← Product Code [MAF](/productcode/MAF) · P150039

# TRYTON SIDE BRANCH STENT (P150039)

_Poseidon Medical, Inc. · MAF · Feb 21, 2017 · Cardiovascular · APPR_

**Canonical URL:** https://fda.innolitics.com/device/P150039

## Device Facts

- **Applicant:** Poseidon Medical, Inc.
- **Product Code:** [MAF](/productcode/MAF.md)
- **Decision Date:** Feb 21, 2017
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Cardiovascular
- **Attributes:** Therapeutic

## Indications for Use

The TRYTON Side Branch Stent is indicated for improving the side branch luminal diameter of de novo native coronary artery bifurcation lesions (Medina Classification 1.1.1; 0.1.1; 1.0.1) with a side branch diameter stenosis of ≥ 50% and a lesion length ≤ 5.0mm, along with reference vessel diameters ≥ 2.5mm to ≤ 3.5mm in the side branch and ≥ 2.5mm to ≤ 4.0mm in the main branch. The device is intended for use in conjunction with commercially available balloon expandable drug-eluting coronary stents in the main branch.

## Device Story

The TRYTON Side Branch Stent is a bare metal, L605 cobalt-chromium alloy stent designed to treat coronary bifurcation lesions. It consists of a Side Branch Zone, a Transition Zone, and a Main Branch Zone. The device is pre-mounted on a rapid exchange delivery catheter (straight or stepped balloon configurations). It is used in the cardiac catheterization lab by interventional cardiologists. The stent is deployed in the side branch of a bifurcation, while a separate, commercially available drug-eluting stent is placed in the main branch. The TRYTON stent provides radial support and scaffolding to the side branch ostium. By maintaining side branch patency and improving luminal diameter, the device aims to reduce the need for revascularization and improve clinical outcomes in complex bifurcation anatomy compared to provisional stenting.

## Clinical Evidence

Evidence includes a prospective, multicenter, randomized controlled trial (Pivotal RCT, N=704) and a single-arm confirmatory study (EA, N=133). Primary endpoint (TVF at 9 months) in the ITT population did not meet non-inferiority. Post-hoc analysis of the intended population (side branch RVD ≥2.25mm) showed TVF rates of 10.5% (TRYTON) vs 14.8% (POBA). The EA study met its primary endpoint (PPMI rate 10.5% vs 17.9% goal). Bench testing confirmed mechanical integrity, fatigue resistance (400 million cycles), and biocompatibility.

## Technological Characteristics

Material: L605 Cobalt Chromium (Co-Cr) alloy (ASTM F90/ISO 5832-5). Design: Three-zone stent (Side Branch, Transition, Main Branch). Delivery: Rapid exchange catheter with radiopaque markers. Sizes: 3 diameters (D5, D5+, D5+ Short). Connectivity: None. Sterilization: Gamma irradiation (SAL 10^-6). MRI: MR Conditional (1.5T/3T).

## Regulatory Identification

The formerly known device, Cardiovascular Stent, coded as "MAF" has been modified and is currently known and classified as a "Coronary Stent".  This device is a metal scaffold placed via a delivery catheter into the coronary artery or saphenous vein graft to maintain the lumen.

## Reference Devices

- TAXUS Liberte
- XIENCE V
- CYPHER
- RESOLUTE Family of Stents
- PROMUS
- PROMUS ELEMENT Family of Stents

## Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Coronary Stent

Device Trade Name: TRYTON Side Branch Stent

Device Procode: MAF

Applicant’s Name and Address: Tryton Medical, Inc.
1000 Park 40 Plaza, Suite 325
Durham, NC 27713

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P150039

Date of FDA Notice of Approval: February 21, 2017

II. INDICATIONS FOR USE

The TRYTON Side Branch Stent is indicated for improving the side branch luminal diameter of de novo native coronary artery bifurcation lesions (Medina Classification 1.1.1; 0.1.1; 1.0.1) with a side branch diameter stenosis of ≥ 50% and a lesion length ≤ 5.0mm, along with reference vessel diameters ≥ 2.5mm to ≤ 3.5mm in the side branch and ≥ 2.5mm to ≤ 4.0mm in the main branch.

The device is intended for use in conjunction with commercially available balloon expandable drug-eluting coronary stents in the main branch.

III. CONTRAINDICATIONS

The TRYTON Side Branch Stent is contraindicated for use in patients with the following conditions or uses:

- Vessels that are totally occluded
- Vessels that have moderate to severe calcification
- Target lesions that have excessive tortuosity unsuitable for stent delivery and deployment
- Angiographic evidence of thrombus in the target vessel
- Lesions in which complete angioplasty balloon inflation cannot be achieved during pre-dilatation
- TRYTON Stent placement without angioplasty pre-dilatation of the main branch and side branch (i.e., direct stenting is contraindicated)
- TRYTON Stent placement alone, without implantation of a main branch stent

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- An untreated significant (> 50%) stenosis proximal or distal to the main branch or side branch target lesion
- Impaired runoff in the treatment vessel with diffuse distal disease
- Ejection fraction ≤ 30%
- Impaired renal function (creatinine > 2.0 mg/dl or 150 mmol/l)
- Platelet count < 100,000 cells/mm³ or > 700,000 cells/mm³, a WBC of < 3,000 cells/mm³, or documented or suspected liver disease (including laboratory evidence of hepatitis)
- Presence of a heart transplant
- Known allergy to cobalt chromium
- Hypersensitivity or contraindication to cobalt-chromium or structurally-related compounds, cobalt, chromium, nickel, or tungsten
- Anticipated use of rotational atherectomy
- Patients in whom the use of a drug eluting stent is contraindicated, e.g., who cannot receive the recommended dual anti-platelet (aspirin and an approved P₂Y₁₂ Inhibitor) and/or anticoagulation therapy

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the TRYTON Side Branch Stent labeling.

## V. DEVICE DESCRIPTION

The TRYTON Side Branch Stent has been designed to treat coronary bifurcation lesions. It is intended to treat and maintain patency in the side branch/carina in conjunction with a currently approved balloon-expandable drug-eluting stent for treatment of the main vessel.

The TRYTON Side Branch Stent is a bare metal stent, composed entirely of L605 Cobalt Chromium (Co-Cr) Alloy. The TRYTON Side Branch Stent is available in three (3) sizes (internally referred to as D5, D5+, and D5+ Short) to address different vessel diameters and main vessel landing zones, and is placed on one (1) of seven (7) delivery systems to address a range of coronary dimensions. The TRYTON Side Branch Stent is composed of three (3) stent zones: a Side Branch Zone that is deployed within the side branch of a coronary artery; a Transition Zone that resides within the ostium of the side branch; and a Main Branch Zone, which is placed within the main vessel of a diseased bifurcated lesion. The TRYTON Side Branch Stent is pre-mounted on a rapid exchange delivery catheter provided in two configurations: standard-(straight) balloon and step-balloon delivery systems.

Table 1 lists the catalog numbers and sizes of the TRYTON Side Branch Stent.

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![img-0.jpeg](img-0.jpeg)
Figure 1: Schematic of TRYTON Side Branch Stent mounted on Stepped Stent Delivery System

Table 1: TRYTON Side Branch Stent Matrix

|  Reference | Proximal Diameter (mm) | Distal Diameter (mm) | Stent Length (mm) | Balloon Configuration | Strut Wall Thickness / Width (μm) | Guide Catheter Compatibility  |
| --- | --- | --- | --- | --- | --- | --- |
|  T5-2525-191-US (D5) | 2.5 | 2.5 | 19 | Straight | 85 / 102 | 5F  |
|  T5-2530-191-US (D5) | 3.0 | 2.5 | 19 | Stepped | 85 / 102 | 5F  |
|  T5-2535-191-US (D5) | 3.5 | 2.5 | 19 | Stepped | 85 / 102 | 5F  |
|  T5-3035-181-US (D5+) | 3.5 | 3.0 | 18 | Stepped | 85 / 102 | 6F  |
|  T5-3540-181-US (D5+) | 4.0 | 3.5 | 18 | Stepped | 85 / 102 | 6F  |
|  T5-3035-151-US (D5+ SHORT) | 3.5 | 3.0 | 15 | Stepped | 85 / 102 | 6F  |
|  T5-3540-151-US (D5+ SHORT) | 4.0 | 3.5 | 15 | Stepped | 85 / 102 | 6F  |

The Side Branch Zone of the stent functions as a standard balloon expandable stent within the side branch. Once deployed, the Side Branch Zone part of the device is intended to provide radial strength, scaffolding, and coverage to the side branch. The length of this zone is approximately  $6\mathrm{mm}$ . The Side Branch Zone of the stent is intended to function similarly to a standard balloon expandable stent deployed in the side branch.

The Transition Zone of the TRYTON Side Branch Stent spans the space between the Main Branch Zone and the Side Branch Zone. When deployed, the Transition Zone is located within the ostium of the side branch. When implanted using a "stepped" balloon configuration, the Transition Zone is initially expanded to a diameter larger than that of the Side Branch Zone of the device to achieve better apposition to the ostium and provide adequate scaffolding when a "step" in vessel size is seen in the target vessel.

The Main Branch Zone is intended to accommodate a standard main branch balloon expandable drug-eluting coronary stent within the TRYTON Side Branch Stent. The Main Branch Zone facilitates the positioning and passage of the standard main branch stent across

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the bifurcation. Upon deployment of the main vessel drug-eluting stent, the fingers or fronds that extend from the Transition Zone into the Main Branch Zone become apposed to the main vessel stent to provide additional scaffolding within the origin of the ostium.

The TRYTON Side Branch Stent delivery system configurations combine a single-lumen proximal shaft with a dual-lumen mid-shaft and a coaxial lumen distal shaft to create a rapid exchange capability. The catheter employs four radiopaque balloon markers; proximal and distal markers indicate the proximal and distal segments of the stent as mounted on the balloon. In addition, two markers in the mid-section of the balloon indicate the boundaries of the Transition Zone. The radiopaque markers aid in positioning the stent and the delivery system during the implantation procedure.

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the treatment of coronary bifurcation lesions. Provisional stenting (stenting the main branch with subsequent balloon angioplasty (POBA) of the side branch) is commonly used to treat bifurcation lesions. The side branch can also be stented if suboptimal results are seen post-POBA. A planned dual stent approach can also be used, employing different techniques such as culotte, crush, double-kiss crush, V-stenting, T-stenting, and simultaneous kissing stents. Other alternative procedures to treat coronary artery disease include medical therapy (e.g., antiplatelet agents, beta-blockers, lipid lowering agents), other transcatheter devices (e.g., conventional balloon angioplasty, plaque removal using cutting balloons or rotational atherectomy, lasers), and coronary artery bypass graft (CABG) surgery.

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 TRYTON Side Branch Stent has been marketed in Europe, Russia, South Africa, Israel, and parts of the Middle East. The TRYTON Side Branch Stent in its current design has not been withdrawn from the market for any reason relating to its safety or 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:

- Acute or subacute closure of the coronary artery
- Acute myocardial infarction
- Aneurysm
- Arrhythmia, including ventricular fibrillation
- Arteriovenous fistulas
- Coronary artery spasm
- Coronary vessel dissection, perforation, rupture or injury

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- Death
- Drug reactions, allergic reactions to contrast medium
- Fever
- Hematoma or hemorrhage
- Hypotension or hypertension
- Hypersensitivity reactions
- Infection
- Myocardial ischemia
- Non-cardiac chest pain
- Pseudoaneurysm
- Restenosis of the dilated vessel
- Stent embolism or migration
- Stroke or cerebral vascular accident
- Total occlusion of the coronary artery or bypass graft
- Unstable or stable angina pectoris
- Vascular thrombosis or embolism

For the specific adverse events that occurred in the clinical studies, please see Section X.

## IX. SUMMARY OF PRECLINICAL STUDIES

A series of non-clinical laboratory studies were performed to evaluate the TRYTON Side Branch Stent. These evaluations included in vitro engineering testing, animal studies, biocompatibility studies, and sterilization.

## A. In Vitro Engineering Testing

Tryton Medical performed mechanical and functional testing to demonstrate that the TRYTON Side Branch Stent and Delivery System meets design input requirements and engineering specifications. Testing was conducted in accordance with FDA Guidance for Industry and Staff: Non-Clinical Engineering Test and Recommended Labeling for Intravascular Stents and Associated Delivery Systems (April 18, 2010). The results show that all design input requirements were met, thus supporting the safety and effectiveness of the TRYTON Side Branch Stent. These tests are summarized in Table 2.

Since the TRYTON Side Branch Stent is intended for coronary bifurcation lesions, the target deployment site was simulated with mock bifurcated vessels in the following tests: fretting corrosion, stress/strain analysis, fatigue analysis, accelerated durability testing, particulate evaluation, and delivery, deployment and retraction. Refer to each individual test in the table below.

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Table 2: Summary of TRYTON In Vitro Engineering Bench Testing

|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Material Characterization  |   |   |   |
|  Material Composition | Material composition testing documents a baseline for evaluation of the effects of future changes in materials. The stent material (L605 Co-Cr alloy) was analyzed for chemical composition. Certification demonstrated that incoming raw materials conform to TRYTON specifications and L605 (ASTM F90/ISO 5832-5) material requirements. | ASTM F90/ISO 5832-5 | Pass  |
|  Corrosion Resistance – Fretting, Pitting and Crevice | Stent corrosion can cause or contribute to premature stent failure. In addition, corrosion byproducts may be toxic or cause other adverse biological and tissue responses. The stent was tested according to ASTM F2129-08 “Standard Test Method for Conducting Cyclic Potentiodynamic Measurements to Determine the Corrosion Susceptibility of Small Implant Devices.” | No evidence of localized corrosion (pitting, crevice, or fretting) after 400 million cycles (10 year equivalent) in a simulated bifurcation model. | Pass  |
|  Corrosion Resistance - Galvanic | Stent corrosion can cause or contribute to premature stent failure. In addition, corrosion byproducts may be toxic or cause other adverse biological and tissue responses. Galvanic corrosion characterization was evaluated with overlapped stents of dissimilar materials in accordance with ASTM G71 “Standard Guide for Conducting and Evaluating Galvanic Corrosion Tests in Electrolytes.” | No evidence of localized corrosion on the overlapping stents (TRYTON Side Branch Stent coupled with a stainless steel stent) in a PBS test solution. | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Stent Dimensional and Functional Attributes  |   |   |   |
|  Dimensional Verification | Accurate stent dimensions help the physician to achieve proper stent sizing and accurate placement in the body. Stent dimensions were measured, including distal and proximal crown heights, strut width, and strut wall thickness. | Must pass visual inspection and 10x magnification. Dimensions must meet TRYTON Stent specifications. | Pass  |
|  Percent Surface Area | The area over which a stent contacts a vessel may affect the biologic response of the vessel. The amount of open, non-contact area may influence tissue prolapse or ingrowth. The percent surface area of the stent for the smallest and largest nominal expanded diameters was calculated. | D5+ and D5+ SHORT: The surface area of the stent as a percent of the full cylindrical surface area of the vessel must be between 7 and 20% per ASTM F2081-06 (Section X1.6). D5: Must be between 10-20% | Pass  |
|  Foreshortening | Foreshortening (i.e., dimensional changes that may occur when deploying a stent), influences final stent length. Knowledge of the foreshortening characteristics aids in proper stent length selection and proper placement in the body. This test determined the percent change in length of the stent between when it is catheter-mounted and when it is expanded to nominal pressure and rated burst pressure (RBP). | Maximum foreshortening ≤15% | Pass  |
|  Recoil for Balloon Expandable Stents | The recoil behavior of balloon expandable stents influences proper device selection, sizing, acute post-implant results, and long-term clinical outcomes. Recoil is a function of stent design and material selection; therefore, knowledge of stent recoil helps to characterize the behavior of a particular stent design. The change in diameter | Maximum recoil ≤15% | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | of the stent was measured between post-balloon expansion and after balloon deflation. Measurements were taken at nominal pressure and rated burst pressure (RBP) or greater. |  |   |
|  Stent Integrity | Stent defects, whether a result of manufacturing flaws or subsequent damage, can contribute to clinical complications. Laser cutting or other manufacturing processes may induce flaws that are not completely removed by polishing. Plastic deformation during loading or balloon expansion may cause cracks or other damage. Therefore, this test was performed to verify that the stent had no clinically significant defects or flaws after deployment, when over expanded. | No fractures or cracks of struts when examined under 10X-40X magnification. The ends and the midsection of the stent must expand uniformly (i.e., no distorted struts) and the space in between struts must be distributed evenly. | Pass  |
|  Radial Stiffness and Radial Strength | These tests characterized the ability of the stent to resist collapse under short-term or long-term external loads. The radial strength test determines the pressure at which the stent experiences irrecoverable deformation. The radial stiffness calculation characterizes the change in stent diameter as a function of uniformly applied external radial pressure. | Radial Strength: No more than 50% area loss at a pressure of 500 mmHg for D5 stent and 300 mmHg for D5+ and D5+ SHORT stentsRadial Stiffness: Characterization only | Pass  |
|  Mechanical Properties | Raw material properties determine incoming material quality and uniformity, and predict subsequent thermomechanical effects. Thermomechanical properties of the implanted stent affect clinical performance, as well as stress and fatigue behavior. The | TRYTON material specifications | Pass  |
|   | stent is a good quality material for the patient. The material is not suitable for the patient due to its low temperature and low pressure. |  |   |
|  Ventilation | Ventilation of the stent is a good quality material for the patient. The ventilation is a good quality material for the patient due to its low temperature and low pressure. | Ventilation: The ventilation is a good quality material for the patient due to its low temperature and pressure. | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | mechanical properties of the stent raw material were evaluated; including ultimate tensile strength (UTS), yield strength (YS), and elongation. |  |   |
|  Stress/Strain Analysis (FEA) | Failure of a loaded stent may result in loss of radial support of the stented vessel or in perforation of the vessel by the stent struts. Stress/strain analysis, combined with fatigue analysis and accelerated durability testing, provides an indication of device durability. Using Finite Element Analysis (FEA), stress and strain analyses were performed on the stent to demonstrate that acceptable safety is maintained in stress loading environments. The analyses included simulation of manufacturing and clinical loading over the implant life. | Calculated static safety factors ≥1 | Pass  |
|  Fatigue Analysis | Failure of a stent due to fatigue may result in loss of radial support of the stented vessel, thrombus formation or focal restenosis, or in perforation of the vessel by the stent struts. Fatigue analysis, combined with stress/strain analysis and accelerated durability testing, provides an indication of device durability. Fatigue analysis was conducted to determine the state of fatigue due to stress loading, including simulation of manufacturing and clinical loading over the implant life. | Calculated static safety factors ≥1 | Pass  |
|  Accelerated Durability | Accelerated durability testing validates fatigue analysis. It evaluates failure modes such as fretting, abrasion, wear, and fracture. Durability testing can | All TRYTON and main vessel stents must be free of defects (scratches, cracks, fractures) when examined at up to 40X magnification in a | Pass  |
|   | stent. | stent analysis, and the results are presented in Table 1. |   |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | help in the identification of device conditions, such as manufacturing anomalies, that were not modeled using analytical or computational methods. The accelerated durability of TRYTON Stents were evaluated when mated with main vessel stents after 400 million cycles (equivalent to 10 years) in a simulated bifurcation model. | simulated bifurcation model. |   |
|  Particulate Evaluation | The system was evaluated for particulates after simulated use through a tortuous track model. Measurement of the total quantity and size of particulates a device system may generate is an indication of embolic risk. | Per USP <788>: ≤6000 particles/container for particle size ≥10 μm ≤600 particles/container for particle size ≥25 μm | Pass  |
|  Magnetic Resonance Imaging (MRI) Safety and Compatibility | MRI Safety Information Non-clinical testing has demonstrated the TRYTON Side Branch Stent (19 mm stent alone and in combination with four 20 mm drug-eluting stainless steel stents, tested for a total stent length of 73 mm) is MR Conditional. A patient with this device can be safely scanned in an MR system meeting the following conditions: • Static magnetic field of 3-Tesla or 1.5-Tesla • Maximum spatial field gradient of 720 Gauss/cm (7.2 T/m) • Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 2.0 W/kg (Normal Operating Mode) | MR Conditional (poses no known hazards under specified conditions) | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | Under the scan conditions defined above, the TRYTON Side Branch Stent is expected to produce a maximum temperature rise of less than 2.7°C after 15 minutes of continuous scanning. In non-clinical testing, the image artifact caused by the device extends a maximum of 11 mm from the TRYTON Side Branch Stent when imaged with a gradient echo pulse sequence and a 3T MRI system. |  |   |
|  Radiopacity | Stent visibility using angiographic and/or radiographic imaging generally assures proper stent placement and allows follow-up and secondary treatment. Radiopacity evaluation was performed to confirm that the TRYTON stent is adequately visible using standard fluoroscopy equipment and that it demonstrates comparable visibility to the main vessel stents. | Must be adequately visible using standard fluoroscopy equipment and demonstrate comparable visibility to the main vessel stents. | Pass  |
|  Delivery System Dimensional and Functional Attributes  |   |   |   |
|  Dimensional Verification | Stent delivery system dimensions influence the ability of the device to track to and across lesions. The crimped profile (distal, proximal), crimped stent length, overall working length, largest catheter ID and OD, and crossing profile were measured. | Crimped profile (distal/proximal), crimped stent length, overall working length, catheter ID/OD, and crossing profile must meet product specifications. | Pass  |
|  Delivery, Deployment, and Retraction | This test assessed the ability of the delivery system to deliver the stent to the intended location, deploy the stent, and retract under simulated use conditions. | The balloon must pass through the following ID gauge size following deployment: D5: 0.056" (5F) D5+: 0.068" (6F) | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   |  | D5+ SHORT: 0.068” (6F) |   |
|  Balloon Rated Burst Pressure | The rated burst pressure (RBP) is the pressure at which 99.9% of balloons can survive with 95% confidence. Failure of a balloon to survive at the RBP could result in device failure or vessel damage. | No burst within working range (>14 atm). No radial failures. | Pass  |
|  Balloon Fatigue | Balloons on stent delivery systems are often inflated multiple times during clinical use. Failure of the balloon to withstand multiple inflations could lead to device failure or vessel damage. Balloons were evaluated for the ability to withstand 10 repeated inflations to RBP without rupture. | Each balloon must pass ten (10) cycles at 14 atm without balloon rupture. | Pass  |
|  Balloon Fatigue - Leakage | The purpose of this test was to demonstrate that there was no balloon leakage or burst following inflation/deflation 10 times from 0 to 14 atm with a dwell time at 14 atm of 30 seconds. | No balloon leakage or burst following inflation cycles to RBP. | Pass  |
|  Stent Diameter vs. Balloon Pressure (Compliance Chart) | The diameter of a deployed balloon expandable stent varies with the balloon inflation pressure. A compliance chart in the labeling that relates stent diameter to balloon pressure guides selection of stent size to fit the target lesion. Incorrect selection of stent size may lead to device failure or vessel damage. This test determines how the diameter of the deployed stent varies with balloon inflation pressure. | Working range: All values must be within +/-10% of the compliance chart values between nominal and rated burst pressure. Overexpansion: Compliance must not exceed 20% of the average overexpansion value. | Pass  |
|  Balloon Inflation and Deflation Time | Balloons occlude the target vessel and obstruct blood flow while inflated. Inflation and deflation times affect occlusion | Inflation Time: D5: <15 seconds D5+: <15 seconds D5+ SHORT: <15 seconds | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | time. Excessively slow inflation or deflation of a balloon could lead to prolonged ischemia and damage to the end organ. This testing was conducted to determine the amount of time required to inflate and deflate the delivery catheter balloon. | Deflation Time: D5: <15 seconds D5+: <30 seconds D5+ SHORT: <30 seconds |   |
|  Catheter Bond Strength and Tip Pull | Failure delivery catheter bonds (including distal tip bonds) could lead to device failure or vessel damage. The tensile strength of all delivery system bonds was evaluated. | Tip Bond: ≥1.5N Shaft to Balloon: ≥3N or ≥5N Shaft to Luer: ≥15N | Pass  |
|  Flexibility and Kink Test | Stent delivery systems were evaluated to determine their ability to withstand flexural forces typical of clinical use. The catheter flexibility and kink resistance was evaluated by tracking samples through a tortuous model, designed in accordance with ASTM F2394 Figure X2.4, which included radii as small as 0.125" (3.2 mm). | No failures related to flexibility and kink in subsequent tests. | Pass  |
|  Flexibility and Kink Test – Bend Fixture Testing | Stent delivery systems may be subjected to tight angulations in tortuous vasculature during use. Inability to withstand flexural forces that are typical of clinical use could lead to device failure or vessel damage. The distal part of the catheter (section between the balloon and transition site) was bent 180° over a mandrel with a radius of 4mm. | No kinking observed on the distal section of the catheter when bending over a radius of 4 mm. | Pass  |
|  Flexibility and Kink Test – Tortuous Tracking 90° | Samples were tracked twice through a tortuous model and exited through a 90° branching artery with a 0.100" radius to simulate challenging anatomical conditions. | No damage or kinks along the catheter. | Pass  |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Torque Strength | Stent delivery systems may be subjected to torsional forces during use. Even non-fixed wire delivery systems could be subject to torsional forces if the tip is inadvertently caught on a previously deployed stent, calcified lesion, etc. Inability to withstand torsional forces that are typical of clinical use could lead to device failure or vessel damage. Stent delivery systems were evaluated to determine their ability to withstand torsional forces typical of clinical use. | Catheter able to withstand a minimum of two rotations without failure. Failure defined as no inflation possible to nominal pressure, leakage of the catheter, or broken/damaged catheter and/or inner lumen. | Pass  |
|  Coating Integrity | Unintended delamination or degradation of a coating may lessen its benefit or otherwise negatively impact its clinical performance. This test examined the amount of coating removed from the shaft during handling in simulated clinical conditions. | No patches of missing coating >0.2 mm² at a minimum of 10x magnification. | Pass  |
|  Particulate Evaluation | The system was evaluated for particulates after simulated use through a tortuous track model. Measurement of the total quantity and size of particulates a device system may generate is an indication of embolic risk. The test assessed the total number of particulates that could theoretically be released into the bloodstream during typical use of the stent system. Samples were preconditioned by advancing and retracting them twice through a tortuous track fixture per ASTM F2394 Fig x2.4. The TRYTON stent systems were then placed using standard accessories along with a DES main vessel stent into the same fixture and deployed. All stent inflations were | Per USP <788>: ≤6000 particles/container for particle size ≥10 μm ≤600 particles/container for particle size ≥25 μm | Pass  |
|   | inhalation of the stent, and the total number of particles that could theoretically be released into the bloodstream during typical use of the stent system. Samples were preconditioned by advancing and retracting them twice through a tortuous track fixture per ASTM F2394 Fig x2.4. The TRYTON stent systems were then placed using standard accessories along with a DES main vessel stent into the same fixture and deployed. All stent inflations were |  |   |

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|  Test | Purpose/Method | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | performed at a minimum of 16 atm. Total particulate was recorded. |  |   |
|  Stent Securement for Unsheathed Stents | Dislodgment of the stent prior to deployment can result in stent embolization. Stents without sheaths may dislodge if they catch on tortuous anatomy, guide catheters, or other devices. This test determined the force needed to remove the stent from the delivery system following passage through a tortuous track on advance (simulating tracking through a lesion) and retract (simulating retraction into a guiding catheter). | Individual D5 stents must pass the specification of ≥1.5 N. Individual D5+ and D5+ SHORT stents must pass the specification of ≥2.0 N. | Pass  |

# B. Animal Studies

The TRYTON Side Branch Stent was evaluated in three (3) animal studies in accordance with 21 CFR 58 Good Laboratory Practice (GLP) regulations in addition to some early product development animal studies. The acute performance characteristics of the D5+ stent were assessed in a porcine coronary artery model. In addition, a 30-day tissue response study was conducted using the D5 stent in a porcine model. These two (2) studies supplemented the safety data of the 180-day ovine study conducted on an earlier version TRYTON Side Branch Stent to assess short and long-term safety and biocompatibility. The results support the conclusion that the TRYTON Side Branch Stent is safe for commercial release. Table 3 below provides an overview of the GLP animal study designs and results.

Table 3: Summary of GLP Animal Studies

|  Study Number | Study Objective and Design | Number and Type of Stents Evaluated | Follow-Up Duration | Results  |
| --- | --- | --- | --- | --- |
|  MEA00007 | Objective: To assess acute handling and performance characteristics of the TRYTON Stent. Design: Three (3) swine were implanted with the TRYTON Side Branch Stent in a bifurcation of the | 5 D5+ TRYTON Side Branch Stents in conjunction with TAXUS Liberte stents | Acute | The handling and performance of the TRYTON Stent were considered acceptable in this porcine model.  |

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|  Study Number | Study Objective and Design | Number and Type of Stents Evaluated | Follow-Up Duration | Results  |
| --- | --- | --- | --- | --- |
|   | coronary bed, in conjunction with a TAXUS Liberte stent in the main vessel. One swine was implanted with two (2) TRYTON stents in separate straight coronary artery segments with no bifurcation/side branch stenting. |  |  |   |
|  MEA00003 | **Objective:** To assess acute performance, safety and tissue response at 30 days.
**Design:** Four (4) treatment groups of six (6) implantations each in a total of 19 porcine models.
**Group 1(Test Group):** TRYTON Stent deployed in bifurcations (overlapped with TAXUS Liberte)
**Group 2 (Control):** T-Stent with TAXUS/BMS Co-Cr Stent
**Group 3 (Control):** Provisional stenting with TAXUS/POBA
**Group 4 (Test Group):** TRYTON Stent deployed in straight segments (overlapped with TAXUS Liberte) | 6 D5 TRYTON Side Branch Stents (in Groups 1 and 4)
6 DES and BMS stents in each of the 4 treatment groups | 30 Days | The TRYTON Stent performed similarly to the controls in this porcine model. There were no side branch occlusions or device-related complications observed in the 19 animals implanted.  |
|  MEA00001 | **Objective:** To assess acute performance, safety and tissue response at 180 days.
**Design:** Twenty-five (25) ovine models were used with up to three (3) treated | 36 SD and LD TRYTON Stents
10 main vessel, drug eluting stents | 5, 90, and 180 Days | There were a total of nine (9) early deaths in the study, associated with luminal thrombosis secondary to mural injury.  |

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|  Study Number | Study Objective and Design | Number and Type of Stents Evaluated | Follow-Up Duration | Results  |
| --- | --- | --- | --- | --- |
|   | segments per animal.
Twenty-one (21) arterial segments, 10 using bifurcation deployment, six (6) using straight overlapping deployment, and five (5) provisional DES controls evaluated at each of the longer timepoints, 3 and 6 months; four (4) arterial segments using bifurcation deployment only were evaluated at 5 days. | (TAXUS Liberte vs. XIENCE V) |  | Device handling characteristics were scored as average.
No adverse effect on the tissue healing response of the stented artery after 180 days. The tissue response was comparable to the provisional control.  |

## C. Biocompatibility Studies

A series of Good Laboratory Practice (GLP) biocompatibility tests were conducted to demonstrate that the materials and components of the TRYTON Side Branch Stent are biocompatible. Testing was conducted separately on the stent implant and the stent delivery system. Tests were conducted on gamma irradiation-sterilized stents and stent delivery system. All biocompatibility testing was conducted in accordance with:

- International Standard ISO 10993-1 “Biological Evaluation of Medical Devices Part 1: Evaluation and Testing”
- Guidance for Industry and FDA Staff “Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems,” (April 18, 2010)
- Good Laboratory Practices Regulations (§21 CFR Part 58)

Tests were chosen based on duration of patient contact of the stent and the delivery system. The stent is an implanted product in contact with cardiovascular tissue and circulating blood, with a permanent (&gt;30 days) duration of contact. The stent delivery system is an externally communicating device in contact with cardiovascular tissue and circulating blood, with a temporary (&lt;24 hours) duration of contact.

All biocompatibility test results for both the stent and the delivery system indicated that the materials and processes used to manufacture the TRYTON Side Branch Stent are biocompatible and suitable for the intended use. Tables 4 and 5 summarize the tests conducted and the results. Chronic toxicity and carcinogenicity testing were not

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conducted on the TRYTON Side Branch Stent; an acceptable justification was given for the omission of these tests.

Table 4: Summary of Stent Biocompatibility Testing

|  Test Name | Test Description | Result  |
| --- | --- | --- |
|  Cytotoxicity | ISO 10993-5: In Vitro Cytotoxicity (MEM Elution) | PASS – Non-cytotoxic  |
|  Sensitization | ISO 10993-10: Sensitization (Guinea Pig Maximization) | PASS – Non-sensitizing  |
|  Intracutaneous Reactivity | ISO 10993-10: Irritation (Injection) | PASS – Non-irritant  |
|  Systemic Toxicity | ISO 10993-11: Systemic Toxicity (Acute) | PASS – Non-toxic  |
|  Pyrogenicity | ISO 10993-11: Systemic Toxicity (Material-Mediated Rabbit Pyrogen) | PASS – Non-pyrogenic  |
|  Subchronic Toxicity | ISO 10993-6: Implantation (Rat) | PASS – Non-toxic  |
|  Genotoxicity | ISO 10993-3: Bacterial Reverse Mutation Assay (Ames Assay) | PASS – Non-mutagenic  |
|   |  ISO 10993-3: In Vivo Mouse Micronucleus Test | PASS – Non-mutagenic  |
|   |  ISO 10993-3: Mouse Lymphoma | PASS – Non-clastogenic  |
|  Hemocompatibility | ISO 10993-4: Direct Hemolysis | PASS – Non-hemolytic  |
|   |  ISO 10993-4: Indirect Hemolysis (Extract) | PASS – Non-hemolytic  |
|   |  ISO 10993-4: In vivo Thrombogenicity (Canine) | PASS – Non-significant thrombosis  |
|   |  ISO 10993-4: Complement Activation C3a & SC5b-9 Assay | PASS – No induction of complement  |
|  Implantation | ISO 10993-6: Implantation (Rat) – 4 weeks | PASS – No different than control  |
|   |  ISO 10993-6: Implantation (Rat) – 13 weeks | PASS – No different than control  |
|  Chronic Toxicity | N/A  |   |
|  Carcinogenicity | N/A  |   |

Table 5: Summary of Delivery System Biocompatibility Testing

|  Test Name | Test Description | Result  |
| --- | --- | --- |
|  Cytotoxicity | ISO 10993-5: In Vitro Cytotoxicity (MEM Elution) | PASS – Non-cytotoxic  |
|  Sensitization | ISO 10993-10: Sensitization (Guinea Pig Maximization) | PASS – Non-sensitizing  |
|  Intracutaneous Reactivity | ISO 10993-10: Irritation (Injection) | PASS – Non-irritant  |
|  Systemic Toxicity | ISO 10993-11: Systemic Toxicity (Acute) | PASS – Non-toxic  |
|  Pyrogenicity | ISO 10993-11: Systemic Toxicity (Material-Mediated Rabbit Pyrogen) | PASS – Non-pyrogenic  |

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|  Test Name | Test Description | Result  |
| --- | --- | --- |
|  Hemocompatibility | ISO 10993-4: Direct Hemolysis | PASS – Non-hemolytic  |
|   |  ISO 10993-4: Indirect Hemolysis (Extract) | PASS – Non-hemolytic  |
|   |  ISO 10993-4: In vivo Thrombogenicity (Canine) | PASS – Non-significant thrombosis  |
|   |  ISO 10993-4: Complement Activation C3a & SC5b-9 Assay | PASS – No induction of complement  |

## D. Sterilization, Packaging, and Shelf-Life

The TRYTON Side Branch Stent is sterilized using gamma irradiation in accordance with ISO 11137-1, Sterilization Of Health Care Products – Radiation – Part 1: Requirements For Development, Validation, And Routine Control Of A Sterilization Process For Medical Devices. Results obtained from the sterilization validation demonstrate that the TRYTON Side Branch Stent meets a Sterility Assurance Level (SAL) of $10^{-6}$ when sterilized with a dose of $25 - 35$ (-0/+10%) kGy.

Packaging verification testing was conducted to demonstrate that the design of the TRYTON Side Branch Stent packaging is robust and can maintain acceptable integrity and sterility throughout the product's shelf life. Functional (bench) testing was conducted on aged product to validate that the device and packaging perform within product specifications for a labeled shelf life of two (2) years.

## X. SUMMARY OF PRIMARY CLINICAL STUDIES

The applicant performed two clinical studies to establish a reasonable assurance of safety and effectiveness of the TRYTON Side Branch Stent for the treatment of native coronary artery bifurcation disease in the US and Europe under IDE # G090167. Data from these clinical studies were the basis for the PMA approval decision. A summary of each clinical study is presented below.

- TRYTON Pivotal Randomized Controlled Trial (RCT) - a prospective, multicenter, single blind controlled study. Subjects were randomized 1:1 to the TRYTON Side Branch Stent with main branch approved DES or side branch balloon angioplasty (POBA) and main branch approved DES for treatment of native coronary artery bifurcation disease.
- TRYTON Extended Access (EA) Confirmatory Study - a non-randomized, single arm extension of the TRYTON Pivotal RCT. Subjects were implanted with the TRYTON Side Branch Stent with main branch approved DES for treatment of native coronary artery bifurcation disease.

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# 1. TRYTON PIVOTAL RANDOMIZED CONTROLLED TRIAL (RCT)

## A. TRYTON Pivotal RCT: Study Design

Patients were treated between December 17, 2010 and November 20, 2012. The database for this PMA reflect data collected through January 30, 2015 and included 704 randomized patients in Europe, Israel, and the United States and 65 US roll-in (non-randomized) patients. There were 66 investigational sites.

The TRYTON Pivotal RCT was designed as a prospective, multicenter, randomized, single blind controlled study with subjects randomized in a 1:1 fashion to the TRYTON Side Branch Stent with main branch approved drug-eluting stent (DES) vs. side branch balloon angioplasty (POBA) and main branch approved DES for treatment of native coronary artery bifurcation disease. The first 187 subjects enrolled in each arm were to return for angiographic follow-up at 9 months. The first 64 subjects randomized to the TRYTON cohort and the first 32 subjects randomized to the Control cohort were to return for IVUS follow-up at 9 months at the same time as the angiographic follow-up at designated IVUS sites.

Sixty-five (65) roll-in subjects with use of the investigational device were allowed in the US for those sites that had not previously used the TRYTON Side Branch Stent (maximum 3 subjects per site and maximum of two (2) subjects per investigator). The purpose of these roll-in subjects was to address learning curve factors for sites with no prior experience with either the study device or equivalent devices. These subjects were not part of the angiographic or IVUS subgroup.

The primary objective of the Pivotal RCT was to demonstrate the safety and effectiveness of the TRYTON Side Branch Stent with main branch approved DES compared to side branch balloon angioplasty and main branch approved DES in the treatment of de novo native coronary artery bifurcation lesions with side branch diameter ranging from $\geq 2.5\,\mathrm{mm}$ to $\leq 3.5\,\mathrm{mm}$ and main branch diameter ranging from $\geq 2.5\,\mathrm{mm}$ to $\leq 4.0\,\mathrm{mm}$.

## Statistical Analysis Plan Summary

**Primary endpoint:** Target vessel failure [TVF, a composite of cardiac death, target vessel MI, and target vessel revascularization (TVR) involving the main branch or side branch] at 9 months

**Primary analysis population for the primary endpoint:** ITT, consisting of all randomized subjects, analyzed according to their randomly assigned group regardless of whether they received device or not; Lead-in subjects were not included

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Sample size calculation parameters: The sample size of 704 subjects for the primary endpoint (non-inferiority) was determined as follows:

- 664 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA
- Assumed TVF rate of 13% for DES+POBA and 11% for DES+TRYTON
- 81% power
- Non-inferiority margin (Delta)=5.5%
- 1-sided binomial test of proportions with a significance level of α=0.025.
- Sample size increased to 704 subjects to account for an expected 6% loss to follow-up

Hypotheses (non-inferiority test):

H0: pTRY ≥ pPOBA + δ

H1: pTRY &lt; pPOBA + δ

Where, pTRY and pPOBA are the 9-month TVF rates in the DES+TRYTON and DES+POBA arms, respectively, and δ is the margin for non-inferiority (5.5%).

The primary analysis of the primary endpoint was performed on subjects with at least 270 days of follow-up or an adjudicated event. In addition, sensitivity analyses were performed to assess the impact of missing values from subjects lost to follow-up for the primary endpoint.

Powered secondary angiographic endpoint: Angiographic in-segment percent diameter stenosis (%DS) in the side branch at 9 months

Sample size calculation parameters: The sample size of 280 subjects for the angiographic endpoint was determined as follows:

- 318 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA
- 90% power to show a reduction of 8%, from 31% in the DES+POBA arm to 22% in the DES+TRYTON, assuming a standard deviation of 22% in both arms
- Two-sided test with a significance level of α=0.05
- Sample size increased to 374 subjects (187 per arm) to account for an expected 12% loss to follow-up

Hypotheses (superiority test):

H0: mTRY = mPOBA

H1: mTRY ≠ mPOBA

Where, mTRY and mPOBA are the mean side-branch DS percentages in the DES+TRYTON and DES+POBA arms, respectively.

A Data Safety Monitoring Board (DSMB) reviewed data to ensure patient safety. An independent Clinical Events Committee (CEC) adjudicated endpoint events. There were independent angiographic, IVUS, and ECG core laboratories.

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Table 6: TRYTON Pivotal RCT Design Summary

|  Study Type/Design | · Multi-center study (66 centers), performed in the U.S., Europe and Israel · Prospective · Randomized two-arms · Patients treated with TRYTON Side Branch Stent with main branch approved DES or side branch balloon angioplasty (POBA) and main branch approved DES  |   |   |   |
| --- | --- | --- | --- | --- |
|  Number of Patients | N= 769 · 704 Randomized (355 TRYTON, 349 POBA) · 65 Roll-in (TRYTON)  |   |   |   |
|  Lesion Criteria | De novo native coronary artery bifurcation lesions with side branch diameter ranging from ≥2.5 mm to ≤3.5 mm and main branch diameter ranging from ≥2.5 mm to ≤4.0 mm. Lesion length ≤28 mm in the main branch (treatable with a single stent) and ≤5 mm in the side branch.  |   |   |   |
|  Stent Sizes Used in Study |  | Stent Length (mm) | Side Branch Nominal Diameter (mm) | Main Branch Nominal Diameter (mm)  |
|   |  D5 | 19 | 2.5 | 2.5  |
|   |  D5 | 19 | 2.5 | 3.0  |
|   |  D5 | 19 | 2.5 | 3.5  |
|   |  D5+ | 18 | 3.0 | 3.5  |
|   |  D5+ | 18 | 3.5 | 4.0  |
|   |  Anti-Platelet Therapy | Aspirin indefinitely and clopidogrel, ticlopidine, prasugrel or ticagrelor for a minimum of 12-months post procedure  |   |   |
|  Primary Endpoint | Target Vessel Failure at 9 months: A composite of cardiac death, target vessel MI and Target Vessel Revascularization (in the main or side branch) at 9-months  |   |   |   |
|  Powered Secondary Endpoint | In-segment percent diameter stenosis in the side branch evaluated at 9 months in the angiographic sub-study  |   |   |   |
|  Follow-Up | 30 days, 6 months, 9 months, 1 year, 2 years, and 3 years  |   |   |   |

# 1. Clinical Inclusion and Exclusion Criteria

Enrollment in the Pivotal RCT was limited to patients who met the following inclusion criteria:

# Key General Inclusion Criteria:

1. The subject was  $\geq 18$  and  $\leq 90$  years of age;
2. Symptomatic ischemic heart disease (CCS class 1-4, Braunwald Class IB, IC, IIB, IIC, IIIB, IIIC, and/or objective evidence of MI);

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3. The intent to treat the side branch of the target bifurcation based on angiographic evaluation;
4. Planned use of one of the following approved and commercially available DES for subject's index procedure: CYPHER, RESOLUTE Family of Stents, PROMUS, PROMUS ELEMENT Family of Stents, or XIENCE Family of Stents.

## Key Angiographic Inclusion Criteria:

5. a) Single *de novo* lesion in a bifurcation involving both the main branch and the side branch
b) The bifurcation: main branch and side branch with a visual diameter stenosis ≥50% (Medina classification 1.1.1; 0.1.1; 1.0.1) by visual assessment

6. Target lesion located in a native coronary artery
7. a) Bifurcation lesion main branch reference vessel diameter ≥2.5 mm and ≤4.0 mm, and
b) Side branch reference vessel diameter ≥2.5 mm and ≤3.5 mm by visual estimate

8. a) Bifurcation lesion main branch lesion length ≤28 mm; and
b) Side branch lesion length ≤5.0 mm (the ability to be treated with a single stent for both main and side branches)

9. Target lesion ≥50% and &lt;100% stenosed by visual estimate in both the main branch and side branch

10. Subjects with multi-vessel coronary disease must have had successful treatment of no more than two distinct non-target lesions (&lt;30% diameter stenosis by visual estimate without intra-procedural complication*) with approved devices during the index procedure and prior to the target lesion treatment, provided non-target lesion(s):

1. included no more than one lesion in the main branch target vessel distinct from and distal to the target lesion provided this non-index lesion was:
a) &gt;10 mm from the margin of the index lesion;
b) ≥2.25 mm in diameter; and
c) met 2, 3, 4, and 5 below

2. were not &gt;28 mm (no overlapping stents);
3. were not 100% occluded at baseline;
4. were not highly calcified requiring rotoblator use; and
5. were not bifurcations.

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*In addition to standard definitions of procedural success, the non-target lesion intervention should have been free of inter-procedural event(s) which were likely to lead to CKMB elevation (i.e., no-reflow, flow-limiting dissection, loss of side branch (&lt;2.25 mm)).

11. Subjects with multi-vessel coronary disease were allowed to undergo successful treatment of no more than two distinct non-target lesions (&lt;30% diameter stenosis by visual estimate without intra-procedural complication*) with approved devices up to 60 days prior to target lesion treatment, provided non-target lesion(s):

1. included no more than one lesion in the main branch target vessel distinct from and distal to the target lesion provided this non-index lesion was:

a) &gt;10 mm from the margin of the index lesion;
b) ≥2.25 mm in diameter, and
c) met 2 and 3 below

2. were not &gt;28 mm (no overlapping stents); and
3. were not bifurcations.

Randomization and inclusion in the ITT cohort occurred after repeat angiography documenting successful treatment of the non-target lesion(s) and baseline characteristics of the target lesion were assessed. If the non-target lesion intervention was performed fewer than 14 days prior to the index procedure intervention, normal baseline CKMB was to be documented.

Note: If CKMB analysis was not available on-site, subjects were allowed to be included if serial Troponins (6 hours apart) were obtained and demonstrated a downward trend. Baseline and follow-up blood samples were to be obtained for central lab CKMB analysis.

Patients were not permitted to enroll in the Pivotal RCT if they met any of the following exclusion criteria:

**Key General Exclusion Criteria:**

1. STEMI within 72 hours preceding the index procedure or &gt;72 hours preceding the index procedure and CK and CKMB had not returned to within normal limits* at the time of procedure
2. Non-STEMI within 7 days prior to index procedure with continued CKMB elevation*
3. Non-target lesion PCI within 14 days prior to index procedure with continued CKMB elevation*
4. Impaired renal function (serum creatinine &gt;2.5 mg/dL or 221 μmol/l) or on dialysis

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5. Platelet count &lt;100,000 cells/mm3 or &gt;700,000 cells/mm3 or a WBC &lt;3,000 cells/mm³
6. History of bleeding diathesis or coagulopathy or subjects in whom antiplatelet and/or anticoagulant therapy was contraindicated
7. Known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, clopidogrel, ticlopidine, prasugrel, ticagrelor, stainless steel alloy, CoCr alloy, rapamycin, everolimus, zotarolimus, paclitaxel, and/or contrast sensitivity that could not be adequately pre-medicated
8. Cardiogenic shock or cardiac arrhythmias that created hemodynamic instability
9. Surgical or other procedure was planned within the following year which would have required discontinuation of dual antiplatelet therapy

## Key Angiographic Exclusion Criteria:

10. Left main CAD (protected and unprotected)
11. Trifurcation lesion
12. Totally occluded target vessel (TIMI flow 0 or 1)
13. Severely calcified target lesion(s)
14. Highly calcified target lesion(s) requiring rotational atherectomy
15. Target lesion had excessive tortuosity unsuitable for stent delivery and deployment
16. Angiographic evidence of thrombus in the target lesion(s)
17. A significant (&gt;50%) stenosis with an RVD of &gt;2.0 mm proximal or distal to the target lesion in either the side branch or main branch that could not be covered by a single stent
18. Diffuse distal disease to target lesion with impaired runoff
19. LVEF ≤30%
20. Planned pre-treatment with devices other than balloon angioplasty. Cutting balloons, AngioSculpt balloons, atherectomy devices, or similar devices were not permitted
21. Lesions located with proximal edge of main branch &lt;10 mm from a non-target large side branch (&gt;2.0mm) causing TRYTON Stent to obstruct large side branch if implanted (for the purposes of this study, septal branches were not included)
22. Lesions with proximal edge of main branch &lt;10 mm from the RCA, LCX or LAD origin causing TRYTON Stent to obstruct parent vessel if implanted.

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2. Follow-up Schedule

The Pivotal RCT enrolled patients (randomized and roll-in patients) in both groups were required to receive dual antiplatelet therapy (DAPT) for 12 months and all patients were scheduled to return for clinical follow-up assessments at 30 days, 6 months, 9 months, 1 year, 2 years and 3 years post-index procedure.

Angiographic follow-up at 9 months was obtained in the first 374 randomized patients (N=195 TRYTON cohort, N=181 POBA cohort). Of those enrolled in the angiographic subgroup, the IVUS subgroup included 59 TRYTON patients and 35 POBA patients.

The following procedures and tests were performed prior to the index procedure and postoperatively, as indicated in Table 7. Adverse events and complications were recorded at all visits.

The key timepoints are shown below in the tables summarizing safety and effectiveness.

Table 7: Schedule of Procedures and Tests

|  PROCEDURE / TEST | Baseline (within 7 days) | Pre-Procedure (within 24 hours) | Procedure | Post-Procedure | 30 days (± 7 days) | 6 months or 180-days (±30 days) | 9 Months or 270-days (+ 30 days)^{8} | 1 year (± 30 days) | 2 year (± 30 days) | 3 year (± 30 days) | Unscheduled visits  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Subject Medical/Clinical History (Age, Gender, Risk Factors, Angina Status, Cardiac History) | ✓ |  |  |  |  |  |  |  |  |  |   |
|  Angina Status | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓  |
|  Subject Informed Consent | ✓ |  |  |  |  |  |  |  |  |  |   |
|  General Eligibility Criteria | ✓ |  |  |  |  |  |  |  |  |  |   |
|  Angiographic Eligibility Criteria |  |  | ✓ |  |  |  |  |  |  |  |   |
|  Clinical Laboratory Test: |  |  |  |  |  |  |  |  |  |  |   |
|  Pregnancy Test (childbearing potential women only) | ✓ |  |  |  |  |  |  |  |  |  |   |
|  CBC, Creatinine, BUN, blood chemistry | ✓ |  |  |  |  |  |  |  |  |  |   |
|  Lipid profile | ✓ |  |  |  |  |  |  |  |  |  |   |
|  CK, CK-MB, or Troponin* |  | ✓^{2} |  | ✓^{3} |  |  |  |  |  |  | ✓^{4}  |

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|  12-Lead ECG |  | ✓² |  | ✓¹ |  |  | ✓ |  |  |  | ✓⁴  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Coronary Angiogram (QCA) |  |  | ✓ |  |  |  | ✓⁸ |  |  |  |   |
|  Intravascular Ultrasound (IVUS) |  |  |  | ✓⁷ |  |  | ✓⁷,⁸ |  |  |  |   |
|  Left Ventriculography |  |  | ✓⁵ |  |  |  |  |  |  |  |   |
|  Study Stent information |  |  | ✓ |  |  |  |  |  |  |  |   |
|  Per Protocol Medications |  | ✓ | ✓ | ✓⁶ | ✓⁶ | ✓⁶ | ✓⁶ | ✓⁶ | ✓⁶ | ✓⁶ | ✓⁶  |
|  Concomitant Cardiac Meds |  |  | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓  |
|  Adverse Events Monitoring |  |  | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓  |

1. Between 12 hours post-procedure and discharge.
2. Within 48 hours pre-procedure will be acceptable except when there is evidence of acute or recent (&lt;72 hours) myocardial infarction or unstable angina prior to the procedure, in which case pre-procedure draws/assessments must be within 24 hours.
3. If CK-MB is elevated ≥2 times upper limit of normal, serial measurements (minimum of two (2) samples 8 hours apart) of CK and CK-MB must be done until a decline is noted. *If CK-MB analysis is not available on-site, patients may be included if serial Troponins are obtained and demonstrate a downward trend. Baseline and follow-up blood samples must be obtained for central lab CK-MB analysis
4. CK and CK-MB and ECG should be obtained for all suspected ischemic events. See note 3 regarding process if CK-MB is not available on-site.
5. LVEF at procedure if not documented within 6 months prior.
6. Clopidogrel, ticlopidine, prasugrel or ticagrelor (dose per manufacturer’s directions for use) must be given for a minimum of 12 months as well as aspirin 75 to 162 mg daily (or dose per standard hospital practice) to be taken indefinitely.
7. IVUS procedures apply only to those subjects enrolled in the IVUS sub-study
8. For those patients in the angiographic and IVUS sub-groups, the clinical evaluation may be performed at the angiographic follow-up visit but **must occur prior** to angiographic/IVUS evaluation. The investigator must declare the presence of ischemic symptoms prior to the angiographic assessment.

## 3. Clinical Endpoints

The primary endpoint of the Pivotal RCT was Target Vessel Failure [TVF, a composite of cardiac death, target vessel MI, and clinically-indicated target vessel revascularization (in main or side branch)] at 9-month follow-up.

Powered secondary endpoint: Percent diameter stenosis in the side branch at 9 months in the angiographic sub study cohort.

Other secondary endpoints included a range of safety and effectiveness parameters including acute success, the individual components of TVF (cardiac death, target vessel MI, and TVR), all-cause mortality, rate of stent thrombosis and MACE (and the individual elements of MACE) evaluated at 30 days, 6 and 9 months and annually up to 3 years.

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Acute success was classified according to the following definitions:

- Device Success: Device success was defined as achievement of a final in-stent residual diameter stenosis of &lt;30% (by quantitative coronary angiography [QCA]), using the assigned device only and without a device malfunction.
- Lesion Success: Lesion success was defined as achievement of a final in-stent residual diameter stenosis of &lt;50% (by QCA) using any percutaneous method.
- Procedure Success: Procedure success was defined as achievement of a final in-stent diameter stenosis of &lt;50% (by QCA) using the assigned device and with any adjunctive devices, without the occurrence of cardiac death, Q-wave or non-Q-wave MI, or repeat revascularization of the target lesion during the hospital stay.

## B. TRYTON Pivotal RCT: Accountability of PMA Cohort

At the time of database lock, of 704 patients enrolled in the PMA study, 92% (645/704) patients are available for analysis at the 2 year post-operative visit.

All 704 randomized subjects (355 TRYTON subjects and 349 POBA subjects) comprised the ITT population, which was the primary analysis set in this trial. Of the 355 subjects randomized to receive the TRYTON Side Branch Stent in conjunction with main branch approved DES, 14 subjects did not receive the TRYTON Stent for the following reasons: stent dislodgment from balloon before reaching the target lesion (n=6); failure of the coronary wire to cross the target lesion (n=2); failure of the stent to cross the target lesion (n=2); side branch not suitable for stenting (occlusive dissection with wire and side branch deemed too small for stenting) (n=2); and randomization error (n=2).

Of the 349 subjects randomized to receive side branch balloon angioplasty in conjunction with main branch approved DES, two (2) subjects (0.6%) received the TRYTON Stent and 34 received a non-study stent post POBA treatment in the side branch.

Table 8 details all deaths, withdrawals and study exits of ITT subjects by treatment group and follow-up through 2 years.

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Table 8: ITT Subject Accountability at Each Follow-Up Through Two Years

|   | 1 Month Follow-Up |   | 6 Months Follow-Up |   | 9 Months Follow-Up |   | 1 Year Follow-Up |   | 2 Years Follow-Up |   | TOTAL  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  TRYTON | POBA | TRYTON | POBA | TRYTON | POBA | TRYTON | POBA | TRYTON | POBA | OVERALL  |
|  Completed Follow-Up Visit | 353 | 343 | 341 | 337 | 342 | 330 | 336 | 329 | 331 | 324 |   |
|  Subjects Eligible for Follow-up | 355 | 347* | 350 | 342 | 349 | 340 | 343 | 335 | 338 | 332 |   |
|  Ineligible for Follow-up: Reasons  |   |   |   |   |   |   |   |   |   |   |   |
|  Death | 4 | 2 | 0 | 2 | 2 | 1 | 4 | 1 | 3 | 2 | 21  |
|  Withdrew Consent | 1 | 3* | 1 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 11  |
|  Exited for Other Reasons | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 2 | 0 | 0 | 7  |

*Two (2) withdrew consent prior to 30 days

## C. TRYTON Pivotal RCT: Study Population Demographics and Baseline Parameters

The demographics of the study population were typical for a coronary stent study performed in the US (Table 9).

Table 9: Baseline Patient Demographics and Clinical Characteristics (Intent-to-Treat)

|   | TRYTON
(N=355 Patients) | POBA
(N=349 Patients)  |
| --- | --- | --- |
|  Age |  |   |
|  Mean±SD (N) | 64.50±10.61 (355) | 64.58±9.40 (349)  |
|  Number of Men | 71.8% (255/355) | 73.4% (256/349)  |
|  Ethnicity |  |   |
|  Hispanic or Latino | 4.9% (17/347) | 6.5% (22/341)  |
|  Not Hispanic or Latino | 95.1% (330/347) | 93.5% (319/341)  |

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|   | TRYTON (N=355 Patients) | POBA (N=349 Patients)  |
| --- | --- | --- |
|  Race |  |   |
|  American Indian or Alaska Native | 0.0% (0/355) | 0.3% (1/349)  |
|  Asian | 1.1% (4/355) | 1.7% (6/349)  |
|  Black or African American | 1.7% (6/355) | 4.3% (15/349)  |
|  Native Hawaiian or Other Pacific Islander | 0.0% (0/355) | 0.6% (2/349)  |
|  White | 95.8% (340/355) | 89.1% (311/349)  |
|  Other | 1.4% (5/355) | 4.0% (14/349)  |
|  Risk Factors |  |   |
|  MI | 30.0% (105/350) | 37.8% (131/347)  |
|  PCI | 38.0% (135/355) | 41.8% (146/349)  |
|  CABG | 2.5% (9/353) | 2.0% (7/349)  |
|  TIA | 2.8% (10/351) | 2.3% (8/346)  |
|  CVA | 2.3% (8/350) | 3.8% (13/343)  |
|  CHF | 1.7% (6/355) | 0.9% (3/349)  |
|  Diabetes Mellitus | 23.9% (85/355) | 28.1% (98/349)  |
|  Hypertension | 73.2% (260/355) | 73.6% (256/348)  |
|  Hypercholesterolemia | 74.1% (260/351) | 77.3% (266/344)  |
|  Renal Insufficiency/failure or on dialysis | 0.0% (0/355) | 0.3% (1/348)  |
|  Premature CAD in a first degree relative | 36.9% (114/309) | 32.5% (101/311)  |
|  Smoking Status |  |   |
|  Current | 17.5% (62/355) | 15.2% (53/348)  |
|  Former | 34.6% (123/355) | 35.9% (125/348)  |
|  Atrial Fibrillation | 10.7% (38/354) | 6.9% (24/348)  |
|  Assessment of Anginal Status |  |   |
|  Intervention prompted by myocardial infarction | 10.7% (38/355) | 9.7% (34/349)  |
|  Angina Type |  |   |
|  Stable | 73.8% (262/355) | 74.8% (261/349)  |
|  Unstable | 20.0% (71/355) | 19.8% (69/349)  |
|  Silent Ischemia | 5.6% (20/355) | 5.2% (18/349)  |
|  No Angina | 0.6% (2/355) | 0.3% (1/349)  |
|  Canadian Cardiovascular Society Class |  |   |
|  I | 13.6% (34/250) | 16.7% (41/245)  |
|  II | 57.6% (144/250) | 55.1% (135/245)  |
|  III | 25.2% (63/250) | 22.9% (56/245)  |
|  IV | 3.6% (9/250) | 5.3% (13/245)  |

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When assessed by the angiographic core laboratory, true bifurcation lesions (Medina Classification 1.1.1; 0.1.1; or 1.0.1) were present at randomization in 89.8% (318/354) of the lesions in the TRYTON group and 86.2% (301/349) of the lesions in the POBA group (Table 10).

Table 10: Medina Classification

|  Medina Classification | Site Reported |   | Core Lab  |   |
| --- | --- | --- | --- | --- |
|   | POBA | TRYTON | POBA | TRYTON  |
|  1,1,1 | 68.7% (239/348) | 73.2% (260/355) | 42.1% (147/349) | 49.2% (174/354)  |
|  1,1,0* | 0.0% (0/348) | 0.0% (0/355) | 4.9% (17/349) | 2.3% (8/354)  |
|  1,0,1 | 12.4% (43/348) | 11.5% (41/355) | 16.0% (56/349) | 15.8% (56/354)  |
|  0,1,1 | 18.7% (65/348) | 14.6% (52/355) | 28.1% (98/349) | 24.9% (88/354)  |
|  1,0,0* | 0.0% (0/348) | 0.3% (1/355) | 2.6% (9/349) | 1.4% (5/354)  |
|  0,1,0* | 0.0% (0/348) | 0.0% (0/355) | 4.0% (14/349) | 2.8% (10/354)  |
|  0,0,1* | 0.3% (1/348) | 0.3% (1/355) | 2.3% (8/349) | 3.4% (12/354)  |
|  0,0,0* | 0.0% (0/348) | 0.0% (0/355) | 0.0% (0/349) | 0.3% (1/354)  |
|  1,1,0 OR 1,0,0 OR 0,1,0 OR 0,0,1 OR 0,0,0* | 0.0% (0/348) | 0.0% (0/355) | 0.0% (0/349) | 0.0% (0/354)  |

*Protocol deviation

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Table 11 details the baseline lesion characteristics of ITT patients.

Table 11: Baseline Lesion Characteristics

|   | Tryton (N = 355) | POBA (N = 349) | P-value  |
| --- | --- | --- | --- |
|  Mean Main Branch Lesion Length ±SD (mm) (N) | 16.8 (±7.3) (354) | 16.0 (±6.8) (348) | 0.109  |
|  Mean Side Branch RVD ±SD (mm) (N) | 2.25 (±0.30) (354) | 2.21 (±0.33) (348) | 0.093  |
|  Mean Side Branch Lesion Length ±SD (mm) (N) | 4.84 (±1.56) (354) | 4.43 (±1.12) (348) | <.001  |
|  Mean Minimum Lesion Diameter ±SD (mm) (N) | 0.95 (±0.34) (354) | 1.02 (±0.34) (347) | 0.009  |
|  Mean Percent Diameter Stenosis ±SD (mm) (N) | 58.0% (±14.3) (354) | 54.0% (±14.5) (347) | <.001  |

# D. TRYTON Pivotal RCT: Safety and Effectiveness Results

The analysis of safety and effectiveness was based on the intent-to-treat cohort of 704 patients available for the 9-month and 2-year evaluations and the Intended Population cohort (QCA-assessed side branch diameter of  $\geq 2.25\mathrm{mm}$ ) post hoc analysis of 289 patients for the 9-month and 2-year evaluations. The key safety and effectiveness outcomes for this study are presented below in Tables 12 to 27 and Figures 2 to 4. Serious adverse events are reported in Table 28.

# Acute Success

As presented in Table 12, device, lesion and procedure success were achieved more frequently in the TRYTON arm compared to the POBA arm:

Device success: Attainment of  $&lt; 30\%$  residual stenosis within the side branch using the assigned device only and without a device malfunction, was achieved in  $90.8\%$  (316/348) of the lesions in the TRYTON group compared to  $39.0\%$  (135/346) of the lesions in the POBA group.

Lesion success: Attainment of  $&lt; 50\%$  residual stenosis using any percutaneous method, was achieved in all  $(100\%; 337/337)$  of the lesions in the TRYTON group compared to  $88.1\%$  (304/345) of the lesions in the POBA group.

Procedure success: Lesion success without the occurrence of in-hospital MACE, was achieved in  $80.3\%$  (281/350) of the subjects in the TRYTON group compared to  $70.5\%$  (102/346) of the subjects in the POBA group.

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Table 12: Acute Success – Intent-to-Treat Analysis Set

|   | TRYTON | POBA  |
| --- | --- | --- |
|  Lesions evaluable for Lesion Success | 337 | 345  |
|  Lesions evaluable for Device Success | 348 | 346  |
|  Patients evaluable for Procedure Success | 350 | 346  |
|   | TRYTON | POBA  |
| --- | --- | --- |
|  Lesion^{1} |  |   |
|  Success | 337 | 304  |
|  % Success | 100.0% (337/337) | 88.1% (304/345)  |
|  Failure | 0 | 41  |
|  % Failure | 0.0% (0/337) | 11.9% (41/345)  |
|  Device^{2} |  |   |
|  Success | 316 | 135  |
|  % Success | 90.8% (316/348) | 39.0% (135/346)  |
|  Failure | 32 | 211  |
|  % Failure | 9.2% (32/348) | 61.0% (211/346)  |
|  Procedure^{3} |  |   |
|  Success | 281 | 244  |
|  % Success | 80.3% (281/350) | 70.5% (244/346)  |
|  Failure | 69 | 102  |
|  % Failure | 19.7% (69/350) | 29.5% (102/346)  |

1Lesion success and failure are presented per lesion.
2Device success and failure are presented per lesion.
3Procedure success and failure are presented per patient.

## Primary Endpoint: ITT Subjects

The primary endpoint (TVF at 9-months) was performed on all ITT subjects who had at least 270 days of follow-up or who experienced a primary endpoint event within 270 days (i.e., available cases). The 9-month TVF rate was 16.7% (58/348) in the TRYTON group compared to 12.6% (43/341) in the POBA group. The difference in 9-month TVF rates between the groups was 4.1% with two-sided 95% CI of [-1.5%, 9.6%]. Since the upper bound of this CI is higher than 5.5% (the delta for non-inferiority), the null hypothesis is not rejected and the TRYTON Stent is not considered non-inferior to POBA (non-inferiority not met) with regards to 9-month TVF (Table 13).

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Table 13: Primary Endpoint at 9 Months

|   | TRYTON (N=355 Patients) | POBA (N=349 Patients) | Difference [95% CI] | Delta  |
| --- | --- | --- | --- | --- |
|  TVF to 270 Days  |   |   |   |   |
|  Intent-to-Treat  |   |   |   |   |
|  Available Cases* | 16.7% (58/348) | 12.6% (43/341) | 4.1% [-1.5%,9.6%] | 5.50%  |
|  Worst Case | 18.3% (65/355) | 12.3% (43/349) | 6.0% [0.4%,11.6%] |   |
|  Multiple Imputation | 17.1% | 13.1% | 4.0% [-2.0%,10.0%] |   |
|  Kaplan-Meier Estimates | 16.4% | 12.4% | 4.0% [-1.2%,9.2%] |   |
|  Per-Protocol  |   |   |   |   |
|  Available Cases* | 16.0% (53/332) | 12.4% (40/323) | 3.6% [-2.1%,9.2%] | 5.50%  |
|  Worse Case | 17.7% (60/339) | 12.1% (40/330) | 5.6% [-0.1%,11.3%] |   |
|  Multiple Imputation | 16.8% | 13.4% | 3.4% [-2.7%,9.5%] |   |
|  Kaplan-Meier Estimates | 15.7% | 12.2% | 3.5% [-1.7%,8.8%] |   |

*Available cases include subjects with at least 270 days of follow-up or subjects who experienced the primary endpoint within 270 days.

Secondary Safety and Effectiveness Endpoints: ITT Subjects

Tables 14 and 15 show the secondary safety and effectiveness endpoints among ITT subjects evaluated in the trial. Data are presented at two time points: 9 months (Table 14) and 2 years (the latest endpoint that all patients had reached at time of data lock, Table 15).

Table 14: Secondary Safety and Effectiveness Endpoints to 270 days (9 Months) – Intent-to-Treat Analysis Set

|  Event1 | TRYTON (N=355 Patients) | POBA (N=349 Patients)  |
| --- | --- | --- |
|  Target Lesion Failure (TLF – Cardiac Death, Target Vessel MI (Modified ARC Definition) and Ischemia Driven or Clinically Indicated Target Lesion Revascularization) | 16.4% (57/348) | 12.0% (41/341)  |
|  Stent Thrombosis (ARC Definite, Probable) | 0.6% (2/347) | 0.3% (1/340)  |

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|  Event^{1} | TRYTON
(N=355
Patients) | POBA
(N=349
Patients)  |
| --- | --- | --- |
|  Main Vessel | 0.6% (2/347) | 0.3% (1/340)  |
|  Side Branch | 0.6% (2/347) | 0.0% (0/339)  |
|  MACE (Death, MI, Emergent CABG, Ischemia Driven or Clinically Indicated Target Lesion Revascularization) | 17.9% (63/352) | 13.1% (45/344)  |
|  **Death** | 1.1% (4/351) | 1.2% (4/343)  |
|  Cardiac | 0.0% (0/347) | 0.0% (0/339)  |
|  Vascular | 0.3% (1/348) | 0.0% (0/339)  |
|  Non-Cardiovascular | 0.9% (3/350) | 1.2% (4/343)  |
|  Non-Cardiac | 1.1% (4/351) | 1.2% (4/343)  |
|  **Modified ARC MI^{2}** | 14.9% (52/348) | 11.1% (38/342)  |
|  Peri-Procedural PCI | 12.9% (45/348) | 10.0% (34/340)  |
|  Peri-CABG | 0.3% (1/347) | 0.0% (0/339)  |
|  Spontaneous | 2.0% (7/347) | 1.5% (5/341)  |
|  Q-wave MI (Cumulative of Target Vessel, Non-Target Vessel, Unknown Vessel) | 0.6% (2/347) | 0.3% (1/339)  |
|  Non-Q-wave MI (Cumulative of Target Vessel, Non-Target Vessel, Unknown Vessel) | 14.4% (50/348) | 10.5% (36/342)  |
|  **Target Vessel MI^{2}** | 14.4% (50/348) | 10.6% (36/341)  |
|  Q-wave MI | 0.6% (2/347) | 0.3% (1/339)  |
|  Non-Q-wave MI | 13.8% (48/348) | 10.0% (34/341)  |
|  Non-Target Vessel MI^{2} | 0.6% (2/347) | 0.6% (2/340)  |
|  Q-wave MI | 0.0% (0/347) | 0.0% (0/339)  |
|  Non-Q-wave MI | 0.6% (2/347) | 0.6% (2/340)  |
|  Emergent CABG | 0.0% (0/347) | 0.3% (1/339)  |
|  **Target Lesion Revascularization (TLR)** | 4.9% (17/347) | 3.2% (11/340)  |
|  **Ischemia Driven or Clinically Indicated Target Lesion Revascularization (TLR)^{3}** | 4.0% (14/347) | 2.9% (10/340)  |
|  Main Vessel | 3.5% (12/347) | 2.4% (8/340)  |
|  Side Branch | 2.6% (9/347) | 1.5% (5/340)  |
|  CABG | 0.3% (1/347) | 0.3% (1/339)  |
|  Main Vessel | 0.3% (1/347) | 0.3% (1/339)  |
|  Side Branch | 0.3% (1/347) | 0.3% (1/339)  |
|  PCI | 3.7% (13/347) | 2.6% (9/340)  |
|  Main Vessel | 3.2% (11/347) | 2.1% (7/340)  |
|  Side Branch | 2.3% (8/347) | 1.2% (4/340)  |

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|  Event1 | TRYTON (N=355 Patients) | POBA (N=349 Patients)  |
| --- | --- | --- |
|  Non-Ischemia Driven TLR | 0.9% (3/347) | 0.6% (2/339)  |
|  Target Vessel Revascularization (TVR) | 5.2% (18/347) | 3.8% (13/340)  |
|  Ischemia Driven or Clinically Indicated Target Vessel Revascularization (TVR)3 | 4.3% (15/347) | 3.5% (12/340)  |
|  Main Vessel | 3.7% (13/347) | 2.9% (10/340)  |
|  Side Branch | 2.6% (9/347) | 1.5% (5/340)  |
|  CABG | 0.3% (1/347) | 0.6% (2/339)  |
|  Main Vessel | 0.3% (1/347) | 0.6% (2/339)  |
|  Side Branch | 0.3% (1/347) | 0.3% (1/339)  |
|  PCI | 4.0% (14/347) | 2.9% (10/340)  |
|  Main Vessel | 3.5% (12/347) | 2.4% (8/340)  |
|  Side Branch | 2.3% (8/347) | 1.2% (4/340)  |
|  Non-Ischemia Driven Target Vessel Revascularization (TVR) | 1.2% (4/347) | 0.6% (2/339)  |
|  Non-Target Vessel Revascularization | 4.0% (14/347) | 3.5% (12/339)  |

1Events in this table have been adjudicated by the CEC.
Denominators reflect the number of patients with an adjudicated event of follow-up through 270 days.
2If the relationship to the target vessel could not be determined, the MI was considered a target vessel MI. ECGs were not available in every MI subject to determine whether a Q-wave or non-Q-wave MI occurred.
Myocardial infarction was defined using a modified version of the Joint ESC/ACC/AHA/WHF Task Force for the Redefinition of Myocardial Infarction and Academic Research Consortium criteria.
3Ischemia-Driven Target Lesion Revascularization (ID-TLR) and Ischemia-Driven Target Vessel Revascularization (ID-TVR) are defined as revascularization at the target lesion/vessel associated with any of the following: (1) Positive functional ischemia study; (2) Ischemic symptoms and angiographic MLD stenosis  $\geq 50\%$  by core laboratory QCA; (3) Revascularization of a target lesion with diameter stenosis  $\geq 70\%$  by core laboratory.
Clinically-Indicated Revascularization (TLR/TVR) is defined as a revascularization of the target lesion/vessel when angiography at follow-up shows a percent diameter stenosis  $\geq 50\%$  (Angiographic Core Laboratory QCA assessment) and if one of the following occurs: (1) A positive history of recurrent angina pectoris, presumably related to the target vessel; (2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; (3) Abnormal results of any invasive functional diagnostic test; (4) A TLR or TVR with a diameter stenosis  $\geq 70\%$  even in the absence of the above-mentioned ischemic signs or symptoms.

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$^{4}$ MI: Myocardial Infarction; ARC: Academic Research Consortium; MACE: Major Adverse Cardiac Event; CABG: Coronary Artery Bypass Graft; PCI: Percutaneous Coronary Intervention; TLR: Target Lesion Revascularization; TVR: Target Vessel Revascularization; ESC/ACC/AHA/WHF: European Society of Cardiology/ American College of Cardiology/American Heart Association/World Heart Federation.

Table 15: Secondary Safety and Effectiveness Endpoints to 730 days (2 years) – Intent-to-Treat Analysis Set

|  Event^{1} | TRYTON
(N=355
Patients) | POBA
(N=349
Patients)  |
| --- | --- | --- |
|  Target Vessel Failure (TVF – Cardiac Death, Target Vessel MI (Modified ARC Definition) and Ischemia Driven or Clinically Indicated Target Vessel Revascularization) | 21.1% (71/337) | 16.9% (56/331)  |
|  Target Lesion Failure (TLF – Cardiac Death, Target Vessel MI (Modified ARC Definition) and Ischemia Driven or Clinically Indicated Target Lesion Revascularization) | 19.6% (66/336) | 15.1% (50/331)  |
|  Stent Thrombosis (ARC Definite, Probable) | 0.6% (2/333) | 0.6% (2/327)  |
|  Main Vessel | 0.6% (2/333) | 0.6% (2/327)  |
|  Side Branch | 0.6% (2/333) | 0.0% (0/325)  |
|  MACE (Death, MI, Emergent CABG, Ischemia Driven or Clinically Indicated Target Lesion Revascularization) | 22.9% (79/345) | 17.1% (57/334)  |
|  Death | 2.9% (10/343) | 1.8% (6/330)  |
|  Cardiac | 0.3% (1/334) | 0.3% (1/326)  |
|  Vascular | 0.9% (3/336) | 0.0% (0/325)  |
|  Non-Cardiovascular | 1.8% (6/339) | 1.5% (5/329)  |
|  Non-Cardiac | 2.6% (9/342) | 1.5% (5/329)  |
|  Modified ARC MI^{2} | 17.6% (59/336) | 12.7% (42/331)  |
|  Peri-Procedural PCI | 13.8% (46/334) | 10.4% (34/328)  |
|  Peri-CABG | 0.6% (2/334) | 0.0% (0/325)  |
|  Spontaneous | 3.9% (13/334) | 3.4% (11/328)  |
|  Q-wave MI (Cumulative of Target Vessel, Non-Target Vessel, Unknown Vessel) | 0.9% (3/334) | 0.9% (3/326)  |
|  Non-Q-wave MI (Cumulative of Target Vessel, Non-Target Vessel, Unknown Vessel) | 16.4% (55/335) | 11.5% (38/330)  |
|  Target Vessel MI^{2} | 15.5% (52/336) | 11.5% (38/330)  |
|  Q-wave MI | 0.9% (3/334) | 0.9% (3/326)  |
|  Non-Q-wave MI | 14.6% (49/335) | 10.3% (34/329)  |
|  Non-Target Vessel MI^{2} | 2.1% (7/333) | 1.5% (5/326)  |

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|  Event1 | TRYTON (N=355 Patients) | POBA (N=349 Patients)  |
| --- | --- | --- |
|  Q-wave MI | 0.0% (0/333) | 0.0% (0/325)  |
|  Non-Q-wave MI | 1.8% (6/333) | 1.5% (5/326)  |
|  Emergent CABG | 0.0% (0/333) | 0.3% (1/326)  |
|  Target Lesion Revascularization (TLR) | 8.7% (29/335) | 6.4% (21/329)  |
|  Ischemia Driven or Clinically Indicated Target Lesion Revascularization (TLR)3 | 6.9% (23/334) | 5.2% (17/328)  |
|  Main Vessel | 5.1% (17/334) | 4.3% (14/328)  |
|  Side Branch | 4.8% (16/334) | 2.1% (7/327)  |
|  CABG | 0.9% (3/334) | 0.6% (2/326)  |
|  Main Vessel | 0.9% (3/334) | 0.6% (2/326)  |
|  Side Branch | 0.6% (2/334) | 0.6% (2/326)  |
|  PCI | 6.3% (21/333) | 4.9% (16/327)  |
|  Main Vessel | 4.5% (15/333) | 4.0% (13/327)  |
|  Side Branch | 4.2% (14/333) | 1.5% (5/326)  |
|  Non-Ischemia Driven TLR | 2.4% (8/334) | 1.5% (5/326)  |
|  Target Vessel Revascularization (TVR) | 10.4% (35/337) | 8.5% (28/329)  |
|  Ischemia Driven or Clinically Indicated Target Vessel Revascularization (TVR)3 | 8.6% (29/336) | 7.3% (24/328)  |
|  Main Vessel | 6.8% (23/336) | 6.4% (21/328)  |
|  Side Branch | 4.8% (16/334) | 2.1% (7/327)  |
|  CABG | 1.2% (4/334) | 0.9% (3/326)  |
|  Main Vessel | 1.2% (4/334) | 0.9% (3/326)  |
|  Side Branch | 0.6% (2/334) | 0.6% (2/326)  |
|  PCI | 7.8% (26/335) | 6.7% (22/327)  |
|  Main Vessel | 6.0% (20/335) | 5.8% (19/327)  |
|  Side Branch | 4.2% (14/333) | 1.5% (5/326)  |
|  Non-Ischemia Driven Target Vessel Revascularization (TVR) | 3.0% (10/334) | 1.5% (5/326)  |
|  Non-Target Vessel Revascularization | 10.4% (35/335) | 8.0% (26/325)  |

1Events in this table have been adjudicated by the CEC.
Denominators reflect the number of patients with an adjudicated event or follow-up through 730 days.
2If the relationship to the target vessel could not be determined, the MI was considered a target vessel MI. ECGs were not available in every MI subject to determine whether a Q-wave or non-Q-wave MI occurred.
Myocardial infarction was defined using a modified version of the Joint ESC/ACC/AHA/WHF Task Force for the Redefinition of Myocardial Infarction and Academic Research Consortium criteria.

PMA P150039: FDA Summary of Safety and Effectiveness Data…

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**Source:** [https://fda.innolitics.com/device/P150039](https://fda.innolitics.com/device/P150039)

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**Cite:** Innolitics at https://innolitics.com