everlinQ endoAVF System

DEN160006 · Tva Medical, Inc. · PQK · Jun 22, 2018 · Cardiovascular

Device Facts

• Record ID: DEN160006
• Device Name: everlinQ endoAVF System
• Applicant: Tva Medical, Inc.
• Product Code: PQK · Cardiovascular
• Decision Date: Jun 22, 2018
• Decision: DENG
• Submission Type: Direct
• Regulation: 21 CFR 870.1252
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The everlinQ® endoAVF System is indicated for the creation of an arteriovenous fistula (AVF) using the ulnar artery and ulnar vein in patients with minimum artery and vein diameters of 2.0 mm and less than 2.0 mm separation between the artery and vein at the fistula creation site who have chronic kidney disease and need hemodialysis.

Device Story

The everlinQ® endoAVF System is a percutaneous, single-use, magnetic catheter system used to create an endovascular arteriovenous fistula (endoAVF) in the arm. The system comprises two 6 Fr catheters (venous and arterial) containing magnets and an RF electrode. Under fluoroscopic guidance, the catheters are inserted into the ulnar artery and vein; magnets align the vessels and the electrode against a ceramic backstop. RF energy is delivered via an external electrosurgical unit (ESU) to create a transmural window, allowing blood flow between the vessels. The procedure is performed by trained physicians in an interventional setting. Adjunctive procedures, such as embolization coil placement in outflow veins, are typically required to direct blood flow and assist maturation. The device provides a minimally invasive alternative to surgical AVF, potentially reducing surgical trauma and recovery time for hemodialysis patients.

Clinical Evidence

The FDA determined the device is safe and effective based on clinical performance testing, animal testing, and non-clinical bench testing. Clinical performance testing evaluated delivery, deployment, and removal; fistula creation success; blood flow rates and diameter; usability for hemodialysis; patency; and adverse event rates. Animal testing assessed delivery, deployment, retrieval, patency, blood flow characterization, and histopathology for vascular injury and embolization.

Technological Characteristics

System consists of two 6 Fr magnetic catheters (venous with RF electrode, arterial with ceramic backstop). Materials are biocompatible (ISO 10993). Energy source: external ESU (RF energy). Connectivity: standalone (requires external ESU/pencil). Sterilization: Ethylene Oxide (EO). Software: None. Dimensions: 6 Fr diameter.

Indications for Use

Indicated for patients with chronic kidney disease requiring hemodialysis who have ulnar artery and vein diameters of at least 2.0 mm and an artery-vein separation of less than 2.0 mm at the fistula creation site.

Regulatory Classification

Identification

This device is a single use percutaneous catheter system that creates an arteriovenous fistula in the arm of patients with chronic kidney disease who need hemodialysis.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Clinical performance testing must evaluate: (i) The ability to safely deliver, deploy, and remove the device; (ii) The ability of the device to create an arteriovenous fistula; (iii) The ability of the arteriovenous fistula to attain a blood flow rate and diameter suitable for hemodialysis; (iv) The ability of the fistula to be used for vascular access for hemodialysis; (v) The patency of the fistula; and (vi) The rates and types of all adverse events. (2) Animal testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be assessed: (i) Delivery, deployment, and retrieval of the device; (ii) Compatibility with other devices labeled for use with the device; (iii) Patency of the fistula; (iv) Characterization of blood flow at the time of the fistula creation procedure and at chronic followup; and (v) Gross pathology and histopathology assessing vascular injury and downstream embolization. (3) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested: (i) Simulated-use testing in a clinically relevant bench anatomic model to assess the delivery, deployment, activation, and retrieval of the device; (ii) Tensile strengths of joints and components; (iii) Accurate positioning and alignment of the device to achieve fistula creation; and (iv) Characterization and verification of all dimensions. (4) Electrical performance, electrical safety, and electromagnetic compatibility (EMC) testing must be performed for devices with electrical components. (5) Software verification, validation, and hazard analysis must be performed for devices that use software. (6) All patient-contacting components of the device must be demonstrated to be biocompatible. (7) Performance data must demonstrate the sterility of the device components intended to be provided sterile. (8) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life. (9) Labeling for the device must include: (i) Instructions for use; (ii) Identification of system components and compatible devices; (iii) Expertise needed for the safe use of the device; (iv) A detailed summary of the clinical testing conducted and the patient population studied; and (v) A shelf life and storage conditions.

Submission Summary (Full Text)

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#### DE NOVO CLASSIFICATION REQUEST FOR EVERLINQ® ENDOAVF SYSTEM

#### REGULATORY INFORMATION

FDA identifies this generic type of device as:

Percutaneous catheter for creation of an arteriovenous fistula for hemodialysis access. This device is a single use percutaneous catheter system that creates an arteriovenous fistula (AVF) in the arm of patients with chronic kidney disease who need hemodialysis.

NEW REGULATION NUMBER: 21 CFR 870.1252

CLASSIFICATION: II

PRODUCT CODE: POK

#### BACKGROUND

DEVICE NAME: everlinQ® endoAVF System

SUBMISSION NUMBER: DEN160006

DATE OF DE NOVO: February 3, 2016

CONTACT: TVA Medical, Inc. 7000 Bee Cave Rd., Suite 250 Austin, TX 78746

#### INDICATIONS FOR USE

The everlinQ® endoAVF System is indicated for the creation of an arteriovenous fistula (AVF) using the ulnar artery and ulnar vein in patients with minimum artery and yein diameters of 2.0 mm and less than 2.0 mm separation between the artery and vein at the fistula creation site who have chronic kidney disease and need hemodialysis.

#### LIMITATIONS

The sale, distribution, and use of the everlinO® endoAVF System are restricted to prescription use in accordance with 21 CFR 801.109.

Only physicians trained and experienced in endovascular techniques, who have received appropriate training with the device, should use the device. Endovascular technique training and experience should include ultrasound vessel access in the arm, guidewire navigation, radiographic imaging, embolization coil placement, and access closure,

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The everlinQ® endoAVF System is contraindicated for patients with a distance between target artery and vein > 2mm, and patients with target vessels < 2mm in diameter.

The TVA Medical everlinQ® System is only to be used with the components specified in the labeling. Do not attempt to substitute a non-approved component or to use any component of this system with any other medical device system. Use of the system with other components, such as braided sheaths, may interfere with proper functioning of the device.

The 6F everlinQ System has only been evaluated for the creation of an AVF using the ulnar artery and ulnar vein. The device should not be used in place of a more distal AVF.

Adjunctive procedures are expected to be required at the time of the index procedure to increase and direct blood flow into the AVF target outflow vein to assist maturation. Care should be taken to proactively plan for any adjunctive procedures, such as embolization coil placement, when using the device.

PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.

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# DEVICE DESCRIPTION

The everlinQ® endoAVF System (everlinQ®) consists of two single-use disposable magnetic catheters: a venous catheter and an arterial catheter, both of which are 6 Fr in diameter. The venous catheter contains an electrode for delivery of radiofrequency (RF) energy while the arterial catheter contains a ceramic backstop that serves as a mechanical stop for the electrode. The everlinQ® is used with a commercially available electrosurgical unit (ESU) and electrosurgical pencil.

Image /page/2/Figure/2 description: The image shows an electrosurgical generator, ground pad, electrosurgical pencil, and everlinQ endoAVF catheters. The electrosurgical generator has a display that reads "060 20 SEC". There is also a detailed diagram of the 6 Fr Rapid Exchange Venous Catheter and the 6 Fr Over-the-Wire Arterial Catheter, showing the electrode housing, radiofrequency electrode, embedded magnets, and electrode backstop.

Figure 1: everlinQ® endoAVF System

The venous and arterial catheters are inserted into the ulnar vein and ulnar artery, respectively. The two catheters are then aligned and rotated, and when they achieve the proper position, the magnets contained in each catheter attract to one another, approximating the vessels while simultaneously aligning the electrode with the backstop. Using the ESU, grounding pad, and electrosurgical pencil, RF energy can then be delivered through the electrode for tissue cutting. This energy creates a small, rectangular hole (approximately 5 mm x 1 mm) in the adjoining vessels, allowing blood to flow from the artery to the vein and thereby creating a nonsurgical, or endovascular, arteriovenous fistula (endoAVF).

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Image /page/3/Figure/0 description: The image shows an x-ray of two catheters, labeled as "Arterial Catheter" and "Venous Catheter". The arterial catheter is on top and appears to have regularly spaced, rectangular, radio-opaque markers. The venous catheter is below the arterial catheter and appears to be a single, continuous tube.

Figure 2: Proper alignment of the catheters

Please refer to the Instructions for Use for additional details.

## SUMMARY OF NONCLINICAL/BENCH STUDIES

# BIOCOMPATIBILITY/MATERIALS

The everlinQ® endoAVF System is an externally communicating device in contact with circulating blood with limited contact duration (< 24 hours). The biocompatibility testing summarized below was performed to demonstrate that the device is biocompatible for its intended use. All tests passed.

| Test | Description (Method) |
|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Cytotoxicity | MEM Elution Assay with L-929 Mouse Fibroblast Cells<br>(ISO 10993-5) |
| Sensitization | Guinea Pig Maximization<br>(ISO 10993-10) |
| Irritation | Intracutaneous Reactivity<br>(ISO 10993-10) |
| Acute System Toxicity | Acute Systemic Injection<br>(ISO 10993-11) |
| Hemocompatibility | ASTM Hemolysis Assay - Direct Contact & Extract Methods<br>(ASTM Method F756-08)<br>Complement Activation C3a and SC5b-9 Determination of SC5b-9 Terminal Chain Complex (TCC) and C3a-desArg Present in Normal Human Serum Through Enzyme Immunoassay<br>(ISO 10993-4)<br>In-vivo Thromboresistance<br>(evaluated as part of the animal studies) |
| Pyrogenicity | Material-mediated Rabbit Pyrogen<br>(USP Rabbit Pyrogen Test Procedure, Section 151)<br>Endotoxin-mediated (LAL)<br>(AAMI ST72) |

| Table 1: Biocompatibility Testing Summary | | | | | |
|-------------------------------------------|--|--|--|--|--|
|-------------------------------------------|--|--|--|--|--|

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## SHELF LIFE/STERILITY

The shelf-life of the everlinQ® endoAVF System has been established at 1 year based on accelerated aging testing equivalent to 1 year (13 months) in accordance with ASTM F 1980 - 07 Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices. Following 2X sterilization, environmental conditioning per ISTA 2A, distribution simulation per ASTM D4169, and accelerated aging, the devices were visually inspected for damage, bubble leak tested per ASTM F2096, and package seals were tested per ASTM F88. Aged devices also underwent repeat engineering bench testing to confirm acceptable performance.

The everlinQ® endoAVF System is labeled as sterile and has a validated sterility assurance level (SAL) of 106. The everlinO® endoAVF System has been validated to be sterilized via ethylene oxide (EO). The sterilization cycle was validated using the half cycle method per ISO 11135-1:2007, and the EO and ECH residuals were shown to meet the limits specified by ISO 10993-7:2008.

### ELECTROMAGNETIC COMPATIBILITY AND ELECTRICAL SAFETY

The electromagnetic compatibility and electrical safety of the everlinQ® endoAVF System was evaluated by demonstrating compliance to the following standards:

| Standard | Name |
|-----------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| AAMI / ANSI<br>ES60601-<br>1:2005/(R)2012 and<br>A1:2012,<br>C1:2009/(R)2012 and<br>A2:2010/(R)2012 | Medical Electrical Equipment - Part 1: General<br>Requirements For Basic Safety And Essential<br>Performance |
| IEC 60601-1-2:2014 | Medical Electrical Equipment - Part 1-2:<br>General Requirements For Basic Safety And<br>Essential Performance - Collateral Standard:<br>Electromagnetic Disturbances - Requirements<br>and Tests |
| IEC 60601-2-2:2009 | Medical Electrical Equipment - Part 2-2:<br>Particular Requirements For The Basic Safety<br>And Essential Performance of High Frequency<br>Surgery Equipment And High Frequency<br>Surgical Accessories |

Table 2: Electrical Performance Testing Summary

# MAGNETIC RESONANCE (MR) COMPATIBILITY

The everlinQ® endoAVF System is intended as a temporary use device and has not been tested for MR compatibility.

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#### SOFTWARE

The everlinQ® endoAVF System does not contain software. The device is intended to be used with a commercially available ESU, electrosurgical pencil, and grounding pad.

#### PERFORMANCE TESTING - BENCH

The everlinQ® endoAVF System was subjected to a series of bench tests to assess its functional performance. These tests were performed on final, sterilized product. The engineering bench testing summarized in Table 3 below was performed to demonstrate acceptable mechanical performance of the device for its intended use.

| | Test | Description/Acceptance Criteria |
|-----------------------------|--------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Dimensional<br>Verification | Electrode Wire<br>Deployment<br>(Distance) | The distance from distal tip of electrode (toe) to catheter shaft must<br>measure .093" $\pm$ .010" when slide collar/electrode are in "fire"<br>position. |
| | Electrode Wire<br>Deployment<br>(Angle) | Angle between flattened surface of the electrode and the centerline<br>of the catheter shaft must measure 7.5° $\pm$ 2.5° when slide<br>collar/electrode are in "fire" position. |
| Simulated<br>Use | Simulated Use<br>Conditioning | Track the device through a simulated worst-case anatomic model<br>using the appropriate accessories (e.g. introducer sheaths). |
| | Handle Actuation | Electrodes must deploy from electrode housing when slide collar is<br>pulled proximal to device and reside in "fire" position. Rotating<br>slide lock must permit electrode to be pulled into the proximal<br>electrode housing such that no part of the electrode protrudes no<br>further than the outside diameter of the catheter. |
| | Device Alignment | With catheters magnetically apposed and electrode deployed,<br>rotational and axial alignment must be held such that the electrode<br>maintains contact within the margins of the arterial backstop in<br>100% of samples tested. |
| | Energy Delivery | Upon application of energy, devices must create heat eddies at the<br>active electrode while exhibiting no degradation in insulative<br>materials near the active electrode. The test also evaluated the<br>ability of the device to deliver energy properly when used with the<br>labeled electrosurgical generator. |
| | Tissue Cutting Test | Electrodes must be able to create a transmural window measuring $\ge$<br>1mm long and $\ge$ .25mm wide in tissue measuring $\ge$ 2.0mm thick<br>when the device is used in conjunction with the labeled<br>electrosurgical unit at the required electrical settings. |
| | Torque Strength | The distal tip of the device was fixed, and the proximal end of the<br>device was rotated until failure. The number of rotations to failure<br>and the failure mode were characterized. |
| | Torque Response | The catheters were rotated 360° clockwise and 360°<br>counterclockwise within the anatomic model, and the process was<br>repeated four times. The torque response was evaluated. |
| | Visual Inspection | Following simulated use, devices must be free from any damage<br>that would prevent it from normal function/use and devices must<br>meet performance requirements established for all subsequent<br>verification tests. |

Table 3: Performance Testing (Bench) Summary

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| Tensile Strength | | Bonds/joints shall maintain mechanical integrity during useEach bond/joint was tested against specifications based on the clinical use of the device | | | | | | | | | | | | | | | | | |
|---------------------------------|---------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|--|
| Corrosion Resistance | | Metallic components of the catheter intended for fluid path contact shall show no signs of corrosion. | | | | | | | | | | | | | | | | | |
| Leak Testing | | Air shall not leak into the hub assembly during aspirationThe hub or catheter shall not leak liquid | | | | | | | | | | | | | | | | | |
| Catheter Lubricity | | The LTL for average pull force over five cycles will be < 50g when tested over a 10cm distance and 500g pinch force. | | | | | | | | | | | | | | | | | |
| Visual Inspection | | Catheters must be free from any damage that would prevent it from normal function or use. This includes, but is not limited to fractures, cracks, kinks, tears, loose components, or inadvertent electrode deployment. | | | | | | | | | | | | | | | | | |
| Radiopacity | | Visibility of the device and alignment under fluoroscopy was demonstrated by representative images taken during the animal studies. | | | | | | | | | | | | | | | | | |
| Coating<br>Integrity<br>Testing | Coating<br>Durability and<br>Coverage<br>Particulate<br>Analysis | Coated venous and arterial catheters were stained with (b) (4) dye and evaluated for stain coverage after moderate finger rubbing.<br>All test samples exhibited at least 90% stain coverage. | | | | | | | | | | | | | | | | | |
| | | | Average # of Particles<br>(Per device pair) Diameter Size Range<br>(μm) Test Group ≥ 10 ≥ 25 ≥ 50 Initial (T = 0) 6382 238 14 Aged (T = 1yr) 3171 152 20 | | | | | | | | | | | | | | | | |
| Electrical Plug<br>Testing | Cord Tensile<br>Strength<br>Shroud Tensile<br>Strength<br>Shroud<br>Compressive<br>Strength | Peak tensile strength between the plug and the cord must be ≥ 5 lbf.<br>Peak tensile strength between the plug and the shroud must be ≥ 5 lbf.<br>Peak compressive strength between the plug and the shroud must be ≥ 5 lbf. | | | | | | | | | | | | | | | | | |

### PERFORMANCE TESTING - ANIMAL &/OR CADAVER

Two main groups of studies were conducted to support the development of the everlin()® endoAVF System: (1) early testing using an early version of the device in a cadaver study along with three non-GLP acute animal studies and (2) a concluding eight-animal GLP chronic and acute study using the final device.

The non-GLP acute animal studies and cadaver study used an early version of the device that was similar to the final device design. These studies demonstrated that an endoAVF could be successfully created, there was no unintended tissue damage, and no thrombus formation was observed. These studies also demonstrated that the device could be successfully delivered to the desired location of the AVF using the labeled accessories and that the device was easy to use. The design and results of the GLP study are summarized in Table 4 below. The GLP study demonstrated that the endoAVF could be created safely with adequate blood flow through the fistula and no adverse

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histopathological findings at 30 days.

| Purpose | Methods | Results |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Evaluate the acute and<br>chronic safety, fistula<br>blood flow<br>characteristics, fistula<br>patency, handling<br>characteristics,<br>visibility under<br>fluoroscopy, thrombus<br>formation, and<br>histopathological<br>response at the<br>treatment site and off-<br>target tissue sites of<br>the final device design<br>according to Good<br>Laboratory Practices | • GLP<br>• N=8 ovine models (N=4 acute<br>study, N=4 chronic study).<br><br><b>Acute Study</b><br>• Insert, track, deploy, and<br>activate device to create a<br>single AVF in N=2 ovine<br>models, then procedure time<br>and energy delivery were<br>recorded.<br>• After creation, fistulas<br>evaluated (by ultrasound,<br>thermal dilution and/or<br>fluoroscopy via contrast<br>injection) to determine patency<br>and fistula flow.<br>• After 0-1 hour survival,<br>necropsy performed to ensure<br>no downstream tissue effects.<br>• AVF site, vessels and tissue in<br>proximity were histologically<br>examined to characterize these<br>tissues.<br>• Insert, track, deploy, and<br>activate device to create 4 or 5<br>AVFs in N=2 additional ovine<br>models.<br>• After 0-1 hour survival,<br>necropsy performed in which<br>the vessels were identified and<br>AVFs photographed.<br><br><b>Chronic Study</b><br>• Insert, track, deploy, and<br>activate device to create a<br>single AVF in N=4 ovine<br>models.<br>• After creation, fistulas<br>evaluated (by ultrasound,<br>thermal dilution and/or<br>fluoroscopy via contrast<br>injection) to determine patency<br>and fistula flow.<br>• After 30 days survival, fistulas<br>again examined to determine<br>patency and fistula flow.<br>• Necropsy performed to ensure<br>no downstream tissue effects.<br>• AVF site, vessels and tissue in | • 14/15 attempts to create fistulas in the 8<br>animals were successful. One attempt<br>failed due to a procedural mistake<br>related to the ovine vasculature, and is<br>not relevant to the intended human<br>anatomy.<br>• All animals survived to the prescribed<br>in-life survival.<br>• There was no morbidity or major<br>unanticipated events that were related<br>to the use of the device.<br>• Fistulas were shown to be patent at 30<br>days following AVF creation using<br>fluoroscopic imagery.<br>• Blood flow was observed after fistula<br>creation and at 30 days.<br>• There was no evidence of mechanical<br>or thermal injury extending beyond the<br>immediate treatment site following the<br>procedure, and fistula sites appeared to<br>heal well by 30 days.<br>• Arterial and venous ostia appeared<br>acceptably uniform in size and<br>appearance.<br>• No gross findings in off-target or<br>downstream tissues which were<br>indicative of device or treatment related<br>events.<br>• Histopathology in acute animals was<br>negative for thromboembolic events in<br>the lungs or coronary bands.<br>• Post-procedure histopathology of<br>treatment sites showed focal<br>perforations in the artery and vein with<br>perivascular hemorrhage into<br>surrounding fat, as well as treated edges<br>of the ostia characterized by focal mild<br>compressions and subtle thermal<br>coagulation. The observations appeared<br>to be expected for the AVF creation<br>procedure and resolved with time.<br>• Histopathology at 30 days showed the<br>fistulae were patent and maturing, with<br>no evidence of thromboemboli<br>generation, vascular remodeling, or<br>injury.<br>• No bleeding was observed at 30 days.<br>• No histopathological observations<br>related to the device were noted in the<br>heart. |
| proximity were histologically<br>examined to characterize these<br>tissues.<br>• Mechanical and thermal injury,<br>inflammation, fibrin/thrombus,<br>fibrosis, mineralization,<br>necrosis, hemorrhage, and<br>intimal proliferation were<br>evaluated.<br>• Gross pathology of treatment<br>sites, subcutaneous tissues on<br>the downstream distal limb, and<br>systemic organs in acute and<br>chronic studies.<br>• Histopathology of acute<br>treatment sites, chronic | • No histopathological findings related to<br>device safety were observed in the<br>lungs. One small, localized fat embolus<br>was observed but was asymptomatic<br>and deemed to be coincidental as it has<br>not been observed to occur during<br>percutaneous interventional procedures<br>in the arteries or veins in humans. | |

Table 4: Summary of GLP Preclinical Study

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### SUMMARY OF CLINICAL INFORMATION

The everlinQ® System was primarily supported by a pivotal study entitled the "Novel Endovascular Access Trial" (NEAT Study). In addition, a supportive global analysis of clinical use of the everlinQ® System ("Global Analysis") was conducted that included data from 4 prospective clinical studies (FLEX, NEAT, EU PMCF and EASE) and 1 commercial use data set (COMM). A pooled analysis of the 4 prospective clinical studies was also presented. Details of the study designs and key clinical outcomes are provided in the following sections. The study names are defined as follows:

- FLEX A Prospective Pilot Clinical Evaluation of the TVA FLEX-1 Device .
- NEAT Novel Endovascular Access Trial .
- EU PMCF Post Market Study of the everlinQ® endoAVF System .
- EASE everlinQ® Endovascular Access System Enhancements Study .
- COMM commercial use data set .

| Data Source | Device Studied | Dates of Index<br>Procedures | # Sites<br>(Countries) | Total<br>Subjects | Subjects in Pooled<br>Analysis5 | |
|-------------|----------------|------------------------------|-----------------------------|-------------------|---------------------------------|---------------|
| | | | | | Safety | Effectiveness |
| FLEX1 | 6Fr FLEX-1 | Aug 2012-Sep<br>2013 | 1 (Paraguay) | 33 | 33 | 33 |
| NEAT | 6Fr everlinQ® | Jan 2014- Aug<br>2015 | 6 (Canada)<br>2 (Australia) | 60 | 60 | 60 |
| EASE2 | 4Fr everlinQ® | May 2016 - Nov<br>2016 | 1 (Paraguay) | 32 | 0 | 32 |
| EU-PMCF | 6Fr everlinQ® | Sep 2016 - Aug<br>2017 | 5 (Germany)<br>3 (England) | 32 | 32 | 32 |
| COMM- All3 | 6Fr everlinQ® | Feb 2015 - Jun<br>2017 | 4 (England)<br>16 (Germany) | 79 | 0 | 0 |

Table 5: Clinical Data Sources

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| COMM -<br>Cannulated4 | Feb 2015 - Aug 2017 | 1 (Netherlands)<br>1 (Switzerland) | 45 | 0 | 0 |
|-----------------------|---------------------|------------------------------------|-----|-----|-----|
| Total Subjects5 | | | 236 | 125 | 157 |

- The FLEX-1 device was a previous version of the subject device. After the FLEX Study, design modifications 1. were made to improve ease of use (i.e. handle ergonomics and user interface). The overall mechanism of action and device function for creating an endoAVF has remained the same throughout all revisions of the 6Fr FLEX-1 and everlinO® devices.
- 2. The EASE subjects were not included in the Pooled Safety Population, since the 4Fr system is a different product compared to the 6Fr systems used in the other data sources.
- 3. No COMM subjects were included in the Pooled Safety or Effectiveness Populations because data were unavailable in the commercial cases, precluding pooling.
- The COMM-Cannulated cases comprise the subset of COMM-All cohort where follow-up data were collected. 4. including safety data and cannulation data.
- The total number of subjects is less than the sum of the "Total Subjects" column because the COMM -5 Cannulated subject cohort is a subset of all the commercial subjects included in the COMM-All data.

# Primary Clinical Data Set: NEAT Study

Objective: The purpose of the NEAT Study was to evaluate the safety and effectiveness of the everlinO endoAVF System among subjects undergoing endoAVF creation.

Study Design: The NEAT study was a prospective, single-arm, multi-center study that enrolled 60 "study cohort" subjects and 20 "roll-in" subjects at 9 sites in Canada, Australia and New Zealand. Candidates for this study were subjects with chronic kidney disease (CKD) who required a hemodialysis vascular access.

Eligibility Criteria Summary: The study population consisted of male and female patients from Canada, Australia, and New Zealand who had chronic kidney disease (CKD), required a hemodialysis vascular access, and were at least 18 years of age.

Key inclusion criteria included the following:

- . Established, non-reversible kidney failure requiring hemodialysis.
- Patients deemed eligible for a native arteriovenous fistula.
- Target artery diameter and target vein diameter both ≥ 2.0 mm.
- Estimated life expectancy > 1 year.
- . Subject was free of clinically significant conditions or illness within 30 days prior to the AV fistula that may compromise the procedure.

Key exclusion criteria included the following:

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- Subjects who are eligible for a distal forearm fistula were excluded from the study. . Exception: If a distal forearm fistula had failed or distal forearm fistula was not the most optimum choice the subject was considered eligible to enroll.
- . Known central venous stenosis or central vein narrowing > 50% based on imaging on the same side as the planned AVF creation.
- . Upper extremity venous occlusion(s) and/or vessel abnormality(ies) on the same side as the planned AVF creation that precludes endovascular AVF creation by everlinQ endoAV System as deemed by the interventionalists' clinical judgment.
- At the time of procedure distance between target artery and vein will not allow magnets . to align vessels sufficiently to create the fistula.
- Prior upper arm surgically created access or functioning surgical access in the planned ● treatment arm.
- Subjects with Body Mass Index (BMI) >35 who, in an expert cannulator's opinion, are ● not appropriate candidates for cannulation.
- "Planned" concomitant major surgical procedure within 6 months of enrollment or previous major surgery within 30 days of enrollment.
- . Immunosuppression, defined as use of immunosuppressive medications used to treat an active condition.
- . New York Heart Association (NYHA) class III or IV heart failure.

Demographics: The total Intent-to-Treat (ITT) population consisted of 60 subjects. Data about the patient demographics and baseline comorbidities are provided in the tables below.

| Characteristic | Summary |
|----------------------------------------------------------|----------------------------------------|
| Gender | |
| Male | 65.0% (39/60) |
| Female | 35.0% (21/60) |
| Age (years) | 59.9 ± 13.6 (60)<br>61.0 [28.0, 85.0] |
| BMI | 27.9 ± 6.1 (60)<br>27.1 [16.1 ,44.1] |
| BMI > 25 | 63.3% (38/60) |
| Target Dialysis Weight (kg) | 80.9 ± 21.9 (60)<br>78.7 [43.0, 138.9] |
| Race | |
| Caucasian | 60.0% (36/60) |
| Asian | 31.7% (19/60) |
| Native Hawaiian/Pacific Islander | 1.7% (1/60) |
| Other | 6.7% (4/60) |
| Smoker (current or previous) | 33.3% (20/60) |
| Previous AVF (prior to study) | 31.7% (19/60) |
| Same arm as used for endoAVF creation | 73.7% (14/19) |
| Contralateral arm as used for endoAVF creation | 26.3% (5/19) |
| Pre-dialysis | 56.7% (34/60) |
| Data displayed as Mean±SD (N);Median [Range] or % (n/N). | |

Table 6: NEAT Study Subject Demographics

Table 7: NEAT Study Baseline Comorbidities

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| Medical Condition/Comorbidity | Summary<br>% (n/N) |
|----------------------------------------------|--------------------|
| Primary Diagnosis Causing ESRD: | |
| Diabetes | 50.0% (30/60) |
| Glomerular based disease | 13.3% (8/60) |
| Hypertension | 15.0% (9/60) |
| Interstitial nephritis | 1.7% (1/60) |
| Polycystic kidney disease | 6.7% (4/60) |
| Other | 11.7% (7/60) |
| Unknown | 1.7% (1/60) |
| Comorbidities: | |
| Chronic Obstructive Pulmonary Disease (COPD) | 3.3% (2/60) |
| Cerebrovascular Disease (CVA/TIA) | 15.0% (9/60) |
| Congestive heart failure (NYHA I or II) | 11.7% (7/60) |
| Coronary artery disease (CAD) | 21.7% (13/60) |
| Diabetes | 65.0% (39/60) |
| Hypertension | 91.7% (55/60) |
| Hyperlipidemia | 48.3% (29/60) |
| Malignancy | 18.3% (11/60) |
| Prior peritoneal dialysis | 30.0% (18/60) |
| Prior renal transplant | 13.3% (8/60) |

Accountability: A total of 183 subjects were screened for participation in the study. Sixteen (16) patients declined to participate and 84 patients failed initial screening. Three (3) additional patients failed final enrollment criteria (distance between target artery and vein too great at time of procedure) and were excluded at the time of index procedure. Most subjects who were excluded from the study did not meet the target vessel criteria of ≥ 2mm. In total, 80 subjects were enrolled in the study; 60 subjects were included in the study cohort and 20 subjects comprised a roll-in cohort.

Figure 3 below depicts the subject disposition in the NEAT Study. The figure shows the number of subjects who were evaluated or exited the study at each time point. Among the 60 study cohort subjects, 3 subjects (5%) died during the study and 8 (13.3%) withdrew for other reasons. A total of 11 subjects (18.3%) exited the study before the 12-month follow-up time point, and 4 additional subjects (6.7%) were not yet eligible for their 12-month evaluation at the final NEAT study report was submitted.

In total, 45/60 subjects (75%) were evaluated at 12 months. Those 45 subjects included 24 predialysis subjects (24/34 = 70.6% of pre-dialysis subjects) and 21 dialysis subjects (21/26 = 80.8% of dialysis subjects).

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Image /page/12/Figure/0 description: This image is a flowchart that shows the progression of subjects through a study. The study started with 183 subjects assessed for eligibility, and 80 were enrolled. Of the 183, 103 were excluded because they did not meet the inclusion criteria or declined participation. The 80 enrolled subjects were divided into two groups: 20 roll-in subjects and 60 study cohort subjects, and the flowchart shows the number of subjects who completed each follow-up visit, as well as the number of subjects who exited the study at each time point.

Figure 3: NEAT Study Subject Disposition Through End of Study

# Primary Endpoints

- 1) Safety: The safety endpoint was the percentage of patients who experienced one or more serious study device related adverse events during the first 3 months following AVF creation as adjudicated by an independent Clinical Events Committee (CEC). There was no formal hypothesis test associated with the safety endpoint. Analysis of the safety endpoint was performed on the study cohort subjects.

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The following definitions were used for the safety analyses:

- Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or . untoward clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not related to the investigational medical device.
- Serious adverse event (SAE): A serious adverse event was defined as an adverse event that:
- a) Led to death,
- b) Led to serious deterioration in the health of the subject, that either resulted in
- i. a life-threatening illness or injury, or
- a permanent impairment of a body structure or a body function, or ii.
- iii. in-patient or prolonged hospitalization, or
- medical or surgical intervention to prevent life-threatening illness or injury or iv. permanent impairment to a body structure or a body function,
- c) led to foetal distress, foetal death or a congenital abnormality or birth defect

NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the Study Protocol, without serious deterioration in health, was not considered an SAE.

- 2) Effectiveness: The primary endpoint of the study was the percentage of patients with fistula maturation/usability at 3 months post-procedure, defined as endoAVF that is free of stenosis or thrombosis, with brachial artery flow of at least 500 ml/min and at least 4 mm vein diameter (as measured by duplex ultrasound) OR patient was dialyzed using 2 needles.
Note: stenosis and thrombosis were defined as flow limiting complications that led to fistula closure at any time during the first 3 months post index procedure. Dialysis using 2 needles were assessed at any time during the first 3 months post index procedure.

This composite endpoint was chosen based on the most common three reasons for AVF failure to mature or lack of AVF usability: 1) thrombosis, 2) stenosis and 3) inadequate flow or diameter of the vein leading to abandoned AVF.

The primary effectiveness endpoint was tested for all 60 study cohort subjects ("Enrolled" population). Subjects in whom an endoAVF was attempted (i.e. RF energy was applied) but not created were included in the analysis as failures. If a patient had missing endpoint data, due to reasons not related to the endoAVF, procedure, or device, they were not included in the primary analysis.

The formal hypothesis tested for the primary endpoint was the 3-months proportion of patients with fistula maturation/usability greater than a historically derived performance goal:

Ho: π ≤ 57.5% vs. Ha: π > 57.5%,

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where T is the proportion of patients with fistula maturation/usability and 57.5% is the historically derived performance goal (PG). The PG was derived based on surgical AVF failure rates reported in clinical literature.

The number and percentage of patients with fistula maturation/usability within 3 months were summarized. A 90% exact confidence interval (CI) was calculated. The lower bound of the confidence interval was compared to the performance goal of 57.5% to determine success.

# Secondary Endpoints

Secondary endpoints were summarized using descriptive statistics. There were no formal hypotheses associated with these endpoints and these analyses were not statistically powered. Analyses for each endpoint were performed on the study cohort subjects unless otherwise noted.

- Procedural success: The successful endoAVF creation rate as assessed via fistulogram . immediately post-procedure or duplex ultrasound, or via presence of thrill/bruit.
- . Time to Fistula Maturation: the number of days between the date of AVF creation and the date of endoAVF maturation (based on primary efficacy endpoint definition of maturation).
- Duration of Central Venous Catheter (CVC) Exposure: The rate of CVC use at 1, 2, 3, 6 and 12 months follow-up. The analysis was performed for pre-dialysis and on dialysis subjects.
- . endoAVF-related Interventions Rate: The intervention rate for endoAVF (defined as any intervention required to maintain or re-establish patency; may be also referred as "reintervention" rate) was calculated at 3, 6 and 12 months post index procedure.
- Primary Patency: The primary patency rate was determined via Kaplan-Meier methods and . based on the time of endoAVF creation until any intervention designed to maintain or reestablish patency or endoAVF abandonment.
- . Secondary Patency: The secondary patency rate was determined via Kaplan-Meier methods and based on the time of endoAVF creation until access abandonment.
- . Additional analyses were summarized using descriptive statistics:
- Rate of serious procedure-related AEs at 3 and 6 months. o
- o Rate of serious device-related AEs at 6 months.
- Rate of device and/or procedure-related infections at 6 months. o
- Arterial flow rates and diameters as measured via DUS at 3, 6 and 12 months post o index procedure.
- o Subject satisfaction and quality of life parameters via Vascular Access questionnaire.
- The percentage of subjects dialyzed using endoAVF (2 needles) for 2/3 of their o dialysis sessions over a 4-week period.

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Results: The principal safety and effectiveness results from patients in the study are provided below. The analyses were performed on all 60 study cohort subjects (excluding roll-in subjects) unless otherwise noted.

Primary Safety Endpoint: At 3 months post index procedure, only one subject experienced one serious device related event (pseudoaneurysm), resulting in an observed percentage of 1.67% (1/60) with a two-sided 95% exact binomial confidence interval of 0.04% - 8.94%.

Primary Effectiveness Endpoint: The primary effectiveness endpoint results are shown in the table below. The primary endpoint was met with a 90-day maturation success rate of 52/57 (91.2%).

| | Subject<br>Success<br>% (n/N) | Exact 90%<br>Confidence<br>Interval | Hypothesis | Decision | Conclusion |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|-------------------------------------|---------------------------------------------|--------------|-------------------------|
| Subject with endoAVF that is<br>free of stenosis or thrombosis1,<br>with brachial artery flow of at<br>least 500 ml/min and at least 4<br>mm vein diameter OR subject<br>was dialyzed using 2 needles<br>1As adjudicated by the CEC. | 91.2%<br>(52/57) | (82.4%,<br>96.5%) | Ho: ps $ \u2264 $ 57.5%<br>HA: ps > 57.5% | Reject<br>Ho | Performance<br>Goal Met |

Table 8: Primary Effectiveness Endpoint Results - 90-Day Maturation Success Rate

The primary effectiveness analysis did not include 3 subjects who either died prior to the 90-dav evaluation, unrelated to the device or procedure (1 subject) or experienced a procedural complication that led to endoAVF sacrifice (2 subjects).

If all 60 study cohort subjects were included in the primary endpoint analysis, the primary endpoint result was 52/60 = 86.7%. The primary endpoint was still met (90% CI: 77.2-93.2%).

Secondary Endpoints: A summary of the secondary endpoint analyses are provided below. All analyses presented below are based on the ITT population unless otherwise noted.

- Procedural Success: Procedural success was achieved in 59/60 subjects (98.3%) per the definition above.
- . Time to Fistula Maturation: The mean time to maturation based on the endpoint criteria was 14.8 days. Additional details are provided in the table below.

Table 9: Time to Fistula Maturation

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| Maturation Time | Mean ± SD (N)<br>Median [Range] |
|---------------------------------------------------|----------------------------------------|
| Days to endoAVF maturation based on DUS | 14.8 ± 26.0 (52)<br>5.0 [1.0, 97.0] |
| Days to endoAVF maturation based on physical exam | 65.0 ± 44.3 (45)<br>58.0 [26.0, 213.0] |

- . Duration of Central Venous Catheter (CVC) Exposure: CVC exposure was evaluated for both pre-dialysis subjects and subjects who were on dialysis. Table 10 below shows the number of subjects who had a CVC in place at each timepoint. In sum, the total NEAT study CVC exposure at 12 months was 14/60 subjects (23.3%), calculated by adding 4/35 CVC only + 0/35 CVC and endoAVF subjects from the pre-dialysis subset, in addition to 6/25 CVC-only + 4/25 CVC and endoAVF subjects from the post-dialysis subset.

| Pre-Dialysis Subjects | |
|-------------------------|---------------|
| 1-Month (0-45 Days) | |
| CVC only | 3/35 (8.6%) |
| endoAVF only | 0/35 (0.0%) |
| CVC + endoAVF | 0/35 (0.0%) |
| Other | 0/35 (0.0%) |
| 3-Month (46-135 Days) | |
| CVC only | 3/35 (8.6%) |
| endoAVF only | 8/35 (22.9%) |
| CVC + endoAVF | 2/35 (5.7%) |
| Other | 0/35 (0.0%) |
| 6-Month (136-270 Days) | |
| CVC only | 3/35 (8.6%) |
| endoAVF only | 8/35 (22.9%) |
| CVC + endoAVF | 4/35 (11.4%) |
| Other | 1/35 (2.9%) |
| 12-Month (271-390 Days) | |
| CVC only | 4/35 (11.4%) |
| endoAVF only | 10/35 (28.6%) |
| CVC + endoAVF | 0/35 (0.0%) |
| Other | 1/35 (2.9%) |
| Post-Dialysis Subjects | |
| 1-Month (0-45 Days) | |
| CVC only | 24/25 (96.0%) |
| endoAVF only | 0/25 (0.0%) |
| CVC + endoAVF | 0/25 (0.0%) |
| Other | 1/25 (4.0%) |
| 3-Month (46-135 Days) | |
| CVC only | 9/25 (36.0%) |
| endoAVF only | 1/25 (4.0%) |
| CVC + endoAVF | 13/25 (52.0%) |
| Other | 1/25 (4.0%) |
| 6-Month (136-270 Days) | |
| CVC only | 4/25 (16.0%) |
| endoAVF only | 6/25 (24.0%) |

#### Table 10: Duration of CVC Exposure

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| Other | 4/25 (16.0%) |
|-------------------------|---------------|
| 12-Month (271-390 Days) | |
| CVC only | 6/25 (24.0%) |
| endoAVF only | 11/25 (44.0%) |
| CVC + endoAVF | 4/25 (16.0%) |
| Other | 4/25 (16.0%) |

- endoAVF-related Interventions Rate: Table 11 below shows the number and types of . adjunctive procedures that were performed at the same time as the endoAVF index procedure. In total, 56/60 subjects (93.3%) required the implantation of at least one coil in their brachial vein at the time of the index procedure to redirect blood flow to the superficial veins and support maturation of the target cannulation area. The mean number of coils used per subject who received them was 1.6, with a range of 1.0-3.0 coils.
Table 12 shows the number of subjects who required at least one reintervention after the index procedure to assist maturation of the endoAVF or to maintain a mature endoAVF. The total number and types of reinterventions are also tabulated.

| Adjunctive Procedure | # of Subjects (%) |
|-----------------------------------|-------------------|
| Therapeutic embolization | 56 (93.3%) |
| Arterial closure device use | 41 (68.3%) |
| PTA | 0 (0.0%) |
| Stent | 0 (0.0%) |
| Other* | 6 (10.0%) |
| Total Subjects with > 1 Procedure | 58/60 (96.7%) |

Table 11: Adjunctive Procedures Performed at Index Procedure

* Other procedures include thrombolysis (1), thrombectomy (2), new surgical AVF (1), open surgical repair for an intraoperative complication (6).

Adjunctive procedures are tabulated by the procedure (i.e. one subject may have more than one adjunctive procedure), except for the last row which tabulates the data at the subject level.

| Reintervention | Indication | 0-90 Days | 0-180 Days | 0-365 Days |
|----------------------------------------|------------------------|--------------|---------------|---------------|
| Coil Embolization | Maturation Assistance | 2 | 2 | 5 |
| Angioplasty | Maturation Assistance | 1 | 1 | 2 |
| Transposition | Facilitate Cannulation | 0 | 3 | 5 |
| Surgical Fistula or Graft | New Access Needed | 0 | 0 | 2 |
| EndoAVF Ligation | Adverse Event | 3 | 3 | 3 |
| Thrombin Injection for Pseudoaneurysm | Adverse Event | 2 | 2 | 2 |
| Surgical Procedure for Complication | Adverse Event | 1 | 1 | 1 |
| Total Reinterventions | - | 9 | 12 | 20 |
| Total Subjects with ≥ 1 Reintervention | - | 7/60 (11.7%) | 10/60 (16.7%) | 17/60 (28.3%) |

Table 12: endoAVF-related Reinterventions in NEAT Study

- Primary Patency: The following primary patency rates were reported: .
- O Primary patency, 6 months: 81.1%

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- Primary patency. 12 months: 73.4% o
- o Assisted primary patency, 6 months: 84.8%
- Assisted primary patency, 12 months: 77.2% O
- Secondary Patency: The following secondary patency rates were reported: .
- 0 Secondary patency, 6 months: 86.4%
- Secondary patency, 12 months: 78.9% o

## Additional Analyses

### Rate of Serious Device- and Procedure-Related AEs

A total of eight (8) serious adverse events (SAEs) in five (5) subjects were adjudicated as procedure and/or device-related. All eight (8) SAEs were adjudicated as procedure-related, and one of the eight (1/8) SAEs (pseudoaneurysm near endoAVF) was adjudicated as related to both the device and the procedure. Seven of the eight (7/8) SAEs occurred within 24 hours of the index procedure. One (1) SAE (steal syndrome) occurred on Day 8 post index procedure, representing the maximum number of days post-index procedure for onset of a serious procedure-related event. A summary of SAEs related to the study procedure and/or device has been provided in Table 13 below.

All SAEs were able to be resolved through intervention or resolved on their own. There were no instances of permanent impairment associated with the device. No new serious procedure and/or device related events were reported beyond 3 months.

| | 0-3 Months | | 3-6 Months | | > 6 Months | | Overall | |
|---------------------------------------------------------------|-----------------|------------------------------------|-----------------|--------------------------------------|-----------------|---------------------------------------|-----------------|------------------------------------|
| Eventsi | Total<br>Events | Subjects<br>Experienced<br>% (n/N) | Total<br>Events | Subjects<br>Experienced<br>% (n/Nii) | Total<br>Events | Subjects<br>Experienced<br>% (n/Niii) | Total<br>Events | Subjects<br>Experienced<br>% (n/N) |
| Overall | 8 | 8.3% (5/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 8 | 8.3% (5/60) |
| Closure device embolization | 2 | 3.3% (2/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 2 | 3.3% (2/60) |
| Dissection of brachial artery | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Pseudoaneurysm near endoAVFiv | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Pseudoaneurysm, access site | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Steal syndrome | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Thrombosis brachial artery, not leading to fistula<br>closure | 2 | 3.3% (2/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 2 | 3.3% (2/60) |

Table 13: NEAT Study SAEs Related to Study Procedure and/or Device (CEC-Adiudicated)

4 Based on the number of subjects still in the study at 3 Month follow-up (i.e. subjects who exited the study after 3 Month follow-up window opened) " Based on the number of subjects still in the study at 6 Month Follow-up (i.e. subjects who exited the study after 6 Month follow-up window opened) 1VThis event is also related to the study device.

A total of 28 adverse events (AEs) in 22 subjects were adjudicated as non-serious and procedure and/or device-related. Of these AEs. all were adjudicated as procedure-related (28/28) and three were adjudicated as related to both the device and the procedure (3/28). Twenty-six of the related AEs (26/28) occurred within 3 months of the index procedure. A summary of the non-serious AEs is provided in Table 14 below.

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All but two procedure-related AE occurred within 3 months post-index procedure resulting in 3month procedure-related AE rate of 33.3% (20/60) and overall rate of 36.7% (22/60) through 12 months.

| | 0-3 Months | | 3-6 Months | | > 6 Months | | Overall | |
|----------------------------------------------------------------|-----------------|------------------------------------|-----------------|------------------------------------|-----------------|------------------------------------|-----------------|------------------------------------|
| Eventsi | Total<br>Events | Subjects<br>Experienced<br>% (n/N) | Total<br>Events | Subjects<br>Experienced<br>% (n/N) | Total<br>Events | Subjects<br>Experienced<br>% (n/N) | Total<br>Events | Subjects<br>Experienced<br>% (n/N) |
| Overall | 26 | 33.3% (20/60) | 2 | 3.5% (2/57) | 0 | 0.0% (0/55) | 28 | 36.7% (22/60) |
| Bruising | 6 | 10.0% (6/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 6 | 10.0% (6/60) |
| Hematoma | 4 | 6.7% (4/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 4 | 6.7% (4/60) |
| Numbness, tingling and/or coolness in the fistula<br>extremity | 3 | 5.0% (3/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 3 | 5.0% (3/60) |
| Pain | 2 | 3.3% (2/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 2 | 3.3% (2/60) |
| Perforation, related to guidewire | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Pseudoaneurysm near endoAVF | 2 | 3.3% (2/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 2 | 3.3% (2/60) |
| Pseudoaneurysm, access site | 2 | 3.3% (2/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 2 | 3.3% (2/60) |
| Spasm and clot | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Steal | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Swelling, irritation or pain | 2 | 3.3% (2/60) | 1 | 1.8% (1/57) | 0 | 0.0% (0/55) | 3 | 5.0% (3/60) |
| Thrombosis Brachial artery, Not leading to fistula<br>closure | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Thrombosis post proc of endoAVF leading to<br>fistula closure | 0 | 0.0% (0/60) | 1 | 1.8% (1/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |
| Thrombosis, intra-procedural leading to fistula<br>closure | 1 | 1.7% (1/60) | 0 | 0.0% (0/57) | 0 | 0.0% (0/55) | 1 | 1.7% (1/60) |

| Table 14: NEAT Study Non-Serious Procedure-Related Adverse Events by Type and Timing | |
|--------------------------------------------------------------------------------------|--|
| (CEC-Adjudicated) | |

¹As adjudicated by the Clinical Events Committee

Based on the number of subjects still in the study at 3 Month follow-up (i.e. subjects who extred the study after 3 Month follow-up window opened)

" Based on the number of subjects still in the study at 6 Month Follow-up (i.e. subjects who exited the study after 6 Month follow-up window opened)

#### Summary of Occlusions and Thromboses

Table 15 below provides a summary of the number of thromboses and occlusions that occurred during the study. The data are presented as acute (defined as 0-42 days to represent the data reported through the 6-week visit) and total events reported through the end of the study's 12month visit. There was 1 acute thrombosis of the endoAVF treated unsuccessfully with thrombolysis, and the endoAVF was eventually abandoned. There were 4 additional (non-acute) thromboses of the endoAVF all leading to endoAVF abandonment. In total, 5/60 (8.3%) subjects experienced thrombosis of the endoAVF at some point during the study. 3/60 (5.0%) subjects experienced thrombosis of the brachial artery during the study. All 3 of these events were acute and were treated (1 thrombolysis, 2 thrombectomy) and did not lead to endoAVF abandonment. 1/60 (1.7%) subjects experienced occlusion of the endoAVF during the study. This event was non-acute and led to endoAVF abandonment. There were no occlusions of the brachial artery during the study.

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All 4 acute thrombosis events listed in Table 15 (1 endoAVF thrombosis and 3 brachial artery thromboses) occurred at the time of the endoAVF index procedure and all were treated via thrombolysis or thrombectomy.

The events were either treated with thrombectomy/thrombolysis or no treatment was provided. 6/9 of the endoAVFs that experienced an occlusion or thrombosis were abandoned, for a total endoAVF abandonment rate of 10.0% at 12 months.

| | | Acute | | Total | | Treatment(s) | Outcome(s) |
|--------------------------------------------------------------------------------|----------------|-----------|-----------------|-----------|----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|
| | N | Abandoned | N | Abandoned | | | |
| Thrombosis - endoAVF | 1/60<br>(1.7%) | 1/1 | 5/60<br>(8.3%) | 5/5 | 1 Thrombolysis<br>4 No Treatment | 2/5 subjects entered study<br>pre-dialysis and exited study<br>pre-dialysis<br>3/5 subjects entered study on-<br>dialysis and exited study on<br>CVC | |
| Thrombosis - Brachial Artery* | 3/60<br>(5.0%) | 0/3 | 3/60<br>(5.0%) | 0/3 | 2 Thrombectomy<br>1 Thrombolysis | 2/3 subjects entered study<br>pre-dialysis and 1 subject<br>exited study on CVC and 1<br>subject exited study early pre-<br>dialysis<br>1/3 subjects entered study on-<br>dialysis and exited study on<br>endoAVF and achieved<br>functional cannulation<br>success | |
| Occlusion - endoAVF | 0/60<br>(0.0%) | - | 1/60<br>(1.7%) | 1/1 | 1 No Treatment | 1/1 subject entered study pre-<br>dialysis and exited study early<br>pre-dialysis…