← Product Code QAN · P200026 # Abre Venous Self-expanding Stent System (P200026) _Medtronic Vascular, Inc. · QAN · Oct 21, 2020 · Cardiovascular · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P200026 ## Device Facts - **Applicant:** Medtronic Vascular, Inc. - **Product Code:** QAN - **Decision Date:** Oct 21, 2020 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Cardiovascular - **Attributes:** Therapeutic ## Indications for Use The Abre Venous Self-expanding Stent System is intended for use in the iliofemoral veins for the treatment of symptomatic venous outflow obstruction. ## Device Story The Abre Venous Self-expanding Stent System is a nitinol, laser-cut, open-lattice stent with integral radiopaque markers, delivered via a 9 Fr, 0.035" guidewire-compatible, triaxial over-the-wire catheter. Used in the iliofemoral veins, the system is operated by physicians under fluoroscopic/IVUS guidance. After vessel dilation, the delivery system is tracked to the lesion; a thumbwheel-actuated mechanism deploys the self-expanding stent, which conforms to the vessel wall to restore patency. The device is intended to treat symptomatic venous outflow obstruction, potentially improving patient quality of life and reducing venous disease symptoms. ## Clinical Evidence Prospective, non-randomized, single-arm, multicenter study (ABRE) of 200 subjects. Primary safety endpoint (30-day composite MAE rate) was 2.0% (95% CI: 0.5%, 5.0%), meeting the 12.5% performance goal (p<0.0001). Primary effectiveness endpoint (12-month primary patency) was 88.0% (95% CI: 82.5%, 92.4%), exceeding the 75% performance goal (p<0.0001). Secondary endpoints included device success (100%), lesion success (100%), and improvements in quality of life (VEINES-QoL, EQ-5D) and functional scores (Villalta, VCSS). ## Technological Characteristics Stent material: Nickel-titanium alloy (nitinol) per ASTM F2063. Design: Laser-machined open lattice with integral radiopaque markers. Delivery system: 9 Fr, triaxial, over-the-wire, thumbwheel-actuated. Sterilization: Ethylene oxide (EO). MRI compatibility: MR Conditional at 1.5T and 3.0T. ## Regulatory Identification A metal scaffold placed via a delivery catheter in the iliac vein to maintain the lumen ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Stent, Iliac Vein Device Trade Name: Abre Venous Self-expanding Stent System Device Procode: QAN Applicant’s Name and Address: Medtronic Vascular, Inc. 3033 Campus Drive Plymouth, Minnesota 55441 Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P200026 Date of FDA Notice of Approval: October 21, 2020 II. INDICATIONS FOR USE The Abre Venous Self-expanding Stent System is intended for use in the iliofemoral veins for the treatment of symptomatic venous outflow obstruction. III. CONTRAINDICATIONS The Abre Venous Self-expanding Stent System is contraindicated for use in: - Patients with known hypersensitivity to nickel titanium (nitinol). - Patients who are judged to have a lesion that prevents complete inflation of a balloon dilatation catheter or proper placement of the stent or the stent delivery system. - Patients in whom anticoagulant or antiplatelet therapy is contraindicated. IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Abre Venous Self-expanding Stent System labeling (Instructions for Use). V. DEVICE DESCRIPTION The Abre Venous Self-expanding Stent System (Abre stent) consists of a stent and stent delivery system designed specifically for implantation in the peripheral venous system. The system consists of a flexible self-expanding stent made of a nickel-titanium alloy (nitinol) provided in multiple lengths and diameters and an over-the-wire stent delivery PMA P200026: FDA Summary of Safety and Effectiveness Data 1 of 42 {1} system. The Abre stent (Figure 1) is laser machined from a continuous seamless piece of nitinol tubing into an open lattice design. The stent includes three integral nitinol markers at each end to enhance visualization of the stent ends both before and after deployment. ![img-0.jpeg](img-0.jpeg) Figure 1. Abre Stent The Abre stent matrix consists of stent diameters ranging from $10 - 20\mathrm{mm}$ and stent lengths ranging from $40 - 150\mathrm{mm}$ . The Abre Venous Self-expanding Stent System size matrix is provided in Table 1. Table 1. Abre Stent Diameters and Lengths | | Stent Length (mm) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | 40 | 60 | 80 | 100 | 120 | 150 | | Stent Diameter (mm) | 10 | x | x | x | x | x | x | | | 12 | | x | x | x | x | x | | | 14 | | x | x | x | x | x | | | 16 | | x | x | x | x | x | | | 18 | | x | x | x | x | x | | | 20 | | x | x | x | x | x | The Abre delivery system (Figure 2) is an over-the-wire (OTW), 9 Fr, 0.035" guidewire compatible, delivery system for deploying the Abre stent. The delivery system is a single configuration used for deployment of all stent sizes. The Abre delivery system consists of a single use, disposable triaxial shaft catheter with a handle containing a thumbwheel-actuated deployment mechanism, providing control and accuracy during stent placement. A locking pin prevents the stent from being deployed prior to use and must be removed to actuate the thumbwheel. A single luer port is located on the proximal end of the deployment handle to allow for saline to be injected to flush air from the system. ![img-1.jpeg](img-1.jpeg) Figure 2. Abre Delivery System PMA P200026: FDA Summary of Safety and Effectiveness Data {2} Upon gaining access to the patient vasculature with an introducer sheath and guidewire, the target vessel is dilated with an appropriately sized balloon per the Abre instructions for use (IFU). Next, the Abre delivery system is introduced over the guidewire through the hemostatic valve and introducer sheath. The Abre delivery system is advanced through the vasculature until the leading edge of the stent extends beyond the target lesion. The Abre stent is then deployed by removing the lock pin from the delivery system handle and rotating the thumbwheel until the stent is fully deployed. Upon release of the stent at the target lesion, the stent expands and conforms to the vessel wall. ## VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several alternatives used in the treatment of symptomatic iliofemoral venous outflow obstruction. Non-interventional management consists of compression therapy, elevation of the extremity, and anticoagulation. In the setting of acute deep vein thrombosis (DVT), active thrombus removal techniques such as pharmacologic thrombolysis and percutaneous mechanical thrombectomy in combination may be employed. Post-thrombotic and non-thrombotic iliofemoral outflow obstruction, or underlying obstruction after acute thrombus removal in the setting of acute DVT, may be treated with venous angioplasty and stenting to re-establish venous patency with another approved stent. Open surgical treatments are also available, including endophlebectomy or bypass. 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 Abre Venous Self-expanding Stent System has been commercially available outside the US since April 2017. It was first marketed in the European Union (EU) and has been commercialized in Argentina, Australia, Colombia, Costa Rica, Ecuador, Guatemala, Honduras, India, Israel, New Zealand, Peru, Russia, Saudi Arabia, Singapore, Turkey, Ukraine, and Vietnam. The Abre Venous Self-expanding Stent System has never been withdrawn from any market as a result of risk of serious adverse health consequences or for any reason related to safety and effectiveness. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device: - Access failure - Access site infection - Allergic reaction to contrast medium or procedure medications PMA P200026: FDA Summary of Safety and Effectiveness Data {3} - Allergic reaction to nitinol or other device materials - Aneurysm - Arteriovenous (AV) fistula - Bleeding - Bruising - Death - Device breakage - Device maldeployment - Edema - Embolization - Fever - Hematoma - Hypertension - Hypotension, nausea, or other vasovagal response - Infection - Myocardial infarction, arrhythmia, or other cardiovascular insufficiency - Open surgical repair - Pain - Pseudoaneurysm - Renal insufficiency or renal failure (new or worsening) - Respiratory distress or pulmonary embolism - Sepsis - Stent fracture - Stent malapposition - Stent malposition - Stent migration - Stroke, paradoxical embolism, transient ischemic attack, or intracerebral hemorrhage - Tissue necrosis - Venous occlusion, restenosis, or thrombosis, within or outside of stented segment - Vessel damage, including intimal injury, dissection, perforation, or rupture For the specific adverse events that occurred in the clinical study, see Section X below. PMA P200026: FDA Summary of Safety and Effectiveness Data 4 of 42 {4} IX. SUMMARY OF NON-CLINICAL STUDIES A series of non-clinical laboratory and animal studies related to the product were performed to evaluate the device. A. Biocompatibility Studies Biocompatibility testing was performed in accordance with ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” and FDA guidance document “Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems” to demonstrate that the components of the Abre Stent and Abre Delivery System are biocompatible. Test samples were manufactured in accordance with standard operating procedures, subjected to two cycles of ethylene oxide sterilization, and are representative of finished product. The stent and delivery system were categorized per ISO 10993-1 based on the intended patient contact and duration. The stent is permanently implanted in the patient’s vasculature and therefore has permanent (>30 days) circulating blood contact. The delivery system catheter, which is not implanted, is categorized as external communicating with limited (<24-hour) circulating blood contact duration. Based on the results of chemical characterization testing and toxicological risk assessments of the stent and the delivery system, subacute/subchronic and chronic toxicity, genotoxicity and carcinogenicity testing were not conducted on the stent and genotoxicity testing was not conducted on the delivery system. The endpoint of thrombogenicity for the stent and the delivery system was assessed in the GLP safety study, as outlined in Section F. In addition to the implantation assessments per ISO 10993-6, the implantation endpoint of the stent was also assessed in the GLP safety study, as outlined in Section F. The tests summarized in Table 2, which passed requirements, were conducted in support of the Abre Stent and the Abre Delivery System, as indicated. PMA P200026: FDA Summary of Safety and Effectiveness Data 5 of 42 {5} Table 2. Summary of Biocompatibility Evaluation for the Abre Venous Self-expanding Stent System | Test | Test Description/ Applicable Standard | Stent | Delivery System | Results | | --- | --- | --- | --- | --- | | Cytotoxicity | L929 MEM Elution ISO 10993-5:2009, Tests for in vitro cytotoxicity | X | X | Non-cytotoxic | | Sensitization | Guinea Pig Maximization ISO 10993-10:2010, Tests for irritation and sensitization | X | X | Non-sensitizing | | Irritation or Intracutaneous Reactivity | Intracutaneous Reactivity ISO 10993-10:2010, Tests for irritation and sensitization | X | X | Non-irritant | | Systemic Toxicity (Acute) | Acute Systemic Toxicity ISO 10993-11:2006, Tests for systemic toxicity | X | X | Non-toxic | | Material Mediated Pyrogenicity | Material Mediated Pyrogenicity ISO 10993-11:2006, Tests for systemic toxicity | X | X | Non-pyrogenic | | Implantation | Intramuscular Implantation ISO 10993-6:2007, Tests for local effects after implantation | X | N/A | Non-irritant | | Hemocompatibility | Hemolysis Direct and Indirect Contact ASTM F756 | X | X | Non-hemolytic | | | Complement Activation (C3a and SC5b-9) ISO 10993-4: 2002, Selection of tests for interactions with blood, as amended 2006 | X | X | Non-activator of the complement system | | | Thrombogenicity (In Vivo) ISO 10993-4: 2002, Selection of tests for interactions with blood, as amended 2006 | N/A | X | Acceptable thrombogenic performance in the presence of anticoagulation | | Chemical Characterization by NVR, LC-MS, GC-MS, and ICP-MS and Toxicological Assessment | ISO 10993-17: 2002, Establishing allowable limits for leachable substances ISO 10993-18: 2005, Chemical Characterization of materials | X | X | Overall assessment demonstrated that the extractables/leachables are not a concern for subacute/subchronic/ chronic systemic toxicity, genotoxicity, or carcinogenicity. | PMA P200026: FDA Summary of Safety and Effectiveness Data {6} B. Laboratory Studies In vitro bench testing was conducted as part of the design verification and validation to support the safety and effectiveness of the Abre Venous Self-expanding Stent System. The testing and results summarized in Table 3 are reflective of requirements per FDA and internationally-recognized standards. Table 3 includes both non-aged (T=0) and 3-year accelerated aging (indicated by “*”) testing. Table 3. Summary of In Vitro Bench Testing | Test | Test Purpose | Acceptance Criteria | | Results | | --- | --- | --- | --- | --- | | Stent Testing | | | | | | Raw Material Composition | To evaluate the stent material composition | Material composition must comply with ASTM F2063-12 and ASTM F2063-05 | | Stent material conforms to material standards. | | Austenite Finish (A_{f}) Temperature Testing | To measure the temperature at which a compacted stent achieves full self-expansion (A_{f} Temperature) | The stent shall have an active Austenite finish temperature in the range of 14-24 degrees Celsius. | | PASS | | Kink Resistance | To assess stent kinking in vessels with high curvature. | The stent shall bend to a radius ≤1.0in without kinking. | | PASS | | Stent Integrity* | To evaluate the ability of stent to achieve full self-expansion post deployment and resist delivery-related damage. | Following deployment, the unconstrained stent shall expand to nominal inner diameter and length, and also be free of visible defects related to delivery. | | PASS | | Stent Visibility /Radiopacity | To evaluate radiopacity of stent for visibility during and after device delivery. | The stent marker shall provide a minimum radiopacity of 52% and a minimum cross-sectional viewing area of 0.596mm². | | PASS | | Flexibility | To evaluate stent flexibility by measuring its resistance to bending under a three-point bend loading mode. | The slope of the bending force-displacement curve using a three-point bend fixture must be less than: | | PASS | | | | Stent Diameter (mm) | Slope Maximum (N/mm) | | | | | 10 | 0.057 | | | | | 12 | 0.108 | | | | | 14 | 0.174 | | | | | 16 | 0.171 | | | | | 18 | 0.201 | | | | | 20 | 0.167 | | | Stent Recovered Inside Diameter (Dimensional Verification) | To determine whether the stent expands to the correct diameter following deployment. | The unconstrained stent diameter after deployment must be ±4% from the labeled diameter. | | PASS | PMA P200026: FDA Summary of Safety and Effectiveness Data {7} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Stent Contact Area | To determine the percent contact area of a deployed stent with the vessel wall. | Contact area of the stent is to be measured or calculated and reported as percent surface area. | 12-18% | | Foreshortening* | Measures the difference between the stent length in the delivery system and the stent length when deployed in a target vessel. | The deployed stent length in a representative path shall be equal to or less than 10 percent, or equal to or less than 5mm different than the stent length in the delivery system, whichever is greater. | PASS | | Normalized Lateral Stiffness (NLS) Minimum | To measure the resistance of the expanded stent to lateral compression as a function of normalized stiffness (NLS). | The minimum normalized lateral stiffness (NLS) for all stent sizes shall be 0.157N/mm. | PASS | | Normalized Lateral Stiffness (NLS) Maximum | | The maximum normalized lateral stiffness (NLS) for all stent diameters shall be 0.294N/mm. | PASS | | Radial Force: Radial outward loading and unloading* | To measure the resistive force of the stent to radial compression, simulating before (unloading) and after (loading) balloon dilation within the vessel. | The radial outward loading force (radial strength) minimum shall be 0.079N/mm and maximum shall be 0.403N/mm. The radial outward unloading force (radial strength) minimum shall be 0.026N/mm. | PASS | | Radial Force: Unloading at maximum vessel diameter (at deployment and life of device)* | | The unloading radial strength at maximum implanted vessel diameter shall be greater than 0.027N/mm. | PASS | | Particulate Evaluation | To measure the size and number of the particulate shed by the stent and delivery system. | Post-sterilization and distribution, the stent and delivery system must not shed particulate that exceed 6000/10μm and does not exceed 600/25μm per USP 788. | PASS | | Mechanical Properties | Characterization testing performed to determine tensile and fatigue properties as inputs to support stress/strain and fatigue analysis. | | | | Finite Element Analysis | Characterization testing performed to determine maximum stresses and strains within the device to support fatigue analysis. | | | | Endurance Limit Analysis | To determine the safety factor of the stent at relevant fatigue failure modes, and determine which modes require physical testing. | All safety factors > 1.0. Worst case testing to be performed for any safety factor < 2.0. | PASS | PMA P200026: FDA Summary of Safety and Effectiveness Data {8} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Accelerated Durability Testing | Evaluate the durability of the stent after a period of 10 years and 50 years. | The stent must withstand an equivalent of 10 years and 50 years of accelerated durability testing without Type III, Type IV or Type V fractures. | PASS The stent showed no Type III, Type IV or Type V strut fractures after 10 years and 50 years of accelerated durability testing. | | MRI Safety and Compatibility | To evaluate stent safety and compatibility with MRI. | The conditions under which the device can be safely scanned are determined for product labeling. | The stent is MR Conditional at a field strength of 1.5T and 3.0T | | Corrosion Resistance | To evaluate the potentiodynamic corrosion resistance of the stent. | The measured breakdown potential (ER) must be at least 200mV greater than the resting potential (ER). | PASS | | Nickel-ion Release | To characterize general/uniform corrosion resistance of the stent. | Stent should exhibit low nickel ion release rate over 60-day period. | Nickel ion release rate over a 60-day period was 0.073 μg/day. The peak nickel ion release rate in one day was 2.13μg/day. | | Delivery System | | | | | Working Length* | Measures the length of the delivery system catheter. | The delivery system working length shall be 90 cm +/- 4.5 cm. | PASS | | Dimensions: Overall Length* | Measures the length of the device. | Overall length of the device shall be 116cm +2cm/-4cm. | PASS | | Dimensions: Lumen ID* | Measures the delivery system lumen ID to ensure compatibility with a .035” guidewire. | Shall be able to insert and withdraw a mandrel with minimum diameter of 0.0360 inch. | PASS | | Dimensions: Crossing Profile* | Measures the crossing profile to ensure fit in a 9Fr introducer sheath. | Crossing profile must be ≤0.122 inches. | PASS | | Tensile: Distal Tip to Tip Tube* | Measures the distal tip to tip tube bond strength. | The distal tip to tip tube bond must withstand ≥3.8 lbf. | PASS | | Tensile: Luer to Tip Tube* | Measures the luer to tip tube bond strength. | The luer hub to tip tube bond must withstand ≥3.8 lbf. | PASS | | Tensile: Luer to Stop Tube* | Measures the luer to stop tube bond strength. | The luer hub to stop tube bond strength must withstand ≥3.8 lbf. | PASS | | Tensile: Outer Clip to Pull Cable* | Measures the outer clip to pull cable bond strength. | The outer clip to pull cable bond must withstand ≥12.6 lbf. | PASS | | Tensile: Thumbwheel to Pull Cable* | Measures the thumbwheel to pull cable bond strength. | The thumbwheel to pull cable bond must withstand ≥12.6 lbf. | PASS | | Tensile: Isolation Sheath to Handle* | Measures the isolation sheath to handle bond strength. | The isolation sheath to handle bond must withstand ≥3.37 lbf. | PASS | PMA P200026: FDA Summary of Safety and Effectiveness Data {9} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Markerband Visibility | Measures the radiopacity and cross-sectional viewing area of the markerband. | The markerband must provide a minimum radiopacity of 64% and a minimum cross-sectional viewing area of 1.62mm2. | PASS | | Tip Visibility | Measures the radiopacity of the tip. | The radiopacity of the tip must be 65±10%. | PASS | | Guidewire Loading Success* | Verifies the ability to insert and track the delivery system over a 0.035-inch guidewire. | Must be able to insert and track the delivery system over a 0.035-inch guidewire 3x in a representative path. | PASS | | No Pre-deployment* | Verifies the ability of the delivery system to maintain stent coverage after tracking. | The delivery system shall be able to maintain stent coverage without pre-deployment after tracking through a representative model. | PASS | | Deployability* | Confirms successful deployment. | Shall be able to successfully deploy a stent from the delivery system while placed in a representative model, and meet deployment force of equal to or less than 4.0 lbf | PASS | | Tracking and withdrawal* | Verifies the delivery system remains intact after insertion and withdrawal. | Must be able to insert and remove delivery system from sheath over a guidewire in a representative path with the delivery system remaining fully intact after withdrawal. | PASS | | Withdrawal* | Verifies the ability of the delivery system to be removed without dislodging the stent. | Must be able to remove delivery system without stent motion or dislodgement. | PASS | | Deployment Force* | Measures the force required to deploy the stent. | The wheel actuation force applied to thumbwheel required to deploy stent shall be equal to or less than 4.0 lbf | PASS | | Lock Pin Removal Force | Measures the force required to remove the lock pin. | Lock pin removal force must be ≤8.1 lbf. | PASS | | Flushing* | Verifies the ability to flush the guidewire lumen. | Ability to flush guidewire lumen using maximum of 10cc of saline | PASS | | Delivery System Freedom from Leakage* | Evaluates the delivery system for leakage. | The delivery system should be evaluated for leakage by flushing with water and no leaks are observed. | PASS | | 3x Tracking Force* | Measures the force required to track the delivery system through the vasculature. | The force required to track the delivery system through a representative model shall be equal to or less than 4.0 lbf. | PASS | PMA P200026: FDA Summary of Safety and Effectiveness Data {10} | Test | Test Purpose | Acceptance Criteria | Results | | --- | --- | --- | --- | | Deployment: Initial Flower to Final Position* | Measures the distance the stent moves upon deployment of the stent. | The movement of distal end of stent from initial flower to final deployment shall be less than or equal to 3mm. | PASS | | Deployment: Proximal Edge of marker band to final position* | | The distance from initial location of marker band to final location of stent shall be less than or equal to 5mm without repositioning. | PASS | | Particulate Evaluation | Measures the particulate shed by the stent and delivery system. | Post-sterilization and distribution, the delivery system must not shed particulate that exceed 6000/10μm and does not exceed 600/25 per USP 788. | PASS | | Delivery System Kink* | Evaluates the flexibility and kink of the delivery system. | The delivery system is evaluated for flexibility and kink performance using progressively tighter radius curves and characterized at the point at which the system starts to kink. | PASS | | Delivery System Torque* | Evaluates the torque strength of the delivery system. | The delivery system is evaluated for torque strength by continually rotating 180 degrees until failure occurs. | PASS | *Denotes testing also conducted for 3-year accelerated aging. ## C. Packaging Packaging verification testing was performed at non-aged and aged conditions to demonstrate integrity of the packaging is maintained over the shelf-life of the device. Testing, which passed pre-determined requirements, included a visual assessment, dye penetration testing, bubble leak testing, and seal strength testing. ## D. Shelf-life Shelf life testing of the device (assessed by the tests denoted with an asterisk in Table 3) and of packaging passed pre-determined requirements. Testing was performed to support a 3-year shelf life. ## E. Sterilization The Abre Venous Self-expanding Stent System is a single-use device. The device is terminally sterilized using 100% ethylene oxide (EO) gas. In accordance with AAMI/ANSI/ISO 11135, "Sterilization of health-care products – Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices", sterilization testing was performed on the Abre Venous Self-expanding Stent System to demonstrate that the device can be adequately sterilized to the desired Sterility Assurance Level (SAL) of 10⁻⁶. Ethylene Oxide and Ethylene Chlorohydrin residuals meet the requirements of ISO 10993-7, "Biological PMA P200026: FDA Summary of Safety and Effectiveness Data {11} Evaluation of Medical Devices – Part 7: Ethylene oxide sterilization residuals". ## F. Animal Studies Three GLP and one non-GLP animal studies were conducted to evaluate the acute handling and performance and the chronic safety of the Abre Venous Self-expanding Stent System. The *in vivo* animal studies demonstrated the safety and overall performance of the Abre Venous Self-expanding Stent System. Table 4 provides a summary of the animal studies performed. Table 4. Summary of Animal Studies | Study | 28-Day GLP Migration Study | | --- | --- | | Study Purpose | Evaluate migration of the Abre stent at 28-days post-implant | | Study Summary and Results | This study was designed to assess the migration of the Abre stent compared to a control stent at 28 days post-implant in a domestic swine animal model. The study met all success criteria with no safety risks identified. All animals survived to the respective 28-day timepoint and were observed to be clinically healthy through the study duration. There were no test or control article malfunctions or adverse events that occurred during the study. The Abre stent demonstrated favorable results compared to the control regarding migration and equivalent performance in regard to stenosis. No stent fractures were observed. The stent sizes chosen were to allow for a 0-10% stent oversizing based upon the outside diameter of the stent. Overall, there was a high correlation with increased stent diameter relative to the native vessel size causing disruption of the venous wall architecture or integrity which induced increased neointimal hyperplasia with resultant increased percent stenosis for both the Abre stent and the control stent. However, even though the Abre stent exhibited a greater average stent diameter than the control stent, the Abre venous stent frequently had equivalent or less percent stenosis and mean neointimal thickness in the animal matched groups. The pathology findings of the study were supportive of an acceptable safety profile for the Abre stent. | | | | | Study | 28-Day GLP Safety Study | | Study Purpose | Evaluate the safety of the Abre stent at 28-days post-implant | | Study Summary and Results | This study was designed to evaluate the safety of the Abre stent compared to a control stent at 28 days post-implant in a domestic swine model. The study met all success criteria with no safety risks identified. The Abre stent and the control stents were implanted in a single configuration and in an overlapped configuration. Nineteen of the twenty animals survived to the respective 28-day timepoint and were observed to be clinically healthy through the study duration. One animal was terminated early due to morbidity unrelated to a test device (animal experienced a femur fracture due to a fall during transport). There were no Abre or control device malfunctions or adverse events that occurred during the study. There were no incidents of stent fractures in the Abre stent; the control stent had one Type I fracture. Overall, Abre slightly outperformed the control for percent stenosis in both the single and overlapped configurations. There was a high correlation with increased stent diameter causing disruption of the venous wall architecture or integrity which induces increased neointimal hyperplasia with resultant increased percent stenosis in the animal matched groups. | PMA P200026: FDA Summary of Safety and Effectiveness Data 12 of 42 {12} PMA P200026: FDA Summary of Safety and Effectiveness Data 13 of 42 | | increased percent stenosis for both the Abre stent and the control stent. However, even though the Abre stent exhibited a greater average stent diameter than the control stent, the Abre stent consistently had equivalent percent stenosis and mean neointimal thickness. The pathology findings of the study were supportive of an acceptable safety profile for the Abre stent in single and overlapping configurations. | | --- | --- | | | | | Study | Acute GLP Animal Study | | Study Purpose | Evaluate the acute performance and handling of the Abre Venous Self-expanding Stent System | | Study Summary and Results | This study was designed to assess the acute performance and handling of the Abre Venous Self-expanding Stent System in a domestic swine animal model. The stent sizes were selected by the implanting physicians based on the estimated vein diameters and the device sizing tables. Fluoroscopy and intravascular ultrasound (IVUS) were used for procedural support and data collection. Performance and handling assessments were performed by two external physicians experienced in venous stenting for each stent that was deployed. Product and performance requirements related to the stent, delivery system compatibility, use of the device in a procedure, and packaging/labeling were evaluated by the physicians on a 1-5 rating scale. Following the final stent implantation, each animal was humanely euthanized and transferred to necropsy for a gross evaluation. Vascular trauma, site specific thrombogenicity, and overall thromboembolism on downstream circulation and downstream end organs were evaluated. The Abre Venous Self-expanding Stent System met all acceptance criteria in the physician assessments. There were no signs of site-specific thrombus formation for any stent, and no signs of potential thromboembolism in any animal. Some degree of vascular trauma was observed, however it was rated as “minimal to mild”. In addition, vessel injury scores were comparable between the Abre stent and the control stent. The study results from physician feedback and pathology results demonstrated that the Abre Venous Self-expanding Stent System performed as intended and met all defined acceptance criteria for evaluation requirements. | | | | | Study | 180-day Non-GLP Study | | Study Purpose | Assess the safety of the Abre stent at 180 days post-implant | | Study Summary and Results | This study was designed to assess the safety of the Abre stent compared to a control stent at 180 days post-implant in a domestic swine animal model. The study met all success criteria with no safety risks identified. All animals survived until their scheduled 180-day timepoint and no major acute and/or sub-acute complications during implant and throughout in-life were experienced. Clinically, all animals experienced some degree of post procedural pain demonstrated by lameness and abnormal posture. This was likely the result of outward migration of the struts, causing compression on perivascular spaces/organs (e.g. sensory nerve fibers) where there is minimal connective tissue present in the domestic swine model. Symptoms of pain resolved quickly in all cases. There were no device or procedure related adverse events for either test or control articles. In all evaluated sites, virtually all stent struts were residing in the perivascular connective/adipose tissue space and were not directly abutting the medial wall of the vein and | {13} there was marked disruption of venous wall architecture or integrity. All struts were surrounded by connective tissue extending from the venous adventitia and invariably associated with inflammation and/or fragments of tunica media. Overall, there was a high correlation with increased stent diameter inducing increased neointimal hyperplasia with resultant increased percent stenosis for both the Abre stent and the control stent. In addition, the control stent exhibited a higher incidence of more severe para-strut and neointimal inflammation than the Abre stent. PMA P200026: FDA Summary of Safety and Effectiveness Data X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study (ABRE Study) to establish a reasonable assurance of safety and effectiveness of iliofemoral venous stenting with the Abre Venous Self-expanding Stent System for symptomatic iliofemoral venous outflow obstruction under IDE G160163. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. A. Study Design The ABRE Study was a prospective, interventional, non-randomized, single-arm, multicenter, global study, with each center following a common protocol. Safety and effectiveness were designed to be evaluated against performance goals developed from the scientific literature. A Statistical Analysis Plan (SAP) was followed for the ABRE Study. Subjects were treated between December 19, 2017 and November 29, 2018. The database for this PMA reflected data collected through January 17, 2020, the data cutoff date. Subjects were categorized as acute DVT, post-thrombotic syndrome (PTS), or non-thrombotic iliac vein lesion (NIVL), for a total of 200 subjects who were implanted with at least one Abre stent at 24 investigational sites in the US and Europe (France, Germany, Ireland, Italy, and United Kingdom). Subjects in the ABRE Study were evaluated at a screening visit, during the index procedure, through hospital discharge, and then at 30 days, 6 months, and 12 months post-procedure. ABRE Study subjects will continue to be followed through 24 months and 36 months post-index procedure. Endpoint-related safety events were adjudicated by an independent Clinical Events Committee (CEC) according to the CEC manual of operations (MOP), and an independent Data Safety Monitoring Board (DSMB) ensured the well-being of the participants of the study and the continued validity and scientific merit of the study, per a DSMB Charter. 1. Clinical Inclusion and Exclusion Criteria Enrollment in the ABRE Study was limited to patients who met the following inclusion criteria: {14} PMA P200026: FDA Summary of Safety and Effectiveness Data 15 of 42 # General Inclusion Criteria 1. Patient is ≥ 18 and ≤ 80 years of age; 2. Patient has at least one of the following clinical manifestations (i.e. symptoms and/or signs) of venous disease in lower extremity: a. Clinical-Etiological-Anatomical-Pathophysiological (CEAP) score ≥ 3 b. Venous Clinical Severity Score pain score (VCSS) ≥ 2 c. Suspected deep vein thrombosis (DVT); 3. Patient is willing and capable of complying with specified follow-up evaluations at the specified times; 4. Patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the appropriate Ethics Board. # Imaging-based Inclusion Criteria 5. Patient has diagnosis of non-malignant venous obstruction within the common iliac, external iliac, and/or common femoral vein. The proximal point of the obstruction may extend to the iliac venous confluence of the inferior vena cava and the distal point may be at or above the deep femoral vein. Diagnosis must be made based on objective imaging by using venography and/or intravascular ultrasound (IVUS). Patient must have good inflow involving either the femoral or deep femoral vein being patent and at least a caudal section of the common femoral vein that is free of significant disease; 6. Patient has an obstructive lesion defined as: i. Occluded, or ii. ≥ 50% in diameter reduction on venography or IVUS, or iii. ≥ 50% area reduction on IVUS 7. Acute DVT patients should be treated with the Abre stent within 14 days after onset of symptoms. Patients with acute DVT must first undergo successful treatment of acute thrombus; successful treatment is defined as 30% or less residual thrombus by venogram, as determined by physician, no bleeding, no symptomatic pulmonary embolism (confirmed by imaging), and no renal compromise (renal compromise defined as glomerular filtration rate (GFR) < 30). Patients with underlying obstructive lesions can then be included in the study within the same procedure; 8. Target vessel can accommodate a 9F Sheath, from insertion site to target segment; 9. Exchangeable guidewire must cross target lesion(s) with successful predilation. Patients were not permitted to enroll in the ABRE Study if they met any of the following exclusion criteria: # General Exclusion Criteria 1. Patient with DVT in the target limb of which the onset of symptoms is {15} between 15 days and 6 months prior to planned treatment or patient has an acute DVT anywhere else than in the target vessel; 2. Patient has peripheral arterial disease-causing symptoms in target limb; 3. Patient is pregnant (female patients of child-bearing potential must have a pregnancy test done within 7 days prior to the index procedure); 4. Patient has a known or suspected systemic infection at the time of the index procedure; 5. Patient has a planned percutaneous or surgical intervention within 30 days prior or 30 days following index procedure, or a contralateral iliofemoral lesion requiring planned treatment within 12 months; 6. Patient requires femoral endovenectomy and patch venoplasty, greater saphenous vein ablation, and/or small saphenous vein stripping during the index procedure; 7. Patient has an active vasculitic inflammatory disorder (e.g. Behcet disease) predisposing the patient to thrombosis and requiring systemic corticosteroid therapy; 8. Patient has impaired renal function (GFR < 30) or is on dialysis; 9. Patient has a platelet count < 50,000 cells/mm³ or > 1,000,000 cells/mm³ and/or a white blood cell count (WBC) < 3,000 cells/mm³ or > 12,500 cells/mm³; 10. Patient has a history of bleeding diathesis or either a history or presence of heparin-induced thrombocytopenia antibodies; 11. Patient has a known hypersensitivity or contraindication to antiplatelets or anticoagulation, nitinol, or a contrast sensitivity that cannot be adequately pre-medicated; 12. Patient has presence of other severe co-morbid conditions, which in the investigator's opinion may interfere with the patient's compliance with study visits and procedures, or may confound interpretation of study data (e.g. congestive heart failure Class III and IV, non-ambulatory patients, severe hepatic dysfunction, life expectancy < 1 year); 13. Patient belongs to a vulnerable population per investigator's judgment or patient has any kind of disorder that compromises his/her ability to give written informed consent and/or to comply with study procedures. Patient must be able to consent for themselves; 14. Patient is currently participating in another investigational drug or device study or observational competitive study. ## Imaging-based Exclusion Criteria 15. Patient has a vena cava obstruction or lesion extending into the inferior vena cava (IVC), or the presence of bilateral iliofemoral venous lesions requiring planned treatment within 12 months; 16. Patient has significant venous bleeding, arterial dissection or other injury requiring additional percutaneous or surgical intervention prior to enrollment; 17. Patient has a previously placed stent in the ipsilateral venous vasculature; 18. Patient has disease that precludes safe advancement of the venous stent to PMA P200026: FDA Summary of Safety and Effectiveness Data 16 of 42 {16} the target lesion(s). # 2. Follow-up Schedule All subjects underwent a clinical evaluation at screening (prior to index procedure); treated subjects underwent a clinical evaluation prior to hospital discharge. All ABRE Study subjects were scheduled to return for follow-up examinations at 30 days, 6 months, and 12 months post-index procedure. Subjects will continue to be followed at 24 months and 36 months post-index procedure. Clinical and imaging follow-up are performed at these timepoints to enable reporting of endpoints related to primary patency, acute success, target lesion revascularization, stent fractures, quality of life, and major adverse events (MAEs). All adverse events and complications were recorded at all visits through the 12-month evaluation. All adverse events and MAEs will continue to be reported through 36 months post-index procedure. Table 5 provides the follow-up schedule and evaluations required through the 36-month visit. Table 5: Schedule of Assessments and Visit Windows | Data Collection Requirement | Screening/Baseline (<30 days before procedure unless otherwise specified) | Procedure | Hospital Discharge | 30 Day (-7/+14 days) | 6 Months (± 30 days) | 12 Months (± 30 days) | 24 & 36 Months (± 30 days) | Unscheduled visit for intervention in target vein | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Informed Consent | X | | | | | | | | | Demographics, Medical History & Physical Examination | X | | | | | | | | | Pregnancy Test1 | X | | | | | | | | | Serum Creatinine, CBC | X | | | | | | | | | INR (if on warfarin) | X | | | X | X | X | X | X | | CEAP Classification | X | | | | | | | | | Physical Assessment of Limbs | X | | X | X | X | X | X | X | | Villalta Score, VCSS | X | | | X | X | X | X | X2 | | VEINES-QOL/Sym, EQ-5D QOL | X | | | | X | X | X | X2 | | Medication3 | X | X | X | X | X | X | X | X | | Document Adverse Events | X4 | X | X | X | X | X | X | X | | Duplex Ultrasound (DUS) | X | | X5 | X | X | X6 | X | X | | Procedure Data | | X | | | | | | X | | Venogram | 7 | X7,8 | | | | 6 | | X | | IVUS | 7 | X7,8 | | | | | | X | | Document Device Deficiencies | | X | X | X | X | X | X | X | PMA P200026: FDA Summary of Safety and Effectiveness Data {17} | Data Collection Requirement | Screening/Baseline (<30 days before procedure unless otherwise specified) | Procedure | Hospital Discharge | 30 Day (-7/+14 days) | 6 Months (± 30 days) | 12 Months (± 30 days) | 24 & 36 Months (± 30 days) | Unscheduled visit for intervention in target vein | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | X-ray | | | | 9 | | X | X | X^{10} | | Discontinuation Information^{11} | | | X | X | X | X | X | X | 1 Pregnancy test was required for women of child-bearing potential only to be completed within 7 days prior to the index procedure. 2 Assessments and questionnaires were required prior to any intervention. 3 Medications collected: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, Calcium-channel blockers, Statins. 4 Adverse Event assessments were completed as of the moment the subject signed and dated the informed consent form. 5 The DUS examination immediately after the index procedure was required to be performed between 0 and 7 calendar days from the index procedure. 6 An additional venogram was required when: (1) DUS assessment was suggestive of ≥50% restenosis or occlusion per investigator assessment, or; (2) DUS was non-diagnostic or suboptimal such as when a subject was obese (e.g. with a BMI >40), or; (3) was clinically required, or in other words when the subject had symptoms of venous disease in the target limb requiring a venogram. 7 Diagnosis was made during the screening/baseline prior to the index procedure based on objective imaging using venography or IVUS. 8 Required pre-stenting and post-stenting 9 X-rays at 30 days were performed on the first 30 included subjects only for the first safety analysis (i.e. stent fracture). 10 Plain x-ray was required pre and post re-intervention to assess for stent fracture. 11 The discontinuation information was required whenever the subject ended involvement in the study. All subjects were required to undergo duplex ultrasound (DUS) assessments for determination of the primary effectiveness endpoint of primary patency at 12 months. An additional venogram was required when the DUS assessment was suggestive of ≥50% restenosis or occlusion per investigator assessment, or when the DUS was non-diagnostic or suboptimal, or when the venogram was clinically required. In cases where both DUS and venography from the 12-month visit were available, venography was used for the primary patency assessment. ## 3. Clinical Endpoints ### Primary safety endpoint The primary safety endpoint was the incidence of composite MAEs at 30 days following stenting of an obstruction in the iliofemoral venous segment. MAEs were adjudicated by a CEC, except for stent thrombosis and stent migration, which were confirmed by core laboratory. The components of the 30-day MAE composite include: - All-cause death occurring post-procedure - Clinically significant pulmonary embolism (i.e., symptomatic, PMA P200026: FDA Summary of Safety and Effectiveness Data {18} confirmed by CT pulmonary angiography) - Major bleeding complication (procedural) - Stent thrombosis confirmed by imaging as assessed by core laboratory - Stent migration confirmed by imaging as assessed by core laboratory Note: Migration excluded dislodgement at the index procedure as may occur with under-sizing of a stent. The statistical hypothesis was that the primary safety rate through 30 days will not exceed a performance goal established from scientific literature: H₀: P ≥ PG Hₐ: P < PG where P was the primary safety endpoint at 30 days in the study population and PG was the performance goal of 12.5%. The review of the literature that provided results on the composite MAE endpoint components suggests an expected rate of 5.6%. The performance goal of 12.5% was set with a margin of 6.9% above the literature derived rate. Exact binomial test was used for the hypothesis testing and the one-sided p-value was reported. The primary safety failure rate was calculated as the number of subjects who had an event within 30 days divided by the number of evaluable subjects who had sufficient follow up (at least 23 days for 30-day visit) without an event plus any subjects who had a MAE within 30 days post-procedure. The primary safety objective was considered to be met if the upper limit of the 97.5% one-sided confidence interval was below 12.5%. Assuming desired power of at least 92% under difference testing relative to the performance goal at a one-sided alpha of 0.025, the required sample size was 193 subjects using exact binomial test for a single proportion. Accounting for attrition, the sample size was augmented by 3.5% to 200 subjects. ## Primary effectiveness endpoint The primary effectiveness endpoint of the study was Primary Patency at 12 months post index procedure, which required meeting all of the following criteria at 12 months post-procedure: - Freedom from occlusion of the stented segment of the target lesion, defined as absence of 100% stenosis as measured by venogram (or DUS in the event venogram not available); - Freedom from restenosis ≥50% of the stented segment of the target lesion, defined as diameter stenosis less than 50% as measured by venogram (or DUS in the event venogram not available); - Freedom from clinically driven target lesion revascularization, defined as absence of clinically driven reintervention, where clinically driven is defined as the recurrence of symptoms present at baseline or the onset of new symptoms including, but not limited to venous pain, swelling, dermatitis, or ulceration related to the target limb. PMA P200026: FDA Summary of Safety and Effectiveness Data {19} The statistical hypothesis was that primary patency through 12 months will exceed a performance goal established from historical literature: $\mathrm{H}_0: \pi \leq \mathrm{PG}$ $\mathrm{H}_{\mathrm{A}}: \pi > \mathrm{PG}$ where $\pi$ was the primary patency rate at 12 months in the study population and PG was the performance goal of 75%. Based on an extensive and independent review of the literature, the estimated patency rate was 84% for acute Deep Vein Thrombosis (aDVT) subjects, 96% for NIVL subjects and 80% for PTS subjects. The distribution of patients in the literature on which our PGs were based are 26%, 30% and 44% for aDVT, NIVL, and PTS, respectively. By subtracting a margin of 10% from the weighted average of patency rates of the three patient categories, the value of 75% was taken as the performance goal for the study. The primary patency rate was calculated as the number of subjects without loss of primary patency divided by the number of subjects having evaluable primary endpoint data for primary patency at 12 months. The primary analysis set was 'included' subjects who were considered evaluable if: (a) the subject experienced at least one clinically-driven target lesion revascularization within 390 days; or (b) the subject had occlusion or restenosis ≥50% of the stented segment of the target lesion confirmed by core laboratory at 12 months visit; or (c) the subject had at least 330 days follow up without an event in the primary effectiveness endpoint. Exact binomial test was used to test the hypothesis and one-sided p-value was reported for primary effectiveness endpoint. The primary effectiveness objective was considered to be met if the lower limit of the 97.5% one-sided confidence interval of the 12-month primary patency rate was above 75%. Assuming desired power of at least 92% under difference testing relative to the performance goal at a one-sided alpha of 0.025, the required sample size was 160 subjects using exact binomial test for a single proportion. Accounting for attrition, the sample size was augmented by 20% to 200 subjects. The overall power of the study, considering primary effectiveness and primary safety, was at least 84%. ## Secondary Endpoints The following secondary endpoints were evaluated through 12 months (24-month and 36-month evaluations will be performed according to each endpoint definition). - Device success, defined as successful delivery and deployment of the Abre stent in the target lesion with successful removal of the delivery system. - Lesion success, defined as venographic evidence of <50% final residual stenosis of the stented segment of the target lesion after post-dilation, when PMA P200026: FDA Summary of Safety and Effectiveness Data 20 of 42 {20} applicable, and as assessed by core laboratory. If the core laboratory was unable to assess the venographic evidence, site-reported "post-stenting" data were used. - Procedure success, defined as lesion success without procedure-related MAEs prior to hospital discharge within 30 days. - Primary assisted patency at 12 months, defined as uninterrupted patency of the stented segment of the target lesion with a secondary intervention, also known as an adjunctive treatment (e.g. balloon venoplasty, subsequent stenting, etc.). - Secondary patency at 12 months, defined as patency of the stented segment of the target lesion after subsequent intervention for an occlusion. - TLR through 30 days, 6, 12, 24, and 36 months, defined as any re-intervention of the stented segment of the target lesion. - MAEs through 6, 12, 24, and 36 months, including all-cause death occurring post-procedure, clinically significant (i.e. symptomatic, confirmed by CT pulmonary angiography) pulmonary embolism, major bleeding complication (post-procedural), stent thrombosis, and stent migration. All MAEs were adjudicated by a CEC, except for stent thrombosis and stent migration, which were confirmed by the core laboratory. - Delayed stent migration at 12, 24, and 36 months, defined as position change of a venous stent observed with an imaging modality >1 cm from its original location at the conclusion of the index procedure, as determined with regard to a reference anatomic structure. - Stent fracture at 30 days, 12, 24, and 36 months, defined as fracture or breakage of any portion of the stent determined by X-ray for the first 30 subjects at 30 days and for all subjects (including the first 30 subjects) at 12, 24, and 36 months. - Change in Venous Insufficiency Epidemiological and Economic Study – Quality of Life/Symptoms (VEINES-QOL/Sym) Scores at 6, 12, 24, and 36 months, compared to baseline. - Change in Villalta Score at 6, 12, 24, and 36 months, compared to baseline. - Change in Euro-Qol 5 Dimension (EQ-5D) Quality of life Score at 6, 12, 24, and 36 months, compared to baseline. - Change in VCSS Score at 6, 12, 24, and 36 months, compared to baseline. - Major bleeding complications at 30 days, 6, 12, 24, and 36 months. PMA P200026: FDA Summary of Safety and Effectiveness Data 21 of 42 {21} - Medical resource utilization through 36 months, including length of stay and re-hospitalizations. ## B. Accountability of PMA Cohort A total of 260 subjects signed the ABRE Study informed consent form and were evaluated against inclusion and exclusion criteria for the study. Of these 260 subjects, 200 were implanted with at least one Abre stent. Out of 200 implanted subjects, 191 subjects returned for a 12-month visit, for a follow-up completion rate of 95.5% (191/200). A total of four subjects exited the study prior to completing the 12-month visit. These study exits included two subject deaths (unrelated to the study device or procedure), one subject who was lost to follow-up, and one subject who exited the study due to incarceration. Five subjects missed the 12-month visit. A detailed breakdown of ABRE subject visit availability per the study follow-up schedule is reported through the 12-month visit and presented in Figure 3. In total, 196 subjects were available for the 12-month visit, and 5 subjects missed the visit for a total of 191 subjects with available 12-month data. PMA P200026: FDA Summary of Safety and Effectiveness Data 22 of 42 {22} Figure 3: Visit Availability ![img-2.jpeg](img-2.jpeg) 260 consented subjects - 60 enrolled not included subjects = 200 included/implanted subjects 200 included subjects - 2 missed visits = 198 subjects completed 30-day follow-up 200 included subjects - 1 exited subject = 199; 199 included subjects still in study - 6 missed visits = 193 subjects completed 6-month follow-up 199 included subjects still in study - 3 exited subjects = 196 included subjects still in study - 5 missed visits = 191 subjects completed 12-month follow-up sum of subjects that exited the study as of the January 17, 2020 data cut-off date PMA P200026: FDA Summary of Safety and Effectiveness Data {23} # C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for the type of study performed in the US and Europe. Site reported subject demographics for all 200 subjects are presented in Table 6 below. Table 6: Demographics | Parameter | ABRE (N=200 Subjects) | | --- | --- | | Age at Time of Enrollment (years) | | | N | 200 | | Mean ± SD | 51.5 ± 15.9 | | Median | 53.0 | | Min, Max | 18, 80 | | Gender at Birth | | | Female | 66.5% (133/200) | | Male | 33.5% (67/200) | | BMI (kg/m2) | | | N | 200 | | Mean ± SD | 29.5 ± 7.1 | | Median | 28.8 | | Min, Max | 14.9, 53.5 | | Ethnicitya | | | Hispanic or Latino | 7.0% (14/200) | | Not Hispanic or Latino | 80.0% (160/200) | | Not Available | 13.0% (26/200) | | Racea | | | White | 78.5% (157/200) | | Black or African American | 8.5% (17/200) | | Asian | 2.0% (4/200) | | Native Hawaiian/Other Pacific Islander | 0.0% (0/200) | | American Indian or Alaska Native | 0.0% (0/200) | | Not Available | 11.0% (22/200) | | Other | 0.0% (0/200) | ${}^{a}$ France does not permit the collection of Race and Ethnicity data from study subjects. Site-reported data PMA P200026: FDA Summary of Safety and Effectiveness Data {24} Site-reported baseline medical history is summarized in Table 7. Table 7: Baseline Medical History | Parameter | ABRE (N=200 Subjects) | | --- | --- | | Hypertension | 31.0% (62/200) | | Hyperlipidemia | 28.5% (57/200) | | Diabetes Mellitus | 10.5% (21/200) | | Smoking | | | Active | 12.0% (24/200) | | Previous | 30.5% (61/200) | | Never | 57.5% (115/200) | | Cancer (Ongoing or Remission) | 11.0% (22/200) | | Pulmonary | 29.5% (59/200) | | Chronic Obstructive Pulmonary Disease | 4.5% (9/200) | | Pulmonary Embolism | 17.0% (34/200) | | Pulmonary Hypertension | 1.0% (2/200) | | Asthma | 12.5% (25/200) | | Vascular | 83.0% (166/200) | | Stroke | 0.0% (0/200) | | TIA | 1.0% (2/200) | | Peripheral Artery Disease | 3.5% (7/200) | | Known Family History of DVT | 22.0% (44/200) | | Previous History of Venous Thromboembolism | 52.0% (104/200) | | Venous Claudication | 30.0% (60/200) | | Lymphedema | 15.0% (30/200) | | Hypercoagulability Syndrome/Thrombophilia | 11.5% (23/200) | | Cardiac | 7.0% (14/200) | | Congestive Heart Failure | 3.0% (6/200) | | Ischemic Heart Disease | 3.5% (7/200) | | Previous Myocardial Infarction | 3.0% (6/200) | Site-reported data PMA P200026: FDA Summary of Safety and Effectiveness Data {25} Table 8 presents site-reported target limb baseline clinical characteristics. Table 8: Target Limb Baseline Clinical Characteristics | Parameter | ABRE (N=200 Subjects) | | --- | --- | | Target Limb | | | Left | 92.0% (184/200) | | Right | 8.0% (16/200) | | Presence of lymphedema | 14.6% (29/198) | | CEAP Classification* | | | C0 - No visible or palpable signs of venous disease | 0.6% (1/166) | | C1 - Telangiectasias or reticular veins | 0.6% (1/166) | | C2 - Varicose veins | 2.4% (4/166) | | C3 - Edema | 62.0% (103/166) | | C4a - Pigmentation or eczema | 13.3% (22/166) | | C4b - Lipodermatosclerosis or atrophie blanche | 6.6% (11/166) | | C5 - Healed venous ulcer | 6.6% (11/166) | | C6 - Active venous ulcer | 7.8% (13/166) | | Villalta Score | | | N | 199 | | Mean ±SD | 11.2 ± 5.7 | | Median | 11.0 | | Min, Max | 0.0, 32.0 | | VCSS Score | | | N | 199 | | Mean ±SD | 8.8 ± 4.7 | | Median | 8.0 | | Min, Max | 1.0, 27.0 | Site-reported data *PTS and NIVL subjects only; CEAP assessment is not applicable for acute DVT subjects D. Procedural Characteristics Site-reported index procedure characteristics are summarized in Table 9. The largest category of subjects (47.5%) were included in the PTS primary indication category, 36.0% were included in the NIVL category, and the remaining 16.5% were categorized as having had an acute DVT. PMA P200026: FDA Summary of Safety and Effectiveness Data {26} Table 9: Procedural Characteristics | Parameter | ABRE (N=200 Subjects) | | --- | --- | | Primary Indication | | | Acute DVT | 16.5% (33/200) | | Post Thrombotic Syndrome | 47.5% (95/200) | | Non-Thrombotic Iliac Vein Lesion | 36.0% (72/200) | | Type of Anesthesia Used | | | General | 81.5% (163/200) | | Spinal | 0.0% (0/200) | | Epidural | 0.0% (0/200) | | Local | 62.0% (124/200) | | Access Site | | | Common Femoral | 23.5% (47/200) | | Femoral | 49.0% (98/200) | | Internal Jugular | 3.5% (7/200) | | Popliteal | 20.0% (40/200) | | Superficial Vein | 2.5% (5/200) | | Other | 1.5% (3/200) | Site-reported data As shown in Table 10, an average of 1.5 stents per subject were implanted during the index procedure. One or more stents were implanted in the common iliac vein in 96% of subjects, in the external iliac vein in 80.5% of subjects, and in the common femoral vein in 44.0% of subjects. The mean total stented length was 134.3 ± 58.0 mm. Table 10: Venography Core Laboratory Stent Implant Data | Parameter | ABRE (N=200 Subjects) | | --- | --- | | Subjects with* | | | 1 Abre Stent Implanted | 55.5% (111/200) | | 2 Abre Stents Implanted | 38.5% (77/200) | | 3 Abre Stents Implanted | 5.5% (11/200) | | > 3 Abre Stents Implanted | 0.5% (1/200) | | Number of Abre Stents Implanted per Subject* | | | N | 200 | | Mean ±SD | 1.5±0.6 | | Median | 1.0 | | Min, Max | 1,4 | | Stented Vein Location* | | | Common Iliac Vein | 96.0% (192/200) | PMA P200026: FDA Summary of Safety and Effectiveness Data {27} | Parameter | ABRE (N=200 Subjects) | | --- | --- | | External Iliac Vein | 80.5% (161/200) | | Common Femoral Vein | 44.0% (88/200) | | % Diameter Stenosis | | | N | 193 | | Mean ±SD | 14.2±8.2 | | Median | 11.7 | | Min, Max | 2,48 | | Length of Overlap with Cranial Stent (mm) per Stent | | | N | 95 | | Mean ±SD | 24.6±11.9 | | Median | 23.3 | | Min, Max | 5,68 | | Total Stented Length (mm) | | | N | 192 | | Mean ±SD | 134.3±58.0 | | Median | 121.5 | | Min, Max | 49,283 | *Site-reported data were used when venography core laboratory-reported data were not available Table 11 displays the stent usage by diameter and length in the study. A total of 302 Abre stents were implanted in the 200 ABRE Study subjects. Table 11: Study Stent Usage by Diameter and Length | Diameter(mm) | Length (mm) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | 40 | 60 | 80 | 100 | 120 | 150 | Total | | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | 12 | NA | 6 | 0 | 0 | 2 | 1 | 9 | | 14 | NA | 5 | 12 | 28 | 32 | 33 | 110 | | 16 | NA | 12 | 27 | 29 | 36 | 35 | 139 | | 18 | NA | 5 | 10 | 12 | 7 | 6 | 40 | | 20 | NA | 0 | 0 | 1 | 1 | 2 | 4 | | Total | 0 | 28 | 49 | 70 | 78 | 77 | 302 | PMA P200026: FDA Summary of Safety and Effectiveness Data {28} # E. Safety and Effectiveness Results # 1. Safety Results For the primary safety endpoint, the MAE rate at 30 days was $2.0\%$ (4/200). The upper bound of the one-sided $97.5\%$ CI was $5.0\%$ , which was significantly lower than the $12.5\%$ performance goal, demonstrating that the primary safety endpoint was met (p-value $< 0.0001$ ). Table 12 displays the data for each component of the composite MAE rate at 30 days. A total of four subjects were reported having a total of four MAEs within 30 days of the index procedure: three stent thrombosis and one clinically significant pulmonary embolism. No subject deaths, major bleeding complications, or stent migrations occurred during the 30 days following the index procedure. Table 12: Primary Safety Composite Endpoint - MAE within 30 Days | Parameter | ABRE (N=200 Subjects) | 95% Confidence Interval | | --- | --- | --- | | Primary Safety Composite Endpoint – MAE within 30 Days | 2.0% (4/200) | [0.5%, 5.0%] | | All-cause Death Occurring Post-Procedure | 0.0% (0/200) | [0.0%, 1.8%] | | Clinically Significant Pulmonary Embolism | 0.5% (1/200) | [0.0%, 2.8%] | | Major Bleeding Complication (Procedural) | 0.0% (0/200) | [0.0%, 1.8%] | | Stent Thrombosis | 1.5% (3/200) | [0.3%, 4.3%] | | Stent Migration | 0.0% (0/200) | [0.0%, 1.8%] | Table 13 displays non-serious adverse events (non-SAEs) occurring from the day of the index procedure through 360 days post index procedure. All data presented herein are site-reported. A total of 276 adverse events (non-SAEs) were reported in 121 subjects. Incidences of Musculoskeletal and connective tissue disorders $(18.0\%)$ , General disorders and administration site conditions $(13.5\%)$ , and Injury, poisoning and procedural complications $(13.5\%)$ were the most commonly reported events. Table 13: Number of Subjects with One or More Adverse Events (Non - SAEs) through 360 Days by MedDRA System-Organ Class and Preferred Term | Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Subjects with One or More Adverse Events | 60.5% (121/200) | | System-organ class/preferred term | | | Blood And Lymphatic System Disorders | 1.5% (3/200) | | Anaemia | 1.0% (2/200) | | Coagulopathy | 0.5% (1/200) | | Leukopenia | 0.5% (1/200) | | Cardiac Disorders | 1.5% (3/200) | PMA P200026: FDA Summary of Safety and Effectiveness Data {29} PMA P200026: FDA Summary of Safety and Effectiveness Data 30 of 42 | Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Angina Pectoris | 0.5% (1/200) | | Atrial Fibrillation | 0.5% (1/200) | | Palpitations | 0.5% (1/200) | | **Ear And Labyrinth Disorders** | **1.0% (2/200)** | | Vertigo | 1.0% (2/200) | | **Endocrine Disorders** | **2.0% (4/200)** | | Hyperthyroidism | 0.5% (1/200) | | Hypothyroidism | 1.5% (3/200) | | **Eye Disorders** | **1.5% (3/200)** | | Chalazion | 0.5% (1/200) | | Conjunctival Haemorrhage | 0.5% (1/200) | | Visual Impairment | 0.5% (1/200) | | **Gastrointestinal Disorders** | **6.5% (13/200)** | | Abdominal Pain | 2.0% (4/200) | | Abdominal Pain Upper | 1.0% (2/200) | | Diarrhoea | 1.0% (2/200) | | Gastritis | 1.0% (2/200) | | Gingival Bleeding | 0.5% (1/200) | | Haematochezia | 1.0% (2/200) | | Ileus | 0.5% (1/200) | | Nausea | 1.0% (2/200) | | Rectal Haemorrhage | 1.0% (2/200) | | **General Disorders And Administration Site Conditions** | **13.5% (27/200)** | | Adverse Drug Reaction | 0.5% (1/200) | | Chest Pain | 0.5% (1/200) | | Crepitations | 0.5% (1/200) | | Cyst | 0.5% (1/200) | | Drug Intolerance | 0.5% (1/200) | | Fatigue | 0.5% (1/200) | | Injection Site Haemorrhage | 0.5% (1/200) | | Medical Device Site Pain | 0.5% (1/200) | | Nodule | 0.5% (1/200) | | Non-Cardiac Chest Pain | 1.0% (2/200) | | Pain | 0.5% (1/200) | | Peripheral Swelling | 0.5% (1/200) | | Pyrexia | 0.5% (1/200) | | Swelling | 0.5% (1/200) | | Vascular Stent Stenosis | 3.0% (6/200) | | Vascular Stent Thrombosis | 3.5% (7/200) | | Vessel Puncture Site Haematoma | 0.5% (1/200) | {30} PMA P200026: FDA Summary of Safety and Effectiveness Data 31 of 42 | Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Vessel Puncture Site Haemorrhage | 0.5% (1/200) | | **Hepatobiliary Disorders** | 0.5% (1/200) | | Cholelithiasis | 0.5% (1/200) | | **Immune System Disorders** | 0.5% (1/200) | | Contrast Media Reaction | 0.5% (1/200) | | **Infections And Infestations** | 11.5% (23/200) | | Abscess Limb | 0.5% (1/200) | | Bacterial Tracheitis | 0.5% (1/200) | | Bronchitis | 2.0% (4/200) | | Cellulitis | 1.0% (2/200) | | Clostridium Difficile Infection | 0.5% (1/200) | | Gastroenteritis | 0.5% (1/200) | | Infectious Mononucleosis | 0.5% (1/200) | | Influenza | 1.5% (3/200) | | Lower Respiratory Tract Infection | 1.5% (3/200) | | Nasopharyngitis | 1.0% (2/200) | | Peritonsillar Abscess | 0.5% (1/200) | | Pneumonia Viral | 0.5% (1/200) | | Sialoadenitis | 0.5% (1/200) | | Sinusitis | 0.5% (1/200) | | Tonsillitis | 0.5% (1/200) | | Upper Respiratory Tract Infection | 0.5% (1/200) | | Urinary Tract Infection | 1.0% (2/200) | | Viral Upper Respiratory Tract Infection | 0.5% (1/200) | | **Injury, Poisoning And Procedural Complications** | 13.5% (27/200) | | Contusion | 3.5% (7/200) | | Device Difficult To Use | 0.5% (1/200) | | Epicondylitis | 0.5% (1/200) | | Fall | 0.5% (1/200) | | Foot Fracture | 1.5% (3/200) | | Joint Dislocation | 0.5% (1/200) | | Ligament Sprain | 0.5% (1/200) | | Limb Injury | 1.0% (2/200) | | Meniscus Injury | 0.5% (1/200) | | Peripheral Nerve Injury | 0.5% (1/200) | | Post Procedural Discharge | 0.5% (1/200) | | Post Procedural Haematuria | 0.5% (1/200) | | Post-Traumatic Pain | 0.5% (1/200) | | Procedural Pain | 0.5% (1/200) | | Skin Laceration | 1.5% (3/200) | {31} PMA P200026: FDA Summary of Safety and Effectiveness Data 32 of 42 | Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Vascular Access Site Bruising | 0.5% (1/200) | | Vascular Access Site Complication | 0.5% (1/200) | | Vascular Access Site Haematoma | 1.0% (2/200) | | **Investigations** | **2.5% (5/200)** | | Blood Urine Present | 0.5% (1/200) | | Cardiolipin Antibody Positive | 0.5% (1/200) | | Haemoglobin Decreased | 1.0% (2/200) | | Oesophagogastroduodenoscopy | 0.5% (1/200) | | **Metabolism And Nutrition Disorders** | **1.5% (3/200)** | | Decreased Appetite | 0.5% (1/200) | | Hypernatraemia | 0.5% (1/200) | | Hypokalaemia | 0.5% (1/200) | | Hypovolaemia | 0.5% (1/200) | | Iron Deficiency | 0.5% (1/200) | | Vitamin B12 Deficiency | 0.5% (1/200) | | **Musculoskeletal And Connective Tissue Disorders** | **18.0% (36/200)** | | Arthralgia | 2.5% (5/200) | | Arthritis | 1.0% (2/200) | | Back Pain | 3.5% (7/200) | | Bursitis | 0.5% (1/200) | | Groin Pain | 1.0% (2/200) | | Intervertebral Disc Degeneration | 0.5% (1/200) | | Limb Discomfort | 0.5% (1/200) | | Muscle Tightness | 0.5% (1/200) | | Musculoskeletal Chest Pain | 0.5% (1/200) | | Musculoskeletal Pain | 1.0% (2/200) | | Pain In Extremity | 6.5% (13/200) | | Patellofemoral Pain Syndrome | 0.5% (1/200) | | Rheumatoid Arthritis | 0.5% (1/200) | | Synovial Cyst | 0.5% (1/200) | | Tendonitis | 0.5% (1/200) | | Tenosynovitis | 0.5% (1/200) | | **Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)** | **1.0% (2/200)** | | Basal Cell Carcinoma | 0.5% (1/200) | | Lipoma | 0.5% (1/200) | | **Nervous System Disorders** | **7.5% (15/200)** | | Carpal Tunnel Syndrome | 0.5% (1/200) | | Coordination Abnormal | 0.5% (1/200) | | Dizziness | 0.5% (1/200) | {32} PMA P200026: FDA Summary of Safety and Effectiveness Data 33 of 42 | Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Headache | 1.0% (2/200) | | Hypoaesthesia | 1.5% (3/200) | | Migraine | 0.5% (1/200) | | Neuralgia | 1.0% (2/200) | | Neuropathy Peripheral | 0.5% (1/200) | | Paraesthesia | 0.5% (1/200) | | Sciatica | 1.0% (2/200) | | Spinal Subdural Haematoma | 0.5% (1/200) | | **Psychiatric Disorders** | **1.0% (2/200)** | | Depression | 0.5% (1/200) | | Stress | 0.5% (1/200) | | **Renal And Urinary Disorders** | **3.5% (7/200)** | | Acute Kidney Injury | 1.0% (2/200) | | Dysuria | 0.5% (1/200) | | Haematuria | 2.0% (4/200) | | Haemoglobinuria | 0.5% (1/200) | | **Reproductive System And Breast Disorders** | **3.5% (7/200)** | | Adenomyosis | 0.5% (1/200) | | Breast Mass | 1.0% (2/200) | | Breast Pain | 0.5% (1/200) | | Pelvic Pain | 0.5% (1/200) | | Postmenopausal Haemorrhage | 0.5% (1/200) | | Prostatitis | 0.5% (1/200) | | **Respiratory, Thoracic And Mediastinal Disorders** | **6.0% (12/200)** | | Asthma | 1.0% (2/200) | | Bronchospasm | 0.5% (1/200) | | Cough | 0.5% (1/200) | | Dyspnoea | 1.0% (2/200) | | Dyspnoea Exertional | 0.5% (1/200) | | Epistaxis | 2.0% (4/200) | | Lung Consolidation | 0.5% (1/200) | | **Skin And Subcutaneous Tissue Disorders** | **7.0% (14/200)** | | Dermatitis Allergic | 1.0% (2/200) | | Dermatitis Contact | 0.5% (1/200) | | Eczema | 0.5% (1/200) | | Neuropathic Ulcer | 0.5% (1/200) | | Psoriasis | 0.5% (1/200) | | Rash | 1.0% (2/200) | | Skin Ulcer | 3.5% (7/200) | | **Vascular Disorders** | **13.0% (26/200)** | {33} Table 14 displays serious adverse events (SAEs) that occurred from the day of the index procedure through 360 days post index procedure. All data presented herein are site-reported. A total of 104 SAEs were reported in 59 subjects. In total, $29.5\%$ of subjects experienced one or more SAEs. Incidences of General disorders and administration site conditions $(12.5\%)$ and Vascular disorders $(6.0\%)$ were the most commonly reported events. Table 14: Number of Subjects with One or More Serious Adverse Events (SAEs) through 360 Days by MedDRA System-Organ Class and Preferred Term | Serious Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Subjects with One or More Serious Adverse Events | 29.5% (59/200) | | System-organ class/preferred term | | | Blood And Lymphatic System Disorders | 1.0% (2/200) | | Anaemia | 1.0% (2/200) | | Cardiac Disorders | 3.0% (6/200) | | Acute Left Ventricular Failure | 0.5% (1/200) | | Acute Myocardial Infarction | 0.5% (1/200) | | Atrial Fibrillation | 2.0% (4/200) | | Cardiac Failure Congestive | 0.5% (1/200) | | Supraventricular Tachycardia | 0.5% (1/200) | PMA P200026: FDA Summary of Safety and Effectiveness Data {34} PMA P200026: FDA Summary of Safety and Effectiveness Data 35 of 42 | Serious Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | **Gastrointestinal Disorders** | 2.5% (5/200) | | Abdominal Hernia | 1.0% (2/200) | | Abdominal Wall Haematoma | 0.5% (1/200) | | Anal Fissure | 0.5% (1/200) | | Haemorrhoids | 0.5% (1/200) | | Retroperitoneal Haematoma | 0.5% (1/200) | | Small Intestinal Obstruction | 0.5% (1/200) | | **General Disorders And Administration Site Conditions** | 12.5% (25/200) | | Fatigue | 0.5% (1/200) | | Multiple Organ Dysfunction Syndrome | 0.5% (1/200) | | Peripheral Swelling | 0.5% (1/200) | | Vascular Stent Stenosis | 4.0% (8/200) | | Vascular Stent Thrombosis | 9.0% (18/200) | | **Infections And Infestations** | 2.5% (5/200) | | Intervertebral Discitis | 0.5% (1/200) | | Pneumonia | 1.5% (3/200) | | Pyelonephritis | 0.5% (1/200) | | Septic Shock | 0.5% (1/200) | | **Injury, Poisoning And Procedural Complications** | 3.0% (6/200) | | Meniscus Injury | 1.0% (2/200) | | Spinal Compression Fracture | 0.5% (1/200) | | Tendon Rupture | 0.5% (1/200) | | Vascular Access Site Haematoma | 1.0% (2/200) | | **Investigations** | 0.5% (1/200) | | Haemoglobin Decreased | 0.5% (1/200) | | **Musculoskeletal And Connective Tissue Disorders** | 3.5% (7/200) | | Arthralgia | 0.5% (1/200) | | Back Pain | 1.0% (2/200) | | Intervertebral Disc Protrusion | 0.5% (1/200) | | Osteoarthritis | 1.5% (3/200) | | **Nervous System Disorders** | 2.0% (4/200) | | Cerebrovascular Accident | 0.5% (1/200) | | Intracranial Aneurysm | 0.5% (1/200) | | Migraine | 0.5% (1/200) | | Nerve Compression | 0.5% (1/200) | {35} | Serious Adverse Event | Included Subjects (N=200 Subjects) | | --- | --- | | Renal And Urinary Disorders | 1.5% (3/200) | | Acute Kidney Injury | 1.0% (2/200) | | Haematuria | 0.5% (1/200) | | Respiratory, Thoracic And Mediastinal Disorders | 4.0% (8/200) | | Bronchiectasis | 0.5% (1/200) | | Dyspnoea Exertional | 1.0% (2/200) | | Epistaxis | 0.5% (1/200) | | Pleural Effusion | 1.0% (2/200) | | Pulmonary Embolism | 0.5% (1/200) | | Respiratory Failure | 0.5% (1/200) | | Skin And Subcutaneous Tissue Disorders | 1.5% (3/200) | | Skin Ulcer | 1.0% (2/200) | | Stasis Dermatitis | 0.5% (1/200) | | Vascular Disorders | 6.0% (12/200) | | Deep Vein Thrombosis | 2.0% (4/200) | | Lymphoedema | 1.0% (2/200) | | Peripheral Artery Stenosis | 0.5% (1/200) | | Peripheral Venous Disease | 0.5% (1/200) | | Varicose Vein | 1.5% (3/200) | | Vena Cava Thrombosis | 0.5% (1/200) | | Venous Haemorrhage | 0.5% (1/200) | | Total Serious Adverse Events | 104 | MedDRA version 22.0 Site-reported data. ## 2 Effectiveness Results The primary patency rate at 12 months was 88.0% (162/184). For the primary effectiveness endpoint, 184 evaluable subjects were included in the primary analysis and 16 subjects were excluded per the SAP due to the following: four subjects did not have sufficient clinical follow-up of at least 330 days (two deaths and two study exits), four subjects missed the 12-month visit. The remaining eight subjects were censored from the analysis due to having a CEC-adjudicated non-clinically driven target lesion revascularization (TLR). The lower limit of the 97.5% one-sided confidence interval (CI) was 82.5%, which was significantly higher than the performance goal of 75%, demonstrating that the primary effectiveness endpoint was met (p-value < 0.0001). Table 15 displays the 12-month PMA P200026: FDA Summary of Safety and Effectiveness Data {36} primary patency rate of 88.0%, as well as the individual components of primary patency. Among the subjects evaluable for primary patency, the freedom from occlusion rate at 12 months was 99.5%, the freedom from restenosis rate at 12 months was 92.9%, and the freedom from clinically driven TLR rate through 12 months was 92.4%. Table 15: Primary Effectiveness Endpoint – Primary Patency at 12 months | Parameter | ABRE (N=200 Subjects) | 95% Confidence Interval | | --- | --- | --- | | Primary Effectiveness Endpoint – Primary Patency at 12 Months | 88.0% (162/184) | [82.5%, 92.4%] | | Freedom from Occlusion of the Stented Segment of the Target Lesion | 99.5% (183/184) | [97.0%, 100.0%] | | Freedom from Restenosis (≥50%) of the Stented Segment | 92.9% (171/184) | [88.2%, 96.2%] | | Freedom from Clinically Driven Target Lesion Revascularization | 92.4% (170/184) | [87.6%, 95.8%] | 3. Secondary Endpoint Results Table 16 shows the results for the acute and late success secondary endpoints. Table 16: Acute and Late Success Secondary Endpoints | Parameter | ABRE (N=200 Subjects) (N=302 Devices) | | --- | --- | | Acute Success | | | Device Success | 100.0% (302/302) | | Lesion Success | 100.0% (200/200) | | Procedure Success | 99.0% (198/200) | | Late Success | | | Primary Assisted Patency at 12 months | 91.8% (169/184) | | Secondary Patency at 12 months | 92.9% (171/184) | Cumulative outcomes for the safety-related secondary endpoints through 12 months are shown below in Table 17. TLR was defined as any reintervention of the stented segment of the target lesion. The TLR rate, which includes both clinically driven and non-clinically driven TLRs, was 11.2% at 12 months. The MAE rate was 6.1% within 360 days. The individual components of this composite MAE rate are also shown. There were two deaths reported in the study, the first occurred 66 days from the index procedure and the second occurred 252 days from the index procedure. Both deaths were adjudicated by the CEC as not related to the procedure PMA P200026: FDA Summary of Safety and Effectiveness Data {37} and not related to the study device. No stent fractures or delayed stent migrations were reported through 12 months. No procedure-related major bleeding complications were reported. Table 17: Cumulative Complications within 12 Months | Parameter | ABRE (N=200 Subjects) | | --- | --- | | TLR within 360 Days† | 11.2% (22/196) | | MAE within 360 Days† | 6.1% (12/197) | | All-cause Death Occurring Post-procedure | 1.0% (2/197) | | Clinically Significant Pulmonary Embolism | 0.5% (1/195) | | Major Bleeding Complication (Post-procedural) | 0.5% (1/195) | | Stent Thrombosis | 4.1% (8/195) | | Stent Migration | 0.0% (0/195) | | Stent Fracture through 12 Months†† | 0.0% (0/180) | | Delayed Stent Migration through 12 Months†† | 0.0% (0/181) | | Major Bleeding Related to Index Procedure within 360 Days† | 0.0% (0/195) | †Safety endpoints (TLR, MAE, and Major Bleeding) included subjects with an event or a minimum number of follow-up days per timepoint. ††Stent Fracture and Delayed Stent Migration within 12 months included subjects who had scheduled visit-based evaluable imaging and unscheduled imaging up to day 420. Clinical endpoints at 12 months evaluated changes in functional assessments (VCSS and Villalta) and quality of life (EQ-5D Index and VEINES-QoL) compared to baseline. Trends toward improvement were noted from baseline to 12 months for all four measures, as shown in Table 18. Table 18: Quality of Life and Venous Functional Assessment Data | Assessment | Baseline Mean ± SE (n) | 6 Months Mean ± SE (n) | 12 Months Mean ± SE (n) | | --- | --- | --- | --- | | VEINES-QoL | 49.9 ± 1.8 (200) | 72.1 ± 1.8 (192) | 72.8 ± 1.8 (192) | | EQ-5D Index | 0.66 ± 0.02 (200) | 0.81 ± 0.01 (192) | 0.80 ± 0.02 (192) | | Villalta score | 11.2 ± 0.4 (199) | 4.7 ± 0.3 (191) | 4.2 ± 0.4 (192) | | VCSS score | 8.8 ± 0.3 (199) | 4.7 ± 0.3 (191) | 4.3 ± 0.3 (192) | ## 4. Subgroup Analyses The primary effectiveness and safety results were analyzed by different subgroups including gender, geographic region, and patient population. The study was not specifically… --- **Source:** [https://fda.innolitics.com/device/P200026](https://fda.innolitics.com/device/P200026) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com