(59 days)
- 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 plasogen 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™ 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.
The provided text describes the acceptance criteria and the study that proves the Solitaire™ 2 Revascularization Device meets those criteria. Here's a structured breakdown of the requested information:
Acceptance Criteria and Reported Device Performance
1. Table of Acceptance Criteria and Reported Device Performance:
The document presents two main categories of performance data: biocompatibility and bench testing. Clinical data is used for comparative effectiveness rather than direct acceptance criteria for the device itself in this specific section.
Biocompatibility Testing:
| Test Category | Test Description | Method | Acceptance Criteria | Conclusion |
|---|---|---|---|---|
| Cytotoxicity | L929 MTT Cytotoxicity | ISO 10993-5 | Viability is ≥70%. | Acceptance criteria met |
| Sensitization | Guinea Pig Maximization Sensitization | ISO 10993-10 | Test article does not elicit a sensitization response. | Acceptance criteria met |
| Irritation | Intracutaneous Irritation Test | ISO 10993-10 | Differences in the mean test and control scores of the extract dermal observations are < 1.0. | Acceptance criteria met |
| Acute Systemic Toxicity | Acute Systemic Injection Test | ISO 10993-11 | No abnormal clinical signs and weight loss in excess of 10%. | Acceptance criteria met |
| Materials Mediated Rabbit Pyrogen | - | Temperature rise ≥0.5°C (Note: This looks like a rejection criterion, implies "no temperature rise ≥0.5°C" would be the acceptance) | Acceptance criteria met | |
| Hemo-compatibility | Hemolysis | ISO 10993-4 | No significant differences between the test article extract and negative control article results. The test article is considered non-hemolytic. | Acceptance criteria met |
| Partial Thromboplastin Time | - | Clotting times are similar to the negative control and the reference material (HDPE) indicating the device materials are not an activator of the intrinsic coagulation pathway. | Acceptance criteria met | |
| Platelet and Leukocyte Count | - | Test article does not adversely affect the platelet and leukocyte components of the blood compared to the reference material. | Acceptance criteria met | |
| Complement Activation C3a and SC5b-9 Assay | - | Levels of C3a and SC5b-9 are comparable and less than the positive control. | Acceptance criteria met | |
| Thrombosis | - | Thrombo-resistance properties are acceptable in clinical use. | Acceptance criteria met | |
| Genotoxicity | Bacterial Mutagenicity Test | ISO 10993-3 | Test article is considered non-mutagenic. | Acceptance criteria met |
| In-vitro Mouse Lymphoma Assay | - | Test article is considered non-mutagenic. | Acceptance criteria met | |
| In-vivo Mouse Micronucleus Assay | - | Test article is considered non-mutagenic. | Acceptance criteria met |
Performance Bench Testing:
| Test Description | Method | Acceptance Criteria | Conclusion |
|---|---|---|---|
| Delivery Force | Peak delivery force was measured through a representative tortuous anatomical model. | Stent must be below delivery force specification. | Acceptance criteria met |
| Re-sheathing Force | Retrieval force was measured through a representative tortuous anatomical model. | Stent must be below re-sheathing force specification. | Acceptance criteria met |
| Total System Length | Total system length was measured from the proximal tip of the push-wire to the distal-most tip of the finger marker coils. | System length must meet product specification. | Acceptance criteria met |
| Fluorosafe Marker Length | The total length of the fluorosafe marker was measured. | Fluorosafe marker length must meet product specification. | Acceptance criteria met |
| Multiple Re-sheathing Durability | Samples were evaluated on their ability to withstand delivery and withdrawal forces in a representative tortuous model beyond the recommended number of passes and re-sheathings allowed per the Instructions for Use (IFU). | Device must reliably deploy and resheath up to four times. | Acceptance criteria met |
| Body Marker Tensile | Body Marker tensile strength testing is performed to verify the strength of the laser weld of the Platinum/Iridium marker coil to the Nitinol distal finger of the device. | Body marker should be greater than or equal to existing tensile strength specification. | Acceptance criteria met |
| Body Marker Radiopacity | Verification analysis of body markers. | The radiopaque body markers must be visible using standard catheter laboratory equipment. | Acceptance criteria met |
| Proximal Marker to Distal Marker | The length of the laser cut and electro-polished stents are measured 100% in process. | Length of stent must meet all inspection criteria. | Acceptance criteria met |
| Torque Response | Samples were evaluated to determine the number of turns required to produce 1 rotation of the distal tip of the device. | Device turns must be less than or equal to torque response criteria. | Acceptance criteria met |
| Torque Strength | Samples were evaluated to determine the number of turns required to break the device in a representative tortuous model. | Device turns must be greater than torque strength criteria. | Acceptance criteria met |
| System Tensile | Samples were evaluated to determine the tensile strength of the full system. | Devices must be greater than or equal to the system tensile criteria. | Acceptance criteria met |
| Af Temperature | In-process 100% tracking of heat set parameters used to set final Af. | Temperature should be less than or equal to existing Af temperature specification. | Acceptance criteria met |
| Radial Force | The radial force was measured 100% in-process. | Stent must be within existing radial force specification. | Acceptance criteria met |
| Kink Resistance | Kink resistance testing verified the device flexibility across various levels of tortuosity. | Device must be able to maintain vessel wall apposition at a minimum radius bend. | Acceptance criteria met |
| Clot Removal in a Simulated Neurovascular Model | Both hard and soft clot retrieval success was evaluated in an in vitro tortuous anatomical model. | Overall success rate of the device (usability and effectiveness) must be equal to or better than the predicate* device. | Acceptance criteria met |
| Particulate Under Simulated Use Conditions | 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> (Same as method, implying conforming to USP<788> limits). | Acceptance criteria met |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Clinical Study (SWIFT PRIME):
- Total Randomized Subjects: 196 (98 in each group: IV t-PA alone vs. IV t-PA + Solitaire)
- Analysis Cohort (after exclusions): 161 subjects (84 in the IV t-PA + Solitaire™ group and 77 with IV t-PA only). Further refined to 144 subjects for primary and secondary efficacy endpoints after additional exclusions.
- Data Provenance: Global, multicenter. The study was a prospective, randomized, open, blinded endpoint (PROBE) clinical study (IDE G120142).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The document does not explicitly state the exact number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth for the clinical study's endpoints. However, it does mention:
- Blinded evaluation of modified Rankin Scale (mRS) for neurological disability outcomes. This implies that the mRS scores, which serve as a critical component of the ground truth for effectiveness, were assessed by experts who were blinded to the treatment arm.
- Clinical Events Committee adjudication for adverse events. This indicates a panel of experts reviewed and categorized adverse events.
- Core Laboratory assessed data for symptomatic ICH, infarct volume, and reperfusion ratio. This suggests specialized facilities with expert staff were responsible for these assessments.
While the specific count and detailed qualifications are not provided, the involvement of blinded evaluators, a Clinical Events Committee, and a Core Laboratory indicates that ground truth was established through expert assessment according to established protocols.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document mentions "Clinical Events Committee adjudication" for adverse events. While it doesn't specify a 2+1 or 3+1 method, "adjudication" implies a process where a committee of experts reviews and resolves discrepancies in event classification or assessment. It suggests a structured review by multiple parties, but the exact number of reviewers per case or tie-breaking mechanism is 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
There is no indication that a multi-reader multi-case (MRMC) comparative effectiveness study was done, or any mention of AI assistance. This study compared a medical device (Solitaire™ 2 Revascularization Device) with or without IV t-PA, not an AI system.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
No, a standalone algorithm performance study was not done, as this document is about a mechanical thrombectomy device, not an algorithm or AI.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical study was established using a combination of:
- Clinical Outcomes Data: Primarily, the 90-day global disability assessed via the blinded evaluation of Modified Rankin Scale (mRS). This is a widely accepted functional outcome scale often based on trained interviewer assessment.
- Imaging-based Assessments: Volume of cerebral infarction, reperfusion ratio, and arterial revascularization (TICI 2b or 3) assessed by a Core Laboratory. This implies expert interpretation of medical images.
- Adjudicated Adverse Events: Reviewed and categorized by a Clinical Events Committee.
8. The sample size for the training set
The document does not describe the development or training of an algorithm or AI. Therefore, there is no training set sample size mentioned. The clinical study (SWIFT PRIME) is a comparative effectiveness study for a medical device in patients.
9. How the ground truth for the training set was established
As there is no training set for an algorithm or AI described in the document, this question is not applicable.
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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 (800) 638-2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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)
-
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.
-
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)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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| 510(K) Summary | K162539 |
|---|---|
| 510(k) Owner:Contact Person: | Micro Therapeutics, Inc. d/b/a ev3 Neurovascular9775 Toledo WayIrvine, CA 92618Establishment Registration No. 2029214Jennifer CorreaSenior Specialist, Regulatory AffairsTelephone: (949) 297-9563E-mail: jennifer.l.correa@medtronic.com |
| Date SummaryPrepared:Trade Name ofDevice: | October 28, 2016Solitaire™ 2 Revascularization Device |
| Common Name ofDevice:Classification ofDevice: | Neurovascular Mechanical Thrombectomy Device for AcuteIschemic Stroke TreatmentClass II, 21 CFR 882.5600, 21 CFR 870.1250 |
| Product Code:Predicate Devices: | POL, NRYTrevo XP ProVue RetrieverDEN150049 |
| Clinical Data: | A global, multicenter, two-arm, prospective, randomized, open,blinded endpoint (PROBE) clinical study (SWIFT PRIME, IDEG120142) comparing neurological disability outcomes (defined bymRS) in Acute Ischemic Stroke (AIS) patients who are treatedwith either IV t-PA alone or IV t-PA in combination with Solitairemechanical thrombectomy intervention was performed. The datafrom the SWIFT PRIME study in comparison to the data from theTrevo clinical study demonstrate that the use of the SolitaireRevascularization device is safe and is substantially equivalent tothe predicate device for reducing disability in patients with apersistent proximal anterior circulation large vessel occlusion andsmaller core infarcts who have first received intravenous tissueplasminogen activator (IV t-PA) for acute ischemic stroke. |
| Conclusion: | The Solitaire™ 2 Revascularization Device is substantiallyequivalent to the Trevo XP ProVue Retriever based on comparisonof the Trevo clinical data to the SWIFT PRIME clinical study data.In addition, the Solitaire™ 2 Revascularization Device issubstantially equivalent to the Trevo XP ProVue Retriever in termsof fundamental scientific technology, including similarities indesign, 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:
-
- 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.
-
- 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 DeviceTrevo XP ProVueRetriever (DEN150049) | Subject DeviceSolitaire™ 2Revascularization Device | Rationale forDifference(if applicable) | |
|---|---|---|---|
| Indicationfor Use | The Trevo ProVue andXP ProVue Retrievers areintended to restore bloodflow in the neurovascularby removing thrombus fortreatment of acuteischemic stroke to reducedisability in patients with | 1. The Solitaire™ 2Revascularization Deviceis indicated for use torestore blood flow in theneurovasculature byremoving thrombus for thetreatment of acute ischemicstroke to reduce disability | Indication 1:N/A, same aspredicatedeviceIndication 2:N/A, same asreference |
| Predicate DeviceTrevo XP ProVue | Subject DeviceSolitaire™ 2 | Rationale forDifference(if applicable) | |
| Retriever (DEN150049) | Revascularization Device | ||
| a persistent, proximalanterior circulation, largevessel occlusion, andsmall core infarcts whohave first receivedintravenous tissueplasminogen activator (IVt-PA). Endovasculartherapy with the deviceshould start within 6 hoursof symptom onset. | in patients with apersistent, proximalanterior circulation, largevessel occlusion, andsmaller core infarcts whohave first receivedintravenous tissueplasminogen activator (IVt-PA). Endovasculartherapy with the deviceshould be started within 6hours of symptom onset.The Solitaire™Revascularization Deviceis indicated to restoreblood flow by removingthrombus from a largeintracranial vessel inpatients experiencingischemic stroke within 8hours of symptom onset.Patients who are ineligiblefor IV t-PA or who fail IVt-PA therapy are candidatesfor treatment. | predicatedevice(K113455,K123378 andK141491cleared underproduct codeNRY) | |
| Principles ofOperation | The device is used in theneurovasculature torestore blood flow fortreatment of acuteischemic stroke | Same | N/A |
| Dimensions and Materials | |||
| DeviceSize(s) | 3x20 mm4x20 mm4x30 mm6x25 mm | 4x15 mm4x20 mm4x40 mm6x20 mm6x30 mm | Both devicesare offered in avariety of sizesdesigned to beused in theneurovasculatureto restoreblood flow. |
| DeviceMaterials | Core Wire Material:Nitinol (nickel titaniumalloy) | Stent: NitinolPushwire: NitinolMarkers: 90% Platinum/10% Iridium | Both devicematerials arebiocompatible, |
| Predicate DeviceTrevo XP ProVueRetriever (DEN150049) | Subject DeviceSolitaire™ 2Revascularization Device | Rationale forDifference(if applicable) | |
| Distal Shaped SectionMaterial: NitinolCoil Material Distal toDistalShaped Section :Platinum/TungstenShaped SectionRadiopaque Wire:Platinum/TungstenCoil Material Proximal toShaped Section: 304Stainless SteelSolder: Gold/TinHydrophilic Coating:Sodium hyaluronatemixture | 10% IridiumPush-wire shrink Tubing:PTFEIntroducer Sheath:PTFE/Grilamid | designed to beused in theneurovasculature, and containradiopaquematerials forvisualization. | |
| Sterilization and Packaging | |||
| PackagingMaterials | Polyethylene Hoop,polycarbonate mountingcard, Tyvek/Film Pouch,HDPE Tubing Clips,Chipboard carton | Stored within dispensercoil, Tyvek pouch, andshipping carton. | Packagingmaterials aresimilar andtypical formedicaldevices. Bothpackagingconfigurationsmaintain asterility of thedevice throughthe shelf life. |
| SterilizationMethod | Ethylene Oxide | Same | N/A |
| HowSupplied | 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:
| TestCategory | TestDescription | Method | Acceptance Criteria | Conclusion |
|---|---|---|---|---|
| Cytotoxicity | L929 MTTCytotoxicity | ISO 10993-5 | Viability is ≥70%. | Acceptance criteriamet |
| Sensitization | Guinea PigMaximizationSensitization | ISO 10993-10 | Test article does notelicit a sensitizationresponse. | Acceptance criteriamet |
| Irritation | IntracutaneousIrritation Test | ISO 10993-10 | Differences in themean test and controlscores of the extractdermal observationsare < 1.0. | Acceptance criteriamet |
| AcuteSystemicToxicity | Acute SystemicInjection Test | ISO 10993-11 | No abnormal clinicalsigns and weight lossin excess of 10%. | Acceptance criteriamet |
| MaterialsMediatedRabbit Pyrogen | Temperature rise≥0.5°C | |||
| TestCategory | TestDescription | Method | Acceptance Criteria | Conclusion |
| Hemo-compatibility | Hemolysis | ISO 10993-4 | No significantdifferences betweenthe test article extractand negative controlarticle results. The testarticle is considerednon-hemolytic | Acceptance criteriamet |
| PartialThromboplastinTime | Clotting times aresimilar to the negativecontrol and thereference material(HDPE) indicating thedevice materials arenot an activator of theintrinsic coagulationpathway. | |||
| Platelet andLeukocyteCount | Test article does notadversely affect theplatelet and leukocytecomponents of theblood compared to thereference material. | |||
| ComplementActivation C3aand SC5b-9Assay | Levels of C3a andSC5b-9 arecomparable and lessthan the positivecontrol. | |||
| Thrombosis | Thrombo-resistanceproperties areacceptable in clinicaluse. | |||
| Genotoxicity | BacterialMutagenicityTest | ISO 10993-3 | Test article isconsidered non-mutagenic | Acceptance criteriamet |
| In-vitro MouseLymphomaAssay | Test article isconsidered non-mutagenic | |||
| In-vivo MouseMicronucleusAssay | Test article isconsidered non-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 | AcceptanceCriteria | Conclusion |
|---|---|---|---|
| Delivery Force | Peak delivery force wasmeasured through arepresentative tortuousanatomical model. | Stent must be belowdelivery forcespecification. | Acceptance criteria met |
| Re-sheathingForce | Retrieval force wasmeasured through arepresentative tortuousanatomical model. | Stent must be belowre-sheathing forcespecification. | Acceptance criteria met |
| Total SystemLength | Total system length wasmeasured from theproximal tip of the push-wire to the distal-most tipof the finger marker coils. | System length mustmeet productspecification. | Acceptance criteria met |
| FluorosafeMarker Length | The total lengthof the fluorosafemarker was measured. | Fluorosafe markerlength must meetproductspecification. | Acceptance criteria met |
| Multiple Re-sheathingDurability | Samples were evaluatedon their ability towithstand delivery andwithdrawal forces in arepresentative tortuousmodel beyond therecommended number ofpasses and re-sheathingsallowed per theInstructions for Use(IFU). | Device must reliablydeploy and resheathup to four times. | Acceptance criteria met |
| Body MarkerTensile | Body Marker tensilestrength testing isperformed to verify thestrength of the laser weldof the Platinum/Iridiummarkercoil to the Nitinoldistal finger of the device. | Body marker shouldbe greater than orequal to existingtensile strengthspecification. | Acceptance criteria met |
| Body MarkerRadiopacity | Verification analysis ofbody markers. | The radiopaquebody markers mustbe visible usingstandard catheterlaboratoryequipment | Acceptance criteria met |
| Test Description | Method | AcceptanceCriteria | Conclusion |
| Proximal Markerto Distal Marker | The length of the laser cutand electro-polishedstents are measured 100%in process. | Length of stent mustmeet all inspectioncriteria | Acceptance criteria met |
| Torque Response | Samples were evaluatedto determine the numberof turns required toproduce 1 rotation of thedistal tip of the device. | Device turns mustbe less than or equalto torque responsecriteria | Acceptance criteria met |
| Torque Strength | Samples were evaluatedto determine the numberof turns required tobreak the device in arepresentative tortuousmodel. | Device turns mustbe greater thantorque strengthcriteria | Acceptance criteria met |
| System Tensile | Samples were evaluatedto determine the tensilestrength of the fullsystem. | Devices must begreater than or equalto the system tensilecriteria | Acceptance criteria met |
| Af Temperature | In-process 100% trackingof heat set parametersused to set final Af | Temperature shouldbe less than or equalto existing Aftemperaturespecification. | Acceptance criteria met |
| Radial Force | The radial force wasmeasured 100% in-process. | Stent must be withinexisting radial forcespecification. | Acceptance criteria met |
| Kink Resistance | Kink resistance testingverified the deviceflexibility across variouslevels of tortuosity. | Device must be ableto maintain vesselwall apposition at aminimum radiusbend. | Acceptance criteria met |
| Clot Removal ina SimulatedNeurovascularModel | Both hard and soft clotretrieval success wasevaluated in an in vitrotortuous anatomicalmodel. | Overall success rateof the device(usability andeffectiveness) mustbe equal to or betterthan the predicate*device. | Acceptance criteria met |
| Test Description | Method | Acceptance Criteria | Conclusion |
| Particulate Under Simulated Use Conditions | 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(no.) |
| Thrombolysis in Cerebral Infarction (TICI) > 1 flow in the intracranial internal carotid artery, M1segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to theSolitaire™ FR Device. | 28 |
| MRI- or CT-assessed core infarct lesion greater than 50 cc; severe hypoperfusion lesion (Tmax>10secslesion 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 middlecerebral 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 ofsigns/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 earlyischemic 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 formechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/largeinfarct 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(no.) |
| arteriovenous malformation. | |
| CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion requiring stentingat 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 devicefrom 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 (90minutes) 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 postrandomization. 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**Per Core Laboratory assessed data |
| Safety Endpoints, RAPID Imaging Requirement Subgroup(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(0.35-2.77) | |
| Symptomatic ICH at 27 hours** | 0.0% (0/30) | 0.0% (0/28) | NA | |
| NA denotes not applicable*Per Clinical Events Committee adjudication**Per Core Laboratory assessed dataPatients enrolled under RAPID were excluded based on the following:a) MRI- or CT-assessed core infarct lesion greater than 50 cc; orb) 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(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 EfficacyEndpoint | IV t-PA Only* | IV t-PA +Solitaire | Odds Ratio/Difference[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 (mRS0-2) 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 the IV t-PA only group withdrew consent 27 hours post randomization. No secondaryclinical efficacy endpoints were available for this subject. | ||||
| ** These p-values are for informative purposes only. Based on the pre-defined hierarchical testing of thesecondary endpoints, these particular endpoints were not achieved. |
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| Secondary Technical Efficacy Endpoints (Analysis Cohort) | |||
|---|---|---|---|
| Secondary Technical EfficacyEndpoint | IV t-PA Only | IV t-PA + Solitaire | Difference[95% CI] |
| Infarct Volume at 27 hours Post-Randomization (cc)** | |||
| N | 77 | 66 | N/A* |
| Mean ± SD | 68.9 ± 75.5 | 51.1 ± 86.1 | N/A* |
| Median | 46.5 | 19.2 | N/A* |
| (min, max) | (0.0, 406.6) | (0.0,530.5) | N/A* |
| Reperfusion Ratio at 27 hours Post-Randomization ** | |||
| N | 44 | 45 | N/A* |
| Mean ± SD | 61.6 ± 56.1 | 87.9 ± 37.2 | N/A* |
| Median | 84.0 | 100.0 | N/A* |
| (min, max) | (-200, 100) | (-94.0,100.0) | N/A* |
| TICI 2b-3 Following Device Use ** | |||
| % (n/N) | N/A | 90.2% (55/61) | N/A |
| *Wilcoxon rank-sum test due to non-normality of data. | |||
| ** Per Core Laboratory assessed data |
Important Safety Results
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
|---|---|---|---|
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| TOTAL Adverse Events(AE) | 93.5% (72/77) [416] | 91.7% (77/84) [449] | 92.5% (149/161)[865] |
| Blood and LymphaticSystem Disorders | 6.5% (5/77) [5] | 13.1% (11/84) [11] | 9.9% (16/161) [16] |
| Anaemia | 3.9% (3/77) [3] | 6.0% (5/84) [5] | 5.0% (8/161) [8] |
| Haemorrhagic Anaemia | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Leukocytosis | 1.3% (1/77) [1] | 7.1% (6/84) [6] | 4.3% (7/161) [7] |
| Cardiac Disorders | 26.0% (20/77) [23] | 31.0% (26/84) [31] | 28.6% (46/161) [54] |
| Atrial Fibrillation | 3.9% (3/77) [3] | 6.0% (5/84) [5] | 5.0% (8/161) [8] |
| Atrial Flutter | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Atrial Thrombosis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Bradycardia | 7.8% (6/77) [6] | 4.8% (4/84) [4] | 6.2% (10/161) [10] |
| Cardiac Arrest | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Cardiac Failure | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Cardiac Failure Congestive | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Intracardiac thrombus | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Ischaemiccardiomyopathy | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Myocardial infarction | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Palpitations | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Sick sinus syndrome | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Sinus arrest | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Supraventriculartachycardia | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Tachycardia | 11.7% (9/77) [9] | 8.3% (7/84) [7] | 9.9% (16/161) [16] |
| Ventriculartachycardia | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Ear and LabyrinthDisorders | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Vertigo | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Endocrine disorders | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Hypothyroidism | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Eye disorders | 1.3% (1/77) [1] | 4.8% (4/84) [4] | 3.1% (5/161) [5] |
| Conjunctivalhaemorrhage | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Eye haemorrhage | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Optic neuropathy | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Photopsia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Visual impairment | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| GastrointestinalDisorders | 37.7% (29/77) [40] | 33.3% (28/84) [43] | 35.4% (57/161) [83] |
| Abdominal pain | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Abdominal pain lower | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Abdominal pain upper | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Constipation | 15.6% (12/77) [13] | 15.5% (13/84) [13] | 15.5% (25/161) [26] |
| Diarrhea | 3.9% (3/77) [3] | 1.2% (1/84) [1] | 2.5% (4/161) [4] |
| Dyspepsia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Dysphagia | 9.1% (7/77) [7] | 7.1% (6/84) [6] | 8.1% (13/161) [13] |
| Faecal incontinence | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Gastritis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Gastrooesophagealreflux disease | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Haematemesis | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Haemorrhoidalhaemorrhage | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Ileus | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Intestinal ischaemia | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Lower gastrointestinalhaemorrhage | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Melaena | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Mouth haemorrhage | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Nausea | 5.2% (4/77) [4] | 8.3% (7/84) [7] | 6.8% (11/161) [11] |
| Oesophageal stenosis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Oral pain | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Retroperitonealhaematoma | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Salivaryhypersecretion | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Vomiting | 3.9% (3/77) [3] | 4.8% (4/84) [4] | 4.3% (7/161) [7] |
| General Disorders andAdministration SiteConditions | 18.2% (14/77) [16] | 25.0% (21/84) [24] | 21.7% (35/161) [40] |
| Application sitepruritus | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Catheter sitehaematoma | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Catheter sitehaemorrhage | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Catheter siteinduration | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Catheter siteinflammation | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Cyst | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Discomfort | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Extravasation | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Fatigue | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Influenza like illness | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Local swelling | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Oedema peripheral | 5.2% (4/77) [4] | 0.0% (0/84) [0] | 2.5% (4/161) [4] |
| Pain | 2.6% (2/77) [2] | 4.8% (4/84) [4] | 3.7% (6/161) [6] |
| Pyrexia | 6.5% (5/77) [5] | 8.3% (7/84) [7] | 7.5% (12/161) [12] |
| Systemic inflammatoryresponse syndrome | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Temperatureintolerance | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| HepatobiliaryDisorders | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Cholecystitis acute | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Cholestasis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Immune SystemDisorders | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Drug hypersensitivity | 1.3% (1/77) [1] | 2.4% (2/84) [2] | 1.9% (3/161) [3] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Immune systemdisorder | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Infections andInfestations | 45.5% (35/77) [53] | 38.1% (32/84) [42] | 41.6% (67/161) [95] |
| Acute sinusitis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Bacterial diseasecarrier | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Bronchitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Candida infection | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Cellulitis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Clostridium colitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Conjunctivitis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Cystitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Endocarditis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Fungal infection | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Fungal skin infection | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Gastroenteritis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Genital infectionfungal | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Hand-foot-and-mouthdisease | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Herpes zoster | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Oral candidiasis | 3.9% (3/77) [3] | 2.4% (2/84) [2] | 3.1% (5/161) [5] |
| Parotitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Pneumonia | 7.8% (6/77) [6] | 9.5% (8/84) [8] | 8.7% (14/161) [14] |
| Respiratory syncytialvirus infection | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Respiratory tractinfection | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Rhinitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Sepsis | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Septic shock | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Sinusitis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Skin candida | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Urinary tract infection | 31.2% (24/77) [28] | 20.2% (17/84) [19] | 25.5% (41/161) [47] |
| Wound infection | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Injury, Poisoning andProceduralComplications | 10.4% (8/77) [8] | 10.7% (9/84) [11] | 10.6% (17/161) [19] |
| Ankle fracture | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Carotid arteryrestenosis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Fall | 3.9% (3/77) [3] | 3.6% (3/84) [3] | 3.7% (6/161) [7] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Joint dislocation | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Post proceduralhaematoma | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Procedural pain | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Procedural vomiting | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Pseudomeningocele | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Subdural haematoma | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Tracheal injury | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Vascularpseudoaneurysm | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Investigations | 14.3% (11/77) [12] | 17.9% (15/84) [19] | 16.1% (26/161) [31] |
| Biopsy salivary gland | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Blood creatinephosphokinaseincreased | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Blood creatinineincreased | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Blood glucoseincreased | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Blood magnesiumabnormal | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Blood pressureincreased | 7.8% (6/77) [6] | 9.5% (8/84) [9] | 8.7% (14/161) [15] |
| Blood urea increased | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Electrocardiogram STsegment depression | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Glycosylatedhaemoglobin increased | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Transaminasesincreased | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Troponin increased | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Urine output decreased | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Metabolism andNutrition Disorders | 40.3% (31/77) [40] | 33.3% (28/84) [42] | 36.6% (59/161) [82] |
| Decreased appetite | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Dehydration | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Diabetes mellitus | 3.9% (3/77) [3] | 0.0% (0/84) [0] | 1.9% (3/161) [3] |
| Dyslipidaemia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Electrolyte imbalance | 7.8% (6/77) [6] | 4.8% (4/84) [4] | 6.2% (10/161) [10] |
| Fluid retention | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Glucose toleranceimpaired | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Gout | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Hypercholesterolaemia | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Hyperglycaemia | 5.2% (4/77) [4] | 4.8% (4/84) [4] | 5.0% (8/161) [8] |
| Hyperlipidaemia | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Hypernatraemia | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Hypervolaemia | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Hypocalcaemia | 2.6% (2/77) [2] | 3.6% (3/84) [3] | 3.1% (5/161) [5] |
| Hypokalaemia | 5.2% (4/77) [4] | 15.5% (13/84) [13] | 10.6% (17/161) [17] |
| Hypomagnesaemia | 5.2% (4/77) [4] | 6.0% (5/84) [5] | 5.6% (9/161) [9] |
| Hyponatraemia | 2.6% (2/77) [2] | 3.6% (3/84) [3] | 3.1% (5/161) [5] |
| Hypophosphataemia | 3.9% (3/77) [3] | 1.2% (1/84) [1] | 2.5% (4/161) [4] |
| Hypoproteinaemia | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Vitamin D deficiency | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Musculoskeletal andConnective TissueDisorders | 20.8% (16/77) [20] | 15.5% (13/84) [15] | 18.0% (29/161) [35] |
| Arthralgia | 6.5% (5/77) [6] | 3.6% (3/84) [4] | 5.0% (8/161) [10] |
| Back pain | 3.9% (3/77) [3] | 3.6% (3/84) [3] | 3.7% (6/161) [6] |
| Groin pain | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Joint swelling | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Muscle spasms | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Musculoskeletal chestpain | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Musculoskeletal pain | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Neck pain | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Osteoarthritis | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Pain in extremity | 5.2% (4/77) [4] | 3.6% (3/84) [3] | 4.3% (7/161) [7] |
| Neoplasms Benign,Malignant andUnspecified (inclcysts and polyps) | 1.3% (1/77) [2] | 0.0% (0/84) [0] | 0.6% (1/161) [2] |
| Appendix cancer | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Haemangioma of liver | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Nervous SystemDisorders | 66.2% (51/77) [90] | 51.2% (43/84) [83] | 58.4% (94/161) [173] |
| Brain oedema | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Carotid arterydissection | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Carotid arterythrombosis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Cerebral arteryembolism | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Cerebral haemorrhage | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Cerebralvasoconstriction | 0.0% (0/77) [0] | 13.1% (11/84) [11] | 6.8% (11/161) [11] |
| Complex regional painsyndrome | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Convulsion | 6.5% (5/77) [5] | 1.2% (1/84) [1] | 3.7% (6/161) [6] |
| Dizziness | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Encephalopathy | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Haemorrhagictransformation stroke | 39.0% (30/77) [31] | 29.8% (25/84) [26] | 34.2% (55/161) [57] |
| Headache | 15.6% (12/77) [12] | 16.7% (14/84) [15] | 16.1% (26/161) [27] |
| Hemianopia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Horner's syndrome | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Hydrocephalus | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Hypertonia | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Intracranial pressureincreased | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Intraventricularhaemorrhage | 3.9% (3/77) [3] | 4.8% (4/84) [4] | 4.3% (7/161) [7] |
| Ischaemic stroke | 9.1% (7/77) [7] | 3.6% (3/84) [4] | 6.2% (10/161) [11] |
| Lethargy | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Migraine | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Monoparesis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Muscle spasticity | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Neuralgia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Paraesthesia | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Partial seizures | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Somnolence | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Status epilepticus | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Stroke in evolution | 10.4% (8/77) [8] | 6.0% (5/84) [5] | 8.1% (13/161) [13] |
| Subarachnoidhaemorrhage | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Syncope | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Transient ischaemicattack | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Tremor | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Psychiatric Disorders | 32.5% (25/77) [29] | 33.3% (28/84) [35] | 32.9% (53/161) [64] |
| Acute psychosis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Agitation | 10.4% (8/77) [8] | 7.1% (6/84) [6] | 8.7% (14/161) [14] |
| Alcohol withdrawalsyndrome | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Anxiety | 3.9% (3/77) [3] | 2.4% (2/84) [3] | 3.1% (5/161) [6] |
| Confusional state | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Depressed mood | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Depression | 14.3% (11/77) [11] | 15.5% (13/84) [13] | 14.9% (24/161) [24] |
| Depressive symptom | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Insomnia | 5.2% (4/77) [4] | 8.3% (7/84) [7] | 6.8% (11/161) [11] |
| Mental status changes | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Restlessness | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Sleep disorder | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Stress | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Renal and UrinaryDisorders | 19.5% (15/77) [16] | 16.7% (14/84) [16] | 18.0% (29/161) [32] |
| Dysuria | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Haematuria | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Hypertonic bladder | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Oliguria | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Polyuria | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Renal failure | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Renal failure acute | 3.9% (3/77) [3] | 4.8% (4/84) [4] | 4.3% (7/161) [7] |
| Renal infarct | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Renal mass | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Urethral pain | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Urge incontinence | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Urinary retention | 3.9% (3/77) [3] | 8.3% (7/84) [7] | 6.2% (10/161) [10] |
| Reproductive Systemand Breast Disorders | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Benign prostatichyperplasia | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Respiratory, Thoracicand MediastinalDisorders | 29.9% (23/77) [27] | 26.2% (22/84) [32] | 28.0% (45/161) [59] |
| Acute respiratoryfailure | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Aspiration | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Atelectasis | 2.6% (2/77) [2] | 3.6% (3/84) [3] | 3.1% (5/161) [5] |
| Chronic obstructivepulmonary disease | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Cough | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Dyspnoea | 1.3% (1/77) [1] | 2.4% (2/84) [2] | 1.9% (3/161) [3] |
| Haemoptysis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Hiccups | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| Hypoxia | 1.3% (1/77) [1] | 2.4% (2/84) [2] | 1.9% (3/161) [3] |
| Oropharyngeal pain | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Pleural effusion | 1.3% (1/77) [1] | 4.8% (4/84) [4] | 3.1% (5/161) [5] |
| CEC Adjudicated Adverse Events (Analysis Cohort) | |||
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| Pneumonia aspiration | 6.5% (5/77) [5] | 7.1% (6/84) [6] | 6.8% (11/161) [11] |
| Pulmonary congestion | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Pulmonary embolism | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Pulmonary oedema | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Respiratory arrest | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Respiratory distress | 5.2% (4/77) [4] | 1.2% (1/84) [1] | 3.1% (5/161) [5] |
| Respiratory failure | 2.6% (2/77) [2] | 3.6% (3/84) [3] | 3.1% (5/161) [5] |
| Sleep apnoeasyndrome | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Wheezing | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Skin andSubcutaneous TissueDisorders | 13.0% (10/77) [10] | 11.9% (10/84) [10] | 12.4% (20/161) [20] |
| Decubitus ulcer | 0.0% (0/77) [0] | 4.8% (4/84) [4] | 2.5% (4/161) [4] |
| Dermatitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Dermatitis contact | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Ecchymosis | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Erythema | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| Intertrigo | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Pruritus | 1.3% (1/77) [1] | 1.2% (1/84) [1] | 1.2% (2/161) [2] |
| Rash | 1.3% (1/77) [1] | 2.4% (2/84) [2] | 1.9% (3/161) [3] |
| Rash erythematous | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Skin lesion | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Surgical and MedicalProcedures | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Gastrostomy tuberemoval | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Vascular Disorders | 20.8% (16/77) [18] | 25.0% (21/84) [26] | 23.0% (37/161) [44] |
| Aortic aneurysm | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Arterial rupture | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Deep vein thrombosis | 7.8% (6/77) [6] | 6.0% (5/84) [5] | 6.8% (11/161) [11] |
| Femoral arteryembolism | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Haematoma | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Hypertension | 3.9% (3/77) [3] | 6.0% (5/84) [5] | 5.0% (8/161) [8] |
| Hypotension | 5.2% (4/77) [4] | 6.0% (5/84) [5] | 5.6% (9/161) [9] |
| Lymphoedema | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Phlebitis | 1.3% (1/77) [1] | 0.0% (0/84) [0] | 0.6% (1/161) [1] |
| Thrombophlebitis | 1.3% (1/77) [1] | 3.6% (3/84) [3] | 2.5% (4/161) [4] |
| Thrombosis | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Vascular occlusion | 0.0% (0/77) [0] | 1.2% (1/84) [1] | 0.6% (1/161) [1] |
| Vasospasm | 0.0% (0/77) [0] | 3.6% (3/84) [3] | 1.9% (3/161) [3] |
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| CEC Adjudicated Serious Adverse Events (Analysis Cohort) | |||
|---|---|---|---|
| MedDRA PreferredTerm | IV t-PA Only | IV t-PA + Solitaire | All Enrolled |
| Units | % (pts/N) [AEs] | % (pts/N) [AEs] | % (pts/N) [AEs] |
| TOTAL Adverse Events(AE) | 33.8% (26/77) [54] | 31.0% (26/84) [44] | 32.3% (52/161) [98] |
| Blood and LymphaticSystem Disorders | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Anaemia | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Cardiac Disorders | 5.2% (4/77) [5] | 8.3% (7/84) [8] | 6.8% (11/161) [13] |
| Cardiac Arrest | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Intracardiac thrombus | 0.0% (0/77) [0] | 2.4% (2/84) [2] | 1.2% (2/161) [2] |
| Tachycardia | 2.6% (2/77) [2] | 0.0% (0/84) [0] | 1.2% (2/161) [2] |
| GastrointestinalDisorders | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Infections andInfestations | 7.8% (6/77) [7] | 3.6% (3/84) [3] | 5.6% (9/161) [10] |
| Sepsis | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Injury, Poisoning andProceduralComplications | 3.9% (3/77) [3] | 3.6% (3/84) [3] | 3.7% (6/161) [6] |
| Nervous SystemDisorders | 20.8% (16/77) [21] | 11.9% (10/84) [12] | 16.1% (26/161) [33] |
| Brain oedema | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Haemorrhagictransformation stroke | 5.2% (4/77) [4] | 0.0% (0/84) [0] | 2.5% (4/161) [4] |
| Ischaemic stroke | 6.5% (5/77) [5] | 2.4% (2/84) [3] | 4.3% (7/161) [8] |
| Stroke in evolution | 10.4% (8/77) [8] | 4.8% (4/84) [4] | 7.5% (12/161) [12] |
| Renal and UrinaryDisorders | 3.9% (3/77) [3] | 3.6% (3/84) [3] | 3.7% (6/161) [6] |
| Renal failure acute | 1.3% (1/77) [1] | 2.4% (2/84) [2] | 1.9% (3/161) [3] |
| Respiratory, Thoracicand MediastinalDisorders | 9.1% (7/77) [8] | 7.1% (6/84) [7] | 8.1% (13/161) [15] |
| Respiratory distress | 3.9% (3/77) [3] | 0.0% (0/84) [0] | 1.9% (3/161) [3] |
| Respiratory failure | 2.6% (2/77) [2] | 2.4% (2/84) [2] | 2.5% (4/161) [4] |
| Vascular Disorders | 5.2% (4/77) [4] | 3.6% (3/84) [3] | 4.3% (7/161) [7] |
| Deep vein thrombosis | 2.6% (2/77) [2] | 1.2% (1/84) [1] | 1.9% (3/161) [3] |
| CEC-Adjudicated Device-Related Adverse Events | |||
|---|---|---|---|
| Terminology | Severity | Outcome | Neurological deteriorationor death |
| Subarachnoid Contrast | Mild | Recovered without sequelae | None |
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| CEC-Adjudicated Device-Related Adverse Events | |||
|---|---|---|---|
| Terminology | Severity | Outcome | Neurological deteriorationor death |
| Extravasation | |||
| Cerebral Vasospasm | Moderate | Recovered without sequelae | None |
| Intraventricular Hemorrhage | Mild | Recovered without sequelae | None |
| Subarachnoid Hemorrhage | Mild | Recovered without sequelae | None |
| Cerebral Vasospasm | Mild | Recovered without sequelae | None |
| Cerebral Vasospasm | Moderate | Recovered without sequelae | Brain edema 1 day post-ADE, alive through studyfollow-up |
Conclusion
In the SWIFT PRIME Study (IDE G120142) 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 than the IV t-PA only group (62.7% of patients versus 36.8% of patients, respectively).
The Trevo clinical data includes a clinical trial comparing 96 randomly selected patients treated with the Trevo device with IV t-PA and medical management of blood pressure and disability symptoms to 249 patients who had only t-PA and medical management. In this study, more patients treated with the Trevo device were functionally independent (ranging from no symptoms to slight disability) at three months after their stroke, compared to patients who were not treated with the Trevo device (29% of patients versus 19% of patients, respectively).
Both the SWIFT PRIME clinical study and the Trevo clinical data evaluated functional independence at 3 months using mRS 0-2 as a measurement for success. The data from the SWIFT PRIME Study demonstrates that the Solitaire™ 2 Revascularization device, in combination with IV t-PA, is substantially equivalent to the Trevo XP ProVue Retriever, in combination with IV t-PA, in 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).
§ 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.