REBEL PLATINUM CHROMIUM CORONARY STENT SYSTEM MONORAIL AND OVER THE WIRE

P130030 · Boston Scientific Corp · MAF · Mar 10, 2026 · Cardiovascular

Device Facts

• Record ID: P130030
• Device Name: REBEL PLATINUM CHROMIUM CORONARY STENT SYSTEM MONORAIL AND OVER THE WIRE
• Applicant: Boston Scientific Corp
• Product Code: MAF · Cardiovascular
• Decision Date: Mar 10, 2026
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The REBEL Platinum Chromium Coronary Stent System is indicated for improving coronary luminal diameter in patients with de novo lesions ≤ 28 mm in length in native coronary arteries with a reference vessel diameter (RVD) of ≥ 2.25 to ≤ 4.50 mm.

Device Story

The REBEL Stent System is a balloon-expandable, bare-metal coronary stent made of platinum chromium (PtCr) alloy. It is pre-mounted on a rapid exchange (Monorail) or Over-the-Wire delivery catheter. Used in the cardiac catheterization lab by interventional cardiologists, the device is delivered to the target coronary lesion via a guidewire. Upon inflation of the delivery balloon, the stent expands to scaffold the vessel, improving luminal diameter. The device features serpentine rings connected by links for flexibility and radiopaque markers for fluoroscopic visualization. It is intended for patients with de novo coronary lesions. Clinical benefits include improved vessel patency and reduced angina compared to medical management, with shorter recovery times than CABG. The device is a single-use, sterile implant.

Clinical Evidence

Evidence includes two prospective, multicenter, single-arm trials. The OMEGA trial (N=328) evaluated the stent in de novo lesions; the primary endpoint (9-month Target Lesion Failure [TLF]) was 11.5%, significantly below the 21.2% performance goal (p<0.0001). The NG PROMUS trial (N=100) evaluated acute deliverability, achieving 99.2% technical success. Preclinical evidence includes extensive biocompatibility (ISO 10993), bench testing (fatigue, radial strength, MRI compatibility), and porcine animal models confirming vascular healing and safety.

Technological Characteristics

Stent material: Platinum Chromium (PtCr) alloy. Strut thickness: 0.081 mm (2.25-3.50 mm diameter) to 0.086 mm (4.00-4.50 mm diameter). Delivery system: Balloon-expandable, Monorail or Over-the-Wire catheter. Energy source: Mechanical (balloon inflation). Sterilization: Ethylene oxide (EO) gas per ISO 11135-1. MR Conditional (1.5T and 3.0T). Compliant with ASTM F138-00 (material) and ASTM F2129-06 (corrosion).

Indications for Use

Indicated for patients ≥ 18 years with symptomatic coronary artery disease or silent ischemia requiring treatment of de novo native coronary artery lesions ≤ 28 mm in length and RVD 2.25–4.50 mm. Contraindicated in patients with hypersensitivity to platinum, chromium, or stainless steel; patients unable to receive anti-platelet/anticoagulant therapy; or patients with lesions preventing complete balloon inflation or proper stent placement.

Regulatory Classification

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

• OMEGA Platinum Chromium Coronary Stent System
• PROMUS PREMIER Everolimus-Eluting Platinum Chromium Coronary Stent System
• TAXUS Element
• TAXUS Liberté
• Xience V (PROMUS)
• Liberté (VeriFLEX)

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Stent, Coronary

Device Trade Name: REBEL™ Platinum Chromium Coronary Stent System (Monorail® and Over-the-Wire) (REBEL Stent System)

Device Procode: MAF

Applicant's Name and Address: Boston Scientific Corporation
One Scimed Place
Maple Grove, MN 55311

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P130030

Date of FDA Notice of Approval: June 27, 2014

II. INDICATIONS FOR USE

The REBEL Platinum Chromium Coronary Stent System is indicated for improving coronary luminal diameter in patients with de novo lesions ≤ 28 mm in length in native coronary arteries with a reference vessel diameter (RVD) of ≥ 2.25 to ≤ 4.50 mm.

III. CONTRAINDICATIONS

Use of the REBEL Stent System is contraindicated in patients with the following:

- Known hypersensitivity to platinum, the platinum chromium alloy, or similar alloy types such as stainless steel.
- Known severe reaction to contrast agents that cannot be adequately premedicated prior to the REBEL Stent placement procedure.

Coronary artery stenting is contraindicated for use in the following:

- Patients who cannot receive recommended anti-platelet and/or anticoagulant therapy.
- Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or delivery device.

IV. WARNINGS AND PRECAUTIONS

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The warnings and precautions can be found in the REBEL Platinum Chromium Coronary Stent System labeling.

## V. DEVICE DESCRIPTION

The REBEL Stent System is a single-use device comprised of a balloon-expandable, intracoronary REBEL stent pre-mounted on a rapid exchange, Monorail®, or Over-the-Wire delivery catheter. The REBEL stent is made from a platinum chromium alloy (PtCr). The stent is laser cut into a pattern which consists of serpentine rings connected by links and are polished to a uniform rounded surface.

The characteristics of the REBEL Stent System are described in Table 1.

Table 1: REBEL Platinum Chromium Coronary Stent System Product Description

| | REBEL
Monorail™ Stent Delivery System | REBEL
Over-the-Wire Stent Delivery
System |
| --- | --- | --- |
| Stent | | |
| Available Stent
Lengths (mm) | 8*, 12, 16, 20, 24, 28, 32* | |
| Available Stent
Diameters (mm) | 2.25*, 2.50*, 2.75, 3.00, 3.50, 4.00, 4.50* | |
| Stent Material | Platinum Chromium (PtCr) Alloy | |
| Stent Strut
Thickness | 0.0032 inches (0.081 mm) for diameters 2.25 mm to 3.50 mm
0.0034 inches (0.086 mm) for diameters 4.00 mm and 4.50 mm | |
| Delivery System | | |
| Effective Length | 144 cm | |
| Delivery System
Ports | Single access port to inflation lumen.
Guidewire exit port is located
approximately 25 cm from tip.
Designed for guidewire ≤0.014
inches (0.36 mm). | Y-Connector (Side arm for access to
balloon inflation/deflation lumen.
Straight arm is continuous with shaft
inner lumen). Designed for
guidewire ≤0.014 inches (0.36 mm). |
| Stent Delivery | A balloon, with two radiopaque balloon markers, nominally placed 0.4 mm
(0.016 inches) beyond the stent at each end. | |
| Balloon Inflation
Pressure | Nominal Inflation Pressure: 11 atm (1117 kPa) | |
| | Rated Burst Inflation Pressure: 18 atm (1827 kPa) | |
| Catheter Shaft
Outer Diameter | 2.1 F (.0.70 mm) proximal
2.7 F (0.95 mm) distal. | 3.4F (≤1.20 mm) proximal for 2.25
to 4.50 mm sizes
2.4F (≤0.85 mm) distal for 2.25 to
2.75 mm sizes
2.7F (≤0.95 mm) distal for 3.00 to
4.50 mm sizes |
| Guide Catheter
Minimum Inner
Diameter
Requirement | ≥0.056 inches (1.42 mm) for 2.25 –
4.00 mm sizes
≥0.066 inches (1.68 mm) for 4.50
mm size | ≥0.066 inches (1.68 mm) |

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* 32 mm length is not available in 2.25 mm and 2.50 mm diameter size. 8 mm length is not available in 4.50 mm diameter size.

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The REBEL stent is available in four stent models across the range of reference vessel diameters indicated:

- Small Vessel (SV): 2.25 mm
- Small Workhorse (SWH): 2.50 mm and 2.75 mm
- Workhorse (WH): 3.00 mm and 3.50 mm
- Large Vessel (LV): 4.00 mm and 4.50 mm

The commercial matrix is shown in Table 2 below:

Table 2: REBEL Stent System US Commercial Matrix

| | Stent Length | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | 8 mm | 12 mm | 16 mm | 20 mm | 24 mm | 28 mm | 32 mm |
| Balloon Diameter / Stent Model | SV | 2.25 mm | X | X | X | X | X | X | |
| | SWH | 2.50 mm | X | X | X | X | X | X | |
| | | 2.75 mm | X | X | X | X | X | X | X |
| | WH | 3.00 mm | X | X | X | X | X | X | X |
| | | 3.50 mm | X | X | X | X | X | X | X |
| | LV | 4.00 mm | X | X | X | X | X | X | X |
| | | 4.50 mm | | X | X | X | X | X | X |

VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of coronary artery disease: exercise, diet, smoking cessation, drug therapy, percutaneous coronary interventions (such as angioplasty and placement of bare metal stents, coated stents, and other drug eluting stents), and coronary artery bypass graft surgery (CABG). 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 REBEL Stent System received CE Mark 05 February 2014. As of 31 May 2014, approximately 1,305 REBEL Stent Systems have been distributed outside the United States. Table 3 contains a list of countries where the REBEL Stent System is currently available. No products have been withdrawn from the market in any country for any reason

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The REBEL Stent System is a design iteration of the CE Marked OMEGA™ Platinum Chromium Coronary Stent System and contains many of the same design elements and materials. As of 31 October 2013, approximately 185,549 OMEGA Stent Systems have been distributed outside the United States. Table 3 contains a list of countries where the OMEGA Stent System is currently available. No products have been withdrawn from the market in any country for any reason.

Table 3: Countries with REBEL (R) or OMEGA (O) Stent System Commercial Availability

| Albania (R,O) | Algeria (R,O) | Andorra (R,O) | Antigua/Barbuda (R,O) |
| --- | --- | --- | --- |
| Argentina (O) | Armenia (R,O) | Aruba (R,O) | Australia (O) |
| Austria (R,O) | Azerbaijan (R,O) | Bahamas (R,O) | Bahrain (R,O) |
| Bangladesh (O) | Barbados (R,O) | Belgium (R,O) | Belize (R,O) |
| Belarus (O) | Bermuda (R,O) | Bolivia (O) | Bosnia (O) |
| Brazil (O) | Brunei (R,O) | Bulgaria (R,O) | Chile (R,O) |
| Colombia (O) | Costa Rica (O) | Croatia (R,O) | Cyprus (R,O) |
| Czech Republic (R,O) | Denmark (R,O) | Djibouti (R,O) | Dominican Republic (R,O) |
| Dutch Antilles (R,O) | Ecuador (O) | Egypt (O) | El Salvador (R,O) |
| Estonia (R,O) | Finland (R,O) | France (R,O) | Georgia (R,O) |
| Germany (R,O) | Great Britain (R,O) | Greece (R,O) | Guatemala (O) |
| Guyana (R,O) | Haiti (R,O) | Honduras (R,O) | Hong Kong (O) |
| Hungary (R,O) | Iceland (R,O) | India (O) | Indonesia (O) |
| Israel (O) | Iraq (R,O) | Ireland (R,O) | Italy (R,O) |
| Jamaica (R,O) | Jordan (O) | Kenya (R,O) | Korea (O) |
| Kuwait (R,O) | Latvia (R,O) | Lebanon (R,O) | Libya (R,O) |
| Liechtenstein (R,O) | Lithuania (R,O) | Luxembourg (R,O) | Macedonia (O) |
| Macau (O) | Malaysia (O) | Malta (R,O) | Martinique (R,O) |
| Moldavia (R,O) | Morocco (R,O) | Myanmar (R,O) | Nepal (R,O) |
| Netherlands (R,O) | New Zealand (O) | Nicaragua (R,O) | Norway (R,O) |
| Oman (R,O) | Pakistan (O) | Palestinian Territory (O) | Panama (O) |
| Paraguay (O) | Peru (O) | Philippines (O) | Poland (R,O) |
| Puerto Rico (O) | Portugal (R,O) | Qatar (R,O) | Romania (R,O) |
| Russia (O) | Saudi Arabia (O) | Serbia (O) | Singapore (O) |
| Slovakia (R,O) | Sri Lanka (O) | Slovenia (R,O) | South Africa (O) |
| Spain (R,O) | Surinam (R,O) | Sweden (R,O) | Switzerland (R,O) |
| Syria (O) | Taiwan (O) | Thailand (O) | Trinidad/Tobago (R,O) |
| Tunisia (R,O) | Turkey (O) | Ukraine (R,O) | United Arab Emirates (R,O) |
| Venezuela (O) | Vietnam (O) | Yemen (R,O) | - |

## 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 REBEL Stent System.

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- Abrupt closure
- Allergic reaction (including to medications, contrast, stent materials)
- Aneurysm (coronary)
- Angina
- Arrhythmias, including ventricular fibrillation and ventricular tachycardia
- Arteriovenous fistula
- Bleeding
- Cardiac tamponade
- Cardiogenic shock
- Cardiomyopathy
- Death
- Emboli (including air, tissue, thrombus, plaque, or device materials)
- Heart failure
- Hematoma
- Hemorrhage
- Hypotension/hypertension
- Infection, local and/or systemic
- Ischemia, myocardial
- Myocardial infarction
- Pain
- Pericardial effusion
- Pseudoaneurysm, femoral
- Pulmonary edema
- Renal insufficiency or failure
- Respiratory failure
- Restenosis of stented segment
- Shock
- Stent embolization
- Stent fracture
- Stent migration
- Stent thrombosis and/or vessel occlusion
- Stroke/cerebrovascular accident/transient ischemic attack
- Total occlusion of coronary artery
- Vessel spasm
- Vessel injury (including dissection, perforation, rupture or trauma)

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

## IX. SUMMARY OF PRECLINICAL STUDIES

### A. Laboratory Testing

#### 1. Biocompatibility Studies

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A series of biocompatibility tests were conducted to demonstrate that the components of the REBEL Stent System are biocompatible. Testing was conducted separately for the stent implant and the stent delivery system. Tests were conducted on ethylene oxide-sterilized bare metal, platinum chromium alloy (PtCr) stents and balloon catheters. These test articles were processed in a manner similar to the finished REBEL Stent System product. There were some manufacturing differences that were determined not to impact the biocompatibility of the final device.

All biocompatibility testing was conducted in accordance with:

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

The tests summarized in Table 4 have been conducted in support of the REBEL stent component as recommended for a permanent implantable device contacting circulating blood for &gt;30 days.

Table 4: Biological Evaluation Tests Performed on Stent

| Test Performed / Applicable ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Cytotoxicity MEM Elution / Part 5 | To determine the potential for cytotoxicity | The test article meets test requirements if none of the cultures treated with the test article show greater than Mild reactivity (Grade 2). | Pass Non Cytotoxic |
| Sensitization Guinea Pig Max / Part 10 | To evaluate the allergenic potential or sensitizing capacity of a test article. | Skin reaction scores received by the test group must be equal or less than the scores received by the negative control group. | Pass Non-Sensitizer |
| Irritation Intracutaneous Reactivity / Part 10 | To screen test article extracts for potential irritation effects. | The requirements of the test are met if the difference between the test article and the control mean score is 1.0 or less (negligible or slight). | Pass Non-Irritant |
| Acute Systemic Toxicity / Part 11 | To screen test article extracts for potential systemic toxic effects. | Test is considered negative if none of the animals injected with the test article show a significantly greater biological reaction than the animals treated with the vehicle control. | Pass Negative, Non-toxic |
| Material-Mediated Rabbit Pyrogenicity / Part 11 | To determine the presence of chemical pyrogens in extracts of a test article causing a febrile response in rabbits. | If no rabbit shows an individual rise in temperature of 0.5°C or more above baseline, the test article meets the requirements of the test. | Pass Non-Pyrogenic |
| Hemolysis Direct Contact / Part 4 | To assess the hemolytic activity of the test article when in direct contact with blood. | Results are considered “pass” if the hemolytic index of test article is 5% or less. | Pass Non-Hemolytic |

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| Test Performed / Applicable ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Hemolysis Indirect Contact / Part 4 | To assess the hemolytic activity of a test article extract in contact with blood. | Results are considered “pass” if the hemolytic index of test article extract is 5% or less. | Pass Non-Hemolytic |
| Complement Activation / Part 4 | Measurement of complement activation indicates whether a test article is capable of inducing a complement-induced inflammatory immune response in humans. | The concentration of C3a and SC5b-9 in serum exposed to the positive control should be significantly greater than those in the corresponding untreated serum. The test article will be considered positive or negative based upon a statistical comparison to the positive control. | Pass Negative for C3a and SC5b-9 assays |
| In Vitro Hemocompatibility Assay / Part 4 | To determine if the test article would adversely affect the various cellular and non-cellular components of the blood. | Test article results should be comparable to the results of the negative blood control or the reference material controls. | Pass Results comparable to negative control |
| Partial Thromboplastin Time / Part 4 | To determine the time citrated plasma exposed to a test material takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride. | Results are considered “pass” if the average clotting time of the test article is at least 50% compared to that of the negative control. | Pass Results comparable to negative control |
| Genotoxicity Ames Assay / Part 3 | To evaluate the mutagenic potential of leachables from the test article. | The test article is considered negative if it does not cause increase in 2-fold the mean revertant in all test strains of bacteria. | Pass Non-Mutagenic |
| Genotoxicity Mouse Lymphoma / Part 3 | To evaluate mutagenicity of the test agents. | The test article is considered negative if the test article-dosed cultures have a mutation frequency (MF) of less than 1.8 fold higher than that of the concurrent negative control plates. | Pass Non-Mutagenic |
| Sub-chronic Toxicity, Implantation/ Part 6 & 11 | To evaluate the potential for local and systemic toxicity of a test article implanted subcutaneously in rats for 13 weeks. | Test is considered negative if the test article did not induce a significantly greater biological reaction than the control article. | Pass No systemic toxicity, Non-Irritant |
| Implantation - In Vivo Thrombogenicity / Part 4 & 6 | This test is to confirm there is no abnormal thrombosis related to the stent. | No significant differences in vascular response between test article and control stents in stent-related mortality or luminal thrombus. | Pass No stent-related mortality. No luminal thrombus. |

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The tests summarized in Table 5 have been performed in support of the REBEL delivery system catheter as recommended for externally communicating device contacting the circulating blood with limited exposure of $&lt; 24$ hours.

Table 5: Biological Evaluation Tests Performed on Delivery System Catheter

| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Cytotoxicity MEM Elution / Part 5 | To determine the potential for cytotoxicity | The test article meets test requirements if none of the cultures treated with the test article show greater than Mild reactivity (Grade 2). | Pass Non-Toxic |
| Sensitization Guinea Pig Maximization / Part 10 | To evaluate the allergenic potential or sensitizing capacity of a test article. | Skin reaction scores received by the test group must be equal or less than the scores received by the negative control group. | Pass Non-Sensitizer |
| Irritation Intracutaneous Reactivity / Part 10 | To screen test article extracts for potential irritation effects. | The requirements of the test are met if the difference between the test article and the control mean score is 1.0 or less (negligible or slight). | Pass Non-Irritant |
| Acute Systemic Toxicity / Part 11 | To screen test article extracts for potential systemic toxic effects. | Test is considered negative if none of the animals injected with the test article show a significantly greater biological reaction than the animals treated with the vehicle control. | Pass Non-Toxic |
| Material-Mediated Rabbit Pyrogenicity / Part 11 | To determine the presence of chemical pyrogens in extracts of a test article causing a febrile response in rabbits. | If no rabbit shows an individual rise in temperature of 0.5°C or more above baseline, the test article meets the requirements of the test. | Pass Non-Pyrogenic |

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| Test Performed / Applicable EN ISO 10993 Part Number | Test Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Hemolysis Direct Contact / Part 4 | To assess the hemolytic activity of the test article when in direct contact with blood. | Results are considered “pass” if the hemolytic index of test article is 5% or less. | Pass Non-Hemolytic |
| Hemolysis Indirect Contact / Part 4 | To assess the hemolytic activity of a test article extract in contact with blood. | Results are considered “pass” if the hemolytic index of test article extract is 5% or less. | Pass Non-Hemolytic |
| Complement Activation / Part 4 | Measurement of complement activation indicates whether a test article is capable of inducing a complement-induced inflammatory immune response in humans. | The concentration of C3a and SC5b-9 in serum exposed to the positive control should be significantly greater than those in the corresponding untreated serum. The test article will be considered positive or negative based upon a statistical comparison to the positive control. | Pass Negative for C3a and SC5b-9 assays |
| In Vitro Hemocompatibility Assay / Part 4 | To determine if the test article would adversely affect the various cellular and non-cellular components of the blood. | Test article results should be comparable to the results of the negative blood control or the reference material controls. | Pass Results comparable to negative control |
| Partial Thromboplastin Time / Part 4 | To determine the time citrated plasma exposed to a test material takes to form a clot when exposed to a suspension of phospholipid particles and calcium chloride. | Results are considered “pass” if the average clotting time of the test article is at least 50% compared to that of the negative control. | Pass Results comparable to negative control |
| USP Physicochemical Test for Plastics <661> / Part 18 | To determine the physical and chemical properties of an extract of a test material. | Non-volatile residue <15mg, residue on ignition <5mg (only performed when Non-volatile residue is > 15 mg), heavy metals <1ppm and buffering capacity <10ml. | Pass |

2. In Vitro Engineering Testing

In vitro engineering testing on the REBEL Stent System was conducted, as applicable, in accordance with:

- FDA Guidance for Industry and Staff: Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, 18 April 2010
- FDA Guidance for Industry and Staff: Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment, August 2008

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The in vitro engineering studies are summarized in Table 5. "Pass" denotes that the test results met product specifications and/or the recommendation in the above-referenced guidance documents.

Table 5: Stent and Delivery Catheter Engineering Testing

| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Material Characterization Testing | | |
| Material Composition | Chemical analysis was conducted on the platinum chromium alloy (PtCr) and is provided by the material supplier to confirm both chemical analysis and inclusion/impurity content as provided by ASTM F138-00 “Standard Specification for Wrought 18 Chromium-14 Nickel-2.5 Molybdenum Stainless Steel Bar and Wire for Surgical Implants (UNS S31673:” | Pass. This is a characterization test. |
| Stent Corrosion Resistance | Uncoated Element stents were tested to determine the corrosion susceptibility using cyclic potentiodynamic polarization per ASTM F2129-06,"Conducting Cyclic Potentiodynamic Polarization Measurements." Galvanic Corrosion characterization was performed when the Uncoated Element stent was overlapped with a stent of different metal/metal alloy per ASTM G7 1-81, "Conducting and Evaluation Galvanic Corrosion Tests in Electrolytes." Fretting Corrosion and Crevice Corrosion was assessed on uncoated Element stents after pulsatile fatigue cycling. The corrosion series testing indicated that the corrosion resistance characteristics of the REBEL stent met product specification. | Pass. The results showed little to no fretting or crevice corrosion. |
| Dimensional Verification | The purpose of this evaluation is to measure and inspect the stent to document that the stent dimensional specifications meet the product design requirements, including un-expanded stent dimensions, expanded diameter, and length (see also Stent Delivery System Dimensional and Functional Attributes testing). Results indicated that the product specifications were met for dimensional verification. | Pass. Products were shown to meet their labeled dimensions within specifications. |
| Percent Surface Area | Stent surface coverage as a function of stent diameter was quantified for the stent. The percent surface area is determined by dividing the measured total contact surface area of the stent by the surface area of the artery based on deployed stent measurements at the nominal stent diameter. | Pass. The percent surface area is identical to the approved PROMUS PREMIER |

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| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Foreshortening | The foreshortening test determined the change in length of the stent between the catheter-mounted condition and the condition in which the stent was expanded (deployed) to the nominal diameter. Results indicated that the product specifications were met for foreshortening. | Pass. Testing showed that the length change after expansion must be less than or equal to 20% of the crimped length or less than or equal to:
2.0mm for diameters of 2.25 through 2.75mm,
2.5mm for diameters of 3.0 and 3.5mm,
3.0mm for 4.0mm diameter, or
4.0mm for 4.5mm diameter; whichever imposes a tighter requirement. |
| Recoil for Balloon Expandable Stents | The stent was evaluated for the amount of elastic recoil. Results indicated that the product specifications were met for recoil of the stent. | Pass. The recoil was less than 5% for stents 3.0mm diameter and larger. The recoil was less than 7% for those stents 2.75mm and shorter. |
| Stent Integrity (Stent Over Expansion) | The purpose of this testing is to verify the stent integrity post-stent deployment when expanded above unconstrained diameter. The stents were examined and exhibited no structural damage after over expansion. | Pass. The stent integrity was shown to be acceptable at over expansion |

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| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Radial Stiffness and Radial Strength (Compression Resistance) | The stent was evaluated for the ability to resist collapse when subject to a radial loads. | Pass. The stent was able to resist all clinically relevant loads |
| Mechanical Properties | Ultimate tensile strength, yield strength, and elongation testing was performed on tubing (pre-processing) used to fabricate the stents. Ultimate tensile strength, yield strength, and elongation testing on pre-processed tubing met product specification. Analysis of SEM images on stent components at various process stages determined that mechanical properties were not altered by processing. | Pass. The mechanical properties were able to be characterized |
| Stress/Strain Analysis/Fatigue Analysis (Finite Element Analysis) | Using Finite Element Analysis (FEA), stress and strain analysis was performed on the stent to demonstrate acceptable safety is maintained in stress loading environments, simulating nominal and overexpansion, and bending and radial conditions. The FEA evaluated the structural integrity of the stent when subjected to the expected loading conditions generated in coronary arteries. The analysis took into account manufacturing, delivery, implantation, and clinical loading over the implant life, and predicted that fatigue failures will not occur over 400 million cycles (10-years) of loading. | Pass. The FEA testing predicted no fatigue failures over a 10 year evaluation. |
| Accelerated Durability Testing | The accelerated durability of the stent was evaluated through the stent platform performance in Overlapping Pulsatile Fatigue on a Curve testing and determined that the structural integrity is maintained following exposure to the pulsatile stresses and strains exceeding those typically experienced by a human coronary artery for 10 years (400 million cycles). | Pass. Testing showed that the stent maintained structural integrity in an overlapped, bent configuration for 400 million cycles (10 years). |
| Particulates Evaluation (Simulated Use) | The system was evaluated for particulates after simulated use through a tortuous vessel model. The product has particulate counts that are similar to VeriFlex stent systems. | Pass. Testing showed that the device had an acceptably low amount of particulates generated after simulated use in a mock vessel. |

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| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Magnetic Resonance Imaging (MRI) Safety and Compatibility | Non-clinical testing has demonstrated that the REBEL stent is MR Conditional for single and overlapped conditions up to 74 mm. A patient with this device can be safely scanned in a Magnetic Resonance system meeting the following conditions:
• Static magnetic field of 3.0 and 1.5 Tesla only
• Maximum spatial gradient magnetic field of 2200 gauss/cm (22 T/m)
• Maximum Magnetic Resonance system reported, whole body averaged specific absorption rate (SAR) of <2 W/kg (Normal Operating Mode)

Under the scan conditions defined above, the REBEL stent is expected to produce a maximum temperature rise of 2.6°C after 15 minutes of continuous scanning. In non-clinical testing, the image artifact caused by the device extends approximately 8 mm from the REBEL stent when imaged with a spin echo pulse sequence and a 3.0 Tesla MRI system. The artifact does not obscure the device lumen. | Pass. The device met conditions to be labeled MR conditional. |
| Radiopacity | The radiopacity of the stent was assessed through porcine model evaluations of stent positioning, expansion, and delivery system removal. The stent exhibits clinically acceptable radiopacity. | Pass. The device is sufficiently radiopaque to be viewed under fluoroscopic imaging. |
| Stent Axial Strength | The ability of the stent to withstand axial length change after being subjected to point-load force was tested. The stent design minimizes the potential for longitudinal stent deformation over the OMEGA stent by effectively increasing axial strength at the proximal end. | Pass. The device has sufficient axial strength to help resist against longitudinal deformation. |
| **Delivery System Dimensional and Functional Attributes** | | |
| Dimensional Verification | The catheter effective length, overall length, crossing profile, and inner diameter were evaluated and met product specifications. | Pass. All dimensions met specifications. |

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| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Delivery, Deployment and Retraction | The delivery, deployment and retraction of stent system was assessed by testing system track, crossing profile, deflated balloon profile, stent deployment, flexibility/kink, guidewire movement, torque strength, and balloon withdrawal from a stent and into the guide catheter. Testing demonstrated that the stent system could be delivered to the target location, deployed, and retracted, thus meeting required acceptance criteria. | Pass. The stent delivery system successfully track, deploy, and retract through the ASTM F2394 Figure X2.4 track model without damage to ancillary devices (guidewire and guide catheter), delivery system, or the stent. |
| Balloon Rated Burst Pressure | Stent systems were evaluated to demonstrate that the stent system met rated (RBP) burst pressure. Results indicated that the product specifications were met and with 95% confidence that at least 99.9% of balloons will not experience loss of integrity at or below the rated burst pressure. | Pass. The device has a labeled RBP of 18 ATM |
| Balloon Fatigue | Stent systems across the range of stent/balloon lengths and diameters were evaluated for the ability to complete 10 pressurization cycles to Rated Burst Pressure (RBP). The results indicated that, with 95% confidence, 90% of the catheters will not experience balloon, shaft, or proximal/distal seal loss of integrity at or below the maximum recommended rated balloon burst pressure. | Pass. Testing showed that the device can handle repeated inflations to RBP without damage to the balloon. |
| Stent Diameter vs. Balloon Pressure | Stent systems were evaluated to determine how the diameter of a deployed stent varies with applied balloon pressures. The stent sizing evaluations verify that the stent systems meet the labeled compliance values. | Pass. The compliance chart is included in the labeling. |
| Balloon Inflation and Deflation Time | Stent systems across the range of balloon lengths and diameters were evaluated for deflation and inflation times. Results indicated that the product specifications were met. | Pass. Inflation and deflation times increase as stent dimensions increase; however, all times were less than 30s |

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| In Vitro Test | Summary of Results | Results |
| --- | --- | --- |
| Catheter Bond Strength | Stent delivery systems were evaluated to determine the balloon bond strength. Results indicated that the product specifications were met or exceed for balloon bond strength. | Pass. All tested samples were well above the acceptable tensile strength of 1.4 lbf. |
| Tip Pull Test | Stent delivery system were tested to determine the tip bond strength. Results met balloon bond strength product specifications. | Pass. The acceptance criteria for each unit was >0.3 lbf (1.33 N). |
| Flexibility and Kink Test | Stent delivery systems were evaluated to determine the ability of the delivery system to withstand kinking. Results indicated that the product specifications were met for flexibility and kink testing. | Pass. At a 15mm radius of curvature, the device did not kink. |
| Torque Strength | Stent delivery systems were evaluated to determine strength of the delivery system catheter when torsional forces were applied. Results indicated that the product specifications were met for torque strength. | Pass. Testing showed that the device can withstand torsional forces seen during use. |
| Catheter Coating Integrity | The acute coating integrity of the stent delivery system coating was evaluated via the results of a series of acute in vitro tests (baseline and simulated use). The test results demonstrate that the hydrophilic coating displays acceptable acute coating integrity. | Pass. The coating had acceptable integrity after simulated use. |
| Stent Securement for Unsheathed Stents | Stent systems were evaluated to assess the forces required to displace a stent from the delivery system (1) directly from the delivery catheters, (2) after tracking and then through a simulated lesion. Results indicated that the product specifications were met for stent securement. | Pass. Results indicated that the stent will remain on the delivery system when tracked across a lesion. |
| Non-Coaxial Withdrawal into a Simulated Guiding Catheter | Stent systems were evaluated for performance during withdrawal of a catheter with a mounted stent non-coaxially into a simulated guide catheter tip following a repeated track conditioning step. Results indicated that the product specifications were met for stent securement. | Pass. The results indicate that the stent can withdraw back into a guide catheter if still mounted to the balloon. |

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## 3. Packaging Testing

Packaging verification testing was performed to demonstrate that the design of the REBEL Stent System packaging can withstand the hazards of the distribution environment and that the sterility of the device is maintained throughout the labeled shelf life.

## 4. Shelf Life Testing

Performance testing was conducted following 3 years of aging for Monorail stent systems and 2 years of aging for Over-the-Wire stent systems to demonstrate that the device and packaging performs within product specifications for a labeled shelf life.

## 5. Sterilization

The REBEL Stent System is sterilized using ethylene oxide (EO) gas and has been validated per AAMI / ANSI / ISO 11135-1:2007, Sterilization of health care products - Ethylene oxide - Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices. Results from the sterilization studies show that the product satisfies a minimum Sterility Assurance Level (SAL) of $10^{-6}$ and residual levels were within acceptable ranges in accordance with ISO 10993-7:2008, Biological Evaluation of Medical Devices - Part 7: Ethylene Oxide Sterilization Residuals.

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# B. Animal Studies

. The versions of the devices (stent and delivery systems) used in the animal studies, the Element, Bare Element and Element BMS were early design iterations of the OMEGA Stent Systems used for the OMEGA clinical study; updates were made prior to the clinical study to improve balloon and stent robustness. The REBEL Coronary Stent System is a design iteration of the OMEGA Coronary Stent system used for the OMEGA clinical study. The OMEGA and REBEL stents share identical primary stent designs, materials, and manufacturing processes, however the REBEL SWH, WH, and LV models have additional connectors at the proximal end to provide more robust performance with relation to axial length change. The Element/OMEGA and REBEL delivery systems share shaft and balloon designs, materials, and manufacturing processes, however the REBEL delivery system has an updated shaft coating and bumper tip to enhance delivery and align with currently marketed devices.

The objective of the animal studies were:

To assess the safety and vascular compatibility of uncoated Element stents in comparison to uncoated Liberté stents.
To evaluate acute device performance of the Element stent and stent delivery system

Preclinical evaluations of the Element stent using the overlapping and single porcine coronary artery stent models supported safety and vascular compatibility, with comparable results to Liberté (VeriFLEX) in key safety parameters including early and late in-stent healing. Stent and delivery system acute performance as assessed in the porcine model demonstrated acceptable clinical performance. Studies were conducted in accordance with §21 CFR 58 (Good Laboratory Practices).

The results support the conclusion that the stent system is safe based on comparison to a commercially approved product, and is appropriate for commercial release. Summaries of the study designs and results are included in Table 6.

Table 6: Summary of Applicable Animal Studies

| Test and/or Study Name | Test Article | Stent Size Diameter and Length (mm) and Number of Stent (n) | Total Drug per Stent / Total Carrier per Stent (μg) | Drug Loading Density (μg/mm2) and Formulation (w% rx) | Vessel Location | Evaluation Time Points | Testing Summary and/or Objectives |
| --- | --- | --- | --- | --- | --- | --- | --- |
| GLP Safety Overlap Study 1133-024* | TAXUS Element | 2.75 x 12 (30 pairs histology, 9 pairs SEM) | 61/638 | 1.0/8.8 | LAD, LCX, RCA | 30, 90, 180 Days | Supports safety. No device related mortality or morbidity. Vascular response |
| | Uncoated Element | 2.75 x 12 (30 pairs histology, 9 pairs SEM) | N/A | N/A | | | |

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| Test and/or Study Name | Test Article | Stent Size Diameter and Length (mm) and Number of Stent (n) | Total Drug per Stent / Total Carrier per Stent (μg) | Drug Loading Density (μg/mm²) and Formulation (w% rx) | Vessel Location | Evaluation Time Points | Testing Summary and/or Objectives |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | TAXUS Liberté Control | 2.75 x 12 (30 pairs histology, 9 pairs SEM) | 83/865 | 1.0/8.8 | | | shows early and late healing, vessel stability and patency over 30, 90, and 180 days. |
| | Uncoated Liberté Controls | 2.75 x 12 (30 pairs histology, 9 pairs SEM) | N/A | N/A | | | |
| GLP Safety Overlap Study 07-032G | PROMUS Element | 3.00 x 8
3.50 x 8 (50 pairs histology, 9 pairs SEM) | 43.0 / 254 | 100 / 1:4.9 | LAD, LCX, RCA | 7, 30, 90, 180, 270 Days | Supports safety. No device related mortality or morbidity. Vascular response shows acceptable healing, vessel stability and patency over 30, 90, 180 days. |
| | Polymer Only Element | 3.00 x 8
3.50 x 8 (43 pairs histology, 9 pairs SEM) | N/A / 254 | N/A | | | |
| | Uncoated Element | 3.00 x 8
3.50 x 8 (43 pairs histology, 9 pairs SEM) | N/A / N/A | N/A | | | |
| | Xience V (PROMUS ) | 3.00 x 8
3.50 x 8 (46 pairs histology, 9 pairs SEM) | 36.5 / 241
52.5 / 347 | 100 / 1:4.9 | | | |
| Non-GLP Acute Performance Study 10-046N | Uncoated Element | 3.0 x 8 (2)
3.5 x 8 (1)
3.5 x 16 (3)
4.0 x 16 (3)
4.5 x 16 (3) | N/A | N/A | LAD, LCX, RCA, Thoracic Artery | Acute | Stent systems perform at or above acceptable level for all performance criteria. |
| GLP Acute Performance Study 10-047G | Uncoated Element | 2.5 x 8 (5)
3.0 x 8 (4)
4.0 x 8 (5) | N/A | N/A | LAD, LCX, RCA | Acute | Stent systems perform at or above acceptable level for all performance criteria. |

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| Test and/or Study Name | Test Article | Stent Size Diameter and Length (mm) and Number of Stent (n) | Total Drug per Stent / Total Carrier per Stent (μg) | Drug Loading Density (μg/mm²) and Formulation (w% rx) | Vessel Location | Evaluation Time Points | Testing Summary and/or Objectives |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Non-GLP Acute Performance Study 11-112T | Uncoated Element | 2.25 x 8 (4) | N/A | N/A | LAD, LCX, RCA | Acute | Stent systems perform at or above acceptable level for all performance criteria. |

*Boston Scientific implemented an internal study numbering convention after the completion of the 1133-024 study, and therefore, study 1133-024 is referenced by the contract research organization study number.

# X. SUMMARY OF PRIMARY CLINICAL STUDY(IES)

The applicant collected clinical data through the OMEGA clinical trial (OMEGA: A Prospective, Multicenter Single-Arm Trial to Assess the OMEGA™ Coronary Stent System for the Treatment of a Single De Novo Coronary Artery Lesion) and the NG PROMUS clinical trial (NG PROMUS: A Prospective, Multicenter Trial to Assess the NG PROMUS Everolimus-Eluting Platinum Chromium Coronary Stent System (NG PROMUS Stent System) for the Treatment of Atherosclerotic Lesion(s)) to evaluate the safety and effectiveness of the REBEL Coronary Stent System for improving coronary luminal diameter in patients with de novo lesions ≤ 28 mm in length in native coronary arteries with a reference vessel diameter (RVD) of ≥ 2.25 mm to ≤ 4.50 mm. The OMEGA clinical trial was evaluated under IDE G110092. Although the OMEGA clinical trial assessed the OMEGA™ Coronary Stent System, the OMEGA and REBEL Coronary Stent Systems utilize the same platinum chromium alloy. The REBEL Coronary Stent System differs from the OMEGA Coronary Stent System in that the REBEL Stent System has supplementary proximal stent connectors for increased axial strength, a short flexible stent delivery system tip, and a PTFE coated proximal hypotube for improved stent deliverability. Given the similarities between the OMEGA and REBEL Coronary Stent Systems and supportive bench and animal study information, the findings from the OMEGA Clinical Trial are applicable to the REBEL Stent System. The NG PROMUS Stent System is the same stent design as the REBEL Stent System, however the NG PROMUS stent is coated with the Everolimus drug. Therefore, data from these clinical trials were the basis for the PMA approval decision. Summaries of the clinical trials are presented below.

# A. OMEGA Clinical Trial

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# A1. Study Design

The OMEGA Clinical Trial is a prospective, single-arm, multicenter study. Eligible patients were to be $\geq 18$ years of age and with left ventricular ejection fraction (LVEF) $\geq 30\%$ . Lesions were to be coverable by a single study stent and to have visually estimated stenosis $\geq 50\%$ and $&lt; 100\%$ with Thrombolysis in Myocardial Infarction (TIMI) flow $&gt;1$ . Patients could have 1 target lesion treated. Patients with a single target lesion could also have 1 de novo native coronary artery lesion within a different epicardial vessel (non-target lesion) treated with a commercially-available treatment (e.g., stent, balloon angioplasty, excluding brachytherapy) during the index procedure. The non-target lesion had to be treated before the target lesion and the treatment had to be a clinical angiographic success (defined as visually assessed stenosis $&lt; 50\%$ [&lt; 30% for stents] with TIMI 3 flow without prolonged chest pain or electrocardiogram [ECG] changes consistent with MI) before the patient could be enrolled. The protocol mandated antiplatelet therapy compliance in accordance with the 2007 ACC/AHA/SCAI Guidelines for PCI.

Baseline and post-procedure angiographic data were collected and assessed by quantitative analysis at a designated core laboratory. An independent Clinical Events Committee adjudicated major adverse clinical events and stent thrombosis.

# A2. Clinical Inclusion and Exclusion Criteria, OMEGA

Subjects were eligible to participate in the study if they met the following inclusion criteria (Table 7).

Table 7: Inclusion Criteria, OMEGA

| Clinical Inclusion Criteria | CI1. Subject must be at least 18 years of age. CI2. Subject (or legal guardian) indicates understanding of the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed. CI3. Subject is eligible for PCI. CI4. Subject has symptomatic coronary artery disease or documented silent ischemia. CI5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG). CI6. Subject has a left ventricular ejection fraction (LVEF) ≥30% as measured within 60 days prior to enrollment. CI7. Subject is willing to comply with all protocol-required follow-up evaluations. |
| --- | --- |
| Angiographic Inclusion Criteria | AI1. Target lesion must be a de novo lesion located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.25 mm and ≤4.50 mm. AI2. Target lesion length must measure (by visual estimate) as follows: ○ ≤28 mm for stent diameter lengths of 2.75 mm, 3.00 mm, 3.50 mm, 4.00 mm and 4.50 mm ○ ≤24 mm for stent diameter lengths of 2.25 mm and 2.50 mm AI3. Target lesion must be in a major coronary artery or branch with visually estimated stenosis ≥50% and <100% with Thrombolysis in Myocardial Infarction (TIMI) flow >1 AI4. Target lesion must be successfully pre-dilated. |

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Subjects were ineligible to participate in the study if they met any of the following exclusion criteria (Table 8).

Table 8: Exclusion Criteria, OMEGA

| Clinical Exclusion Criteria | CE1. Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute MI. CE2. Subject with unstable angina or recent MI (clinically diagnosed within 3 days) must have CK/CK-MB or troponin documented prior to the procedure and are excluded if any of the following criteria are met at the time of the index procedure: 1. If CK-MB >2× upper limit of normal (ULN), the subject is excluded regardless of the CK Total. 2. If CK Total >2× ULN, CK-MB must be drawn and the subject is excluded if CK-MB is abnormal. 3. If CK/CK-MB results are not available at the time of the procedure, the subject is excluded if troponin >1× ULN and the subject has at least one of the following: ○ Subject has ischemic symptoms and ECG changes indicative of ongoing ischemia (e.g., >1 mm ST segment elevation or depression in consecutive leads or new left bundle branch block [LBBB]) ○ Development of pathological Q-waves in the ECG or; ○ Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality Note: Subjects who do not have unstable angina or recent MI must still have CK/CK-MB drawn prior to the index procedure. However, the results for these subjects do not need to be available prior to the index procedure and there are no exclusion criteria based on these studies. CE3. Subject is receiving chronic (≥72 hours) anticoagulation therapy (e.g., heparin, coumadin) for indications other than acute coronary syndrome. CE4. Subject has a platelet count <100,000 cells/mm3or >700,000 cells/mm3. CE5. Subject has a white blood cell (WBC) count <3,000 cells/mm3. CE6. Subject has documented or suspected liver disease, including laboratory evidence of hepatitis. CE7. Subject is on dialysis or has known renal insufficiency (e.g. serum creatinine level >2.0 mg/dL). CE8. Subject has active peptic ulcer disease, an active gastrointestinal (GI) bleed, other bleeding diathesis or coagulopathy or will refuse transfusions. CE9. Subject has had a cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months, or has any permanent neurologic defect that may cause non-compliance with the protocol. CE10. Target vessel (including side branches) has been treated with any type of PCI (e.g., balloon angioplasty, stent, cutting balloon, atherectomy) within 12 months prior to the index procedure. CE11. Target vessel has been treated within 10 mm proximal or distal to the target lesion (by visual estimate) with any type of PCI (e.g., balloon angioplasty, stent, cutting balloon, or atherectomy) at any time prior to the index |
| --- | --- |

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Table 8: Exclusion Criteria, OMEGA

| | procedure. CE12. Non-target vessel or side branch has been treated with any type of PCI (e.g., balloon angioplasty, stent, cutting balloon, atherectomy) within 1 day prior to the index procedure. Note: 1 lesion in a non-target vessel may be treated during the index procedure prior to the treatment of the target (study) lesion. CE13. Planned or actual target vessel treatment with an unapproved device, directional or rotational coronary atherectomy, laser, cutting balloon, or transluminal extraction catheter immediately prior to stent placement. CE14. Planned PCI or CABG after the index procedure. CE15. Subject previously treated at any time with coronary intravascular brachytherapy. CE16. Subject has known allergy to the study stent system or protocol-required concomitant medications (e.g., stainless steel, platinum, chromium, nickel, iron, thienopyridines and ASA) and contrast (that cannot be adequately premedicated). CE17. Subject has any other serious medical illness (e.g., cancer, congestive heart failure) that may reduce life expectancy to less than 12 months. CE18. Subject has current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.). CE19. Subject has a planned procedure that may cause non-compliance with the protocol or confound data interpretation. CE20. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint or intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure. CE21. Subject is female of childbearing potential with a positive pregnancy test within 14 days before the index procedure, is lactating, or intends to become pregnant during the study. CE22. Subject has more than 1 target lesion, or more than 1 target lesion and 1 non-target lesion, which will be treated during the index procedure. |
| --- | --- |

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Table 8: Exclusion Criteria, OMEGA

| Angiographic Exclusion Criteria (visual estimate) | AE1. Target lesion meets any of the following criteria: ○ Aorto-ostial location (i.e., lesion located within 5 mm of the ostium by visual estimate) ○ Left main location ○ Located within 5 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery or RCA by visual estimate ○ Located within a saphenous vein graft or an arterial graft ○ Will be accessed via a saphenous vein graft or an arterial graft ○ Involves a side branch ≥2.0 mm in diameter by visual estimate ○ Involves a side branch <2.0 mm in diameter by visual estimate that has a clinically significant stenosis at the ostium ○ TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing ○ Excessive tortuosity proximal to or within the lesion ○ Extreme angulation proximal to or within the lesion ○ Target lesion and/or target vessel proximal to the target lesion is moderately to severely calcified by visual estimate ○ Restenotic from previous intervention ○ Thrombus, or possible thrombus, present in the target vessel ○ Target lesion cannot be covered by a single study stent (unplanned bailout stenting is allowed) AE2. Non-target lesion to be treated during the index procedure meets any of the following criteria: ○ Located within the target vessel ○ Located within a bypass graft (venous or arterial) ○ Left main location ○ Chronic total occlusion ○ Involves a complex bifurcation (e.g., bifurcations requiring treatment with more than 1 stent) ○ Requires additional unplanned stents (treatment of the non-target lesion with more than one stent is permitted as long as the stents are initially planned) ○ Treatment not deemed a clinical angiographic success ○ Treatment not completed prior to treatment of target lesion AE3. Subject has unprotected left main coronary artery disease (>50% diameter stenosis). AE4. Subject has protected left main coronary artery disease and a target lesion in the LAD or LCx. AE5. Subject has an additional clinically significant lesion(s) in the target vessel for which an intervention within 12 months after the index procedure may be required. |
| --- | --- |

# A3. Follow-up Schedule, OMEGA

Enrolled patients underwent clinical follow-up in hospital and at 30 days, 9 months and 12 months after the index procedure. Final 12-month follow-up for the OMEGA trial was

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completed on January 7, 2014. Follow-up included clinical assessments at 30 days, 9 and 12 months post-index procedure.

## A4. Clinical Endpoints, OMEGA

Adverse events are collected throughout the study with a prespecified subset of events adjudicated by an independent Clinical Events Committee.

The primary endpoint was the rate of target lesion failure (TLF), defined as any ischemia-driven revascularization of the target lesion (TLR), myocardial infarction (MI; Q-wave and non-Q-wave) related to the target vessel, or cardiac death, at 9 months post-index procedure. The rate of the primary endpoint was compared to a predefined performance goal (PG) of 21.2%, which was calculated based on historical bare metal stent (BMS) results. The PG equals the historical BMS 9-month TLF rate adjusted for differences in the non-Q-wave MI definition (15.2%) + margin (6.0%). A one-group exact binomial test was used to test the hypothesis that the primary endpoint rate in the OMEGA cohort is less than the PG.

## A5. Accountability of PMA Cohort, OMEGA

A total of 328 patients were enrolled (the ITT analysis set) at 37 sites in the United States and Europe in the OMEGA Trial. Clinical follow-up or death at 9-months was 98.2% (322/328). Four patients were lost to follow-up and 2 patients missed their 9-month visit. Details of 9-month follow-up compliance are provided in Table 9.

Clinical follow-up or death at 12-months was 97.6% (320/328). Seven patients were lost to follow-up and 1 patient missed their 12-month visit.

Table 9: Subject Disposition, Clinical Follow-up Compliance Intent-to-Treat, All Subjects (N=328)

| | Subjects |
| --- | --- |
| Subjects enrolled (Intent-to-Treat analysis set) | 328 |
| Death ≤ 300 days with no 9-Month Clinical Follow-up Performed | 6 |
| Eligible for 9-Month Clinical Follow-up^{a} | 322 |
| 9-Month Clinical Follow-up Performed^{b} | 98.1% (316/322) |
| Office Visit | 286 |
| Telephone Contact | 30 |
| No 9-Month Clinical Follow-up Performed | 6 |
| Prematurely Discontinued | 4 |
| Death > 300 days | 0 |
| Withdrew Consent | 0 |
| Lost to Follow-up | 4 |
| Adverse Event | 0 |
| Investigator Discretion | 0 |
| Transplant or Removal of Target Organ | 0 |
| Other | 0 |
| Missed 9-Month Visit | 2 |
| With Later Follow-up Visit Performed | 2 |
| No Later Follow-up Visit Performed | 0 |
| 9-Month Clinical Follow-up or Death^{c} | 98.2% (322/328) |
| 9-Month Clinical Follow-up Patient Accountability^{d} | 96.3% (316/328) |

Numbers are n or % (count/sample size).

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# A6. Study Population and Baseline Parameters, OMEGA

Table 10 and Table 11 present demographics and baseline clinical characteristics for the ITT analysis set $(N = 328)$ . The ITT population was predominantly male (67.7%) with a history of medically treated hyperlipidemia (70.8%) and hypertension (75.0%). Medically treated diabetic subjects accounted for 17.4% of ITT subjects. Unstable angina was reported for 33.8% of subjects and 29.6% had a history of MI.

Table 10: Baseline Demographics and General Medical History, ITT Analysis Set (N=328 Subjects)

| Parameter | OMEGA (N=328) | [95% CI] |
| --- | --- | --- |
| Male | 67.7% (222/328) | [62.3%, 72.7%] |
| Age (yr) | 65.46±11.23 (328) (32.00, 95.00) | [64.25, 66.68] |
| Ethnicity and Race | | |
| American Indian or Alaska native | 0.0% (0/328) | [0.0%, 1.1%] |
| Asian | 0.0% (0/328) | [0.0%, 1.1%] |
| Black, of African heritage | 2.7% (9/328) | [1.3%, 5.1%] |
| Caucasian | 77.4% (254/328) | [72.5%, 81.8%] |
| Hispanic or Latino | 0.6% (2/328) | [0.1%, 2.2%] |
| Native Hawaiian or other Pacific Islander | 0.0% (0/328) | [0.0%, 1.1%] |
| Other | 0.6% (2/328) | [0.1%, 2.2%] |
| Not disclosed | 18.6% (61/328) | [14.5%, 23.2%] |
| Smoking, Ever | 66.1% (211/319) | [60.7%, 71.3%] |
| Current | 28.2% (90/319) | [23.3%, 33.5%] |
| Previous | 37.9% (121/319) | [32.6%, 43.5%] |
| Medically Treated Diabetes | 17.4% (57/328) | [13.4%, 21.9%] |
| Insulin Requiring | 5.5% (18/328) | [3.3%, 8.5%] |
| Non-Insulin Requiring | 11.9% (39/328) | [8.6%, 15.9%] |
| Diabetes Treated with Diet Only | 7.0% (23/328) | [4.5%, 10.3%] |
| Hyperlipidemia Requiring Medication | 70.8% (230/325) | [65.5%, 75.7%] |
| Hypertension Requiring Medication | 75.0% (243/324) | [69.9%, 79.6%] |
| History of Bleeding Disorder | 2.5% (8/326) | [1.1%, 4.8%] |
| Gastrointestinal | 2.5% (8/326) | [1.1%, 4.8%] |
| Hematologic Dyscrasia | 0.0% (0/326) | [0.0%, 1.1%] |
| History of TIA or CVA | 7.7% (25/326) | [5.0%, 11.1%] |
| History of TIA | 3.7% (12/326) | [1.9%, 6.3%] |
| History of CVA | 4.3% (14/326) | [2.4%, 7.1%] |
| History of Renal Disease | 4.3% (14/326) | [2.4%, 7.1%] |

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Table 11: Cardiac History, ITT Analysis Set (N=328 Subjects)

| Parameter | OMEGA (N=328) | [95% CI] |
| --- | --- | --- |
| Stable Angina | 55.5% (182/328) | [49.9%, 60.9%] |
| Angina Class (CCS) | | |
| 1 | 14.0% (46/328) | [10.5%, 18.3%] |
| 2 | 27.4% (90/328) | [22.7%, 32.6%] |
| 3 | 11.9% (39/328) | [8.6%, 15.9%] |
| 4 | 1.8% (6/328) | [0.7%, 3.9%] |
| Unknown | 0.3% (1/328) | [0.0%, 1.7%] |
| Unstable Angina | 33.8% (111/328) | [28.7%, 39.2%] |
| Braunwald Classification | | |
| IA | 0.9% (3/328) | [0.2%, 2.6%] |
| IB | 5.5% (18/328) | [3.3%, 8.5%] |
| IC | 0.3% (1/328) | [0.0%, 1.7%] |
| IIA | 0.3% (1/328) | [0.0%, 1.7%] |
| IIB | 18.3% (60/328) | [14.3%, 22.9%] |
| IIC | 0.3% (1/328) | [0.0%, 1.7%] |
| IIIA | 0.3% (1/328) | [0.0%, 1.7%] |
| IIIB | 5.5% (18/328) | [3.3%, 8.5%] |
| IIIC | 0.6% (2/328) | [0.1%, 2.2%] |
| Unknown | 1.8% (6/328) | [0.7%, 3.9%] |
| No Angina | 10.7% (35/328) | [7.5%, 14.5%] |
| Silent Ischemia | 19.9% (54/272) | [15.3%, 25.1%] |
| Family History of CAD | 43.4% (131/302) | [37.7%, 49.2%] |
| Previous MI | 29.6% (94/324) | [24.7%, 34.9%] |
| History of CHF | 6.4% (21/327) | [4.0%, 9.6%] |
| New York Heart Association Classification | | |
| I | 1.5% (5/327) | [0.5%, 3.5%] |
| II | 3.4% (11/327) | [1.7%, 5.9%] |
| III | 0.9% (3/327) | [0.2%, 2.7%] |
| IV | 0.3% (1/327) | [0.0%, 1.7%] |
| Unknown | 0.3% (1/327) | [0.0%, 1.7%] |
| History of PCI | 29.1% (95/326) | [24.3%, 34.4%] |
| History of CABG | 4.6% (15/327) | [2.6%, 7.5%] |
| History of Arrhythmia | 12.3% (40/326) | [8.9%, 16.3%] |
| Left Ventricular Ejection Fraction (LVEF, %) | 58.50±9.25 (325) (30.00, 88.00) | [57.50, 59.51] |
| LVEF not Measured or not Known | 0.9% (3/328) | [0.2%, 2.6%] |
| History of Multivessel Disease | 28.5% (93/326) | [23.7%, 33.8%] |

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| Parameter | OMEGA (N=328) | [95% CI] |
| --- | --- | --- |
| History of Left Main Disease | 1.8% (6/327) | [0.7%, 4.0%] |

Numbers are presented as mean±standard deviation (n) or % (count/sample size), or mean±SD (n) (minimum, maximum).

Abbreviation: ITT=intent-to-treat; CAD=coronary artery disease; MI=myocardial infarction; CHF=congestive heart failure; PCI=percutaneous coronary intervention; CABG=coronary artery bypass graft surgery; LVEF= Left Ventricular Ejection Fraction

# A7. Safety and Effectiveness Results, OMEGA

The principal safety and effectiveness results through 9 months are summarized below and presented in Tables 12 and 13.

For the primary endpoint analysis, the ITT 9-month rate of target lesion failure was $11.5\%$ (37/323) with a one-sided upper confidence bound of $14.79\%$ , significantly less than the performance goal of $21.2\%$ ( $P &lt; 0.0001$ )
Similar results were found when the primary endpoint was analyzed on a per protocol or intent-to-treat basis
There were 4 cardiac deaths $(1.2\%)$ , 12 myocardial infarctions $(3.7\%)$ , and 2 patients experienced definite stent thrombosis $(0.6\%)$ through 9 months
The technical success rate was $98.5\%$ (332/337)
The clinical procedural success rate was $95.4\%$ (313/328)

Table 12: Primary Endpoint: TLF at 9 Months

| Population | OMEGA | 95% Confidence Interval | 95% UCBa | Performance Goalb | 1-sided P value |
| --- | --- | --- | --- | --- | --- |
| ITTc(N=328) | 11.5% (37/323) | [8.2%, 15.4%] | 14.79% | 21.2% | <0.0001 |
| Per-protocol (N=325) | 11.6% (37/320) | [8.3%, 15.6%] | 14.93% | 21.2% | <0.0001 |

P value is based on the exact binomial test.
a: One-sided $95\%$ Clopper-Pearson upper confidence bound
b: Based on historical BMS results
c: Primary analysis

Abbreviations: ITT=intent-to-treat; TLF=target lesion failure (including any ischemia-driven revascularization of the target lesion, myocardial infarction [Q-wave and non-Q-wave] related to the target vessel, or cardiac death); UCB=upper confidence bound

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Table 13: Principal Effectiveness and Safety Results (9 Months), ITT Analysis Set

| Parameter | OMEGA (N=328) | 95% Confidence Interval |
| --- | --- | --- |
| 9-Month Clinical Endpoints | | |
| All death, MI, TVR | 12.9% (42/325) | [9.5%, 17.1%] |
| All death or MI | 5.5% (18/325) | [3.3%, 8.6%] |
| All death | 1.8% (6/325) | [0.7%, 4.0%] |
| Cardiac death^{a} | 1.2% (4/325) | [0.3%, 3.1%] |
| Non-cardiac death | 0.6% (2/325) | [0.1%, 2.2%] |
| MI^{a,b} | 3.7% (12/325) | [1.9%, 6.4%] |
| TVR^{c} | 8.6% (28/325) | [5.8%, 12.2%] |
| TLR^{c} | 7.4% (24/325) | [4.8%, 10.8%] |
| Non-TLR TVR^{c} | 1.8% (6/325) | [0.7%, 4.0%] |
| Cardiac death or MI | 4.9% (16/325) | [2.8%, 7.9%] |
| TLF | 11.5% (37/323) | [8.2%, 15.4%] |
| TVF | 12.4% (40/323) | [9.0%, 16.5%] |
| ARC stent thrombosis (definite/probable)^{d} | 0.6% (2/318) | [0.1%, 2.3%] |
| Peri-procedural Endpoints | | |
| Clinical procedural success^{e} | 95.4% (313/328) | [92.6%, 97.4%] |
| Technical success^{f} | 98.5% (332/337) | [96.6%, 99.5%] |

Numbers are % (counts/sample size)
a: All events were related to the target vessel
b: All MI were target vessel-related non-Q-wave MI
c: All revascularizations were by PCI.
d: All stent thromboses were determined to be ARC definite stent thromboses.
e: Mean lesion diameter stenosis &lt;30% in 2 near-orthogonal projections with TIMI 3 flow, as visually assessed by the physician, without the occurrence of in-hospital MI, TVR, or cardiac death
f: Technical success is successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization.
Abbreviations: ARC=Academic Research Consortium; ITT=intent-to-treat; TLF=target lesion failure (including any ischemia-driven revascularization of the target lesion [TLR], myocardial infarction [MI; Q-wave and non-Q-wave] related to the target vessel, or cardiac death); TVF=target vessel failure (any ischemia-driven revascularization of the target vessel [TVR], MI related to the target vessel, or death related to the target vessel).

The principal safety and effectiveness results through 12 months are summarized in Table 14. There were 4 cardiac deaths (1.2%), 13 myocardial infarctions (4.0%), and 2 patients experienced definite stent thrombosis (0.6%) through 12 months post-index procedure. These results support the continued safety and effectiveness of the OMEGA stent through 12 months of follow-up.

Table 14 Principal Effectiveness and Safety Results (12 Months), ITT Analysis Set

| Parameter | OMEGA (N=328) | 95% Confidence Interval |
| --- | --- | --- |
| 12-Month Clinical Endpoints | | |
| All death, MI, TVR | 14.3% (46/322) | [10.7%, 18.6%] |

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Table 14 Principal Effectiveness and Safety Results (12 Months), ITT Analysis Set

| Parameter | OMEGA (N=328) | 95% Confidence Interval |
| --- | --- | --- |
| All death or MI | 5.9% (19/322) | [3.6%, 9.1%] |
| All death | 1.9% (6/322) | [0.7%, 4.0%] |
| Cardiac death^{a} | 1.2% (4/322) | [0.3%, 3.1%] |
| Non-cardiac death | 0.6% (2/322) | [0.1%, 2.2%] |
| MI^{a, b} | 4.0% (13/322) | [2.2%, 6.8%] |
| TVR^{c} | 9.9% (32/322) | [6.9%, 13.7%] |
| TLR^{c} | 8.4% (27/322) | [5.6%, 12.0%] |
| Non-TLR TVR^{c} | 2.2% (7/322) | [0.9%, 4.4%] |
| Cardiac death or MI | 5.3% (17/322) | [3.1%, 8.3%] |
| TLF | 12.8% (41/320) | [9.4%, 17.0%] |
| TVF | 13.8% (44/320) | [10.2%, 18.0%] |
| ARC stent thrombosis (definite/probable)^{d} | 0.6% (2/314) | [0.1%, 2.3%] |

Numbers are % (counts/sample size)
a: All events were related to the target vessel
b: All MI were target vessel-related non-Q-wave MI
c: All revascularizations were by PCI.
d: All stent thromboses were determined to be ARC definite stent thromboses.
Abbreviations: ARC=Academic Research Consortium; ITT=intent-to-treat; TLF=target lesion failure (including any ischemia-driven revascularization of the target lesion [TLR], myocardial infarction [MI; Q-wave and non-Q-wave] related to the target vessel, or cardiac death); TVF=target vessel failure (any ischemia-driven revascularization of the target vessel [TVR], MI related to the target vessel, or death related to the target vessel).

## A8. Subgroup Analyses, OMEGA

OMEGA data were evaluated retrospectively for possible gender-based differences in clinical outcomes. OMEGA was not designed or powered to study safety or effectiveness of the OMEGA Stent in gender-specific subgroups, so these analyses were performed post hoc and are considered hypothesis-generating.

In the OMEGA ITT population, of the 328 enrolled patients, 222 patients were male (67.7%) and 106 patients were female (32.3%).

In the United States, an estimated 15.4 million adults of 20 years and older (7.9% of men and 5.1% of women) suffer from coronary artery disease (CAD) $^{1}$ . However, it is estimated that only about 33% of the annual PCIs are performed in women. In PCI clinical trials, women represent only 25-35% of the enrolled populations, and there are relatively little gender-specific data. The disproportionate enrollment distribution in this study may be partly attributable to gender differences in pathophysiology, risk factors and symptoms which may lead to under-diagnosis and under-referral of female patients with CAD $^{2,3}$ . Once diagnosed and treated, poorer revascularization outcomes have been reported in women due to smaller coronary arteries and increased prevalence of baseline comorbidities including advanced age, diabetes, hypertension, and peripheral vascular disease compared with men.

In patients treated with the OMEGA stent, the 9-month rate of TLF was 12.3% in males and 9.6% in females. This post hoc analysis shows similar treatment effect between genders for

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the primary endpoint of 9-month TLF and its components. This suggests that the overall conclusions of the trial regarding both safety and effectiveness of the OMEGA stent can be generalized to males and females.

Table 15 OMEGA 9-Month TLF Results by Gender, Intent-to-Treat, All Patients (N=328)

| Event | OMEGA Females (N=106) | [95% CI] | OMEGA Males (N=222) | [95% CI] |
| --- | --- | --- | --- | --- |
| 9-Month TLF | 9.6% (10/104) | [4.7%, 17.0%] | 12.3% (27/219) | [8.3%, 17.4%] |

This trial was not sized to determine the rate of low frequency events with a pre-specified precision. Numbers are % (count/sample size). 9-Month TLF is the proportion of patients who experience a target lesion failure (defined as any ischemia-driven revascularization of the target lesion [TLR], MI [Q-wave and non-Q wave] related to the target vessel, or cardiac death) up to 270 days post-procedure out of the population that have been followed for at least 240 days or who have experienced a TLF up to 270 days post-procedure.

Table 16 shows OMEGA 9-Month clinical results for male and female patients. Given the small number of patients enrolled, no conclusions can be drawn from these data.

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Table 16 9-Month Clinical Endpoints by Gender, Intent-to-Treat, All Patients

| | OMEGA Female Patients (N=106) | OMEGA Male Patients (N=222) |
| --- | --- | --- |
| Efficacy | | |
| TVR, Overall | 7.6% (8/105) | 9.1% (20/220) |
| TLR, Overall | 6.7% (7/105) | 7.7% (17/220) |
| TLR, PCI | 6.7% (7/105) | 7.7% (17/220) |
| TLR, CABG | 0.0% (0/105) | 0.0% (0/220) |
| Non-TLR TVR, Overall | 2.9% (3/105) | 1.4% (3/220) |
| Non-TLR TVR, PCI | 2.9% (3/105) | 1.4% (3/220) |
| Non-TLR TVR, CABG | 0.0% (0/105) | 0.0% (0/220) |
| Safety | | |
| All Death | 1.0% (1/105) | 2.3% (5/220) |
| Cardiac Death or MI | 3.8% (4/105) | 5.5% (12/220) |
| Cardiac Death | 0.0% (0/105) | 1.8% (4/220) |
| MI | 3.8% (4/105) | 3.6% (8/220) |
| Q-wave MI | 0.0% (0/105) | 0.0% (0/220) |
| Non-Q-wave MI | 3.8% (4/105) | 3.6% (8/220) |
| ARC Stent Thrombosis | 1.0% (1/104) | 0.5% (1/214) |
| Definite or Probable | 1.0% (1/104) | 0.5% (1/214) |
| Definite | 1.0% (1/104) | 0.5% (1/214) |
| Probable | 0.0% (0/104) | 0.0% (0/214) |
| Peri-Procedural Endpoints | | |
| Procedural Success | 95.3% (101/106) | 95.5% (212/222) |
| Technical Success^{a} | 99.1% (106/107) | 98.3% (226/230) |

a: denominator is number of study stents attempted
Numbers are % (count/sample size).
This trial was not sized to determine the rate of low frequency events with a pre-specified precision.
Abbreviations: ARC=Academic Research Consortium; CABG=coronary artery bypass graft; MI=myocardial infarction; PCI=percutaneous coronary intervention; TLR=target lesion revascularization; TVR=target vessel revascularization.

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# B. NG PROMUS Clinical Trial

B.1. Study Design: NG PROMUS was a prospective, single arm, multicenter, observational study designed to evaluate clinical and periprocedural angiographic and IVUS outcomes for the Promus PREMIER Everolimus-Eluting Platinum Chromium Coronary Stent System in the treatment of subjects with atherosclerotic lesions ≤34 mm in length (by visual estimate) in native coronary arteries ≥2.50 mm to ≤4.00 mm in diameter (by visual estimate).

# B2. Clinical Inclusion and Exclusion Criteria, NG PROMUS

Subjects were eligible to participate in the study if they met the following inclusion criteria (Table 17).

Table 15: Inclusion Criteria, NG PROMUS

| Clinical Inclusion Criteria | CI1. Subject must be at least 18 years of age
CI2. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed
CI3. Subject is eligible for percutaneous coronary intervention (PCI)
CI4. Subject has symptomatic coronary artery disease with objective evidence of ischemia or silent ischemia
CI5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG)
CI6. Subject is willing to comply with all protocol-required follow-up evaluation |
| --- | --- |
| Angiographic Inclusion Criteria | AI1. Target lesion(s) must be located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.50 mm and ≤4.0 mm
AI2. Target lesion(s) length must be ≤34 mm (by visual estimate)
AI3. Target lesion(s) must have visually estimated stenosis ≥50% and <100% with thrombolysis in Myocardial Infarction (TIMI) flow >1 and one of the following (stenosis ≥70%, abnormal fractional flow reserve (FFR), abnormal stress test or imaging stress test, or elevated biomarkers) prior to procedure
AI4. Coronary anatomy is likely to allow delivery of a study device to the target lesions(s)
AI5. The first lesion treated must be successfully pre-dilated/pretreated
*Note:* Successful pre-dilatation/pretreatment refers to dilatation with a balloon catheter of appropriate length and diameter, or pretreatment with directional or rotational coronary atherectomy, laser or cutting/scoring balloon with no greater than 50% residual stenosis and no dissection greater than National Heart, Lung, Blood Institute (NHLBI) type C. |

Subjects were ineligible to participate in the study if they met any of the following exclusion criteria (Table 18).

Table 16: Exclusion Criteria, NG PROMUS

| Clinical Exclusion Criteria | CE1. Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI)
CE2. Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmias, or ongoing intractable angina
CE3. Subject has received an organ transplant or is on a waiting list for an organ transplant |
| --- | --- |

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Table 16: Exclusion Criteria, NG PROMUS

| | CE4. Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure CE5. Planned PCI (including staged procedures) or CABG after the index procedure CE6. Subject previously treated at any time with intravascular brachytherapy CE7. Subject has a known allergy to contrast (that cannot be adequately premedicated) and/or the trial stent system or protocol-required concomitant medications (e.g., platinum, platinum-chromium alloy, stainless steel, everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors, or aspirin) CE8. Subject has one of the following (as assessed prior to the index procedure): • Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 24 months • Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.) • Planned procedure that may cause non-compliance with the protocol or confound data interpretation CE9. Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, coumadin) for indications other than acute coronary syndrome CE10. Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3 CE11. Subject has a white blood cell (WBC) count < 3,000 cells/mm3 CE12. Subject has documented or suspected liver disease, including laboratory evidence of hepatitis CE13. Subject is on dialysis or has baseline serum creatinine level >2.0 mg/dL (177μmol/L) CE14. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions CE15. Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months CE16. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding CE17. Subject has signs or symptoms of active heart failure (i.e., NYHA class IV) at the time of the index procedure CE18. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint CE19. Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure CE20. Subject with known intention to procreate within 12 months after the index procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure) CE21. Subject is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential) |
| --- | --- |
| Angiographic Exclusion Criteria (visual estimate) | AE1. Planned treatment of more than 3 lesions. AE2. Planned treatment of lesions in more than 2 major epicardial vessels AE3. Planned treatment of a single lesion with more than 1 stent AE4. Subject has 2 target lesions in the same vessel that are separated by less than 15 mm (by visual estimate) AE5. Target lesion(s) is located in the left main AE6. Target lesion(s) is located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery by visual estimate. AE7. Target lesion(s) is located within a saphenous vein graft or an arterial graft AE8. Target lesion(s) will be accessed via a saphenous vein graft or arterial graft |

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Table 16: Exclusion Criteria, NG PROMUS

| | AE9. Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing AE10. Target lesion(s) treated during the index procedure that involves a complex bifurcation (e.g., bifurcation lesion requiring treatment with more than 1 stent) AE11. Target lesion(s) is restenotic from a previous stent implantation or study stent would overlap with a previous stent AE12. Subject has unprotected left main coronary artery disease (>50% diameter stenosis) AE13. Subject has been treated with any type of PCI (i.e., balloon angioplasty, stent, cutting balloon atherectomy) within 24 hours prior to the index procedure AE14. Thrombus, or possible thrombus, present in the target vessel (by visual estimate) |
| --- | --- |

# B3. Follow-up Schedule, NG PROMUS

Clinical follow-up by telephone at 30 days

# B4. Clinical Endpoints, NG PROMUS

Adverse events are collected throughout the study with a prespecified subset of events adjudicated by an independent Clinical Events Committee.

The Primary Endpoint is technical success rate, defined as successful delivery and deployment of the study stent to the target lesion, without balloon rupture or stent embolization, and post-procedure diameter stenosis of $&lt; 30\%$ assessed in 2 near-orthogonal projections with TIMI 3 flow in the target lesion, as visually assessed by the physician

# B5. Accountability of PMA Cohort, NG PROMUS

Table 19 shows subject disposition. There were 100 subjects enrolled (intent-to-treat [ITT] analysis set) and implanted (as-treated analysis set) at 9 investigative centers in Australia, New Zealand, and Singapore from 20-Nov-2012 to 12-Mar-2013.

Clinical follow-up at 30 days was $99.0\%$ (98/99). One subject died before the 30-day follow-up window and 1 subject missed the 30-day visit.

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Table 17: Subject Disposition, Clinical Follow-up Compliance Intent-to-Treat, All Subjects (N=100)

| | Subjects |
| --- | --- |
| Subjects enrolled (Intent-to-Treat analysis set) | 100 |
| Subjects treated with at least 1 study stent | 100 |
| Death ≤30 days with no 30-day clinical follow-up performed | 1 |
| Eligible for 30-day clinical follow-up^{a} | 99 |
| 30-Day clinical follow-up visit completed^{b} | 99.0% (98/99) |
| Office Visit | 11 |
| Telephone contact | 87 |
| No 30-Day clinical follow-up performed | 1 |
| Premature discontinuation | 0 |
| Withdrew consent | 0 |
| Lost to f…