascular Stent System (P070014) is comprised of the LifeStent® Vascular Stent (stents 20 – 80 mm) and the LifeStent® XL Vascular Stent (stents 100 – 170 mm), as well as the Bard® LifeStent® Solo™ Vascular Stent System (stents 20-200 mm; approved via P070014/S022). All devices contain self-expanding, flexible, nitinol stents that expand to a preset diameter upon exposure to body temperature. The stents are equivalent to one another in design with only one difference located at the crown section; the LifeStent® and LifeStent® Solo™ stents contain 6 tantalum radiopaque markers on both the distal and proximal ends of the stent, while the LifeStent® XL stent does not have markers (Figures 1 and 2, respectively). Please see Table 1 for the delivery system summary as well as respective size matrix for the implant. **Figure 1: LifeStent® and LifeStent® Solo™ Stent**  **Figure 2. LifeStent® XL Stent** P070014/S037: FDA Summary of Safety and Effectiveness Data Page 2 {2}  Table 1: LifeStent® Delivery Systems Summary | | System | Stent | Deployment Mechanisms | | --- | --- | --- | --- | | LifeStent® | LifeStent®Available system lengths: 80 and 130 cm | ∅6mm X 20-80mm∅7mm X 20-80mmContains 6 radiopaque tantalum markers on each end | 1.2 Thumbwheel2.2 Rapid Deployment Lever3.2 Rapid Deployment Ring | | LifeStent®XL | LifeStent® XLAvailable system lengths: 80 and 130 cm | ∅6mm X 100-170mm∅7mm X 100-170mmNo radiopaque markers | 1. Thumbwheel2. Rapid Deployment Lever | | LifeStent®SoloTM | LifeStent® SoloTMAvailable system lengths: 100 and 135 cm | ∅6mm X 20-200mm∅7mm X 20-200mmAll stents contain 6 radiopaque tantalum markers on each end | 1. Trigger for slow (micro clicks) and rapid stent deployment (full pumps of the trigger) | P070014/S037: FDA Summary of Safety and Effectiveness Data Page 3 {3} ## **VI. ALTERNATIVE PRACTICES AND PROCEDURES** There are several other alternatives for the correction of peripheral arterial disease. Some of these alternatives include: non-invasive lifestyle changes, drug therapy, drug-coated balloons, and angioplasty. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. ## **VII. MARKETING HISTORY** The LifeStent and LifeStent XL Vascular Stent Systems have been approved in the US since February 13, 2009 with the indication to improve luminal diameter in the treatment of symptomatic de novo or restenotic lesions up to 160 mm in length in the native SFA and proximal popliteal artery with reference vessel diameters ranging from 4.0 – 6.5 mm. These indications for use were expanded on December 23, 2010 (P070014/S010) to include lesions up to 240 mm in length. The LifeStent and LifeStent XL Vascular Stent Systems have been approved for the primary stenting of de-novo or restenotic lesions of the peripheral arteries including the full popliteal artery in the following countries: European Union, Canada, Russia, Ukraine, China, Korea, Taiwan, Thailand, Vietnam, Singapore, Australia, Brazil, Mexico, Columbia, and Uruguay. The LifeStent® Solo™ Vascular Stent System was approved in the US (P070014/S022) on September 16, 2011 with the indication to improve luminal diameter in the treatment of symptomatic de novo or restenotic lesions up to 240 mm in length in the native SFA and proximal popliteal artery with reference vessel diameters ranging from 4.0 – 6.5 mm. LifeStent® Solo™ Vascular Stent System has been available in the following countries: European Union, Canada, Uruguay, Colombia, Brazil, Argentina, Turkey. The LifeStent Vascular Stent Systems are currently being marketed in the locations listed above and have not been withdrawn from marketing for any reason related to its safety or effectiveness. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Potential adverse effects (e.g., complications) that may occur include, but are not limited to, the following: - Allergic/anaphylactoid reaction - Amputation - Aneurysm - Angina/coronary ischemia - Arterial occlusion/thrombus, near the puncture site - Arterial occlusion/thrombus, remote from puncture site - Arterial occlusion/restenosis of the treated vessel - Arteriovenous fistula P070014/S037: FDA Summary of Safety and Effectiveness Data Page 4 {4} - Arrhythmia - Bypass surgery - Death related to procedure - Death unrelated to procedure - Embolization, arterial - Embolization, stent - Fever - Hemorrhage/bleeding requiring a blood transfusion - Hematoma bleed, remote site - Hematoma bleed at needle, device path: nonvascular procedure - Hematoma bleed, puncture site: vascular procedure - Hypotension/hypertension - Incorrect positioning of the stent requiring further stenting or surgery - Intimal injury/dissection - Ischemia/infarction of tissue/organ - Liver failure - Local infection - Malposition (failure to deliver the stent to the intended site) - Open surgical repair - Pain - Pancreatitis - Pulmonary embolism/edema - Pneumothorax - Pseudoaneurysm - Renal failure - Respiratory arrest - Restenosis - Septicemia/bacteremia - Stent fracture - Stent migration - Stroke - Vasospasm - Venous occlusion/thrombosis, remote from puncture site - Venous occlusion/thrombosis, near the puncture site For the specific adverse events that occurred in the clinical studies conducted to support the original indication, please see Section X of the original SSED. #### **IX. SUMMARY OF PRECLINICAL STUDIES** The designs of the Bard® LifeStent® Vascular Stent Systems are not changed from the currently-marketed devices. Therefore, the potential effects of the new intended anatomy formed the basis for the preclinical test strategy. P070014/S037: FDA Summary of Safety and Effectiveness Data Page 5 {5} The pre-clinical data reviewed under P070014 were found to be adequate to support the enhanced indication of treatment in the SFA and full popliteal artery in the current PMA Supplement in the following technical areas: - Pre-clinical animal studies ### A. Laboratory Studies Because the device design has not changed, appropriate non-clinical data were leveraged from P070014 and its supplements to support this supplement. Testing relevant to the new intended anatomy in the distal popliteal artery was performed, as described in Table 2 below. **Table 2: Supporting Non-clinical Tests** | Test | Purpose/Objective | Acceptance Criteria | Results | | --- | --- | --- | --- | | Material Composition | To verify the chemical composition of the nitinol (nickel-titanium) and tantalum of the implant. | Characterization study | Leveraged* | | Shape Memory and Superelasticity | To ensure incoming tubing used in the manufacture of the implant complies with visual, dimensional, and performance specifications. | Characterization Study; Af temperature between 16° - 25° | Leveraged* | | Mechanical Properties | To characterize the implant's raw material mechanical properties (for uniaxial tensile strength and fatigue strength) to support stress/strain and fatigue analyses. | Characterization study | Leveraged* | | Pitting and Crevice Corrosion | To verify the implant's ability to resist corrosion via in vitro testing and ensure that the implant maintains corrosion resistance following implantation. | Breakdown Potential (Eb) > 300mV | Leveraged* | | Fretting Corrosion | | Eb>300mV | Leveraged* | | Galvanic Corrosion. | | Material loss less than 2µm / year | Leveraged* | | Dimensional Verification - Implant | To verify that critical implant dimensions (outer diameter and length) are met post-deployment under simulated physiological conditions. | 6mm size: 6.08 – 6.68mm 7mm size: 7.08 – 7.68mm | Pass | | Percent Surface Area | To characterize the implant's percent free surface area. | 7-20% | Leveraged* | | Foreshortening | To quantify the relationship between length and diameter for the implant from its crimped to deployed form as well as in the freely expanded state. | < =5% | Pass | P070014/S037: FDA Summary of Safety and Effectiveness Data Page 6 {6} | Test | Purpose/Objective | Acceptance Criteria | Results | | --- | --- | --- | --- | | Integrity (post-deployment) | To evaluate the integrity of the implant post deployment. To verify that the implant shows no defects that would render it unsuitable for the intended use. | No cracks, bends, kinks or fractures at 20x magnification | Pass | | Radial Stiffness and Radial Strength | To verify that the implant has sufficient Radial stiffness and radial strength to resist collapse under short-term or long-term external loads. | Radial Resistive Force (RRF) >= 0.07N/mm | Leveraged* | | Radial Outward Force | To characterize force exerted by the implant as a function of implant diameter. | Chronic Outward Force (COF)<=0.12N/mm | Leveraged* | | Stress / Strain Analysis | To characterize the stress / strain behaviors of the implant when subjected to worst-case physiological loads and ensure structural integrity of the stent for the intended use. | Characterization study to determine worst case loading condition and stent configuration (size and oversizing) for use in accelerated durability tests | Pass | | Fatigue Analysis | | Stent durability needs to be suitable for the intended use | Pass | | Accelerated Durability / Non Radial Fatigue | To evaluate the durability (maintenance of structural integrity) of the implant under worst case non radial fatigue conditions simulating 10 years of use. | Stent integrity must be maintained after 10.6 Mill. cycles | Pass | | MRI Safety and Compatibility | To evaluate MRI safety and compatibility. | The presence of the stent must no pose an additional unacceptable risk to patients when subjected to 1.5T and 3.0T magnetic fields | Leveraged* | | Radiopacity | To evaluate the radiopacity of the implant with radiographic and angiographic imaging. | Stent visualization needs to be rated clinical acceptable | Leveraged* | | Crush Resistance | To evaluate the ability of the implant to resist permanent deformation and demonstrate the stent's resistance to localized compressive loads. | Mean stent diameter not decrease more than 5% | Leveraged* | | Kink Resistance | To evaluate the implant's flexibility in its deployed configuration. | No luminal compromise | Leveraged* | P070014/S037: FDA Summary of Safety and Effectiveness Data Page 7 {7} | Test | Purpose/Objective | Acceptance Criteria | Results | | --- | --- | --- | --- | | Dimensional Verification – Delivery System | To verify that the delivery system meets it dimensional pre- and post-deployment. | Max outer diameter LifeStent DS: 0.0795' Max outer diameter LifeStent XL DS: 0.0825' | Leveraged* | | Delivery, Deployment and Retraction | To characterize the system with respect to flushability / leakproofness and luer lock compatibility; trackability, pushability, torqueability, premature deployment; deployment force and accuracy; stent conformability and ability to withdraw. | Various acceptance criteria for delivery, deployment and retraction, Placement accuracy <= 2.5mm | Pass | | Bond Joint Strength | To determine the bond strength of the joints and/or fixed connections of the delivery system and verify that the strength of the bond joints are adequate for the intended use. | Various acceptance criteria for different bonding joints | Leveraged* | | Tip Pull Test | To determine the bond strength of the tip joint of the delivery system and verify that the strength of the bond joint is adequate for the intended use. | Tensile strength of tip to inner catheter joint > 1.12lbf | Leveraged* | | Flexibility / Kinkability | To ensure that the system does not kink during delivery, deployment or withdrawal to and from the target deployment site under anticipated use conditions. | Delivery systems do not show any relevant kinks during visual inspection post deployment | Leveraged* | | Torque Strength | To determine the torsional bond strength between relevant components of the delivery system and to verify the strength of the bond joints are adequate for the intended use. | No breaks or failures | Leveraged* | | Stability of Product for Labeled Shelf Life | To ensure that the product performance characteristics are maintained for the stated shelf life of the product. | | Leveraged* | | Biocompatibility | To ensure that product materials are biologically safe and biocompatible | | Leveraged* | | *Results indicated were performed as part of the original PMA and results support the popliteal indication. | | | | ### **B. Animal Studies** No new animal testing was conducted to support the new indication. Information from animal study data from the previously-approved systems was appropriately leveraged based on the device and anatomical similarities. ### **C. Additional Studies** The Bard® LifeStent® Vascular Stent System has a labeled shelf-life of 2 years. Device packaging materials and the sterilization method are the same. Therefore, sterilization P070014/S037: FDA Summary of Safety and Effectiveness Data Page 8 {8} and packaging testing are leveraged from the previously approved systems. No new testing was performed for this supplement. # X. SUMMARY OF PRIMARY CLINICAL STUDY A physician sponsored study, the ETAP trial, was a prospective, randomized, multi-center study designed to compare the LifeStent® Vascular Stent Systems to percutaneous transluminal angioplasty (PTA) in the treatment of patients with stenosis and occlusion of the popliteal artery¹. In total, 246 subjects were randomized between the two study arms at nine European centers, with 119 subjects treated with the LifeStent® Vascular Stent and 127 with PTA. The primary endpoint was the restenosis rate at 12 months. Subjects were followed for 24 months. # A. Study Design The ETAP physician-sponsored study was conducted at nine European centers as a prospective, randomized, controlled study to investigate the use of LifeStent® Vascular Stent System in patients with stenosis and occlusion of the SFA and popliteal artery (including the P2 and P3 segments) in comparison to PTA alone. A total of 246 patients were recruited and randomized into the two treatment groups, PTA or stent, with 119 patients in the stent group and 127 patients in the PTA group. Eligible patients had de novo occlusion of the popliteal artery or de novo stenosis of the popliteal artery with >70% diameter reduction. At least one artery of the lower leg had to be open (stenosis grade ≤ 60%) along its entire length with no significant inflow stenosis. Patients also had to have a clinical Fontaine stage IIa-IV or Rutherford category 2 to 6. For patients randomized to the PTA group, a balloon angioplasty was performed, representing standard clinical care of these lesions. For patients randomized to the stent group, nitinol stent placement was performed after successful crossing of the guidewire with the goal of not pre-dilating the lesion before stent placement. For the PTA group, if there was a persistent stenosis of >30% after repeated and prolonged PTA or a flow-limiting dissection, a study stent was to be placed at the target lesion. All patients were given 100 mg of aspirin daily through the duration of the study. If the patient was not taking aspirin before the procedure, a 500-mg loading dose was administered before the intervention. In addition, a loading dose of clopidogrel (1×300 mg PO) was administered on the day of the intervention, followed by a daily dose of 75 mg for a minimum of 4 weeks. Patients were followed for 24 months with scheduled visits after 6, 12, and 24 months. Of the 246 patients recruited in the study, 152 patients received a LifeStent® Vascular Stent System while 93 patients received PTA alone. The difference between assigned and treated patients is related to those PTA patients who crossed over into the stent group. P070014/S037: FDA Summary of Safety and Effectiveness Data Page 9 {9} The primary study endpoint was 1-year primary patency, defined as freedom from target-lesion restenosis (luminal narrowing of ≥50%) as detected by duplex ultrasound. Secondary end points included target-lesion revascularization (TLR) rate and changes in Rutherford-Becker class. The study was conducted to evaluate stenting versus PTA in the SFA and popliteal segments. Because the Lifestent® Vascular System was previously FDA-approved for treatment of the SFA and proximal popliteal segment (P1), an additional post-hoc analysis was conducted to compare outcomes for the P1 segment and P2/P3 segments. ### B. Accountability of PMA Cohort Subject accountability is described below in Table 3. At the 12-month interval, the overall compliance rate was greater than 91% for all groups. For patients treated with stents in the P1 segment, the overall compliance rate was 100% of available subjects completing the visit. For the P2/P3 group, the overall compliance rate was 99% of available subjects at the 12-month follow-up visit. The available 24-month data for both groups are provided below. However, German informed consent laws did not allow identification of specific patients and compliance rates were not available. Table 3: Patient Accountability P1 & P2/P3 Subsets ITT Populations | | P1 | | P2/P3 | | | --- | --- | --- | --- | --- | | Study Status | Treatment Groups | | | | | | PTA | Stent | PTA | Stent | | Randomized Enrollment | 37 | 35 | 90 | 84 | | LTF all follow-ups* | 4 | 4 | 17 | 13 | | 12 Month – Available/Completed Visit | 30/33 (91%) | 31/31 (100%) | 68/73 (93%) | 70/71 (99%) | | Lost to Follow-Up/Missing | 1 | 10 | 6 | 10 | | 24 Month – Available ** | 32 | 28 | 67 | 52 | | Death (total) | 2 | 4 | 4 | 4 | * Documented LTF, deaths and withdrawn consent. ** P1 and P2/P3 subset compliance was not stratified at the 24 month interval due to the fact that the deaths verified from Protocol Version 1.0 could not be confirmed to specific patient ID numbers. ### C. Study Population Demographics and Baseline Parameters The demographics of the study population are shown in Table 4, and the lesion characteristics are shown in Table 5. Note that these data are for the entire study cohort, including treatment of SFA and P1 segment lesions. Table 4. Study Demographics | Characteristic (ITT population) | PTA (N=127) | Stent (N=119) | Total (N=246) | | --- | --- | --- | --- | P070014/S037: FDA Summary of Safety and Effectiveness Data Page 10 {10} | Characteristic (ITT population) | PTA (N=127) | Stent (N=119) | Total (N=246) | | --- | --- | --- | --- | | Age (years) Median | 73 | 72 | 72 | | Gender N (%) | 45 (35.4) | 43 (36.1) | 88 (35.8) | | Female | | | | | Rutherford Category N (%) | | | | | Category 1 | 3 (2.4) | 4 (3.4) | 7 (2.8) | | Category 2 | 12 (9.4) | 24 (20.2) | 36 (14.8) | | Category 3 | 76 (59.8) | 68 (57.1) | 144 (58.5) | | Category 4 | 8 (6.3) | 4 (3.4) | 12 (4.9) | | Category 5 | 22 (17.3) | 16 (13.4) | 38 (15.4) | | Category 6 | - | 1 (0.8) | 1 (0.4) | | Missing | 6 (4.7) | 2 (1.7) | 8 (3.3) | | Hypertension (%) | 112 (88.2) | 98 (82.4) | 210 (85.4) | | Hypercholesterolemia (%) | 104 (81.9) | 90 (75.6) | 194 (78.9) | | Smoking (%) | 29 (23) | 26 (21.8) | 55 (22.4) | **Table 5. Lesion Characteristics** | Variable (ITT Population) | PTA (N=127) | Stent (N=119) | | --- | --- | --- | | Mean Lesion Length (mm) | 43.2 | 41.3 | | (STD) | (28.1) | (31.3) | | Stenosis (%) | 92.5 | 92.9 | | (STD) | (7.9) | (7.2) | | Lesion Location, (% patients) | | | | Popliteal I | 37 (29.1) | 35 (29.4) | | Popliteal II | 54 (42.5) | 48 (40.3) | | Popliteal III | 6 (4.7) | 7 (5.9) | | Popliteal I + II | 23 (18.1) | 20 (16.8) | | Popliteal II + III | 6 (4.7) | 7 (5.9) | | Popliteal I + II + III | 1 (0.8) | 2 (1.7) | | Lesion Calcification, (%, patients) | | | | Missing | 35 (27.6) | 32 (26.9) | | Unable to Determine | 1 (0.8) | - | | None | 14 (11.0) | 8 (6.7) | | Little | 21 (16.5) | 33 (27.7) | | Moderate | 11 (8.7) | 14 (11.8) | | Severe | 45 (35.4) | 32 (26.9) | #### **D. Safety and Effectiveness Results** P070014/S037: FDA Summary of Safety and Effectiveness Data Page 11 {11} In order to highlight the results specific to the popliteal segments behind the knee (i.e., P2/P3 segments) which represent the most clinically challenging anatomy treated in the study and the popliteal segments previously not included in the approved indications for use for this device, results for a post-hoc sub-analysis were primarily considered in order to support the marketing application. # 1. Effectiveness Results As shown in Table 6, patients in the stent group had a lower restenosis rate than patients in the PTA group, when the crossover procedure was considered to be a TLR and by definition a restenosis. Table 6. Restenosis 12 and 24 Months – PVR > 2.4 | | P1 | | P2/P3 | | | --- | --- | --- | --- | --- | | | Number (%) pts | | Number (%) pts | | | | PTA (N=37) | Stent (N=35) | PTA (N=90) | Stent (N=84) | | 12 months | 17 (53.1%) | 12 (40.0%) | 42 (56.0%) | 19 (29.2%) | | Evaluable* | 32 | 30 | 75 | 65 | | 24 months | 15 (57.7%) | 10 (43.5%) | 42 (72.4%) | 16 (32.0%) | | Evaluable * | 26 | 23 | 58 | 50 | This data collection was using ultrasound PVR>2.4 *evaluable accounts for missing data Figures 3 and 4 demonstrate the Kaplan-Meier restenosis results for the P1 and P2/3 segments, respectively. Provisional stent placement with a LifeStent® Vascular Stent System was observed during this study in 27% of the randomized PTA population. Figure 3. Freedom from Restenosis for Popliteal Segment 1 P070014/S037: FDA Summary of Safety and Effectiveness Data Page 12 {12}  | Time | Control PTA | | | | Test Stent | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Survival %[95% CI] | Subjects with Event | Censored Subjects | Subjects at Risk | Survival %[95% CI] | Subjects with Event | Censored Subjects | Subjects at Risk | | 180 days | 72.8% [65.4, 80.1] | 10 | 2 | 25 | 93.8% [89.5, 98.0] | 2 | 3 | 30 | | 365 days | 43.7% [35.3, 52.1] | 20 | 4 | 13 | 68.8% [60.6, 76.9] | 10 | 4 | 21 | | 730 days | 43.7% [45.3, 61.3] | 20 | 11 | 6 | 51.4% [42.3, 60.5] | 15 | 11 | 9 | P070014/S037: FDA Summary of Safety and Effectiveness Data Page 13 {13} **Figure 4. Freedom from Restenosis for Popliteal P2/P3**  | Time | Control PTA | | | | Test Stent | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Survival %[95% CI] | Subjects with Event | Censored Subjects | Subjects at Risk | Survival %[95% CI] | Subjects with Event | Censored Subjects | Subjects at Risk | | 180 days | 70.8% [66.0, 75.6] | 26 | 6 | 58 | 94.7% [92.1, 97.3] | 4 | 9 | 71 | | 365 days | 46.5% [40.9, 52.0] | 45 | 17 | 28 | 75.8% [70.8, 80.7] | 18 | 19 | 47 | | 730 days | 39.8% [33.8, 45.8] | 48 | 33 | 9 | 67.0% [61.3, 72.8] | 23 | 39 | 22 | Analysis of secondary endpoints suggest a beneficial clinical trend in favor of stent placement. Preoperative Rutherford scores in the high risk population (Rutherford category 3 or higher) for both the PTA group and stent group improved post-operatively at both the 12- and 24-month intervals. One- and two-year freedom from TLR trended higher in the stented group than the PTA group for treatment in the P2/P3 segment. However, conclusions regarding significance of these individual endpoints may not be made. ## 2. Safety Results A separate prospective safety hypothesis was not included in the study. Death, major amputation and minor amputation, TLR (including need for surgical revascularization), and myocardial infarction were defined as major adverse events and they were cumulatively collected for 370 days after index procedure. All clinical P070014/S037: FDA Summary of Safety and Effectiveness Data Page 14 {14} endpoints and major adverse events were adjudicated by an independent clinical events committee. As described in Table 7, 13 patients had died by Month 24, 4 patients who were treated with PTA and 9 patients who received a stent. The Clinical Events Committee determined that none of the adverse events causing death were related to LifeStent® Stent or procedure. No concerning trends were noted regarding overall safety when the LifeStent® Vascular Stent System was compared to PTA for multiple safety endpoints. **Table 7. Safety Events** | | P1 | | P2/P3 | | | --- | --- | --- | --- | --- | | | Number (%) pts | | Number (%) pts | | | | PTA (n=37) | Stent (n=35) | PTA (n=90) | Stent (n=84) | | **Severe Cardiovascular Events*** | | | | | | 12 month Evaluable Subjects^ | 8 (23.5%) n=34 | 8 (23.5%) n=34 | 22 (28.2%) n=78 | 19 (26.0%) n=73 | | 24 month Evaluable Subjects^ | 9 (33.3%) n=27 | 9 (31.0%) n=29 | 24 (41.4%) n=58 | 22 (35.5%) n=62 | | **Adverse Events**** | | | | | | 12 month Evaluable Subjects^ | 25 (69.4%) n=36 | 18 (52.9%) n=34 | 46 (56.8%) n=81 | 41 (54.7%) n=75 | | 24 month Evaluable Subjects^ | 27 (81.8%) n=33 | 23 (76.7%) n=30 | 53 (75.7%) n=70 | 43 (64.2%) n=67 | | **Death***** | | | | | | 12 month Evaluable Subjects^ | 1 (2.9%) 34 | 1 (3.1%) 32 | 1 (1.4%) 74 | 2 (2.7%) 74 | | 24 month Evaluable Subjects^ | 2 (7.4%) 27 | 3 (11.5%) 26 | 4 (8.0%) 50 | 4 (7.1%) 56 | ### 3. Stent Fracture Analysis The stent fracture rate was assessed for patients who received stent treatment (TR set, N=152). At Month 12, valid x-ray data were available for 60 patients with 67 stents (53 patients with one stent and 7 patients with two stents). Stent fracture was identified in four patients. Of the seven patients with two stents, none had a stent fracture in both stents. One patient had occlusions in the treated limb following a stent fracture. The reported fracture rate was 5.4% at 12-months and 11.1% at 24-months for P2/P3 segment treatment. The number of available x-rays was 37 and 45 x-rays at the 12-month and 24-month time-point respectively (see Table 8 below). Fractures are counted once, at the first time the fracture was reported. P070014/S037: FDA Summary of Safety and Effectiveness Data Page 15 {15} During the ETAP study, patients in the P2/P3 group experienced three Type I, one Type II, one Type III and two Type IV fractures, while, the P1 group had one Type III and one Type II fracture. No correlation could be found between the incidence of stent fractures and either restenosis or TLR. **Table 8. X-ray Reported Stent Fractures** | | X-ray(s) Reviewed | | Stent Fractures | | | --- | --- | --- | --- | --- | | | P1 (N=43) | P2/P3 | P1 | P2/P3 | | 12-month | 23 | 37 | 2 (8.6%) | 2 (5.4%) | | 24-month | 25 | 45 | 0 | 5 (11.1%) | *Fractures were recorded the first time they were reported. ### **E. Financial Disclosure** The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires applicants who submit a marketing application to include certain information concerning the compensation to, and financial interests and arrangement of, any clinical investigator conducting clinical studies covered by the regulation. The ETAP physician-sponsored study was conducted at nine European centers as a prospective, randomized, controlled study to investigate the use of LifeStent® Vascular Stent System in patients with stenosis and occlusion of the popliteal artery in comparison to PTA alone. There are no disclosable financial interests/arrangements as defined in sections 54.2(a), (b), (c), and (f). The information provided does not raise any questions about the reliability of the data. ## **XI. SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION** Please refer to the previous Summaries of Safety and Effectiveness Data (P070014 and P070014/S010) for the clinical data that supported the originally and subsequently approved indications for the LifeStent® Vascular Stent System (P070014). ## **XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES** ### **A. Safety and Effectiveness Conclusions** Non-clinical and clinical testing support the expansion of the indications to the entire popliteal artery. The in vitro engineering testing conducted on the stent demonstrated that the performance characteristics continue to meet product specifications. Results from the post-hoc analysis from the ETAP physician-sponsor study demonstrate that the device is acceptable for clinical use. The primary study endpoint was 1-year primary patency, defined as freedom from target-lesion restenosis (luminal narrowing of $\geq 50\%$) as detected by duplex ultrasound. Specifically in the P2/P3 segment of the popliteal artery, stenting resulted in a lower restenosis rate than PTA (29.2% compared to 56.0%), when the crossover procedure was considered to be a TLR and by definition a restenosis. Although a separate prospective safety hypothesis was not P070014/S037: FDA Summary of Safety and Effectiveness Data Page 16 {16} included, major adverse events defined as death, major amputation and minor amputation, TLR (including need for surgical revascularization), and myocardial infarction were similar between the two groups with no major adverse events attributed to the device or procedure. The reported stent fracture rate was 5.4% at 12-months and 11.1% at 24-months for P2/P3. ### **B. Benefit-Risk Conclusion** The probable benefits of the LifeStent® Vascular Stent System are based on the data collected in the clinical study conducted to support PMA approval, as described above. The results of the ETAP study show positive clinical outcomes in terms of the primary and secondary endpoints and outweigh risks when used as intended according to the Instructions for Use. The clinical study results demonstrate that the LifeStent® Vascular Stent System can be safely implanted in the treatment of the P2/P3 segment of the popliteal artery and can provide an effective treatment with acceptable freedom from reintervention rates and fracture. #### **1. Patient Perspectives** This submission did not include specific information on patient perspectives for this device. ### **C. Overall Conclusions** Based on the provided evidence, the data supports the conclusion that the probable benefits of implanting the LifeStent® Vascular Stent System in the distal popliteal artery outweigh the probable risks when used as indicated in accordance with the labeling and Instructions for Use (IFU). ## **XIII. CDRH DECISION** CDRH issued an approval order on May 31, 2016. The final conditions of approval cited in the approval order are described below. The applicant has agreed to actively participate in the Society for Vascular Surgery Patient Safety Organization governed Vascular Quality Initiative (VQI) Peripheral Vascular Intervention (PVI) Registry and undertake such activities to ensure that surveillance occurs for the Bard LifeStent Vascular Stent System. All patients in the PVI Registry that receive the device to treat symptomatic de novo or restenotic lesions in the popliteal artery (i.e. P2/P3 segments), as specified in the indications for use, should be included in this surveillance effort, with at least 74 patients being from the United States. The surveillance should monitor through two years freedom from major adverse events, freedom from target lesion revascularization (TLR), target vessel revascularization (TVR), acute lesion success, acute procedure success, primary patency, primary assisted patency, secondary patency, sustained clinical success, sustained hemodynamic success, limb ischemia assessed by Rutherford classification, ankle brachial index and stent fracture assessed at revascularization. P070014/S037: FDA Summary of Safety and Effectiveness Data Page 17 {17} The applicant’s manufacturing facilities has/have been inspected and found to be in compliance with the device Quality System (QS) regulation (21 CFR 820). #### **XIV. APPROVAL SPECIFICATIONS** Directions for use: See device labeling. Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling. Post-approval Requirements and Restrictions: See approval order. #### **XV. REFERENCES** 1. Rastan A, Krankenberg H, Baumgartner I, et al. Stent placement vs. balloon angioplasty for popliteal artery treatment: Two-year results of a prospective, multicenter, randomized trial. J Endovasc Ther. 2015; 22:22-27 P070014/S037: FDA Summary of Safety and Effectiveness Data Page 18