StrokeNet Thrombectomy Endovascular Platform

STEP is a Randomized, Multifactorial, Adaptive Platform trial that seeks to optimize the care of patients with acute ischemic stroke (AIS) due to large (LVO) or medium vessel occlusions (MVO).

The StrokeNet Thrombectomy Endovascular Platform (STEP) is conducted within NIH StrokeNet at 38 comprehensive stroke centers across the US. The primary goal is to optimize all aspects of care of acute ischemic stroke patients with a large or a medium vessel occlusion. The platform trial operates under an overarching Master Protocol in an inferentially integrated framework. The platform trial is designed to support the studies of three broad categories of therapeutics: expansion of endovascular treatment (EVT) indications, innovative EVT devices and concomitant medical therapies, and novel pre- and early-hospital technologies and systems of care. As new interventions are put forth, they will be added to the Master Protocol as a new Domain or part of an existing Domain. STEP utilizes a flexible Bayesian design with frequent adaptive analyses to assess whether a given intervention is superior, inferior, or equivalent either within a Domain or for specific populations within the Domain.

Eligibility Criteria:
STEP PLATFORM INCLUSION CRITERIA:

1. Suspected diagnosis acute ischemic stroke
2. Likely causative intracranial large or medium vessel occlusion

STEP PLATFORM EXCLUSION CRITERIA:

1. Proven contraindication to endovascular thrombectomy
2. Prisoners/incarcerated

DOMAIN-SPECIFIC ELIGIBILITY CRITERIA:

Each domain may have additional eligibility criteria.

STEP EVT INDICATION EXPANSION DOMAIN INCLUSION CRITERIA:

1. Age 18 years or older 2. Pre-stroke modified Rankin Scale score 0-2 3. Presentation to enrolling hospital within 24 hours of last known well/stroke onset 4. Has one of the following presentations:

1. LVO patients with mild deficits/low NIHSS (must have both):

   1. Mild presenting neurologic deficits - NIHSS 0-5
   2. Occlusion of the intracranial Internal Carotid Artery (ICA) or M1 Middle Cerebral Artery (MCA)
2. Medium/Distal Vessel Occlusion (must have all 4):

   1. Visualized occlusion or perfusion deficit supportive of a cortical branch occlusion (10 cc volume of Tmax \>4s) in one of the following vessels: i) Non-dominant/Co-dominant M2 (defined as serving \< 50% of entire overall MCA territory) ii) M3 iii) M4 iv) A1 v) A2 vi) A3 vii) P1 viii) P2 ix) P3
   2. Less than 50% core in the territory supplied by the occluded vessel as evident by hypodensity and loss of grey-white border on NCCT or ADC \<620 mm2/s on diffusion MRI or rCBF\<30% on CTP after 6h of symptom onset.
   3. NIHSS \> 4 or NIHSS 2-3 with clearly disabling deficits at presentation to enrolling hospital
   4. Able to initiate arterial puncture within 2 hours from qualifying CTA/MRA or CTP/MRP imaging.

      * CT/MR and qualifying CTA/MRA or CTP/MRP should be repeated if more than 120 minutes have elapsed since the imaging and randomization has not been performed.

STEP EVT INDICATION EXPANSION DOMAIN EXCLUSION CRITERIA:

1. Clinical

   1. Presumed septic embolus; suspicion of bacterial endocarditis
   2. Seizure at stroke onset or between onset and enrollment
   3. Known anaphylactic reaction to contrast material that precludes endovascular reperfusion therapy
   4. Intracranial occlusion suspected to be chronic, based on history and/or imaging
   5. Intracranial dissection, based on history and/or imaging
   6. Cerebral vasculitis, based on history and/or imaging
   7. Known pregnancy
   8. Known pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
   9. Known serious, advanced, or terminal illness or life expectancy less than 6 months in the investigator judgment
2. Laboratory

   a. Known platelet count \<100,000/uL
3. Imaging

   1. CT ASPECT score \<6 (MRI ASPECT score \<7)
   2. Unfavorable vascular anatomy that limits access to the occluded artery precluding endovascular reperfusion therapy.
   3. Acute occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
   4. Significant mass effect with midline shift (\>5mm)
   5. Evidence of intra-axial tumor (except small meningioma)
   6. Evidence of acute intracranial hemorrhage