(243 days)
No
The device description and performance studies focus on the mechanical aspects of the revascularization device and its clinical outcomes, with no mention of AI or ML.
Yes
The device is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemia, which directly relates to treating a medical condition and improving patient health.
No
This device is a revascularization device designed to restore blood flow by removing thrombus. It is a treatment device, not a diagnostic one.
No
The device description clearly states it is a physical device made of nitinol with radiopaque markers, designed for mechanical clot retrieval. It is not software.
Based on the provided information, the Solitaire™ Revascularization Device is not an In Vitro Diagnostic (IVD) device.
Here's why:
- Intended Use/Indications for Use: The device is intended for use within the body to physically remove thrombus and restore blood flow in the neurovasculature. This is a therapeutic intervention, not a diagnostic test performed on samples taken from the body.
- Device Description: The description details a physical device designed for mechanical clot retrieval. It does not describe reagents, test kits, or equipment used to analyze biological samples.
- Lack of IVD Characteristics: There is no mention of analyzing biological samples (blood, urine, tissue, etc.), detecting specific analytes, or providing diagnostic information based on laboratory testing.
The device is a medical device used for treatment, specifically for mechanical thrombectomy in stroke patients.
N/A
Intended Use / Indications for Use
-
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 (=2b post-procedure: 65.6% (21/32).
- Reperfusion and Recanalization 24 hours Post-Procedure (mITT):
- Reperfusion rate (%): Solitaire 92.6 ± 20.2 ([100.0]) vs. Control 48.7 ± 46.0 ([53.8]).
- Successful reperfusion (>90%): Solitaire 83.3% (20/24) vs. Control 17.5% (11/63).
- Complete recanalization at 24h: Solitaire 82.8% (24/29) vs. Control 19.2% (14/73).
- Imaging Endpoints (Infarct volume/growth) at 24h (ITT):
- Infarct volume (ml) at 24h: Solitaire 64.5 ± 67.2 ([35.0]) vs. Control 74.3 ± 80.7 ([41.0]).
- Infarct growth (ml) at 24h: Solitaire 48.6 ± 61.4 ([19.9]) vs. Control 57.6 ± 70.6 ([32.8]).
- Primary Safety Outcomes (ITT):
- All-cause mortality at 90 days: Solitaire 10.5% (4/38) vs. Control 25.6% (23/90).
- Symptomatic ICH: Solitaire 2.6% (1/38) vs. Control 4.4% (4/90).
- Procedural Complications (ITT - Solitaire group only): Vessel perforation: 2.6% (1/38). Other complications (arterial dissection, access site complication, embolization to previously unaffected territory) were 0.0%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Functional Independence (mRS 0-2) at 90 days: Solitaire 31.2% (10/32) vs. Control 15.3% (13/85)
- Early neurological improvement: Solitaire 31.6% (12/38) vs. Control 5.6% (5/89)
- TICI>=2b post-procedure: Solitaire 65.6% (21/32)
- Successful reperfusion (>90%): Solitaire 83.3% (20/24) vs. Control 17.5% (11/63)
- Complete recanalization at 24h: Solitaire 82.8% (24/29) vs. Control 19.2% (14/73)
- All-cause mortality: Solitaire 10.5% (4/38) vs. Control 25.6% (23/90)
- Symptomatic ICH: Solitaire 2.6% (1/38) vs. Control 4.4% (4/90)
- Vessel perforation: 2.6% (1/38)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Solitaire™ 2 Revascularization Device (K162539)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Solitaire™ Platinum Revascularization Device (K153071, K160641, K161879)
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
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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,
S
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 ( ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---------------------------------------------------------------------------------------------------------|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(K) Summary - K181807
| 510(k) Owner: | Micro Therapeutics, Inc. d/b/a ev3 Neurovascular
9775 Toledo Way
Irvine, CA 92618
Establishment Registration No. 2029214 |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Jennifer Correa
Program Manager, Regulatory Affairs
Telephone: (949) 297-5494
E-mail: jennifer.l.correa@medtronic.com |
| Alternate
Contact: | Helen Chow
Sr. Specialist, Regulatory Affairs
Telephone: (949) 297-5474
E-mail: helen.h.chow@medtronic.com |
| Date Summary
Prepared: | March 5, 2019 |
| Trade Name of
Device: | Solitaire™ 2 Revascularization Device,
Solitaire™ Platinum Revascularization Device
(Solitaire™ Revascularization Device) |
| Common Name of
Device: | Neurovascular Mechanical Thrombectomy Device for Acute
Ischemic Stroke Treatment |
| Classification of
Device: | 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:
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.
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:
-
- 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.
-
- 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™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 (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:
-
- Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke
-
- Age 18-90 years
-
- Baseline NIHSS is ≥ 6 and remains ≥ 6 immediately prior to randomization
-
- 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).
-
- Modified Rankin Scale (mRS) less than or equal to 2 prior to qualifying stroke (functionally independent for all ADLs)
-
- 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 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 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 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 400mg/dL (22.20 mmol) ●
- Baseline platelet count 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 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, was | ||
| available 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) | ||
|---|---|---|
| Solitaire | ||
| Mean ± SD (N) | ||
| [Median] (IQR) | ||
| or % (n/N) | Control | |
| Mean ± 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. Reperfusion | ||
| percentage and successful reperfusion were available on 24 of 32 subjects in the Solitaire group, and | ||
| 63 of 85 subjects in the control group. Complete recanalization was available on 29 of 32 subjects in | ||
| the 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* | Solitaire | |
| Mean ± 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 or | |
| transfusion (per site) | 0.0% (0/38) |
| Embolization to previously unaffected territory (per | |
| site) | 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.
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| (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 and | ||
| procedural 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 and | ||
| administration 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 and | ||
| administration 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 and | ||
| mediastinal 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 and | ||
| procedural 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.