Acute Ischemic Stroke
Conditions
Brief summary
The primary study objective is to determine if subjects experiencing an acute ischemic stroke due to large vessel occlusion, treated with combined IV t-PA and Solitaire Revascularization Device within 6 hours of symptom onset have less stroke-related neurological disability (mRS) than those subjects treated with IV t-PA alone
Interventions
Standard therapy with Intravenous (IV) recombinant human tissue plasminogen activator (rtPA)
DEVICESolitaire revascularization device
Clot retrieval with the Solitaire revascularization device after patients have received standard therapy with intravenous tissue plasminogen activator
Sponsors
Medtronic Neurovascular Clinical Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 - 80 2. Clinical signs consistent with acute ischemic stroke 3. Prestroke Modified Rankin Score ≤ 1 4. NIHSS ≥ 8 and \< 30 at the time of randomization 5. Initiation of IV t-PA within 4.5 hours of onset of stroke symptoms (onset time is defined as the last time when the patient was witnessed to be at baseline), with investigator verification that the subject has received / is receiving the correct IV t-PA dose for the estimated weight prior to randomization. 6. Thrombolysis in Cerebral Infarction (TICI) 0-1 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 Device. 7. Subject is able to be treated within 6 hours of onset of stroke symptoms and within 1.5 hours (90 minutes) from CTA or MRA to groin puncture. 8. Subject is willing to conduct protocol-required follow-up visits. 9. An appropriate signed and dated Informed Consent Form (as allowed according to country regulations and approved by ethics committee and/or IRB) has been obtained 10. Subject is affiliated with a social security system (if required by individual country regulations). 11. Subject meets national regulatory criteria for clinical trial participation.
Exclusion criteria
1. Subject who is contraindicated to IV t-PA as per local national guidelines. 2. Female who is pregnant or lactating or has a positive pregnancy test at time of admission. 3. As applicable by French law, subject who is a protected individual such as an incompetent adult or incarcerated person. 4. Rapid neurological improvement prior to study randomization suggesting resolution of signs/symptoms of stroke. 5. Known serious sensitivity to radiographic contrast agents. 6. Known sensitivity to Nickel, Titanium metals or their alloys. 7. Current participation in another investigational drug or device treatment study. 8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. (A subject without history or suspicion of coagulopathy does not require INR or prothrombin time lab results to be available prior to enrollment.) 9. Renal Failure as defined by a serum creatinine \> 2.0 mg/dl (or 176.8 μmol/l) or Glomerular Filtration Rate \[GFR\] \< 30Warfarin therapy with INR greater than 1.7. 10. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason 11. Life expectancy of less than 90 days. 12. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal. 13. Suspicion of aortic dissection. 14. Subject with a co-morbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments. 15. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day). 16. 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. Imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | 90 days | mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. 0 No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death Due to Any Cause at 90 Days | 90 days | — |
| Functional Independence as Defined by Modified Rankin Scale (mRS) Score ≤2 at 90 Days | 90 days | — |
| Change in NIH Stroke Scale Score at 27 ± 6 Hrs Post Randomization | Baseline to 27±6 hours post randomization | The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. NIHSS scores range from 0 - 42. A score of 0 indicates no stroke symptoms. Higher scores indicate incremental levels of neurological impairment. |
| Volume of Cerebral Infarction as Measured by a CT or MRI Scan at 27±6 Hours Post Randomization | 27±6 hours post randomization | — |
| Arterial Revascularization Measured by TICI 2b or 3 Following Device Use | Post procedure | — |
| 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 | 27±6 hours post randomization | — |
| Reperfusion Measured by Reperfusion Ratio on CT or MRI Scan 27±6 Hours Post Randomization | 27±6 hours post randomization | — |
Other
| Measure | Time frame |
|---|---|
| Incidence of All Serious Adverse Events (SAEs) | Through 90 days |
| Incidence of sICH at 27±6 Hours Post Randomization | 27±6 hours post randomization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV t-PA With Solitaire™ Revascularization Device Dual IV tPA therapy and adjunctive treatment with the Solitaire™ FR | 98 |
| IV t-PA IV infusion of tPA | 96 |
| Total | 194 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 12 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | IV t-PA With Solitaire™ Revascularization Device | IV t-PA | Total |
|---|---|---|---|
| Age, Continuous | 64.99 years STANDARD_DEVIATION 12.49 | 66.32 years STANDARD_DEVIATION 11.277 | 65.64 years STANDARD_DEVIATION 11.89 |
| NIHSS | 16.69 Scores on a scale STANDARD_DEVIATION 4.68 | 16.49 Scores on a scale STANDARD_DEVIATION 4.6 | 16.59 Scores on a scale STANDARD_DEVIATION 4.63 |
| Region of Enrollment Austria | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Denmark | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 8 participants | 4 participants | 12 participants |
| Region of Enrollment Germany | 20 participants | 22 participants | 42 participants |
| Region of Enrollment Spain | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Switzerland | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 65 participants | 66 participants | 131 participants |
| Sex: Female, Male Female | 44 Participants | 51 Participants | 95 Participants |
| Sex: Female, Male Male | 54 Participants | 45 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 98 | 88 / 97 |
| serious Total, serious adverse events | 35 / 98 | 30 / 97 |
Outcome results
Primary
90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS).
mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. 0 No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead
Time frame: 90 days
Population: Final assessment unavailable for 5 subjects that withdrew consent or investigator withdrew consent in IV t-PA arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 0 | 17 Participants |
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 1 | 25 Participants |
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 2 | 17 Participants |
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 3 | 12 Participants |
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 4 | 15 Participants |
| IV t-PA With Solitaire™ Revascularization Device | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 5/6 | 12 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 4 | 20 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 0 | 8 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 3 | 16 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 1 | 10 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 5/6 | 24 Participants |
| IV t-PA | 90-day Global Disability Assessed Via the Blinded Evaluation of Modified Rankin Score (mRS). | mRS 2 | 15 Participants |
Secondary
Arterial Revascularization Measured by TICI 2b or 3 Following Device Use
Time frame: Post procedure
Population: Final assessment not available for all subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Arterial Revascularization Measured by TICI 2b or 3 Following Device Use | 73 Participants |
Secondary
Change in NIH Stroke Scale Score at 27 ± 6 Hrs Post Randomization
The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. NIHSS scores range from 0 - 42. A score of 0 indicates no stroke symptoms. Higher scores indicate incremental levels of neurological impairment.
Time frame: Baseline to 27±6 hours post randomization
Population: Final assessment not available for all subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Change in NIH Stroke Scale Score at 27 ± 6 Hrs Post Randomization | -8.5 units on a scale | Standard Deviation 7.1 |
| IV t-PA | Change in NIH Stroke Scale Score at 27 ± 6 Hrs Post Randomization | -3.9 units on a scale | Standard Deviation 6.2 |
Secondary
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
Time frame: 27±6 hours post randomization
Population: Final assessment not available for all subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | 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 | 0.46 Correlation |
Secondary
Death Due to Any Cause at 90 Days
Time frame: 90 days
Population: One subject in the IV t-PA arm withdrew and requested all data be removed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Death Due to Any Cause at 90 Days | 9 Participants |
| IV t-PA | Death Due to Any Cause at 90 Days | 12 Participants |
Secondary
Functional Independence as Defined by Modified Rankin Scale (mRS) Score ≤2 at 90 Days
Time frame: 90 days
Population: Final assessment unavailable for 5 subjects that withdrew consent or investigator withdrew consent in IV t-PA arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Functional Independence as Defined by Modified Rankin Scale (mRS) Score ≤2 at 90 Days | 59 Participants |
| IV t-PA | Functional Independence as Defined by Modified Rankin Scale (mRS) Score ≤2 at 90 Days | 33 Participants |
Secondary
Reperfusion Measured by Reperfusion Ratio on CT or MRI Scan 27±6 Hours Post Randomization
Time frame: 27±6 hours post randomization
Population: Final assessment not available for all subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Reperfusion Measured by Reperfusion Ratio on CT or MRI Scan 27±6 Hours Post Randomization | 81 Reperfusion ratio | Standard Deviation 67.3 |
| IV t-PA | Reperfusion Measured by Reperfusion Ratio on CT or MRI Scan 27±6 Hours Post Randomization | 61.9 Reperfusion ratio | Standard Deviation 53 |
Secondary
Volume of Cerebral Infarction as Measured by a CT or MRI Scan at 27±6 Hours Post Randomization
Time frame: 27±6 hours post randomization
Population: Final assessment not available for all subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Volume of Cerebral Infarction as Measured by a CT or MRI Scan at 27±6 Hours Post Randomization | 60.2 cc | Standard Deviation 86 |
| IV t-PA | Volume of Cerebral Infarction as Measured by a CT or MRI Scan at 27±6 Hours Post Randomization | 65.9 cc | Standard Deviation 73.5 |
Other Pre-specified
Incidence of All Serious Adverse Events (SAEs)
Time frame: Through 90 days
Population: One subject in the IV t-PA arm withdrew and requested all data be removed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Incidence of All Serious Adverse Events (SAEs) | 35 Participants |
| IV t-PA | Incidence of All Serious Adverse Events (SAEs) | 30 Participants |
Other Pre-specified
Incidence of sICH at 27±6 Hours Post Randomization
Time frame: 27±6 hours post randomization
Population: One subject in the IV t-PA arm withdrew and requested all data be removed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV t-PA With Solitaire™ Revascularization Device | Incidence of sICH at 27±6 Hours Post Randomization | 0 Participants |
| IV t-PA | Incidence of sICH at 27±6 Hours Post Randomization | 3 Participants |