Superselective Administration of VErapamil During Recanalization in Acute Ischemic Stroke

This trial represents the first time that verapamil will be evaluated in human subjects as a
superselectively administered neuroprotective agent administered in an acute time frame as
an adjunct to intra-arterial thrombolysis. The methods for administration, along with the
routinized followup, will provide a paradigm for studying other potential neuroprotective
agents. Subjects will undergo cerebral angiography with intra-arterial thrombolysis, which
is standard of care. 'Intra-arterial thrombolysis will include possible intra-arterial
administration of tPA, as well as possible mechanical thrombectomy with an accepted
thrombectomy device. This includes the Mercí Retriever (Concentric Medical, Mountain View,
CA), the Penumbra System (Penumbra, Alameda, CA), the Solitaire stent-triever (EV3,
Covidien, Irvine, CA), and the Trevo stent-triever (Concentric Medical, Mountain View, CA).
Immediately after the intra-arterial thrombolysis component of the angiographic procedure is
completed, the microcatheter used during the procedure will be left in or guided into the
vessel location of the clot. 10mg of verapamil in 20cc of normal saline will be administered
over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously
obstructed by clot. At the conclusion of infusion, the microcatheter will be removed.
Angiography through the guide catheter of the cerebral circulation in question will be
performed to ensure no new thromboembolic event from the microcatheterization (standard of
care). The catheters will be removed, and the arterial puncture site closed in the standard
fashion. Patients will receive a noncontrast CT scan or MRI approximately 24 hours after
intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after
intervention. This would be considered standard practice for intra-arterial thrombolysis.
Both imaging studies can detect ICH, and the choice of one or the other will be determined
by clinical criteria; CT or MRI may be preferable for different reasons depending upon the
patient's clinical scenario. The determination of hemorrhage will be made by the official
dictation of a diagnostic neuroradiologist not directly involved in the study. The
hemorrhage will be considered an adverse event if it is deemed symptomatic in accordance
with the criteria used in the International Management of Stroke (IMS) III study. Briefly, a
hemorrhage is defined as symptomatic if occurring within 24+/-6 hours after study inclusion,
temporally related to the intervention, and occurs with worsening neurological status as
documented in the clinical exam. A 4 point or more increase in the NIHSS stroke scale would
qualify as a significant worsening in status. Furthermore, hemorrhage that requires
intervention surgically or endovascularly would be deemed significant.

Inclusion Criteria:

1. Patients 21-85 years old, male or female

2. Suspected acute ischemic stroke based on clinical and radiographic evidence as
determined and documented by the Stroke Neurology team at University of Kentucky.

3. Patients must meet criteria for intra-arterial thrombolysis as determined and
documented by Interventional Neuroradiology attending physician (JF or AA).

4. Patients must have an acute thromboembolus within an intracranial artery (internal
carotid, anterior cerebral, middle cerebral, posterior cerebral, basilar, vertebral)
which undergoes pharmacologic (tissue plasminogen activator - tPA) and/or mechanical
(eg. Merci or Penumbra clot retrieval) thrombolysis.

5. Patients with impaired capacity may be included, as the pathology to be studied
(stroke) may impair their capacity (please see attached required documentation
regarding impaired capacity).

6. Patients must have a TICI 2A or better revascularization via intra-arterial
thrombolysis.

For reference, the TICI Scale is defined below:

0 = No Perfusion

1. = Perfusion past the initial obstruction but limited distal branch filling with
little or slow distal perfusion

2. A = Perfusion of less than 50% of the vascular distribution of the occluded artery

2B = Perfusion of 50% or greater (but not complete) of the vascular distribution of the
occluded artery 3 = Full perfusion with filling of all distal branches

Exclusion Criteria:

1. Pregnant women (would not qualify for intra-arterial thrombolysis as standard of
care).

2. Patients who undergo intra-arterial thrombolysis for acute stroke, in whom only TICI
0 or 1 revascularization is obtained.

3. Patients with occlusion of the cervical common or internal carotid artery will be
excluded from the study.