Trial Outcomes & Findings for Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM) (NCT NCT03691727)

Last Updated: 2022-01-10

Results Overview

The hypothesis is that the prevalence of intracranial hemorrhage (symptomatic and asymptomatic) secondary to ventriculostomy/VPS placement during the course of Aggrastat use is within 10% difference when compared to control using Day 1 and Day 7 non-contrast head CT to determine.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Day 1 to Day 7

Results posted on

2022-01-10

Participant Flow

Participant milestones

Participant milestones
Measure	Tirofiban Hydrochloride (AGGRASTAT®) tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires tirofiban hydrochloride (AGGRASTAT®): Participants will have intravenous 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. MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.	Standard of Care Control Arm Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Standard of Care Treatment: Participants will receive standard of care treatment and will not receive study drug.
Overall Study STARTED	18	12
Overall Study COMPLETED	16	11
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tirofiban Hydrochloride (AGGRASTAT®) n=18 Participants tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires tirofiban hydrochloride (AGGRASTAT®): Participants will have intravenous 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. MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.	Standard of Care Control Arm n=12 Participants Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Standard of Care Treatment: Participants will receive standard of care treatment and will not receive study drug.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=99 Participants	11 Participants n=107 Participants	25 Participants n=206 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Sex: Female, Male Female	12 Participants n=99 Participants	12 Participants n=107 Participants	24 Participants n=206 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	0 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	13 Participants n=99 Participants	9 Participants n=107 Participants	22 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants	2 Participants n=107 Participants	6 Participants n=206 Participants
Region of Enrollment United States	18 Participants n=99 Participants	12 Participants n=107 Participants	30 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 7

Outcome measures

Outcome measures
Measure	Tirofiban Hydrochloride (AGGRASTAT®) n=18 Participants tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires tirofiban hydrochloride (AGGRASTAT®): Participants will have intravenous 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. MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.	Standard of Care Control Arm n=12 Participants Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Standard of Care Treatment: Participants will receive standard of care treatment and will not receive study drug.
Number of Participants With Intracranial Hemorrhage (Symptomatic and Asymptomatic)	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 7

The measurement of then incidence of delayed cerebral ischemia /clinical vasospasm in Tirofiban/Aggrastat group vs. placebo

Outcome measures

Outcome measures
Measure	Tirofiban Hydrochloride (AGGRASTAT®) n=18 Participants tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires tirofiban hydrochloride (AGGRASTAT®): Participants will have intravenous 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. MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.	Standard of Care Control Arm n=12 Participants Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Standard of Care Treatment: Participants will receive standard of care treatment and will not receive study drug.
Number of Participants With Delayed Cerebral Ischemia /Clinical Vasospasm	1 Participants	4 Participants

Adverse Events

Tirofiban Hydrochloride (AGGRASTAT®)

Serious events: 18 serious events

Other events: 18 other events

Deaths: 1 deaths

Standard of Care Control Arm

Serious events: 12 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

David Hasan

University of Iowa

Phone: 319-384-8669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tirofiban Hydrochloride (AGGRASTAT®) n=18 participants at risk tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires tirofiban hydrochloride (AGGRASTAT®): Participants will have intravenous 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. MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.	Standard of Care Control Arm n=12 participants at risk Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires MRI: Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. Neurological Exam: Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Questionnaires: Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits. Vital Signs: Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. Standard of Care Treatment: Participants will receive standard of care treatment and will not receive study drug.
Respiratory, thoracic and mediastinal disorders Acute Hypoxic Respiratory Failure	11.1% 2/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Cerebral Edema	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Clinical Vasospasm	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	33.3% 4/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Vascular disorders Deep Vein Thrombosis (DVT)	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	16.7% 2/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Product Issues External Ventricular Drain (EVD) Malfunction	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Ventriculitis	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Encephalopathy	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Infections and infestations Enterocolitis Infectious	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Infections and infestations Pneumonia	11.1% 2/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Cardiac disorders Atrial Fibrillation	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Cardiac disorders Atrial fibrillation with rapid ventricular response	11.1% 2/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Frontal Lobe Ischemia	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Cardiac disorders Hypotension	22.2% 4/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Ileus	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Intracranial Hypertension	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Intracranial Hypertension with Cerebral Edema	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Neurogenic Pulmonary Edema	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Parietal Punctate Infarcts	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Radiographic Vasospasm	11.1% 2/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Nervous system disorders Subdural Hematoma	0.00% 0/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	8.3% 1/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Psychiatric disorders Suicidal Ideation	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.
Blood and lymphatic system disorders Vasogenic Edema	5.6% 1/18 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.	0.00% 0/12 • Enrollment to 1 year follow up appointment (+/- 1 month from enrollment) All adverse events were collected for 11 days after initial dose. From Day 11 until 6 weeks serious adverse events and adverse events of special interest were monitored. From 6 weeks until 1 year follow up appointment only serious adverse events were monitored.