Imaging Guided Patient Selection for Interventional Revascularization Therapy
Condition: Acute Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke
Study type: Interventional

Summary: 
      The primary objective of this clinical evaluation is to determine the safety and
      effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from
      symptom and with a known core infarct volume at admission. The secondary objective is to
      determine if there is a correlation between infarct volume and functional outcome in treated
      patients at 90 days post-procedure.
    

Detailed description: 
      Study Title: The START Trial: Clinical Outcome in Acute Stroke Treatment after Imaging Guided
      Patient Selection for Interventional Revascularization Therapy

      Study Objective: The objective of this clinical evaluation is to determine the safety and
      effectiveness of the Penumbra System in a stroke cohort who presents within 8 hours from
      symptom onset and with a known core infarct volume at admission. The data will also be used
      to determine if there is a correlation between infarct volume and functional outcome at 90
      days post-procedure. Safety is defined by the procedural serious adverse events, and
      effectiveness is defined by the rate of revascularization (TIMI 2-3/TICI 2a-3) and good
      functional outcome. Good functional outcome is defined by a modified Rankin scale (mRS) score
      of 2 or less at 90 days post-procedure. Core infarct volume at admission will be assessed by
      computed tomography perfusion (CTP), computed tomography angiography (CTA) or magnetic
      resonance DWI scans. The core infarct volumes will be sub-grouped by <50cc, 50-100cc and
      >100cc to determine the correlation with patient functional outcome.

      Study Design: A prospective, single arm, multi-center trial. Up to 200 patients at up to 45
      centers will be enrolled in the study. It is anticipated that up to 150 evaluable patients
      will be needed for analysis.

      Patient Population: Patients presenting with symptoms of acute ischemic stroke within 8 hours
      from symptom onset and with a known imaging-defined infarct volume will be enrolled for
      interventional treatment by the Penumbra System to achieve revascularization of the target
      vessel territory.

      Indication: The Penumbra System is intended for use in the revascularization of patients with
      acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the
      internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries)
      within 8 hours of symptom onset.

      Sample Size Justification: Up to 200 subjects will be enrolled in order to obtain up to 150
      evaluable patients. Assuming a post-procedure angiographic success (TIMI 2-3/TICI 2a-3) rate
      of 80% (120/150), the expected two-sided exact binomial 95% confidence interval is (72.7%,
      86.1%). Assuming a 90-day mRS success (mRS 0-2) rate of 30%, the expected two-sided exact
      binomial 95% confidence interval is (22.8%, 38.0%). Additionally, the study results will be
      used for sample size estimates for a potential future randomized, concurrent controlled
      trial.

      Core Laboratory and Clinical Event Committee An independent Core Lab will review and score
      all imaging scans for infarct volume, TIMI, TICI and ICH. A Clinical Event Committee will
      adjudicate all Serious Adverse Events for severity and causality (disease-, procedure-,
      drug-, or device-relatedness.

      Study Rationale: Use of interventional revascularization techniques offer several potential
      clinical benefits by improving cerebral perfusion to the target vascular territory in certain
      patients. The validation of a simple, pragmatic, and executable image guided patient
      selection paradigm may identify a cohort of acute stroke patients who will benefit from
      interventional treatment by the Penumbra System and in whom revascularization as a treatment
      for acute stroke will be indicated.
    

Intervention name(s): Penumbra System
Intervention type(s): Device
Intervention description(s): The Penumbra System is used to revascularize clotted cerebral blood vessels.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute stroke; Large cerebral vessel occlusion; Core infarct volume; Penumbra System; Revascularization; Intracerebral hemorrhage; mRS; NIHSS; Procedural serious adverse events; All cause mortality