Interventional Management of Stroke (IMS) III Trial

Stroke remains a major cause of death and disability. Acute thrombolytic therapy offers the
potential to achieve early recanalization (reopening of blocked arteries), save tissues, and
improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator
(rt-PA) is the only approved acute stroke therapy. IV rt-PA is an effective therapy for
acute ischemic stroke but has substantial limitations when used alone to open blocked
arteries The Interventional Management of Stroke (IMS III) Trial is a multi-center study
that will compare two different treatment approaches for restoring blood flow to the brain.
One approach, giving the clot-dissolving drug rt-PA, is already FDA-approved when given
through a vein (IV). This treatment will be compared to a new approach, giving rt-PA at a
lower dose first through IV in the arm and then, if a blood clot in the brain artery is
found, through a small tube or catheter at the site of the blood clot (intra-arterial or IA)
to see which is better. Both approaches must be initiated within three hours of stroke
onset.

The primary goal of this trial is to determine if individuals with ischemic stroke treated
with rt-PA using a combined IV/IA approach to recanalization started within 3 hours of onset
are more likely to have a better outcome than individuals treated with standard IV rt-PA
alone.

Nine hundred participants with moderate to severe ischemic stroke will be enrolled at more
than 50 centers in the United States, Canada, and Australia. Participants will be assigned
randomly to one of 2 groups. Two participants will be randomized to the combined approach
for every one participant randomized to standard IV rt-PA. Group one will receive the
standard dose of IV rt-PA given over an hour. Group two will receive the standard dose of
IV rt-PA for only 40 minutes and then undergo an angiogram test (cerebral angiography) right
after the medicine is given to check for blood clots. If a clot is not seen then no more
treatment will be given. If a clot is seen, the doctor (a neurointerventionalist) will then
choose, based on the location and extent of the blood clot, one of 4 possible IA treatments
given directly in the brain artery that will be most effective in reopening the blocked
artery. All of the IA treatments used—embolectomy therapy with either the Merci® Retriever
or The Penumbra System™, or rt-PA infusion through the EKOS® Micro-Infusion Catheter,
concurrent with delivery of low-intensity ultrasound energy, or infusion of rt-PA though a
standard microcatheter at the site of the blood clot in the brain artery.

The primary measure of benefit in this trial is the ability of the individual with stroke to
live and function independently 3 months after the stroke. This trial will also determine
and compare the safety and cost effectiveness of the combined IV/IA approach to the standard
IV rt-PA approach.

Duration of the study for participants is approximately 12 months.