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:
Participant gender:
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.