MR WITNESS: A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients

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
• Systolic pressure greater than 185 mm Hg or diastolic pressure greater than 110 mm Hg, or aggressive treatment (intravenous medication) necessary to reduce blood pressure to these limits.
• 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.