IV vs. IA tPA (Activase) in Acute Ischemic Stroke With CTA Evidence of Major Vessel Occlusion

• Status: Completed
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Stroke is the third leading cause of death in the United States, responsible for 158,488 deaths in 1998 (American Heart Association). Nationwide, each year, an estimated 600,000 to 750,000 people suffer a new or recurrent stroke. Cerebral infarction comprises 80% of all strokes and is the result of a complex series of cellular metabolic events that occur rapidly after interruption of blood flow to a region of the brain. The extent of the brain damage is dependent on the duration and severity of the cerebral ischemia. Acute thrombus formation or migration is the principal cause of blood flow interruption in at least 75% of cerebral infarctions. In several animal models of focal cerebral ischemia, restoration of cerebral blood flow within two to six hours after initial occlusion has been associated with smaller volumes of cerebral infarction and improved functional outcome. An effective way of dissolving the thrombus is by administration of recombinant tissue plasminogen activator or Activase (Alteplase, rt-PA), which promotes the proteolytic action of plasmin from plasminogen at the site of a clot. In this study, the drug, Activase, will be administered in subjects with acute ischemic stroke (AIS) intravenously (IV) or by local intra-arterial (IA) injection. The use of the intravenous administration within 3 hours of stroke symptom onset is FDA approved whereas the intra-arterial administration, despite evidence of potential benefit, is not currently FDA approved. Although not FDA approved, this study will evaluate the effectiveness of IA thrombolysis with Activase, used in AIS because of its higher rate of recanalization , potential expansion of the time window out to 6 hours, and lower doses of thrombolytic agent used compared with systemic or intravenous Activase. The study is designed to test the feasibility and provide preliminary safety data regarding the relative benefits and risks of IA Activase as compared to IV Activase when administered per the NINDS rt-PA stroke study protocol, i.e. randomized within 3 hours of onset of symptoms of ischemic stroke then treated within 3 hours in the IV Activase arm and within 4 hours in the IA Activase arm.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Genentech, Inc.
• Treatments: Tissue Plasminogen Activator

Criteria

Inclusion Criteria:Subjects will be eligible if the following criteria are met:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study.

• Age > 18 years

• NIHSS ≥ 4 or isolated aphasia or isolated hemianopsia

Exclusion Criteria:

• NIHSS >30

• Coma

• Rapidly improving symptoms

• History of stroke in the last 6 weeks

• Seizure at onset

• Subarachnoid Hemorrhage (SAH ) or suspected SAH

• Any history of Intracrannial Hemorrhage (ICH)

• Neoplasm

• Septic embolism

• Surgery, biopsy, trauma or LP in last 30 days

• Head trauma in the last 90 days

• Bleeding diathesis, or INR >1.7 or PTT >1.5 times baseline or platelet <100K

• SBP >180 or DBP ≥100 despite treatment with 3 doses of IV Labetalol (10-20 mg Q10")

• Lacunar stroke syndrome

• CT: Hemorrhage, tumor (except small meningioma), significant mass effect, midline shift, acute hypodensity or >1/3 MCA territory sulcal effacement

• Radiological contrast hypersensitivity

• Angiographic: Dissection, lack of access, lack of occlusion, or nonatherosclerotic arteriopathy