A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients
Condition: Acute Stroke
MeSH terms: Stroke
Intervention: IV rt-PA
Intervention description: open-label
Intervention MeSH terms: Tissue Plasminogen Activator
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: acute stroke, IV rt-PA, Activase, Alteplase

Summary:

      This study was jointly developed and is jointly led by investigators at Massachusetts General
      Hospital and the intramural division of NINDS. We are doing this research study to find out
      if Activase ® (also called alteplase or rt-PA) can safely be given to people with an acute
      ischemic stroke when their stroke onset was not witnessed making them ineligible for standard
      thrombolytic (clot busting) therapy. We also want to find out if rt-PA can help people
      recover better from their stroke.

      The purpose of this study is to: 1) see if it is safe to give intravenous (IV) rt-PA to
      people with unwitnessed stroke but with MRI evidence of early ischemic stroke, 2) see if
      rt-PA is effective if given to people who are selected for treatment based on MRI evidence of
      an early stroke, and 3) get information about this new MRI diagnostic methods for guiding
      stroke treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age, 18 to 85 years inclusive

          -  Brain MRI findings consistent with early stroke onset

          -  Clinical diagnosis of acute ischemic stroke with disabling neurological deficit

          -  Stroke symptoms present for at least 30 minutes with no significant improvement before
             treatment

          -  Be last known well (without stroke symptoms) within 24 hours of triage

          -  Be able to receive IV rt-PA within 4.5 hours from the time the symptoms were
             discovered.

          -  MRI diagnostic of acute ischemic stroke and consistent with clinical syndrome

          -  Time between completion of qualifying MRI studies to treatment initiation ≤ 1 hour

        Exclusion Criteria:

          -  History of intracranial hemorrhage

          -  Symptoms rapidly improving or only minor before start of study drug.

          -  Severe stroke as assessed clinically (e.g., NIHSS score >25) or by appropriate imaging
             techniques (lesion volume > one-third of MCA by visual inspection or >100 cm3 using
             the ellipsoid estimation formula of ABC/2)

          -  Stroke or serious head trauma within the previous 3 months

          -  Administration of heparin within the 48 hours preceding the onset of stroke, with an
             activated partial-thromboplastin time at presentation exceeding the upper limit of the
             normal range

          -  Platelet count of less than 100,000 per cubic millimeter

          -  Uncontrolled hypertension defined as systolic blood pressure > 185 mm Hg or diastolic
             blood pressure > 110 mm Hg that cannot be controlled except with continuous parenteral
             antihypertensive medication

          -  Blood glucose less than 50 mg per deciliter or greater than 400 mg per deciliter

          -  Symptoms suggestive of subarachnoid hemorrhage, even if CT/MRI scan was normal

          -  Oral anticoagulant treatment, regardless of INR.

          -  Major surgery or severe trauma within the previous 3 months

          -  Other major disorders associated with an increased risk of bleeding

          -  Eligible for rt-PA therapy per institutional protocol as part of routine clinical
             practice

          -  Non-ischemic etiology demonstrated by neuroimaging

          -  Neuroimaging (CT or gradient echo MRI) evidence of acute or chronic ICH
             (non-microbleed)

          -  Presence of 10 or more microbleeds on GRE (suggestive of amyloid angiopathy)

          -  Any contraindication for MRI, e.g. presence of a pacemaker, ferromagnetic aneurysm
             clip, etc, pre-menopausal women with a positive pregnancy blood test, or severe
             claustrophobia.

          -  Poor quality MRI- images are not interpretable

          -  In the opinion of the investigator, the patient is not an appropriate candidate for IV
             rt-PA

          -  Women known to be pregnant, lactating or having a positive or indeterminate pregnancy
             test.