Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)

This is a phase 1/2a, single-center, randomized, open-label, control vs. Aggrastat study. The
generalized investigational plan is to explore the safety profile of Aggrastat administered
continuously over the course of 7 days in the setting of subarachnoid hemorrhage at least 12
hours post clinically indicated Endovascular Coil Embolization procedure.

As a part of the study, qualifying subjects will undergo 2 MRIs administered within 24 hours
post Coil Embolization procedure and prior to discharge to monitor for the ischemic changes,
neurological exam and vital signs administered at screening and/or randomization visit(s),
daily during drug administration, and at follow-up visits. Additional interventions include
administration of questionnaires including mRS score documentation, IADL, QOLIBRI-OS.

Inclusion Criteria:

Inclusion Criteria:

- Age >= 18 and <= 80 years

- Historical modified Rankin Scale Score 0-1

- WFNS SAH Scale grade <= 4, due to a spontaneous subarachnoid hemorrhage attributable
to a ruptured cerebral aneurysm.

- Initial WFNS grade may be determined at admission or enrollment, preferably after the
patient's mental status has been optimized by resuscitation and interval treatment of
hydrocephalus (i.e., placement of intraventricular catheter) or reversal/wearing-off
of sedating medications used commonly during patient transfers and transport or
procedure related anesthesia.

- Admission head CT showing modified Fisher grade 1-3 aSAH Snapshot images of up to four
relevant axial cuts from the admission head CT will need to be uploaded via the
imaging database to confirm the modified Fisher grade 1-3 eligibility of the potential
subject prior to enrollment. Minimal intraventricular hemorrhage is acceptable.

- The Modified Fisher CT rating scale: Grade 1 (minimal or diffuse thing SAH without
IVH); Grade 2 (minimal or thin SAH with IVH), Grade 3 (thick cisternal clot without
IVH), Grade 4 (thick cisternal clot with IVH)

- Angiographic location of the aneurysm will be confirmed by catheter digital
subtraction angiography (DSA) usually obtained during the coil embolization procedure.
Onset of symptoms of aSAH (ictus) occurred < 24 hours prior to presentation at the
treating facility.

- Initiation of aneurysm securement procedure occurred < 48 hours from the ictus AND
less than 12 hours from admission to the treating facility.

- In patients where the exact time of the ictus is uncertain, an estimated time of ictus
may be assigned and that time will be used for the inclusion criteria above assuming
the estimation is deemed to be reasonably reliable [i.e., actual time is highly likely
to be within 6 hours of estimated time].

- All aneurysm(s) suspected to be responsible for the hemorrhage or potentially
responsible for the hemorrhage must be secured in the following manner prior to
enrollment.

- Endovascular Coil Embolization with a post-embolization Raymond-Roy Score of 1
(Complete) or 2 (Residual Neck)

- Ability to screen the patient and obtain head CT and CT perfusion on admission and
follow after recovering from anesthesia following the aneurysm coiling procedure, the
patient must remain a WFNS SAH grade <= 4 without evidence of a significant new focal
neurological deficit including monoparesis / monoplegia, hemiparesis / hemiplegia, or
receptive, expressive or global aphasia. New minor cranial nerve defect without any
other new findings is permissible. If an NIHSS score was obtained prior to the
aneurysm coiling procedure, a post-coiling (pre-enrollment) NIHSS score must not have
increased by >= 4 points and GCS score must not be decreased by <= 2 points. The
clinician at the local site should use their best clinical judgment as to whether a
significant neurological decline has occurred due to the procedure.

- Patient or their Legally Authorized Representative (LAR) has provided written informed
consent.

- Ability to obtain MRI for ischemic changes evaluation

Exclusion Criteria:

- Angio-negative SAH.

- A likely hemorrhage event within several days prior to admission related hemorrhage
ictus due to the increased risk of early vasospasm. Prior sentinel headache with
negative CT or prior sentinel headache where the patient did not seek medical
attention does not exclude the patient.

- Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same
admission prior to enrollment.

- SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic,
blister or fusiform type by catheter DSA.

- Any intracranial stent placement or non-coil intra-aneurysmal device (i.e., stent-
assisted coiling with Neuroform, Enterprise, LVIS, LVIS Jr, Barrel Stent, Pulse Rider,
WEB, LUNA, Medina or a similar device) where the stent device is implanted to treat
the ruptured aneurysm and / or antiplatelet therapy is needed.

- Patient has remaining aneurysm(s) that are untreated and could reasonably be
considered a possible alternate cause of the aSAH based on the observed bleeding
pattern. Adequate treatment of these aneurysms by coiling embolization would result in
the aneurysms no longer causing an exclusion. MRI may be used in some situations to
determine that the associated aneurysms did not rupture based on lack of blood seen
adjacent to the additional aneurysms.

- Femoral arteriotomy stick above the inferior epigastric artery OR angiographic, CT, or
clinical evidence of an arteriotomy related retroperitoneal hematoma or large flank
hematoma. A stable groin hematoma is not an exclusion.

- Thrombocytopenia (platelet count less than 100,000 - assuming clumping has been ruled
out as a cause), confirmed active disseminated intravascular coagulation (DIC) at the
time of enrollment OR a documented history of coagulopathy or bleeding diathesis.

- Diagnosis of sepsis (SIRS criteria plus the presence of known or suspected infection)
or current documented active bacterial or viral infection prior to enrollment
(Example: significant URI, community-acquired pneumonia). A minor noncomplicated
community-acquired urinary tract infection would not be an exclusion but should be
treated promptly.

- New parenchymal hemorrhage or new infarction larger the 15cc in volume, or significant
increased mass effect as seen on the post coiling pre-enrollment head CT when compared
to baseline admission head CT. New hyperdensity on CT scan related to contrast
staining is not an exclusion.

- Patient developed SAH-induced cardiac stunning prior to enrollment, with an ejection
fraction< 40%, or requiring IV medications for blood pressure maintenance.

- Thrombolytic therapy within 24 hours prior to enrollment (rtPA, urokinase, etc.)

- Concurrent significant intracranial pathology identified prior to enrollment,
including but not limited to, Moyamoya disease, high suspicion or documented CNS
vasculitis, severe fibromuscular dysplasia, arteriovenous malformation, arteriovenous
fistula, significant cervical or intracranial atherosclerotic stenotic disease >= 70%,
or malignant brain tumor.

- Uncontrollable hypertension (>180 systolic and/or >110 diastolic) that is not
correctable prior to enrollment.

- Known seizure or epilepsy disorder (diagnosed prior to this aSAH diagnosis)where
anti-epileptic medication was previously taken by the patient or have been recommended
to be taken by the patient. Childhood seizures that have resolved and no longer
require treatment are not part of this exclusion criteria

- Serious co-morbidities that could confound study results including but not limited to:
Multiple Sclerosis, dementia, severe major depression, cancer likely to cause death in
2 years, multi-system organ failure, or any other conditions that could cause any
degree of cognitive impairment.

- Immunosuppression therapy including chronic corticosteroid usage.

- Remote history of previous ruptured cerebral aneurysm.

- History of gastrointestinal hemorrhage or major systemic hemorrhage within 30 days,
hemoglobin less than 8 g/dL, INR=1.5, severe liver impairment (AST< ALT< AP 2 x
normal or cirrhosis), creatinine > 2.0 mg/dL, or estimated GFR <60 ml/min.

- Major surgery (including open femoral, aortic, or carotid surgery) within previous 30
days.

- Currently pregnant.

- Contraindication for MRI

- Aspirin and Clopidogrel resistant.

- Pregnancy and breast feeding mothers