| Eligibility |
Inclusion criteria:
1. Age greater than or equal to 18 and less than or equal to 75 years.
2. Historical modified Rankin Scale Score (mRS) 0-1 (pre-subarachnoid hemorrhage onset).
3. World Federation of Neurosurgical Societies SAH Scale (WFNS) grade less than or equal
to 4, due to a spontaneous SAH attributed 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 lumbar puncture [LP])
or reversal/wearing-off of sedating medications used commonly during patient transfers
and transport or procedure related anesthesia.
4. Admission head CT showing modified Fisher grade 1-4 due to aneurysmal subarachnoid
hemorrhage (aSAH) primarily in the supratentorial space. The Modified Fisher CT rating
scale is: Grade 1 (minimal or diffuse thing SAH without intraventricular hemorrhage);
Grade 2 (minimal or thin SAH with intraventricular hemorrhage), Grade 3 (thick
cisternal clot without intraventricular hemorrhage), Grade 4 (thick cisternal clot
with intraventricular hemorrhage).
5. Location and pattern of the SAH must have the majority of the SAH in the
supratentorial space caused by either an intradural anterior circulation aneurysm or a
basilar apex/posterior circulation aneurysm with primarily supratentorial hemorrhage
extension. Angiographic location of the aneurysm will be confirmed by catheter digital
subtraction angiography usually obtained during the coil embolization procedure.
6. Onset of symptoms of aSAH (ictus) occurred < 24 hours prior to presentation at the
treating facility.
7. Initiation of aneurysm securement procedure occurred < 48 hours from the ictus and
less than 12 hours from admission to the treating facility.
8. 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).
9. 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 less than or equal to 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 a national
institute of health stroke scale (NIHSS) score was obtained prior to the aneurysm
coiling procedure, a post-coiling (pre-enrollment) NIHSS score must not have increased
by 4 points or more and Glasgow coma score must not be decreased by 2 points or less.
The clinician should use their best clinical judgment as to whether a significant
neurological decline has occurred due to the coiling procedure.
10. Ability to obtain MRI for ischemic changes evaluation.
11. Subject's Legally Authorized Representative (LAR) has provided written informed
consent.
Exclusion Criteria:
1. Angio-negative SAH.
2. A likely hemorrhage event within several days prior to admission related hemorrhage
ictus due to the increased risk of early vasospasm.
3. Prior sentinel headache with negative CT or prior sentinel headache where the patient
did not seek medical attention does not exclude the patient.
4. Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same
admission prior to enrollment.
5. SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic,
blister or fusiform type by catheter Digital Subtraction Angiography (DSA).
6. 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,
LUNA, Medina or a similar device) where the stent device is implanted to treat the
ruptured aneurysm and / or antiplatelet therapy is needed.
7. Subject 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.
8. Diagnosis of sepsis (systemic inflammatory response syndrome [SIRS] criteria plus the
presence of known or suspected infection) or current documented active bacterial or
viral infection prior to enrollment (Example: significant upper respiratory infection
(URI), community-acquired pneumonia). A minor non-complicated community-acquired
urinary tract infection (UTI) would not be an exclusion but should be treated
promptly.
9. New parenchymal hemorrhage or new infarction larger the 15 milliliters 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.
10. Subject developed SAH-induced cardiac stunning prior to enrollment, with an ejection
fraction< 30%, or requiring intravenous medications for blood pressure maintenance.
11. 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
(greater or equal to 70%), or malignant brain tumor.
12. 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.
13. 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.
14. Immunosuppression therapy including chronic corticosteroid usage.
15. Remote history of previous ruptured cerebral aneurysm.
16. History of gastrointestinal hemorrhage or major systemic hemorrhage within 30 days,
hemoglobin less than 8 g/dL, international normalized ratio greater than or equal
to1.5, severe liver impairment, creatinine greater than 2.0 mg/dL, or estimated
glomerular filtration rate less than 60 ml/min.
17. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30
days.
18. Currently pregnant.
19. Contraindication for MRI.
20. No hydrocephalus requiring EVD or LP.
21. Known hypersensitivity to Deferiprone or to any of the excipients in the formulation.
22. If endovascular treatment of their aneurysm requires adjunctive antiplatelet
treatment.
23. Uncontrollable hypertension (>180 systolic and/or >110 diastolic) that is not
correctable prior to enrollment.
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