The Solitaire™ Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ische 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.
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.
The Solitaire™ Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ische to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (< 70 cc by CTA or MRA, < 25 cc by MR-DWI). Endovascular therapy with the device should start within 6-16 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.

Device Description

The Solitaire™ Revascularization Device is designed to restore blood flow in patients experiencing ischemic stroke due to large intracranial vessel occlusion 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™ Revascularization Device facilitates clot retrieval and has Platinum/Iridium radiopaque markers on the proximal and distal ends. The Solitaire™ Platinum Revascularization Device also features radiopaque markers along the circumference of the working length of the devices are supplied sterile and intended for single-use only.

AI/ML Overview

The provided document describes the 510(k) premarket notification for the Solitaire™ Revascularization Device, seeking expanded indications for use. The acceptance criteria and the study used to demonstrate the device meets these criteria are detailed below.
It's important to note that this document is for a medical device, not an AI algorithm. Therefore, many of the requested fields related to AI-specific performance metrics (e.g., human readers improvement with AI, standalone algorithm performance, AI data provenance, training set size, etc.) are not applicable here. The study focuses on the clinical effectiveness and safety of the physical device.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a medical device approval and not an AI algorithm, formal "acceptance criteria" in the sense of specific performance metrics with numerical thresholds are not explicitly stated as they would be for an AI submission. Instead, the study aims to demonstrate clinical safety and effectiveness for the expanded indications, primarily measured by patient outcomes. The key performance indicators are derived from the study endpoints.

Outcome Measure	Acceptance Criteria (Not explicitly stated as numerical targets, but implied favorable outcome)	Reported Device Performance (Solitaire Group vs. Control)
Primary Efficacy Endpoint: Modified Rankin Scale (mRS) at 90 days	The device should demonstrate a favorable shift in the distribution of mRS scores, indicating reduced post-stroke neurological disability, compared to standard medical therapy. Implicitly, this means a statistically significant improvement in functional outcomes.	Favorable shift in mRS scores (p-value=0.014). Median mRS: Solitaire = 3.0 (IQR 2.0, 4.0) vs. Control = 4.0 (IQR 3.0, 6.0). For mRS 0-2 (functional independence): Solitaire = 31.2% (10/32) vs. Control = 15.3% (13/85). For mRS 6 (death): Solitaire = 12.5% (4/32) vs. Control = 27.1% (23/85).
Primary Safety Endpoint: All-cause mortality at 90 days	Mortality rate with the device should be acceptable and ideally lower than or comparable to the control group, demonstrating an acceptable safety profile.	All-cause mortality: Solitaire = 10.5% (4/38) vs. Control = 25.6% (23/90). (Lower mortality in Solitaire group)
Primary Safety Endpoint: Symptomatic Intracranial Hemorrhage (sICH) within 36 hours	The occurrence of sICH should be low and acceptable, indicating a safe procedure.	Symptomatic ICH: Solitaire = 2.6% (1/38) vs. Control = 4.4% (4/90). (Low rate in both groups, slightly lower in Solitaire)
Technical Efficacy: (mTICI score)	The device should achieve successful reperfusion (mTICI 2b/3) in a significant proportion of treated patients.	mTICI ≥ 2b post-procedure (central reading): Solitaire = 65.6% (21/32). (mTICI was not assessed for the control group immediately post-procedure as they did not undergo endovascular therapy).
Imaging Outcomes: Reperfusion rate (Tmax > 6 seconds)	The device should demonstrate a high rate of successful reperfusion (>90% reduction in region of perfusion delay) compared to control.	Reperfusion rate (%): Solitaire = 92.6 ± 20.2 (24) [Median 100.0] vs. Control = 48.7 ± 46.0 (63) [Median 53.8]. Successful reperfusion (>90%): Solitaire = 83.3% (20/24) vs. Control = 17.5% (11/63).
Imaging Outcomes: Complete recanalization at 24h	The device should achieve a high rate of complete recanalization of the primary arterial occlusive lesion.	Complete recanalization at 24h: Solitaire = 82.8% (24/29) vs. Control = 19.2% (14/73).
Imaging Outcomes: Infarct volume (ml) at 24h	The device should ideally result in smaller infarct volumes and less infarct growth compared to control.	Infarct volume (ml) at 24h per core lab: Solitaire = 64.5 ± 67.2 (38) [Median 35.0] vs. Control = 74.3 ± 80.7 (89) [Median 41.0]. (Slightly smaller median volume in Solitaire group, but mean is similar). Infarct growth (ml) at 24h per core lab: Solitaire = 48.6 ± 61.4 (38) [Median 19.9] vs. Control = 57.6 ± 70.6 (89) [Median 32.8]. (Smaller median growth in Solitaire group).
Additional Safety: Procedural Complications	Low rates of arterial dissection, access site complications requiring surgical repair/transfusion, embolization to previously unaffected territory, and vessel perforation, indicating procedure safety.	Arterial dissection: 0.0% (0/38). Access site complication requiring surgical repair or transfusion: 0.0% (0/38). Embolization to previously unaffected territory: 0.0% (0/38). Vessel perforation: 2.6% (1/38).

2. Sample size used for the test set and the data provenance

Test Set (Analysis Cohort - mITT):
- Solitaire group: 32 subjects (from an initial 38 out of 182 total in DEFUSE 3 where Solitaire was the first device used)
- Control group: 85 subjects (from an initial 90 out of 182 total in DEFUSE 3)
- Total mITT: 117 subjects
- Data provenance: The original DEFUSE 3 study was a multicenter, randomized, open-label trial (prospective). The document doesn't specify countries, but DEFUSE 3 was a US-based trial involving multiple sites across the United States. The analysis performed for this submission was a sub-analysis (post-hoc) of previously collected prospective clinical trial data.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not specify the number or qualifications of experts involved in establishing "ground truth" for the test set. However, it mentions several elements that would have required expert interpretation:

Blinded outcome assessment: The primary outcome (mRS at day 90) was evaluated by blinded assessors, implying qualified personnel.
Central reading of imaging: mTICI scores and other imaging outcomes were assessed by a "central reader" and "core lab," which implies expert radiologists/neurologists, though specific numbers or qualifications are not provided in this document.
RAPID software: Used for imaging analysis (ischemic core volume, mismatch ratio, mismatch volume), suggesting a standardized, software-assisted approach to image interpretation for eligibility and outcomes.

4. Adjudication method for the test set
The document does not explicitly describe an adjudication method like 2+1 or 3+1 for the test set. Instead, it states:

"Blinded outcome assessment" for the modified Rankin Scale (mRS) at day 90.
"Central reading" for mTICI and other imaging parameters by a "core lab."
These practices typically involve a single expert or a panel of experts making determinations in a blinded fashion, but specific adjudication rules are not detailed.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This submission is for a physical medical device (revascularization device), not an Artificial Intelligence (AI) algorithm. Therefore, an MRMC study comparing human readers with and without AI assistance was not performed or relevant to this submission.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Not applicable. This submission is for a physical medical device, not an AI algorithm. Therefore, a standalone performance assessment of an algorithm was not performed. The "Solitaire" device itself is the intervention being evaluated.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" or reference standard for evaluating the device's effectiveness and safety was based on:

Clinical outcomes data: Primarily the Modified Rankin Scale (mRS) scores at 90 days, which are well-established clinical measures of functional independence after stroke.
Mortality rates: All-cause mortality at 90 days.
Safety event rates: Occurrence of symptomatic intracranial hemorrhage (sICH) and other adverse events.
Imaging-based outcomes: Reperfusion rates (TICI scores), complete recanalization, infarct volume, and infarct growth, assessed by central readers/core labs, serving as objective measures of the device's action.

8. The sample size for the training set

Not applicable. This submission is for a physical medical device, not an AI algorithm. There is no "training set" in the context of machine learning. The clinical data from the DEFUSE 3 study served as the primary evidence for the device's clinical performance.

9. How the ground truth for the training set was established

Not applicable. As noted above, there is no "training set" for an AI algorithm in this context. The "ground truth" for the clinical study (DEFUSE 3) involves established clinical endpoints (mRS, mortality, sICH) and imaging assessments by expert clinicians and core labs, as described in point 7.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logos of the U.S. Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left, featuring a stylized human figure. To the right is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" and "ADMINISTRATION" in blue text.

March 6. 2019

Micro Therapeutics, Inc. d/b/a ev3 Neurovascular Helen Chow, PhD, RAC Senior Specialist, Regulatory Affairs 9775 Toledo Way Irvine, California 92618

Re: K181807

Trade/Device Name: Solitaire™ 2 Revascularization Device, Solitaire™ Platinum Revascularization Device (Solitaire™ 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: February 1, 2019 Received: February 4, 2019

Dear Helen Chow, PhD, RAC:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

{1}------------------------------------------------

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 of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Digitally signed by John John Marler -Marler -S Date: 2019.03.06 19:37:30 -05'00'

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

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K181807

Device Name

Solitaire™ 2 Revascularization Device, Solitaire™ Platinum Revascularization Device (Solitaire™ Revascularization Device)

Indications for Use (Describe)

The Solitaire™ Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ische 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.
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.
The Solitaire™ Revascularization Device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ische to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (< 70 cc by CTA or MRA, < 25 cc by MR-DWI). Endovascular therapy with the device should start within 6-16 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.

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

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(K) Summary - K181807

510(k) Owner:	Micro Therapeutics, Inc. d/b/a ev3 Neurovascular9775 Toledo WayIrvine, CA 92618Establishment Registration No. 2029214
Contact Person:	Jennifer CorreaProgram Manager, Regulatory AffairsTelephone: (949) 297-5494E-mail: jennifer.l.correa@medtronic.com
AlternateContact:	Helen ChowSr. Specialist, Regulatory AffairsTelephone: (949) 297-5474E-mail: helen.h.chow@medtronic.com
Date SummaryPrepared:	March 5, 2019
Trade Name ofDevice:	Solitaire™ 2 Revascularization Device,Solitaire™ Platinum Revascularization Device(Solitaire™ Revascularization Device)
Common Name ofDevice:	Neurovascular Mechanical Thrombectomy Device for AcuteIschemic Stroke Treatment
Classification ofDevice:	Class II, 21 CFR 882.5600, 21 CFR 870.1250
Product Code:	POL, NRY
Predicate Devices:	Solitaire™ 2 Revascularization Device (K162539),
Reference Devices:	Solitaire™ Platinum Revascularization Device (K153071,K160641, K161879)

Device Description:

There have been no changes to the design of the Solitaire™ Revascularization Device from the currently cleared device (K153071, K160641, K161879, K162539) to support the proposed additional indication. The currently cleared Solitaire™ 2 Revascularization Device is used as a predicate device and the Solitaire™ Platinum Revascularization Devices are used as a reference device for previously completed bench, animal, and clinical data.

{4}------------------------------------------------

Indications for Use:

1. The Solitaire™M 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.
1. 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.
1. The Solitaire™M 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 of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (< 70 cc by CTA or MRA, < 25 cc by MR-DWI). Endovascular therapy with the device should start within 6-16 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.

Device Comparison:

A comparison of the technological characteristics of the subject Solitaire™ Revascularization Device and the predicate Solitaire™ 2 Revascularization Device (K162539) is provided in Table 1. The subject Solitaire™ Revascularization device is identical to the predicate Solitaire™ 2 Revascularization Device and reference Solitaire™ Platinum Revascularization Device, apart from the expanded indications for use.

Table 1: Device Comparison
	Predicate Solitaire™ 2 Revascularization Device (K162539)	Subject Solitaire™ Revascularization Device	Rationale for Difference (if applicable)
Indication for Use	1. The Solitaire™ 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.	1. The Solitaire™ 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.	The DEFUSE 3 study data analysis has demonstrated that the expanded indications for use does not raise any new or different questions of safety or effectiveness.
	Predicate Solitaire™2 Revascularization Device(K162539)	Subject Solitaire™Revascularization Device	Rationale forDifference(if applicable)
	2. The Solitaire™Revascularization Device isindicated to restore bloodflow by removing thrombusfrom a large intracranialvessel in patientsexperiencing ischemicstroke within 8 hours ofsymptom onset. Patientswho are ineligible for IV t-PA or who fail IV t-PAtherapy are candidates fortreatment.	2. The Solitaire™Revascularization Device isindicated to restore bloodflow by removing thrombusfrom a large intracranialvessel in patients experiencingischemic stroke within 8hours of symptom onset.Patients who are ineligible forIV t-PA or who fail IV t-PAtherapy are candidates fortreatment.3. The Solitaire™Revascularization Device isindicated for use to restoreblood flow in theneurovasculature by removingthrombus for the treatment ofacute ischemic stroke toreduce disability in patientswith a persistent, proximalanterior circulation, largevessel occlusion of theinternal carotid artery (ICA)or middle cerebral artery(MCA)-M1 segments withsmaller core infarcts (< 70 ccby CTA or MRA, < 25 cc byMR-DWI). Endovasculartherapy with the deviceshould start within 6-16 hoursof time last seen well inpatients who are ineligible forintravenous tissueplasminogen activator (IV t-PA) or who fail IV t-PAtherapy.
PrinciplesofOperation	The device is used in theneurovasculature to restoreblood flow for treatment ofacute ischemic stroke	Same	N/A
Dimensions and Materials
DeviceSize(s)	4-15 mm4-20 mm4-40 mm6-20 mm6-30 mm	4-15 mm4-20 mm4-40 mm6-20 mm6-30 mm4-20-05 mm4-20-10 mm4-40-10 mm6-20-10 mm	The subject deviceincludes sizescleared in both thepredicate Solitaire™2 and referenceSolitaire™ PlatinumRevascularizationDevice
Table 1: Device Comparison
	Predicate Solitaire™2 Revascularization Device(K162539)	Subject Solitaire™Revascularization Device	Rationale forDifference(if applicable)
DeviceMaterials	Stent: NitinolPushwire: NitinolMarkers: 90% Platinum/ 10%IridiumPush-wire shrink Tubing: PTFEIntroducer Sheath:PTFE/Grilamid	6-40-10 mmSame	N/A
Sterilization and Packaging
PackagingMaterials	Stored within dispenser coil,Tyvek pouch, and shippingcarton.	Same	N/A
SterilizationMethod	Ethylene Oxide	Same	N/A
HowSupplied	Sterile, Single Use	Same	N/A

{5}------------------------------------------------

{6}------------------------------------------------

Leveraged Non-Clinical Data:

There are no changes to the subject Solitaire™ Revascularization Device in design, manufacturing process, sterilization, material formulation, principles of operation, or fundamental scientific technology. The only change is the expanded Indications for Use. Therefore, no new or additional non-clinical testing was required or performed.

Performance Testing - Clinical:

Clinical data from the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) study was used to support the expanded indication for the subject Solitaire™ Revascularization Device. The DEFUSE 3 study allowed the use of various cleared endovascular therapy devices. To support substantial equivalence of the subject Solitaire™ Revascularization Device, a sub-analysis of the DEFUSE 3 study data was performed and was limited to subjects treated with the Solitaire™ Revascularization Device in the endovascular plus standard medical therapy (endovascular therapy group) vs. those treated with standard medical therapy alone (control/medicaltherapy group).

Study Design

The DEFUSE 3 study was a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in subjects 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Subjects with proximal middlecerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovasculartherapy group) or standard medical therapy alone (control/medical-therapy group). The primary outcome was the ordinal score on

1 Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine. Feb 22 2018;378(8):708-718.

{7}------------------------------------------------

the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.

Sample Size

The DEFUSE 3 Study was designed to assess the safety and effectiveness of endovascular therapy using FDA cleared mechanical thrombectomy devices, and was not designed to assess a specific neurothrombectomy device. The DEFUSE 3 study included a total of 182 subjects (92 in the endovascular therapy group and 90 in the control group). Solitaire was the first device used amongst all mechanical thrombectomy devices for 38 subjects in the endovascular therapy group.

Statistical Analysis

A subgroup analysis was conducted including all subjects randomized to endovascular intervention and in whom Solitaire was the first device used amongst all mechanical thrombectomy devices, and all subjects randomized to the control group. Results between the two groups thus defined were summarized and compared, including formal statistical hypothesis testing on the primary efficacy endpoint.

All analyses were carried out consistent with the principle of intention-to-treat in that the randomized assignments in DEFUSE 3 as a whole were preserved in making group assignments, and in whom Solitaire was the first device used amongst all mechanical thrombectomy devices (that is, intention-to-treat with Solitaire) constitute the Analysis Cohort. The intention-to-treat (ITT) Analysis Cohort is thus comprised of 90 in the control group and 38 in the Solitaire group.

The DEFUSE 3 study allowed IV t-PA use beyond 3 hours, although IV t-PA is not approved in the United States beyond 3 hours. A total of 11 subjects (5 from the control group and 6 from the Solitaire group) were excluded from the primary and secondary efficacy endpoint analyses due to receiving IV t-PA beyond 3 hours and/or carotid stenting. Therefore, the primary and secondary efficacy endpoint analyses consist of 117 subjects (Analysis Cohort - mITT). In the mITT Analysis Cohort, subjects with multiple interventions (n=8) were treated as failures. All analyses presented for the Analysis Cohort (ITT and mITT) are post-hoc analyses. As such, there may be uncertainty in the interpretation of the clinical study results and any statistically meaningful conclusions due to the post-hoc nature of the analyses, limitations in sample size, and lack of pre-specified hypothesis testing.

Study Endpoints

The primary efficacy outcome was the ordinal score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage (sICH) within 36 hours, defined as an increase of at least 4 points in the NIHSS score that was associated with brain hemorrhage on imaging within 36 hours after symptom onset.

Imaging outcomes were:

. infarct volume measured at 24 hours (with a window of ± 6 hours) after randomization;
lesion growth (increase in volume of the infarct) between baseline imaging and 24 hours; ●

{8}------------------------------------------------

reperfusion, defined as a greater than 90% reduction in the region of perfusion delay ● (Tmax of > 6 seconds) between baseline and 24 hours; and
complete recanalization of the primary arterial occlusive lesion at 24 hours on CTA or ● MRA.

The technical efficacy of the endoyascular procedure in establishing reperfusion was defined in the endovascular-therapy group by a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b (50 to 99% reperfusion) or 3 (complete reperfusion).

Inclusion Criteria

Clinical inclusion criteria:

1. Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke
1. Age 18-90 years
1. Baseline NIHSS is ≥ 6 and remains ≥ 6 immediately prior to randomization
1. Endovascular treatment can be initiated (femoral puncture) between 6 and 16 hours of stroke onset. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).
1. Modified Rankin Scale (mRS) less than or equal to 2 prior to qualifying stroke (functionally independent for all ADLs)
1. Patient/Legally Authorized Representative has signed the Informed Consent form.

Neuroimaging inclusion criteria:

ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or ● without tandem MCA lesions) by MRA or CTA
AND
. Target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml. mismatch ratio is > 1.8 and mismatch volume* is > 15 ml)
*Notes: The mismatch volume is determined by the RAPID software in real time based on the difference between the ischemic core lesion volume and the Tmax > 6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. Only an intracranial MRA is required for patients screened with MRA; cervical MRA is not required. Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.

Alternative neuroimaging inclusion criteria (if perfusion imaging or CTA/MRA is technically inadequate):

A. If CTA (or MRA) is technically inadequate:
Tmax>6s perfusion deficit consistent with an ICA or MCA-M1 occlusion AND

Target Mismatch Profile (ischemic core volume is < 70 ml, mismatch ratio is >1.8 and mismatch volume is >15 ml as determined by RAPID software)

B. If MRP is technically inadequate:

{9}------------------------------------------------

ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI)

AND

MR Diffusion Weighted Imaging (DWI) lesion volume < 25 ml

C. If CTP is technically inadequate: Patient can be screened with MRI and randomized if neuroimaging criteria are met.

Exclusion Criteria

Clinical exclusion criteria:

Other serious, advanced, or terminal illness (investigator judgment) or life expectance is ● less than 6 months.
. Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
Pregnant ●
Unable to undergo a contrast brain perfusion scan with either MRI or CT
Known allergy to iodine that precludes an endovascular procedure ●
Treated with t-PA > 4.5 hours after time last known well
Treated with t-PA 3-4.5 hours after last known well AND any of the following: age > 80, current anticoagulant use, history of diabetes AND prior stroke, NIHSS >25
. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR > 3 (recent use of the new oral anticoagulants is not an exclusion if estimated GFR > 30 ml/min).
Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
Baseline blood glucose of < 50 mg/dL (2.78 mmol) or > 400mg/dL (22.20 mmol) ●
Baseline platelet count < 50,000/uL ●
Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure > 110 mmHg)
Current participation in another investigational drug or device study ●
Presumed septic embolus; suspicion of bacterial endocarditis
Clot retrieval attempted using a neurothrombectomy device prior to 6 hours from symptom onset
. Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed

Neuroimaging exclusion criteria:

ASPECT score < 6 on non-contrast CT (if patient is enrolled based on CT perfusion ● criteria)
. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
Significant mass effect with midline shift
Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device

{10}------------------------------------------------

Acute symptomatic arterial occlusions in more than one vascular territory confirmed on ● CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion).

Demographic and other Baseline Characteristics (Analysis Cohort - ITT)

Subject demographics and baseline characteristics are presented in Table 2. Subject age, gender, race, ethnicity, baseline NIHSS, systolic blood pressure and diastolic blood pressure did not differ significantly between the Solitaire and control groups. Median age was 71 years in each treatment group, while gender was similarly balanced with a total of 54% (69/128) females. The majority of the subject population was non-Hispanic and white. Baseline median NIHSS scores were 17 in the Solitaire group and 16 in control, indicating a moderate to severe stroke population.

Table 2: Demographics and Baseline Characteristics (Analysis Cohort - ITT)
	SolitaireMean ± SD (N)[Median] (IQR)or % (n/N)	ControlMean ± SD (N)[Median] (IQR)or % (n/N)	p-value	AllMean ± SD (N)[Median] (IQR)or % (n/N)
Outcome
Age (years)	68.2 ± 13.0 (38)[71.0] (58.3,76.8)	68.9 ± 13.4 (90)[71.0] (59.3,80.0)	0.797	68.7 ± 13.2 (128)[71.0] (59.0,79.0)
Gender			0.329
Male	39.5% (15/38)	48.9% (44/90)		46.1% (59/128)
Female	60.5% (23/38)	51.1% (46/90)		53.9% (69/128)
Race			0.765
American Indian or AlaskaNative	0.0% (0/38)	1.1% (1/90)		0.8% (1/128)
Asian	2.6% (1/38)	3.3% (3/90)		3.1% (4/128)
Black or African American	10.5% (4/38)	5.6% (5/90)		7.0% (9/128)
White	86.8% (33/38)	88.9% (80/90)		88.3% (113/128)
Unknown	0.0% (0/38)	1.1% (1/90)		0.8% (1/128)
Ethnicity			0.266
Hispanic or Latino	18.4% (7/38)	11.1% (10/90)		13.3% (17/128)
Not Hispanic or Latino	81.6% (31/38)	88.9% (80/90)		86.7% (111/128)
NIHSS at baseline	16.5 ± 5.4 (38)[17.0] (14.3,20.0)	16.9 ± 6.4 (90)[16.0] (12.0,21.0)	0.749	16.7 ± 6.1 (128)[17.0] (12.0,21.0)
Systolic blood pressure (mmHg)	140.8 ± 23.7 (38)[139.5](123.3,158.0)	145.5 ± 19.5 (90)[147.0](130.5,159.0)	0.255	144.1 ± 20.9 (128)[146.0](130.0,159.3)
Diastolic blood pressure (mmHg)	74.8 ± 12.9 (38)[74.0] (68.0,82.0)	79.3 ± 15.9 (90)[81.0] (67.0,88.8)	0.122	78.0 ± 15.1 (128)[77.0] (67.0,87.0)

Procedural Characteristics (Analysis Cohort - ITT)

Procedural characteristics are summarized in Table 3. Among both treatment groups, a majority of subjects were transferred to the endovascular enrolling hospital from an external facility. In the Solitaire group, IV t-PA was administered for 18.4% (7/38) of subjects and general anesthesia was administered in 36.8% (14/38) of subjects. The median time from arrival at the enrolling hospital to arterial puncture was 118.5 minutes, with a median of 65.5 minutes from imaging to arterial puncture. The median time from symptom onset to emergency department

{11}------------------------------------------------

(ED) arrival was 530.0 minutes. Workflow intervals between stroke onset and randomization, ED arrival, arterial puncture and reperfusion times are also provided.

Table 3: Procedural Characteristics (Analysis Cohort - ITT)
	Solitaire	Control*
	Mean ± SD (N)	Mean ± SD (N)
	[Median] (IQR)	[Median] (IQR)
Outcome	or % (n/N)	or % (n/N)
Transfer Subject	68.4% (26/38)	70.0% (63/90)
IV t-PA Administration	18.4% (7/38)	8.9% (8/90)
General Anesthesia	36.8% (14/38)	-
Onset to randomization (min)	631.2 ± 162.2 (38)	653.0 ± 153.5 (90)
	[644.5] (474.5,742.0)	[644.5] (522.8,780.8)
Onset to arterial puncture (min)	667.9 ± 160.1 (38)	-
	[674.5] (527.8,778.0)	-
Time of onset to ED arrival (min)	520.7 ± 162.6 (38)	-
	[530.0] (405.5,637.8)	-
ED arrival to arterial puncture (min)	147.2 ± 120.8 (38)	-
	[118.5] (80.8,156.8)	-
Imaging to arterial puncture (min)	69.9 ± 31.3 (38)	-
	[65.5] (46.0,86.8)	-
Onset to reperfusion (min)	719.0 ± 167.5 (34)	-
	[708.0] (569.8,855.2)	-
*Note: Data provided for control group where available

Primary Efficacy Outcomes

In the DEFUSE 3 endovascular-therapy group, treatment was associated with a favorable shift in the distribution of mRS scores at 90 days compared to the control group. Similarly, in the modified ITT Analysis Cohort, the Solitaire cohort shows a favorable shift in the distribution of mRS scores at 90 days compared to the control (p-value=0.014), as presented in Table 4. The shift toward better outcomes was consistent in direction across all levels of the mRS (Figure 1).

Table 4: Primary Effectiveness Endpoint (Analysis Cohort – mITT)
	Solitaire	Control
	Mean ± SD (N)	Mean ± SD (N)
	[Median] (IQR)	[Median] (IQR)
mRS Score at 90 days	or % (n/N)	or % (n/N)	p-value
-	3.2 ± 1.7 (32)	4.0 ± 1.8 (85)	0.014
	[3.0] (2.0,4.0)	[4.0] (3.0,6.0)
0	6.2% (2/32)	8.2% (7/85)
1	12.5% (4/32)	3.5% (3/85)
2	12.5% (4/32)	3.5% (3/85)
3	25.0% (8/32)	15.3% (13/85)
4	21.9% (7/32)	27.1% (23/85)
5	9.4% (3/32)	15.3% (13/85)
6	12.5% (4/32)	27.1% (23/85)	-

{12}------------------------------------------------

Image /page/12/Figure/0 description: This image is a bar graph comparing the number of people in the Solitaire group (n=32) and the Control group (n=85) across different categories labeled 0 through 6. In the Solitaire group, the numbers are 6, 13, 13, 25, 22, 9, and 13 for categories 0 to 6, respectively. For the Control group, the numbers are 8, 4, 4, 15, 27, 15, and 27 for categories 0 to 6, respectively.

Image /page/12/Figure/1 description: This image contains the title "Patients (%)" and the text "Figure 1: mRS at 90 days (Analysis Cohort - mITT)". The text indicates that the figure likely presents data related to the modified Rankin Scale (mRS) scores of patients at 90 days. The analysis is based on the modified intent-to-treat (mITT) cohort. The figure likely shows the percentage of patients achieving different mRS scores at the specified time point.

Secondary Efficacy Outcome

The proportion of subjects functionally independent at 90 days (mRS 0-2) favors the Solitaire group over control (31.2% vs 15.3%). Results are presented in Table 5.

Table 5: Secondary Efficacy Endpoint, mRS 0-2 at 90 days (Analysis Cohort – mITT)
Outcome	Solitaire% (n/N)	Control% (n/N)
Functional Independence (mRS 0-2) at 90 days	31.2% (10/32)	15.3% (13/85)

Additional Efficacy, Imaging and Technical Efficacy Outcomes

Early neurological improvement was defined as a > 8-point improvement in NIHSS from baseline to the 24-hour visit, or an NIHSS score of 0-1 attained at the 24-hour visit irrespective of the baseline value of NIHSS. Results are presented in Table 6.

{13}------------------------------------------------

Table 6: Early neurological improvement at 24 Hours (Analysis Cohort – ITT)
Outcome	Solitaire% (n/N)	Control% (n/N)
Early neurological improvement	31.6% (12/38)	5.6% (5/89*)
*Note: NIHSS at 24 hours, which is needed to compute early neurological improvement, wasavailable for 89 of 90 subjects in the control group.

In the Solitaire group, arterial reperfusion as measured by the modified TICI score by the central reader, was assessed immediately post-procedure. Results are presented in Table 7.

Table 7: TICI Immediate Post-Procedure* (Analysis Cohort – mITT)
Outcome	Solitaire% (n/N)
TICI post-procedure (central reading)
0	21.9% (7/32)
2a	12.5% (4/32)
2b	43.8% (14/32)
3	21.9% (7/32)
TICI≥2b post-procedure	65.6% (21/32)
*TICI was not assessed for Control Group immediately post-procedure

Reperfusion was analyzed both as a continuous metric and dichotomized to define successful reperfusion (> 90% reperfused) at 24 hours post-procedure. Complete recanalization of the primary arterial occlusive lesion was assessed on CTA or MRA at 24 hours postprocedure. Results are presented in Table 8.

Table 8: Reperfusion and Recanalization 24 hours Post-Procedure* (Analysis Cohort – mITT)
	SolitaireMean ± SD (N)[Median] (IQR)or % (n/N)	ControlMean ± SD (N)[Median] (IQR)or % (n/N)
Outcome
Reperfusion rate (%)	92.6 ± 20.2 (24)[100.0] (99.0,100.0)	48.7 ± 46.0 (63)[53.8] (24.7,84.7)
Successful reperfusion (>90%)	83.3% (20/24)	17.5% (11/63)
Complete recanalization at 24h	82.8% (24/29)	19.2% (14/73)
* Results are presented for subjects in the mITT analysis cohort with available data. Reperfusionpercentage and successful reperfusion were available on 24 of 32 subjects in the Solitaire group, and63 of 85 subjects in the control group. Complete recanalization was available on 29 of 32 subjects inthe Solitaire group and 73 of 85 subjects in the control group.

Additional imaging endpoints at 24 hours post procedure were assessed by the core lab and are presented in Table 9.

{14}------------------------------------------------

Table 9: Imaging Endpoints (Analysis Cohort – ITT)
Imaging Outcomes*	SolitaireMean ± SD (N)[Median] (IQR)	Control**Mean ± SD (N)[Median] (IQR)
Infarct volume (ml) at 24h per core lab	64.5 ± 67.2 (38)[35.0] (18.6,81.2)	74.3 ± 80.7 (89)[41.0] (25.4,106.2)
Infarct growth (ml) at 24h per core lab	48.6 ± 61.4 (38)[19.9] (3.4,79.9)	57.6 ± 70.6 (89)[32.8] (18.3,74.8)
Tmax6 volume (ml) at 24h per core lab	9.2 ± 32.5 (30)[0.0] (0.0,0.0)	59.5 ± 59.6 (68)[46.6] (11.1,78.7)

*Measured by Rapid Software

**One subject in the control group was missing imaging data 24-hours post-procedure.

Primary Safety Outcomes

All-cause mortality at the 90-day follow-up visit was less frequent in the Solitaire group compared to control (10.5% vs 25.6%). The rate of sICH was low in both study groups, with a rate of 2.6% (1/38) with Solitaire and 4.4% (4/90) in control. Results are presented in Table 10.

Table 10: Primary Safety Outcomes (Analysis Cohort – ITT)
Outcome	Solitaire% (n/N)	Control% (n/N)
All-cause mortality	10.5% (4/38)	25.6% (23/90)
Symptomatic ICH	2.6% (1/38)	4.4% (4/90)

Additional Important Safety Results

Procedural complications for the Solitaire group were reported by the clinical site and are presented in Table 11.

Table 11: Procedural Complications (Analysis Cohort – ITT)
Outcome	Solitaire% (n/N)
Arterial dissection (per site)	0.0% (0/38)
Access site complication requiring surgical repair ortransfusion (per site)	0.0% (0/38)
Embolization to previously unaffected territory (persite)	0.0% (0/38)
Vessel perforation (per site)	2.6% (1/38)

Adverse events observed during the study were reported and coded via the MedDRA classification system and are presented in Table 12 through Table 14.

{15}------------------------------------------------

(Analysis Cohort – ITT)
System Organ Class	Solitaire% (n/N) [events]	Control% (n/N) [events]
TOTAL	28.9% (11/38) [14]	4.4% (4/90) [4]
Cardiac disorders	2.6% (1/38) [1]	1.1% (1/90) [1]
Injury, poisoning andprocedural complications	2.6% (1/38) [1]	-
Nervous system disorders	23.7% (9/38) [10]	1.1% (1/90) [1]
Vascular disorders	5.3% (2/38) [2]	-
General disorders andadministration site conditions	-	1.1% (1/90) [1]
Investigations	-	1.1% (1/90) [1]

Table 12: Procedure Related Adverse Events by MedDRA Classification

Table 13: All Adverse Events by MedDRA Classification
(Analysis Cohort – ITT)
	Solitaire	Control
System Organ Class	% (n/N) [events]	% (n/N) [events]
TOTAL	78.9% (30/38) [97]	86.7% (78/90) [229]
Blood and lymphatic system disorders	5.3% (2/38) [2]	6.7% (6/90) [7]
Cardiac disorders	21.1% (8/38) [10]	16.7% (15/90) [19]
Gastrointestinal disorders	21.1% (8/38) [11]	12.2% (11/90) [11]
General disorders and administration site conditions	13.2% (5/38) [5]	12.2% (11/90) [12]
Infections and infestations	10.5% (4/38) [4]	24.4% (22/90) [28]
Injury, poisoning and procedural complications	7.9% (3/38) [3]	4.4% (4/90) [4]
Investigations	5.3% (2/38) [2]	5.6% (5/90) [5]
Metabolism and nutrition disorders	13.2% (5/38) [7]	14.4% (13/90) [17]
Musculoskeletal and connective tissue disorders	7.9% (3/38) [3]	4.4% (4/90) [5]
Nervous system disorders	42.1% (16/38) [22]	58.9% (53/90) [64]
Psychiatric disorders	13.2% (5/38) [5]	4.4% (4/90) [4]
Renal and urinary disorders	10.5% (4/38) [4]	4.4% (4/90) [5]
Respiratory, thoracic and mediastinal disorders	13.2% (5/38) [5]	25.6% (23/90) [29]
Skin and subcutaneous tissue disorders	2.6% (1/38) [1]	-
Vascular disorders	26.3% (10/38) [13]	16.7% (15/90) [16]
Congenital, familial and genetic disorders	-	1.1% (1/90) [1]
Eye disorders	-	1.1% (1/90) [1]
Product issues	-	1.1% (1/90) [1]

{16}------------------------------------------------

Table 14: Serious Adverse Events by MedDRA Classification
(Analysis Cohort -ITT)
	Solitaire	Control
System Organ Class	% (n/N) [events]	% (n/N) [events]
TOTAL	47.4% (18/38) [26]	53.3% (48/90) [68]
Cardiac disorders	5.3% (2/38) [2]	4.4% (4/90) [5]
Gastrointestinal disorders	7.9% (3/38) [4]	3.3% (3/90) [3]
General disorders andadministration site conditions	2.6% (1/38) [1]	1.1% (1/90) [1]
Infections and infestations	2.6% (1/38) [1]	7.8% (7/90) [8]
Nervous system disorders	23.7% (9/38) [10]	31.1% (28/90) [30]
Psychiatric disorders	2.6% (1/38) [1]	-
Renal and urinary disorders	5.3% (2/38) [2]	-
Respiratory, thoracic andmediastinal disorders	10.5% (4/38) [4]	14.4% (13/90) [15]
Vascular disorders	2.6% (1/38) [1]	3.3% (3/90) [3]
Injury, poisoning andprocedural complications	-	2.2% (2/90) [2]
Product issues	-	1.1% (1/90) [1]

Conclusion

The DEFUSE 3 study was a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted.

The primary effectiveness endpoint (90-day mRS shift) in the Solitaire group when compared to the control group demonstrates a favorable shift of reduced post-stroke neurological disability over the entire outcome range (p-value=0.014). When combined with the safety findings of a low symptomatic intracranial hemorrhage and all-cause mortality rates of 2.6% and 10.5%, respectively, these provide clinical evidence for the safe and effective use of the Solitaire™ Revascularization Device in this late-window (6-16 hours from last seen well) AIS population.

Summary of Substantial Equivalence:

The subject Solitaire™ Revascularization device is identical to the predicate Solitaire™ 2 Revascularization Device and reference Solitaire™ Platinum Revascularization Device, except for the expanded indications for use. The DEFUSE 3 study data analysis demonstrates that the expanded indications for use does not raise any new or different questions of safety or effectiveness of the Solitaire™ Revascularization Device in the late-window (6-16 hours from last seen well) AIS population. Therefore, the subject Solitaire™ Revascularization device is substantially equivalent to the cleared predicate Solitaire™ 2 Revascularization device.

Regulation Number and Section

§ 882.5600 Neurovascular mechanical thrombectomy device for acute ischemic stroke treatment.

(a)
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.(b)
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.