Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours

RandomizEd Trial of reVascularizAtion With Solitaire FR® Device Versus Best mediCal Therapy in the Treatment of Acute Stroke Due to anTerior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset

To evaluate the hypothesis that mechanical embolectomy with the Solitaire FR device is superior to medical management alone in achieving favorable outcome in the distribution of the modified Rankin Scale scores at 90 days in subjects presenting with acute large vessel ischemic stroke < 8 hours from symptom onset.

Prospective, multi-center, randomized, controlled, open, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical embolectomy with the CE MARK approved stentriever Solitaire FR® versus medical management alone. Randomization will be done under a minimization process using age, baseline NIHSS, therapeutic window and vessel occlusion site. For the primary endpoint, subjects will be followed for 90 days post-randomization.

Interim analysis will be performed as preplanned and interpreted by the Data Safety Monitoring Board (DSMB) after the first 174, 346 and 518 patients representing 25%, 50% and 75% of the planned sample size have completed their 90-day follow-up. The DSMB will advise the executive committee (EC) on recommendations to stop the trial early either for reasons of safety, efficacy, futility or to adjust the sample size. The latter may be necessary as given the paucity of data regarding natural history of the non-treated patients assumptions regarding rates of favorable outcomes in this group of patients may be incorrect. Of note, sample size adjustment based on different than expected outcomes rates is permitted, but it is not permitted to adjust the sample size based on change in the pre-specified treatment effect which is set at 10%.

Subject population: Subjects presenting with acute ischemic stroke within 8 hours from symptom onset and whose strokes are attributable to an occlusion of the internal carotid or proximal MCA (M1) arteries. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization.

Inclusion Criteria:

• 1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the treatment is contraindicated (e.g., subject presents beyond recommended time from symptom onset), or where patient has received IV thrombolytic therapy without recanalization after a minimum of 30 min from start of iv tPA infusion
• 2. No significant pre-stroke functional disability (mRS ≤ 1)
• 3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 6 points
• 4. Age ≥18 and ≤ 85.
• 5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions), MCA-M1 segment or tandem proximal ICA/MCA-M1 suitable for endovascular treatment, as evidenced by CTA, MRA or angiogram, with or without concomitant cervical carotid occlusion or stenosis
• 6. Patient treatable within eight hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as groin puncture.
• 7. Informed consent obtained from patient or acceptable patient surrogate

Exclusion Criteria:

• Clinical criteria
• 1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0
• 2. Baseline platelet count < 30.000/µL
• 3. Baseline blood glucose of < 50mg/dL or >400mg/dl
• 4. Severe, sustained hypertension (SBP > 185 mm Hg or DBP > 110 mm Hg)
• 5. Patients in coma (NIHSS item of consciousness >1) (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation).
• 6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS
• 7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
• 8. History of life threatening allergy (more than rash) to contrast medium
• 9. Subjects who has received iv t-PA treatment beyond 4,5 hours from the beginning of the symptoms
• 10. Renal insufficiency with creatinine ≥ 3 mg/dl
• 11. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
• 12. Subject participating in a study involving an investigational drug or device that would impact this study.
• 13. Cerebral vasculitis
• 14. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤ 1. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
• 15. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).

Neuroimaging criteria:

• 16. Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of <7 on NCCT or <6 on DWI MRI. Patients 81 to 85 years old with ASPECTS score on non-contrast CT or DWI MRI <9 must be excluded. ASPECTS must be evaluated by CBV maps of CT Perfusion, CTA source imaging (CTA-SI) or DWI-MR in patients whose vascular occlusion study (CTA/MRA) confirming qualifying occlusion, is performed beyond 4.5 hours of last seen well.
• 17. CT or MR evidence of hemorrhage (the presence of microbleeds is allowed).
• 18. Significant mass effect with midline shift.
• 19. Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection in the extracranial or petrous segment of the internal carotid artery that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment
• 20. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
• 21. Evidence of intracranial tumor (except small meningioma).