Solitaire 2 Revascularization Device

K162539 · Micro Therapeutics, Inc. d/b/a ev3 Neurovascular · POL · Nov 10, 2016 · Neurology

Device Facts

• Record ID: K162539
• Device Name: Solitaire 2 Revascularization Device
• Applicant: Micro Therapeutics, Inc. d/b/a ev3 Neurovascular
• Product Code: POL · Neurology
• Decision Date: Nov 10, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.5600
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

1. The Solitaire™ 2 Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should be started within 6 hours of symptom onset. 2. The Solitaire™ Revascularization Device is indicated to restore blood flow by removing thrombus from a large intracranial vessel in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for IV t-PA or who fail IV t-PA therapy are candidates for treatment.

Device Story

Neurovascular mechanical thrombectomy device; removes thrombus from intracranial vessels (ICA, M1/M2 MCA, basilar, vertebral arteries) to restore blood flow. Input: thrombus in neurovasculature. Operation: distal nitinol stent retriever deployed via catheter; captures clot; retrieved through guide catheter. Output: restored blood flow. Used in clinical/interventional settings by physicians. Benefits: reduced neurological disability in acute ischemic stroke patients. Output visualized via radiopaque markers; affects clinical decision-making by confirming reperfusion (TICI 2b-3).

Clinical Evidence

Prospective, randomized, open, blinded endpoint (PROBE) clinical study (SWIFT PRIME, N=144 analysis cohort). Compared IV t-PA + Solitaire vs. IV t-PA alone. Primary endpoint: 90-day mRS score. Results: 62.7% (42/67) of Solitaire group achieved functional independence (mRS 0-2) vs. 36.8% (28/76) in IV t-PA only group (p=0.003). Safety: Serious adverse events 31.0% (Solitaire) vs 33.8% (t-PA only).

Technological Characteristics

Stent retriever; Nitinol (nickel-titanium) stent and push-wire; Platinum/Iridium radiopaque markers; PTFE push-wire shrink tubing; PTFE/Grilamid introducer sheath. Dimensions: 4x15mm to 6x30mm. Sterilization: Ethylene Oxide (ISO 11135-1). Biocompatibility: ISO 10993-1. Single-use.

Indications for Use

Indicated for acute ischemic stroke patients with persistent, proximal anterior circulation, large vessel occlusion and smaller core infarcts (within 6 hours of onset, post-IV t-PA) or large intracranial vessel occlusion (within 8 hours of onset, ineligible for or failed IV t-PA).

Regulatory Classification

Identification

A neurovascular mechanical thrombectomy device for acute ischemic stroke treatment is a prescription device used in the treatment of acute ischemic stroke to improve clinical outcomes. The device is delivered into the neurovasculature with an endovascular approach, mechanically removes thrombus from the body, and restores blood flow in the neurovasculature.

Special Controls

In combination with the general controls of the FD&C Act, the Neurovascular Mechanical Thrombectomy Device for Acute Ischemic Stroke Treatment is subject to the following special controls:

*Classification.* Class II (special controls). The special controls for this device are:(1) The patient contacting components of the device must be demonstrated to be biocompatible. (2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use, including: (i) Mechanical testing to demonstrate the device can withstand anticipated tensile, torsional, and compressive forces. (ii) Mechanical testing to evaluate the radial forces exerted by the device. (iii) Non-clinical testing to verify the dimensions of the device. (iv) Non-clinical testing must demonstrate the device can be delivered to the target location in the neurovasculature and retrieve simulated thrombus under simulated use conditions. (v) Non-clinical testing must demonstrate the device is radiopaque and can be visualized. (vi) Non-clinical testing must evaluate the coating integrity and particulates under simulated use conditions. (vii) Animal testing must evaluate the safety of the device, including damage to the vessels or tissue under anticipated use conditions. (3) Performance data must support the sterility and pyrogenicity of the patient contacting components of the device. (4) Performance data must support the shelf-life of the device by demonstrating continued sterility, package integrity, and device functionality over the specified shelf-life. (5) Clinical performance testing of the device must demonstrate the device performs as intended for use in the treatment of acute ischemic stroke and must capture any adverse events associated with the device and procedure. (6) The labeling must include: (i) Information on the specific patient population for which the device is intended for use in the treatment of acute ischemic stroke, including but not limited to, specifying time from symptom onset, vessels or location of the neurovasculature that can be accessed for treatment, and limitations on core infarct size. (ii) Detailed instructions on proper device preparation and use for thrombus retrieval from the neurovasculature. (iii) A summary of the clinical testing results, including a detailed summary of the device- and procedure-related complications and adverse events. (iv) A shelf life.

Predicate Devices

• Trevo XP ProVue Retriever (DEN150049)

Reference Devices

• Solitaire FR Revascularization Device (K113455)
• Solitaire 2 Revascularization Device (K123378)
• Solitaire 2 Revascularization Device (K141491)
• Merci Retrievers (K113455)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

November 10, 2016

Micro Therapeutics, Inc. d/b/a ev3 Neurovascular Jennifer Correa Sr. Regulatory Affairs Product Specialist 9775 Toledo Way Irvine, California 92618

Re: K162539

Trade/Device Name: Solitaire 2 Revascularization Device Regulation Number: 21 CFR 882.5600 Regulation Name: Neurovascular Mechanical Thrombectomy Device for Acute Ischemic Stroke Treatment Regulatory Class: Class II Product Code: POL, NRY Dated: September 9, 2016 Received: September 12, 2016

Dear Ms. Jennifer Correa:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you; however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in

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the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Carlos L. Pena -SFD/△

Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K162539

Device Name Solitaire™ 2 Revascularization Device

#### Indications for Use (Describe)

1. The Solitaire™ 2 Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should be started within 6 hours of symptom onset.

2. The Solitaire™ Revascularization Device is indicated to restore blood flow by removing thrombus from a large intracranial vessel in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for IV t-PA or who fail IV t-PA therapy are candidates for treatment.

Type of Use (Select one or both, as applicable)

| <span style="font-size:10pt;"> <span style="font-family:Wingdings;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D)</span> |
|----------------------------------------------------------------------------------------------------------------------------------|
| <span style="font-size:10pt;"> <span style="font-family:Wingdings;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C)</span> |

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| 510(K) Summary | K162539 |
|-----------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Owner:<br>Contact Person: | Micro Therapeutics, Inc. d/b/a ev3 Neurovascular<br>9775 Toledo Way<br>Irvine, CA 92618<br>Establishment Registration No. 2029214<br>Jennifer Correa<br>Senior Specialist, Regulatory Affairs<br>Telephone: [phone]<br>E-mail: [e-mail] |
| Date Summary<br>Prepared:<br>Trade Name of<br>Device: | October 28, 2016<br>Solitaire™ 2 Revascularization Device |
| Common Name of<br>Device:<br>Classification of<br>Device: | Neurovascular Mechanical Thrombectomy Device for Acute<br>Ischemic Stroke Treatment<br>Class II, 21 CFR 882.5600, 21 CFR 870.1250 |
| Product Code:<br>Predicate Devices: | POL, NRY<br>Trevo XP ProVue Retriever<br>DEN150049 |
| Clinical Data: | A global, multicenter, two-arm, prospective, randomized, open,<br>blinded endpoint (PROBE) clinical study (SWIFT PRIME, IDE<br>G120142) comparing neurological disability outcomes (defined by<br>mRS) in Acute Ischemic Stroke (AIS) patients who are treated<br>with either IV t-PA alone or IV t-PA in combination with Solitaire<br>mechanical thrombectomy intervention was performed. The data<br>from the SWIFT PRIME study in comparison to the data from the<br>Trevo clinical study demonstrate that the use of the Solitaire<br>Revascularization device is safe and is substantially equivalent to<br>the predicate device for reducing disability in patients with a<br>persistent proximal anterior circulation large vessel occlusion and<br>smaller core infarcts who have first received intravenous tissue<br>plasminogen activator (IV t-PA) for acute ischemic stroke. |
| Conclusion: | The Solitaire™ 2 Revascularization Device is substantially<br>equivalent to the Trevo XP ProVue Retriever based on comparison<br>of the Trevo clinical data to the SWIFT PRIME clinical study data.<br>In addition, the Solitaire™ 2 Revascularization Device is<br>substantially equivalent to the Trevo XP ProVue Retriever in terms<br>of fundamental scientific technology, including similarities in<br>design, principles of operation, and indications for use. |

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# Device Description:

The Solitaire™ 2 Revascularization Device is designed to restore blood flow in patients experiencing ischemic stroke due to large intracranial vessel occlusion. The Solitaire™ 2 Revascularization Device is designed for use in the neurovasculature such as the Internal Carotid Artery (ICA). M1 and M2 segments of the middle cerebral artery, basilar, and the vertebral arteries. The distal nitinol portion of the Solitaire™ 2 Revascularization Device facilitates clot retrieval and has Iridium radiopaque markers on the proximal and distal ends. The devices are supplied sterile and are intended for single-use only.

There have been no changes to the Solitaire™ 2 Revascularization Device from the currently cleared Solitaire devices (K113455, K123378 and K141491) to support the proposed additional indication. Indication for Use #2 is the same indication as the currently cleared Solitaire Devices under product code NRY (K113355, K123378 and K141491). The currently cleared Solitaire™ 2 Revascularization device is used as a reference device for Indication for Use, previously completed bench, animal, and clinical data.

## Indications for Use:

- 1. The Solitaire™ 2 Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should be started within 6 hours of symptom onset.
- 2. The Solitaire™ Revascularization Device is indicated to restore blood flow by removing thrombus from a large intracranial vessel in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for IV t-PA or who fail IV t-PA therapy are candidates for treatment.

### Device Comparison:

The table below provides a comparison of the technological characteristics of the Solitaire™ 2 Revascularization Device and the predicate Trevo XP ProVue Retriever (DEN150049).

| | Predicate Device<br>Trevo XP ProVue<br>Retriever (DEN150049) | Subject Device<br>Solitaire™ 2<br>Revascularization Device | Rationale for<br>Difference<br>(if applicable) |
|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indication<br>for Use | The Trevo ProVue and<br>XP ProVue Retrievers are<br>intended to restore blood<br>flow in the neurovascular<br>by removing thrombus for<br>treatment of acute<br>ischemic stroke to reduce<br>disability in patients with | 1. The Solitaire™ 2<br>Revascularization Device<br>is indicated for use to<br>restore blood flow in the<br>neurovasculature by<br>removing thrombus for the<br>treatment of acute ischemic<br>stroke to reduce disability | Indication 1:<br>N/A, same as<br>predicate<br>device<br><br>Indication 2:<br>N/A, same as<br>reference |
| | Predicate Device<br>Trevo XP ProVue | Subject Device<br>Solitaire™ 2 | Rationale for<br>Difference<br>(if applicable) |
| | Retriever (DEN150049) | Revascularization Device | |
| | a persistent, proximal<br>anterior circulation, large<br>vessel occlusion, and<br>small core infarcts who<br>have first received<br>intravenous tissue<br>plasminogen activator (IV<br>t-PA). Endovascular<br>therapy with the device<br>should start within 6 hours<br>of symptom onset. | in patients with a<br>persistent, proximal<br>anterior circulation, large<br>vessel occlusion, and<br>smaller core infarcts who<br>have first received<br>intravenous tissue<br>plasminogen activator (IV<br>t-PA). Endovascular<br>therapy with the device<br>should be started within 6<br>hours of symptom onset.<br><br>The Solitaire™<br>Revascularization Device<br>is indicated to restore<br>blood flow by removing<br>thrombus from a large<br>intracranial vessel in<br>patients experiencing<br>ischemic stroke within 8<br>hours of symptom onset.<br>Patients who are ineligible<br>for IV t-PA or who fail IV<br>t-PA therapy are candidates<br>for treatment. | predicate<br>device<br>(K113455,<br>K123378 and<br>K141491<br>cleared under<br>product code<br>NRY) |
| Principles of<br>Operation | The device is used in the<br>neurovasculature to<br>restore blood flow for<br>treatment of acute<br>ischemic stroke | Same | N/A |
| Dimensions and Materials | | | |
| Device<br>Size(s) | 3x20 mm<br>4x20 mm<br>4x30 mm<br>6x25 mm | 4x15 mm<br>4x20 mm<br>4x40 mm<br>6x20 mm<br>6x30 mm | Both devices<br>are offered in a<br>variety of sizes<br>designed to be<br>used in the<br>neurovasculature<br>to restore<br>blood flow. |
| Device<br>Materials | Core Wire Material:<br>Nitinol (nickel titanium<br>alloy) | Stent: Nitinol<br>Pushwire: Nitinol<br>Markers: 90% Platinum/<br>10% Iridium | Both device<br>materials are<br>biocompatible, |
| | Predicate Device<br>Trevo XP ProVue<br>Retriever (DEN150049) | Subject Device<br>Solitaire™ 2<br>Revascularization Device | Rationale for<br>Difference<br>(if applicable) |
| | Distal Shaped Section<br>Material: Nitinol<br>Coil Material Distal to<br>Distal<br>Shaped Section :<br>Platinum/Tungsten<br>Shaped Section<br>Radiopaque Wire:<br>Platinum/Tungsten<br>Coil Material Proximal to<br>Shaped Section: 304<br>Stainless Steel<br>Solder: Gold/Tin<br>Hydrophilic Coating:<br>Sodium hyaluronate<br>mixture | 10% Iridium<br>Push-wire shrink Tubing:<br>PTFE<br>Introducer Sheath:<br>PTFE/Grilamid | designed to be<br>used in the<br>neurovasculatu<br>re, and contain<br>radiopaque<br>materials for<br>visualization. |
| | Sterilization and Packaging | | |
| Packaging<br>Materials | Polyethylene Hoop,<br>polycarbonate mounting<br>card, Tyvek/Film Pouch,<br>HDPE Tubing Clips,<br>Chipboard carton | Stored within dispenser<br>coil, Tyvek pouch, and<br>shipping carton. | Packaging<br>materials are<br>similar and<br>typical for<br>medical<br>devices. Both<br>packaging<br>configurations<br>maintain a<br>sterility of the<br>device through<br>the shelf life. |
| Sterilization<br>Method | Ethylene Oxide | Same | N/A |
| How<br>Supplied | Sterile, Single Use | Same | N/A |

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# Sterilization and Shelf Life:

The Solitaire™ 2 Revascularization Device is sterilized using a validated, Ethylene Oxide (EO) sterilization cycle. The sterilization cycle has been validated to ensure a sterility assurance level (SAL) of 106 in accordance with 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. There have been no changes to device sterilization in support of this submission. Therefore, no additional sterilization validation testing is required.

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Aging studies for the Solitaire™ 2 Revascularization Device have established the Solitaire™ 2 Revascularization Device packaging remains functional and maintains sterility for up to two years. Aging studies for packaging integrity, seal strength and device functionality were performed and met all acceptance criteria. There have been no changes to the materials of construction, design, manufacturing process, packaging, or sterile load configurations in support of this submission. Therefore, no additional shelf life validation testing is required.

## Biocompatibility:

Biocompatibility data for the Solitaire device family was tested for the reference Solitaire™ FR Revascularization Device. The biocompatibility data for the Solitaire™ FR was adopted for the Solitaire™ 2 Revascularization Device. The Solitaire™ Revascularization Device is biocompatible and has been tested in accordance with AAMI/ANSI/ISO 10993-1: 2009, Biological evaluation of medical devices-Part 1: Evaluation and testing within a risk management process. There have been no changes to the finished device or the manufacturing processes in support of this submission. Therefore, no additional biocompatibility is required. Biocompatibility testing completed for the reference Solitaire™ FR Revascularization Device includes:

| Test<br>Category | Test<br>Description | Method | Acceptance Criteria | Conclusion |
|-------------------------------|-----------------------------------------------------|--------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|
| Cytotoxicity | L929 MTT<br>Cytotoxicity | ISO 10993-5 | Viability is ≥70%. | Acceptance criteria<br>met |
| Sensitization | Guinea Pig<br>Maximization<br>Sensitization | ISO 10993-10 | Test article does not<br>elicit a sensitization<br>response. | Acceptance criteria<br>met |
| Irritation | Intracutaneous<br>Irritation Test | ISO 10993-10 | Differences in the<br>mean test and control<br>scores of the extract<br>dermal observations<br>are < 1.0. | Acceptance criteria<br>met |
| Acute<br>Systemic<br>Toxicity | Acute Systemic<br>Injection Test | ISO 10993-11 | No abnormal clinical<br>signs and weight loss<br>in excess of 10%. | Acceptance criteria<br>met |
| | Materials<br>Mediated<br>Rabbit Pyrogen | | Temperature rise<br>≥0.5°C | |
| Test<br>Category | Test<br>Description | Method | Acceptance Criteria | Conclusion |
| Hemo-<br>compatibility | Hemolysis | ISO 10993-4 | No significant<br>differences between<br>the test article extract<br>and negative control<br>article results. The test<br>article is considered<br>non-hemolytic | Acceptance criteria<br>met |
| | Partial<br>Thromboplastin<br>Time | | Clotting times are<br>similar to the negative<br>control and the<br>reference material<br>(HDPE) indicating the<br>device materials are<br>not an activator of the<br>intrinsic coagulation<br>pathway. | |
| | Platelet and<br>Leukocyte<br>Count | | Test article does not<br>adversely affect the<br>platelet and leukocyte<br>components of the<br>blood compared to the<br>reference material. | |
| | Complement<br>Activation C3a<br>and SC5b-9<br>Assay | | Levels of C3a and<br>SC5b-9 are<br>comparable and less<br>than the positive<br>control. | |
| | Thrombosis | | Thrombo-resistance<br>properties are<br>acceptable in clinical<br>use. | |
| Genotoxicity | Bacterial<br>Mutagenicity<br>Test | ISO 10993-3 | Test article is<br>considered non-<br>mutagenic | Acceptance criteria<br>met |
| | <i>In-vitro</i> Mouse<br>Lymphoma<br>Assay | | Test article is<br>considered non-<br>mutagenic | |
| | <i>In-vivo</i> Mouse<br>Micronucleus<br>Assay | | Test article is<br>considered non-<br>mutagenic | |

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# Performance Data – Bench:

Performance testing conducted to support this Solitaire™ 2 Revascularization Device submission includes particulate testing under simulated use conditions. Performance Bench testing completed for this submission and previously conducted for the reference device, the currently cleared Solitaire™ 2 Revascularization device, includes:

| Test Description | Method | Acceptance<br>Criteria | Conclusion |
|----------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|
| Delivery Force | Peak delivery force was<br>measured through a<br>representative tortuous<br>anatomical model. | Stent must be below<br>delivery force<br>specification. | Acceptance criteria met |
| Re-sheathing<br>Force | Retrieval force was<br>measured through a<br>representative tortuous<br>anatomical model. | Stent must be below<br>re-sheathing force<br>specification. | Acceptance criteria met |
| Total System<br>Length | Total system length was<br>measured from the<br>proximal tip of the push-<br>wire to the distal-most tip<br>of the finger marker coils. | System length must<br>meet product<br>specification. | Acceptance criteria met |
| Fluorosafe<br>Marker Length | The total length<br>of the fluorosafe<br>marker was measured. | Fluorosafe marker<br>length must meet<br>product<br>specification. | Acceptance criteria met |
| Multiple Re-<br>sheathing<br>Durability | Samples were evaluated<br>on their ability to<br>withstand delivery and<br>withdrawal forces in a<br>representative tortuous<br>model beyond the<br>recommended number of<br>passes and re-sheathings<br>allowed per the<br>Instructions for Use<br>(IFU). | Device must reliably<br>deploy and resheath<br>up to four times. | Acceptance criteria met |
| Body Marker<br>Tensile | Body Marker tensile<br>strength testing is<br>performed to verify the<br>strength of the laser weld<br>of the Platinum/Iridium<br>markercoil to the Nitinol<br>distal finger of the device. | Body marker should<br>be greater than or<br>equal to existing<br>tensile strength<br>specification. | Acceptance criteria met |
| Body Marker<br>Radiopacity | Verification analysis of<br>body markers. | The radiopaque<br>body markers must<br>be visible using<br>standard catheter<br>laboratory<br>equipment | Acceptance criteria met |
| Test Description | Method | Acceptance<br>Criteria | Conclusion |
| Proximal Marker<br>to Distal Marker | The length of the laser cut<br>and electro-polished<br>stents are measured 100%<br>in process. | Length of stent must<br>meet all inspection<br>criteria | Acceptance criteria met |
| Torque Response | Samples were evaluated<br>to determine the number<br>of turns required to<br>produce 1 rotation of the<br>distal tip of the device. | Device turns must<br>be less than or equal<br>to torque response<br>criteria | Acceptance criteria met |
| Torque Strength | Samples were evaluated<br>to determine the number<br>of turns required to<br>break the device in a<br>representative tortuous<br>model. | Device turns must<br>be greater than<br>torque strength<br>criteria | Acceptance criteria met |
| System Tensile | Samples were evaluated<br>to determine the tensile<br>strength of the full<br>system. | Devices must be<br>greater than or equal<br>to the system tensile<br>criteria | Acceptance criteria met |
| Af Temperature | In-process 100% tracking<br>of heat set parameters<br>used to set final Af | Temperature should<br>be less than or equal<br>to existing Af<br>temperature<br>specification. | Acceptance criteria met |
| Radial Force | The radial force was<br>measured 100% in-<br>process. | Stent must be within<br>existing radial force<br>specification. | Acceptance criteria met |
| Kink Resistance | Kink resistance testing<br>verified the device<br>flexibility across various<br>levels of tortuosity. | Device must be able<br>to maintain vessel<br>wall apposition at a<br>minimum radius<br>bend. | Acceptance criteria met |
| Clot Removal in<br>a Simulated<br>Neurovascular<br>Model | Both hard and soft clot<br>retrieval success was<br>evaluated in an in vitro<br>tortuous anatomical<br>model. | Overall success rate<br>of the device<br>(usability and<br>effectiveness) must<br>be equal to or better<br>than the predicate*<br>device. | Acceptance criteria met |
| Test Description | Method | Acceptance Criteria | Conclusion |
| <b>Particulate Under Simulated Use Conditions</b> | Device was evaluated for particulate generation under simulated use in a representative tortuous anatomical model per USP<788> | Device was evaluated for particulate generation under simulated use in a representative tortuous anatomical model per USP<788> | Acceptance criteria met |

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*Predicate for K113455, Merci® Retrievers

# Performance Data - Animal:

No additional animal performance testing was conducted to support this Solitaire™ 2 Revascularization Device submission. Performance Animal testing previously conducted to support clearance of the reference device, the Solitaire™ 2 Revascularization device, includes:

- An acute and 30 day animal study was performed that assessed safety . effectiveness, and usability of the Solitaire™ 2 device as compared to the predicate* device. Safety was evaluated for tissue damage, hemorrhage, and thrombi using angiographic images and histopathological evaluation.
- Histological findings of the Solitaire™ 2 device and the predicate* device for the . acute and chronic study demonstrated that the vessel response to neurothrombectomy was comparable between the two devices with no histological remarkable difference in the vessel in regards to tissue injury, hemorrhagic evaluation and thrombogenic evaluation.
- Usability for the acute and chronic study were assessed by an interventionalist on ● the following attributes after each pass: delivery through catheter, ability to position stent retriever at intended target zone, ability to deplov retriever, ability to re-sheath and reposition, ability to retrieve the device through a guide catheter and device condition. The safety and usability results from the acute and 30-day animal studies suggest that the Solitaire™ 2 device is safe, usable and is equivalent to the predicate* device.

*Predicate for K113455, Merci® Retrievers

### Performance Testing - Clinical:

#### Study Design

SWIFT PRIME (Solitaire™ FR or Solitaire™ 2 With the Intention For Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) is a global, multicenter, two-arm, prospective, randomized, open, blinded endpoint (PROBE) clinical Investigation Device Exemption (IDE) study comparing neurological disability outcomes (defined by mRS) in Acute Ischemic Stroke (AIS) patients who are treated with either IV t-PA alone or IV t-PA in combination with Solitaire™ FR or Solitaire™ 2 mechanical thrombectomy intervention. Subjects receiving IV t-PA within 4.5 hours of symptom onset were randomized 1:1 to mechanical thrombectomy with Solitaire within 6 hours of onset, or to continuation with IV t-PA alone. Within this group, the Analysis cohort was

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defined as those subjects who were administered IV t-PA within 3 hours of symptom onset.

## Sample Size

A total of 196 subjects were randomized into the SWIFT PRIME Study (98 in each group). The SWIFT PRIME study allowed IV t-PA use beyond 3 hours, although IV t-PA is not approved in the United States beyond 3 hours. Patients treated with IV t-PA beyond 3 hours did not factor strongly in the evaluation of the Solitaire 2 revascularization device and have been excluded from the analyses. The resulting Analysis Cohort consists of 161 subjects (84 in the IV t-PA plus Solitaire™ group and 77 with IV t-PA only). Additionally, 17 subjects in the IV t-PA plus Solitaire™ group were excluded from the primary and secondary efficacy endpoint analyses. These 17 subjects either received carotid stenting and/or angioplasty or were treated in a manner inconsistent with the Solitaire Instructions for Use. Therefore, the primary and secondary efficacy endpoint analyses cohort consists of 144 subjects.

## Statistical Analysis

Standard summary statistics were calculated for all study variables and subject data were analyzed according to the group to which they were randomized. For continuous variables, statistics included means, standard deviations, medians and ranges. Categorical variables were summarized in frequency distributions.

For the primary efficacy endpoint, statistical significance was declared using bounds predefined in the group sequential analysis plan, which accounts for multiplicity due to interim analyses. Elsewhere, one-sided statistical tests having p-values less than 0.025 were deemed significant while two-sided tests having p-values less than 0.05 were deemed significant.

For adverse event reporting, the primary analysis is based on subject counts, not event counts. Both subject counts and event counts are presented in tabular summaries of results.

### Study Endpoints

The primary effectiveness endpoint of the study is 90-day global disability assessed via the blinded evaluation of modified Rankin Scale (mRS). Secondary clinical efficacy endpoints of the study are:

- Death due to any cause at 90 days.
- Functional independence as defined by mRS score < 2 at 90 days. .
- Change in NIHSS score at 27 ± 6 hours post randomization. ●

The secondary technical efficacy endpoints of the study are:

- Volume of cerebral infarction as measured by a CT or MRI scan at 27 ± 6 hours post randomization.
- Reperfusion measured by reperfusion ratio on CT or MRI scan 27 ± 6 hours post ● randomization
- Arterial revascularization measured by TICI 2b or 3 following device use.

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- . Correlation of RAPID-assessed core infarct volume with 27 ± 6 hours post randomization stroke infarction in subjects who achieved TICI 2b-3 reperfusion without intracranial hemorrhage.
Inclusion Criteria

- Subject or subject's legally authorized representative has signed and dated an ● Informed Consent Form
- . Age 18 - 80
- . Clinical signs consistent with acute ischemic stroke
- . Pre-stroke Modified Rankin Score less than or equal to 1
- . National Institute of Health Stoke Scale (NIHSS) score of at least 8 and less than 30 at the time of randomization
- . Initiation of IV t-PA within 4.5 hours of onset of stroke symptoms
- . Thrombolysis in Cerebral Infarction (TICI) 0 to 1 flow in the intracranial internal carotid artery, M1 segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to the Solitaire™ FR or Solitaire™ 2 device
- . Subject is able to be treated within 6 hours of stroke symptoms onset and within 1.5 hours from CTA or MRA to groin puncture
- . Subject is willing to conduct follow-up visits

Exclusion Criteria

- Subject who is contraindicated to IV t-PA as per local national guidelines ●
- . Females who are pregnant or lactating
- . Rapid neurological improvement prior to randomization suggesting resolution of signs/symptoms of stroke
- . Known serious sensitivity to radiographic contrast agents
- . Known sensitivity to Nickel, Titanium metals or their alloys
- . Current participation in another investigational drug or device study
- . Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiencv
- . Renal failure as defined by a serum creatinine greater than 2.0 mg/dl (or 176.8 umol/1) or Glomerular Filtration Rate [GFR] less than 30
- . Requires hemodialysis or peritoneal dialysis, or who have contraindication to an angiogram
- . Life expectancy less than 90 days
- . Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
- . Suspicion of aortic dissection
- . Co-morbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments
- . Currently uses or has a recent history of illicit drug(s) or abuses alcohol
- . Known history of arterial tortuosity, pre-existing stent, and/or other arterial disease which would prevent the device from reaching the target vessel and/or preclude safe recovery of the device

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- . Additionally, subjects were also considered ineligible for study participation if they met any of the following imaging exclusion criteria:
- CT or MRI evidence of hemorrhage on presentation, mass effect or o intracranial tumor (except small meningioma), cerebral vasculitis, basilar artery (BA) occlusion or posterior cerebral artery (PCA) occlusion, carotid dissection, or complete cervical carotid occlusion requiring stenting at the time of the index procedure
- CT showing hypodensity or MRI showing hyperintensity involving greater o than 1/3 of the middle cerebral artery (MCA) territory (or in other territories, >100 cc of tissue) on presentation
- Baseline non-contrast CT or DWI MRI evidence of a moderate/large core o defined as extensive early ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) less than 6. Patients enrolled under RAPID were excluded based on the following:
- a) MRI- or CT-assessed core infarct lesion greater than 50 cc; or
- b) Severe hypoperfusion lesion (10 sec or more Tmax lesion larger than 100 cc; or
- c) Ischemic penumbra < 15 cc and mismatch ratio ≤1.8.
- Evidence that suggests, in the opinion of the investigator, the subject is not о appropriate for mechanical thrombectomy intervention

Reason for Screen Failure

| Table 12. Screen Failure | |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------|
| Reason for Screen Failure | Subjects<br>(no.) |
| Thrombolysis in Cerebral Infarction (TICI) > 1 flow in the intracranial internal carotid artery, M1<br>segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to the<br>Solitaire™ FR Device. | 28 |
| MRI- or CT-assessed core infarct lesion greater than 50 cc; severe hypoperfusion lesion (Tmax>10secs<br>lesion greater than 100 cc); and/or Ischemic penumbra < 15 cc and mismatch ratio ≤1.8. | 17 |
| CT showing hypodensity or MRI showing hyperintensity involving greater than 1/3 of the middle<br>cerebral artery (MCA) territory (or in other territories, >100 cc of tissue) on presentation. | 6 |
| NIHSS < 8 or ≥ 30 at the time of randomization | 9 |
| CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion. | 3 |
| CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma). | 3 |
| Rapid neurological improvement prior to study randomization suggesting resolution of<br>signs/symptoms of stroke. | 4 |
| Pre-stroke Modified Rankin Score> 1 | 2 |
| Baseline non-contrast CT or DWI MRI evidence of a moderate/large core defined as extensive early<br>ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) < 6. | 3 |
| Imaging evidence that suggests, in the opinion of the investigator, the subject is not appropriate for<br>mechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/large<br>infarct with poor collateral circulation, etc.). | 3 |
| Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, cerebral aneurysm, or | 2 |

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| Table 12. Screen Failure | |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------|
| Reason for Screen Failure | Subjects<br>(no.) |
| arteriovenous malformation. | |
| CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion requiring stenting<br>at the time of the index procedure (i.e., mechanical thrombectomy). | 3 |
| Subject is unwilling to conduct protocol-required follow-up visits. | 1 |
| Age >80 years old | 1 |
| Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. | 1 |
| Contraindication to IV t-PA as per local national guidelines. | 1 |
| History of stroke in the past 3 months. | 1 |
| Arterial tortuosity, calcification, pre-existing stent, and/or stenosis which would prevent the device<br>from reaching the target vessel and/or preclude safe recovery of the device. | 2 |
| Subject is unable to be treated within 6 hours of onset of stroke symptoms and within 1.5 hours (90<br>minutes) from qualifying imaging to groin puncture. | 2 |
| CT or MRI evidence of a basilar artery (BA) occlusion or posterior cerebral artery (PCA) occlusion. | 1 |
| No certified rater available to assess ASPECTS prior to study enrollment | 1 |
| Total | 77* |
| * Column does not sum to 77 due to some subjects having more than 1 screen failure reason | |

### Primary Safety and Efficacy Outcomes

The proportion of patients functionally independent (mRS 0-2) at the 90-day visit was higher in the IV t-PA plus Solitaire™ device group.

| Primary Effectiveness Endpoint (Analysis Cohort) | | | |
|-----------------------------------------------------------------------------------------------------------------------------------------------|---------------|---------------------|---------|
| mRS Score at 90 days | IV t-PA Only* | IV t-PA + Solitaire | p-value |
| | | | 0.0007 |
| 0 | 7.9% (6/76) | 16.4% (11/67) | |
| 1 | 11.8% (9/76) | 31.3% (21/67) | |
| 2 | 17.1% (13/76) | 14.9% (10/67) | |
| 3 | 18.4% (14/76) | 11.9% (8/67) | |
| 4 | 18.4% (14/76) | 13.4% (9/67) | |
| 5/6 | 26.3% (20/76) | 11.9% (8/67) | |
| Missing data at 90-day was imputed using LOCF (except baseline data not used) | | | |
| *One subject from the IV t-PA only group withdrew consent 27 hours post<br>randomization. No 90 day mRS Score was available for this subject. | | | |

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Image /page/16/Figure/2 description: This image is a bar chart comparing the outcomes of two different treatments: Solitaire + IV tPA and IV tPA. For Solitaire + IV tPA (N=67), the outcomes are distributed as follows: 16, 31, 15, 12, 13, and 12. For IV tPA (N=76*), the outcomes are distributed as follows: 8, 12, 17, 18, 18, and 26. The chart visually represents the distribution of outcomes for each treatment group.

Patients (%)

* One subject from the IV t-PA only group withdrew consent 27 hours post randomization. No 90 day mRS Score was available for this subject.

Modified Rankin Shift at 90 days (Analysis Cohort)

| Primary Safety Endpoints (Analysis Cohort) | | | |
|------------------------------------------------------------------------------------|---------------|---------------------|------------------|
| Safety Endpoint | IV t-PA Only | IV t-PA + Solitaire | Odds Ratio |
| Primary Safety Variables | | | |
| Any serious adverse event* | 33.8% (26/77) | 31.0% (26/84) | 0.88 (0.45-1.70) |
| Symptomatic ICH at 27 hours** | 3.9% (3/77) | 0.0% (0/84) | NA |
| NA denotes not applicable | | | |
| *Per Clinical Events Committee adjudication<br>**Per Core Laboratory assessed data | | | |

| Safety Endpoints, RAPID Imaging Requirement Subgroup<br>(Analysis Cohort) | | | | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|---------------------|---------------------|--|
| Safety Endpoint | IV t-PA Only | IV t-PA + Solitaire | Odds Ratio | |
| All Serious Adverse Events* | 43.3% (13/30) | 42.9% (12/28) | 0.98<br>(0.35-2.77) | |
| Symptomatic ICH at 27 hours** | 0.0% (0/30) | 0.0% (0/28) | NA | |
| NA denotes not applicable<br>*Per Clinical Events Committee adjudication<br>**Per Core Laboratory assessed data<br>Patients enrolled under RAPID were excluded based on the following:<br>a) MRI- or CT-assessed core infarct lesion greater than 50 cc; or<br>b) Severe hypoperfusion lesion (10 sec or more Tmax lesion larger than 100 cc; or | | | | |

c) Ischemic penumbra < 15 cc and mismatch ratio ≤1.8.

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| Safety Endpoints, ASPECTS Imaging Requirement Subgroup | | | |
|--------------------------------------------------------|---------------|---------------------|---------------------|
| (Analysis Cohort) | | | |
| Safety Endpoint | IV t-PA Only | IV t-PA + Solitaire | Odds Ratio |
| All Serious Adverse Events* | 29.8% (14/47) | 25.0% (14/56) | 0.79<br>(0.33-1.88) |
| Symptomatic ICH at 27 hours** | 6.4% (3/47) | 0.0% (0/56) | NA |

# Key Secondary Outcomes

| Secondary Clinical Efficacy Endpoints (Analysis Cohort) | | | | |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|------------------------|---------------------------------------|----------|
| Secondary Clinical Efficacy<br>Endpoint | IV t-PA Only* | IV t-PA +<br>Solitaire | Odds Ratio/<br>Difference<br>[95% CI] | p-value |
| Mortality at 90 days | 10/76 (13.2%) | 6/67 (9.0%) | 0.65 (0.22-1.89) | 0.596 |
| Functional Independence (mRS<br>0-2) at 90 days | 28/76 (36.8%) | 42/67 (62.7%) | 2.88 (1.46-5.68) | 0.003** |
| Change in NIHSS at 27 hours Post randomization | | | | |
| N | 76 | 66 | | <0.001** |
| Mean ± SD | -4.3 ± 6.4 | -9.9 ± 7.2 | -5.6 (-7.9, -3.3) | |
| Median | -3.0 | -9.5 | | |
| (min, max) | (-24, 9) | (-27.0,10.0) | | |
| *One subject from th…