StrokeNet Thrombectomy Endovascular Platform

Official title

STEP: StrokeNet Thrombectomy Endovascular Platform

Overview

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).

Detailed description

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.

Interventions

• Device Endovascular thrombectomy with any FDA-approved category POL or NRY device
  Endovascular thrombectomy with any FDA-approved category POL or NRY device - Neurovascular Mechanical Thrombectomy Device For Acute Ischemic Stroke Treatment (POL), and/or Catheter, Thrombus Retriever (NRY)
• Other Medical Management
  Medical Management (MM) may involve any combination of the following: intravenous thrombolysis, antiplatelets, anti-hypertensives, cholesterol-lowering medications, and rehabilitative care.

Primary outcome measures

• Global disability measured by Modified Rankin Score [Time frame: 90-day]

Eligibility criteria

STEP PLATFORM INCLUSION CRITERIA:

• Suspected diagnosis acute ischemic stroke
• Likely causative intracranial large or medium vessel occlusion

STEP PLATFORM EXCLUSION CRITERIA:

• Proven contraindication to endovascular thrombectomy
• 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. 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. The exception is for LVO Mild deficit/Low NIHSS 0-5 for which imaging would only need to be repeated if there has been significant improvement in the NIHSS prior to randomization.

5\. Has one of the following presentations:

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

• Mild presenting neurologic deficits - NIHSS 0-5 (Must have some focal neurological deficit attributable to the target occlusion if NIHSS 0)
• Complete occlusion of the intracranial Internal Carotid Artery (ICA) or M1 Middle Cerebral Artery (MCA)
• Medium/Distal Vessel Occlusion:

• Visualized complete occlusion or perfusion deficit (Tmax > 4s) supportive of a cortical branch occlusion in one of the following vessels:

i) Non-dominant/Co-dominant M2 (defined as serving < 50% of entire overall MCA territory) ii) M3

• If symptom onset is > 6h, the core must be less than 50% of the territory supplied by the occluded vessel as evident by either:

i) Hypodensity and loss of grey-white border on NCCT or ii)ADC <620 mm2/s on diffusion MRI or rCBF<30% on CTP

• NIHSS > =8

STEP EVT INDICATION EXPANSION DOMAIN EXCLUSION CRITERIA:

• Clinical

• Presumed septic embolus; suspicion of bacterial endocarditis
• Seizure at stroke onset or between onset and enrollment
• Known anaphylactic reaction to contrast material that precludes endovascular reperfusion therapy
• Intracranial occlusion suspected to be chronic, based on history and/or imaging
• Intracranial dissection, based on history and/or imaging
• Cerebral vasculitis, based on history and/or imaging
• Known pregnancy
• Known pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
• Known serious, advanced, or terminal illness or life expectancy less than 6 months in the investigator judgment
• Known or high suspicion for underlying intracranial atherosclerotic disease (ICAD)
• Laboratory

a. Known platelet count <100,000/uL

• Imaging

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 41 centers

• University of Alabama Hospital — Birmingham
• UCSD Health La Jolla — La Jolla
• Kaiser Permanente Los Angeles Medical Center — Los Angeles
• Ronald Reagan UCLA Medical Center — Los Angeles
• UCSD Medical Center - Hillcrest Hospital — San Diego
• Stanford University Medical Center — Stanford
• Hartford Hospital — Hartford
• Yale New Haven Hospital — New Haven
• … and 33 more centers

Publications

• Seners P, Cereda CW. Thrombectomy in Stroke With a Large Vessel Occlusion and Mild Symptoms: "Striving to Better, Oft We Mar What's Well?". Stroke. 2023 Sep;54(9):2276-2278. doi: 10.1161/STROKEAHA.123.044205. Epub 2023 Aug 1. No abstract available. PMID 37526012
• Feil K, Matusevicius M, Herzberg M, Tiedt S, Kupper C, Wischmann J, Schonecker S, Mengel A, Sartor-Pfeiffer J, Berger K, Dimitriadis K, Liebig T, Dieterich M, Mazya M, Ahmed N, Kellert L. Minor stroke in large vessel occlusion: A matched analysis of patients from the German Stroke Registry-Endovascular Treatment (GSR-ET) and patients from the Safe Implementation of Treatments in Stroke-Internation PMID 35122371

Identifiers

NCT: NCT06289985 · STEP · 1OT2NS129366-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗