Solitaire™ With the Intention For Thrombectomy as PRIMary Endovascular Treatment (SWIFT PRIME) Trial

Study Overview
=================
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

Official Title
-----------------
Solitaire™ FR With the Intention For Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) Clinical Trial

Conditions
-----------------
Acute Ischemic Stroke

Intervention / Treatment
-----------------
* Drug: Intravenous (IV) recombinant human tissue plasminogen activator (rtPA)
* Device: Solitaire revascularization device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 - 80 Clinical signs consistent with acute ischemic stroke Prestroke Modified Rankin Score ≤ 1 NIHSS ≥ 8 and < 30 at the time of randomization 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. 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. 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. Subject is willing to conduct protocol-required follow-up visits. 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 Subject is affiliated with a social security system (if required by individual country regulations). Subject meets national regulatory criteria for clinical trial participation. Exclusion Criteria: Subject who is contraindicated to IV t-PA as per local national guidelines. Female who is pregnant or lactating or has a positive pregnancy test at time of admission. As applicable by French law, subject who is a protected individual such as an incompetent adult or incarcerated person. Rapid neurological improvement prior to study 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 treatment study. 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.) 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. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason Life expectancy of less than 90 days. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal. Suspicion of aortic dissection. 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. 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). 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 Exclusion Criteria: Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of hemorrhage on presentation. CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma). CT or MRI evidence of cerebral vasculitis. CT showing hypodensity or MRI showing hyperintensity involving greater 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 defined as extensive early ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) < 6. CT or MRI evidence of a basilar artery (BA) occlusion or posterior cerebral artery (PCA) occlusion. CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy) Imaging evidence that suggests, in the opinion of the investigator, the subject is not appropriate for mechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/large infarct with poor collateral circulation, etc).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV t-PA with Solitaire™ revascularization device<br>Dual IV tPA therapy and adjunctive treatment with the Solitaire revascularization device | Device: Solitaire revascularization device<br>* Clot retrieval with the Solitaire revascularization device after patients have received standard therapy with intravenous tissue plasminogen activator<br>|
| Active Comparator: IV t-PA<br>Infusion of intravenous tissue plasminogen activator (IV t-PA) | Drug: Intravenous (IV) recombinant human tissue plasminogen activator (rtPA)<br>* Standard therapy with Intravenous (IV) recombinant human tissue plasminogen activator (rtPA)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 No significant disability despite symptoms; able to carry out all usual duties and activities Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance Moderate disability; requiring some help, but able to walk without assistance Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Severe disability; bedridden, incontinent and requiring constant nursing care and attention Dead | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Baseline to 27±6 hours post randomization | 
| Volume of Cerebral Infarction as Measured by a CT or MRI Scan at 27±6 Hours Post Randomization |  | 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 | 
| 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 |