The Vesalio Neva VS for the Treatment of Symptomatic Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage (aSAH) (The VITAL Study)
Phase: NA
Conditions: Cerebral Vasospasm
Sponsor: Vesalio

THE VESALIOTM  NEVA VS FOR THE TREATMENT OF 
SYMPTOMATIC CEREBRAL VASOSPASM FOLLOWING 
ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH) 
(VITAL) 
Protocol VS-002 / E 
NCT03611790
September 23, 2020 
SPONSOR 
Vesalio 
200 West End Ave, Ste 500 
Nashville, TN 37203 
Clinicaltrials.gov Cover Sheet

Protocol VS-002/E 
CONFIDENTIAL 
Vesalio 
Page 1 of 92 
THE VESALIOTM  NEVA VS FOR THE TREATMENT OF 
SYMPTOMATIC CEREBRAL VASOSPASM FOLLOWING 
ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH) 
(VITAL) 
Protocol VS-002 / E 
September 23, 2020 
SPONSOR 
Vesalio 
200 West End Ave, Ste 500 
Nashville, TN 37203 
DISCLOSURE STATEMENT 
This document contains information that is confidential and proprietary to Vesalio (a dba of 
Legacy Ventures LLC).  This information is being provided to you solely for the purpose of 
evaluating or conducting a clinical study for Vesalio.  You may disclose the contents of this 
document only to study personnel under your supervision who need to know the contents for this 
purpose and to your Institutional Review Board (IRB), otherwise the contents of this document 
may not be disclosed without the prior authorization from Vesalio.  The foregoing shall not apply 
to disclosure required by governmental regulations or laws.  Any supplemental information that 
may be added to this document also is confidential and proprietary to Vesalio and must be kept 
in confidence in the same manner as the contents of this document. 

 
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INVESTIGATOR’S AGREEMENT 
 
 
I, the undersigned, am responsible for the conduct of the study at the site below and agree to the 
following:   
 
• I understand that this protocol is a confidential document.  I agree that the information within 
it will not be disclosed to anyone without prior written authority from the sponsor, Vesalio, 
except to the extent necessary to conduct this study and obtain approval from the Institutional 
Review Board (IRB) or other approving body.   
• I understand and will conduct the study according to the protocol, any approved protocol 
amendments, ICH GCP and all applicable regulatory authority requirements and national 
laws.   
• I will not deviate from the protocol without prior written permission from the Sponsor and 
prior review and written approval from the IRB, except where necessary to prevent any 
immediate danger to the subject.   
• I have sufficient time to properly conduct and complete the study within the agreed study 
period, and I have available an adequate number of qualified staff and adequate facilities for 
the foreseen duration of the study to conduct the study properly and safely.   
• I will ensure that any staff members at my site(s) who are involved in the study conduct are 
adequately trained regarding this trial’s operations, the protocol and their responsibilities. In 
the case of delegating any of my study responsibilities I will provide the sponsor with a 
delegation of investigators responsibilities log.   
• I understand that the study may be terminated, or enrollment may be suspended at any time 
by Vesalio with or without cause, or by me or my institution if it becomes necessary to 
protect the best interest of the study subjects.   
 
 
 
Principal Investigator’s Name (print) 
 
 
 
Title 
 
 
 
Address 
 
 
 
Signature / Date 
 
 
 

 
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STUDY SYNOPSIS 
 
PROTOCOL TITLE 
The VesalioTM Neva VS for the Treatment of Symptomatic 
Cerebral Vasospasm Following Aneurysmal Subarachnoid 
Hemorrhage (aSAH) (The VITAL Study) 
 
INVESTIGATIONAL 
DEVICE 
NeVa VS device 
POPULATION 
Subjects aged ≥ 18 years presenting with symptomatic cerebral 
vasospasm despite maximal medical management following aSAH. 
 
STUDY DESIGN 
A prospective, open label, single-arm study designed to assess the 
safety and probable benefit of the Neva VS device in patients 
presenting with symptomatic cerebral vasospasm following aSAH.   
 
Up to 150 eligible subjects at up to 15 sites will participate in the 
study.  Safety will be monitored throughout the study and assessed 
regularly by an independent Data Safety Monitoring Board (DSMB). 
 
STUDY OBJECTIVES 
The objective of the study is to assess the safety and probable benefit 
of the Neva VS device in patients presenting with symptomatic 
cerebral vasospasm despite maximal medical management following 
aSAH.   
 
Outcomes include safety, procedural success and clinical 
improvement.    
  
INCLUSION CRITERIA 
1. Age ≥ 18 years. 
2. Subarachnoid hemorrhage secondary to ruptured aneurysm. 
3. Ruptured aneurysm secured with surgical clipping or 
endovascular intervention. 
4. Digital subtraction angiography (DSA) or CT angiography at the 
time of aSAH clinical presentation or aSAH intervention with 
well-visualized intra-cerebral vessels is available for review.  
5. Vasospasm in one or more of the following: the internal carotid 
artery (ICA), basilar, middle cerebral artery (MCA), anterior 
cerebral artery (ACA), or posterior cerebral artery (PCA) territory 
on transcranial Doppler (TCD), and/or CT angiography, and/or 
clinical signs of symptomatic vasospasm (change in level of 
consciousness, focal neurological deficit) confirmed by > 50% 
stenosis in these territories on DSA. 
6. Vasospasm despite maximized medical management defined as 
oral Nimodipine (unless contraindicated), systemic hypertension 
with systolic blood pressure (SBP) greater than 130 mmHg and 
euvolemia. 

 
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7. Target vessel pre-vasospasm diameter ≥ 2.0 mm and ≤ 4.0 mm. 
8. Subject or legal representative is able and willing to give 
informed consent. 
 
EXCLUSION CRITERIA 
1. The presence of an unsecured ruptured aneurysm.  Note 
unsecured unruptured aneurysms remote to the site of treated 
aSAH are not an exclusionary.  
2. Symptoms attributable to other causes (e.g., hydrocephalus, 
metabolic, infection). 
3. Hunt and Hess Grade of 5 
4. Large infarct on CT scan defined as ASPECTS 0-5. 
5. Intracranial hemorrhage not caused by aneurysm rupture. 
6. History of bleeding disorders. 
7. Baseline platelets < 30,000 
8. International normalized ratio (INR) > 1.7. 
9. Any known contraindications to mechanical dilation of 
vasospastic vessels including but not limited to: 
 
• Excessive vessel tortuosity that prevents the placement of the 
device 
• Evidence of rapidly improving neurological signs of stroke 
• Large territory completed cerebral infarction, edema with 
mass effect and intra-parenchymal hemorrhage in vascular 
territory to be treated, or 
• any other vascular anatomic variants or anomalies  
 
10. Pre-existing neurological or psychiatric disease that would 
confound the neurological or functional evaluations, e.g. dementia 
with prescribed anti-cholinesterase inhibitor (e.g. Aricept). 
11. History of severe allergy to contrast medium. 
12. Known allergy to NeVa materials (nitinol, stainless steel). 
13. Suspected or confirmed septic embolus, or bacterial endocarditis. 
14. Septic shock or central nervous system (CNS) infection confirmed 
via cerebrospinal fluid (CSF) sampling. 
15. Known current or recent use of illicit drugs or alcohol abuse.  
16. Females who are pregnant or breastfeeding. 
17. Any other condition that, in the opinion of the investigator, 
precludes an endovascular procedure or poses a significant hazard 
to the subject if an endovascular procedure is performed. 
STUDY PROCEDURES 
Screening should be completed within 21 days post initial ictus 
(aSAH).  Due to the emergent nature of vasospasm, all patients 
admitted with SAH secondary to a ruptured aneurysm that was 
secured with surgical clipping or endovascular intervention with a 
Hunt and Hess Scale grade of 4 or less will proceed with screening. 
 

 
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Prior to screening, subjects (or their legal representative) will give 
informed consent.  Screening procedures include relevant medical 
history, vital signs, pre-hospital and current modified Rankin Scale 
(mRS), NIH Stroke Scale (NIHSS), non-contrast head CT-scan 
(NCCT) to determine ICH, concomitant medications, coagulation 
panel, and urine pregnancy test (unless already conducted at hospital 
admission; women of childbearing potential only).  Laboratory testing 
does not need to be repeated if testing was performed within the past 
72 hours.  The modified Fisher grade and Hunt-Hess grading system 
at time of aSAH will be documented.  
 
Note, the site will determine eligibility based on the in/exclusion 
criteria listed above.  Although, the core lab will assess specific 
parameters at Screening that are part of the eligibility criteria, the 
assessment by the Core Lab is for consistency across study 
participants and sites. 
 
On Day 0, (day of the NeVa VS intervention), subjects with 
confirmed vasospasm (defined as > 50% stenosis in the ICA, basilar, 
MCA, ACA, or PCA territory as demonstrated by DSA or CTA) 
within 21 days post SAH ictus will be eligible to undergo the 
interventional procedure.  All study images will be sent to the Core 
Lab. 
 
Eligible subjects will be treated with the appropriate sized NeVa VS 
device in all suitable affected vessels.  The NeVa VS device is a 
percutaneously introduced transluminal cerebral vasodilatation 
device that is temporarily inserted into the cerebral vasculature for 
the dilation of targeted spastic vessels with controlled expansive 
radial force.  The Neva VS device will be navigated into the affected 
vascular territory and deployed in the most distal size compatible 
segment.  The Neva VS device will be deployed from a distal 
location to proximal location by unsheathing and re-sheathing the 
device, retracting the microcatheter and unsheathing and re-sheathing 
more proximally until the entire size compatible, affected area has 
been treated.  A final DSA will be performed at the end of the 
procedure to characterize the degree of narrowing in the treated 
portion of the target vessel.  Procedural complications and procedural 
success will be documented.  Use of any balloon angioplasty 
intervention as a rescue therapy is off-label and prohibited in this 
study. 
 
At 24-hours (±6 hours) post intervention, a non-contrast head CT 
scan and TCD will be obtained as indicated. In addition, a NIHSS 
will be obtained.  Vital signs, concomitant medications, and adverse 
events will also be assessed.  

 
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At Day 21 post aSAH or hospital discharge (whichever occurs first), 
a non-contrast head CT-scan, TCD, NIHSS, mRS will be obtained.  
Concomitant medications, and adverse events will be assessed. 
 
At Day 30 (± 7 days) post intervention (treatment with NeVa VS), 
mRS, and adverse events will be assessed.  
 
If vasospasm recurs in a previously treated segment or in another 
(different) vessel / territory or different segment of a previously 
treated vessel after treatment of the initial vasospasm segment (s) but 
prior to hospital discharge, treatment with the NeVa VS is allowed if 
the subject still meets all study entry criteria.  If a subject is retreated, 
he or she will be followed up for 30 more days per the retreatment 
schedule in Appendix 1.  All treated areas will be imaged 
accordingly. 
 
CONCOMITANT 
MEDICATIONS / 
PROCEDURES 
Subjects for whom oral nimodipine is indicated are treated with oral 
nimodipine at standard dose of 60mg PO/NGT Q 6 hours without 
prevention of the development of vasospasm.  
 
Use of any balloon angioplasty intervention as a rescue therapy is 
off-label and prohibited in this study. 
 
SCHEDULE OF 
EXAMINATIONS 
Screening (Day 0 to 21 post-aSAH) 
Day 0 – NeVa VS intervention (within 21 days post aSAH) 
24 hrs ± 6 hrs post NeVa VS intervention 
Day 21 ± 2 days post aSAH or discharge (whichever occurs first) 
Day 30 post initial intervention with NeVa VS ± 7 days 
  
STUDY OUTCOMES 
• Procedural Success - defined as 50% or greater vessel caliber on 
DSA compared to baseline, as determined by the core laboratory. 
• Retreatment / additional treatment – the rate of retreatment or 
treatment of additional territories will be quantified. 
• Symptomatic Improvement - for clinically symptomatic patients, 
a decrease at 24 hours of ≥ 3-points from Screening as measured 
by NIHSS and/or resolution of pre-procedural clinical deficits.   
• Change in ASPECT Score –change in ASPECT score on NCCT 
from Screening to Day 21 post aSAH or discharge, whichever 
occurs first  
• Clinical Status – Change in modified Rankin Scale score from 
Screening at Day 30 
 
SAFETY 
All subjects that have a Neva VS device introduced into their 
vasculature (regardless of the ability to reach the target location) will 
be included in the safety analysis population.  Adverse events 

 
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(including serious adverse device effects, procedure related serious 
adverse events, and any adverse events leading to treatment 
discontinuation) throughout the 30-Day follow-up will be described 
according to severity and to their relationship with the study device 
and procedure.  Descriptive statistics (N, mean, median, SD, 
minimum and maximum values, where applicable) will be used to 
characterize safety parameters. 

 
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TABLE OF CONTENTS 
 
INVESTIGATOR’S AGREEMENT ...................................................................................................... 2 
STUDY SYNOPSIS ............................................................................................................................. 3 
TABLE OF CONTENTS ..................................................................................................................... 8 
ABBREVIATIONS ........................................................................................................................... 11 
PERSONNEL AND FACILITIES ....................................................................................................... 12 
1. 
DELAYED CEREBRAL ISCHEMIA DUE TO SYMPTOMATIC CEREBRAL VASOSPASM FOLLOWING 
ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH) ........................................................13 
1.1. 
Pathophysiology .....................................................................................................13 
1.2. 
Current Treatment Options ....................................................................................14 
1.3. 
Unmet Clinical Need..............................................................................................14 
1.4. 
Mechanical Dilatation for Prevention of Vasospasm ............................................14 
1.5. 
Study Goals ............................................................................................................16 
2. 
NEVA VS DEVICE DESCRIPTION AND PRINCIPLES OF OPERATION .........................................16 
2.1. 
Device Description.................................................................................................16 
2.1.1. 
The Expandable Tip .................................................................................17 
2.1.2. 
Pusher Assembly ......................................................................................19 
2.2. 
Proposed Indications for Use .................................................................................19 
2.3. 
Principles of Operation ..........................................................................................19 
2.3.1. 
Vasodilation with the NeVa VS ...............................................................22 
2.3.2. 
Preclinical Data ........................................................................................23 
3. 
GOOD CLINICAL PRACTICES (GCP) STATEMENT ...................................................................24 
4. 
INVESTIGATIONAL PLAN ........................................................................................................25 
4.1. 
Study Objectives ....................................................................................................25 
4.2. 
Study Design ..........................................................................................................25 
4.3. 
Subject Population .................................................................................................27 
4.3.1. 
Inclusion Criteria ......................................................................................27 
4.3.2. 
Exclusion Criteria .....................................................................................27 
4.4. 
Study Procedures ...................................................................................................28 
4.4.1. 
Informed Consent .....................................................................................28 
4.4.2. 
Subject Identification ...............................................................................28 
4.4.3. 
Screening (Day 0 to Day 21 Post aSAH) .................................................29 
4.4.3.1. 
Screen Failures .........................................................................29 
4.4.4. 
Day 0 – NeVa VS Intervention ................................................................30 
4.4.4.1. 
Digital Subtraction Angiography (DSA) .................................30 
4.4.4.2. 
Endovascular Treatment ..........................................................30 
4.4.5. 
24 Hrs ± 6 hours post treatment with Neva VS ........................................31 
4.4.6. 
Day 21 ± 2 Days post aSAH or Discharge (whichever occurs first) ........31 
4.4.7. 
Day 30 ± 7 Days post initial treatment with NeVa VS ............................31 
4.4.8. 
Additional Treatment or Retreatment After Initial Intervention ..............31 
4.4.9. 
Unscheduled Visits ...................................................................................31 

 
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4.5. 
Study Completion ..................................................................................................32 
4.5.1. 
Completed Subjects ..................................................................................32 
4.5.2. 
Discontinued Subjects ..............................................................................32 
4.5.3. 
Premature Study Termination ..................................................................32 
4.6. 
Investigational Device Accountability ...................................................................33 
4.7. 
Concomitant Medication ........................................................................................34 
5. 
EXAMINATIONS AND EVALUATIONS ......................................................................................34 
5.1. 
Evaluations Conducted at Screening Only ............................................................34 
5.1.1. 
Medical History ........................................................................................34 
5.1.2. 
Laboratory Testing ...................................................................................35 
5.1.3. 
Pregnancy Test (women of childbearing potential only) .........................35 
5.1.4. 
Modified Fisher Scale ..............................................................................35 
5.1.5. 
Hunt-Hess Grading System ......................................................................35 
5.2. 
Evaluations Conducted During the Study ..............................................................36 
5.2.1. 
Vital Signs ................................................................................................36 
5.2.2. 
Imaging to Determine Intracranial Hemorrhage ......................................36 
5.2.3. 
Transcranial Doppler (TCD) ....................................................................37 
5.2.4. 
CT Angiography .......................................................................................37 
5.2.5. 
Digital Subtraction Angiography (DSA) ..................................................37 
5.2.6. 
Modified Rankin Scale (mRS) .................................................................37 
5.2.7. 
NIH Stroke Scale (NIHSS) .......................................................................38 
5.2.8. 
Concomitant Medications .........................................................................38 
6. 
EVALUATION OF ADVERSE EVENTS .......................................................................................38 
6.1. 
Definitions..............................................................................................................39 
6.2. 
Assessment of Adverse Events (AEs)....................................................................39 
6.3. 
Reporting/Recording of AEs..................................................................................41 
6.4. 
SAEs Requiring Expedited Reporting ...................................................................41 
6.5. 
Anticipated Complications/AEs.............................................................................42 
6.6. 
Device Malfunction ...............................................................................................44 
7. 
STATISTICAL METHODS .........................................................................................................45 
7.1. 
Patient Categorization ............................................................................................45 
7.2. 
Study Outcomes .....................................................................................................45 
7.3. 
Safety .....................................................................................................................46 
7.4. 
Statistical Analyses ................................................................................................46 
8. 
IMAGING CORE LABORATORY ...............................................................................................46 
9. 
DATA SAFETY MONITORING BOARD (DSMB) .......................................................................46 
10. 
ACCESS TO STUDY DOCUMENTS AND STUDY MONITORING...................................................46 
11. 
QUALITY CONTROL AND ASSURANCE....................................................................................47 
11.1. 
Training ..................................................................................................................47 
12. 
INSTITUTIONAL REVIEW BOARD (IRB) ..................................................................................47 
13. 
INFORMED CONSENT PROCESS ...............................................................................................48 
14. 
CONFIDENTIALITY .................................................................................................................49 

 
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15. 
PROTOCOL AMENDMENTS .....................................................................................................49 
16. 
DATA MANAGEMENT .............................................................................................................49 
17. 
RECORD KEEPING AND RETENTION .......................................................................................50 
18. 
INVESTIGATOR FINAL REPORT ...............................................................................................51 
19. 
STUDY REPORT AND PUBLICATION ........................................................................................51 
20. 
REFERENCES ..........................................................................................................................53 
 
 
FIGURES &TABLES 
 
Figure 1. 
Arterial anatomy ............................................................................................. 15 
Figure 2. 
NeVa VS device .............................................................................................. 17 
Figure 3. 
NeVa VS Expandable tip ................................................................................ 17 
Figure 4. 
NeVa VS Central twisting tether design ......................................................... 18 
Figure 5. 
NeVa VS Distal marker configurations (a) standard (b) extended ................. 18 
Figure 6. 
NeVa VS Pusher Assembly ............................................................................ 19 
Figure 7. 
Microcatheter Navigation to the Target Vessel .............................................. 20 
Figure 8. 
Advancement of the NeVa VS in a Target Vessel .......................................... 20 
Figure 9. 
Deployment of the NeVa VS in a Target Vessel, including placement in artery 
branch (right) .................................................................................................. 21 
Figure 10. 
Example of Dilation Forces with the NeVa VS .............................................. 21 
Figure 11. 
Serial Segment Vessel Dilation with the NeVa VS ........................................ 22 
Figure 12. 
ASPECTS score .............................................................................................. 36 
 
Table 1. 
Feature Comparison Between the NeVa VS, and the Commercially Available 
Solitaire, and Trevo Stent Retrievers .............................................................. 22 
Table 2. 
Modified Fisher Scale ..................................................................................... 35 
Table 3. 
Hunt Hess Grading System ............................................................................. 35 
Table 4. 
mRS................................................................................................................. 38 
Table 5. 
NIHSS ............................................................................................................. 38 
 
 
TABLE OF APPENDICES 
 
Appendix 1. 
Schedule of Evaluations and Visits................................................................. 59 
Appendix 2. 
Sample Informed Consent............................................................................... 62 
Appendix 3. 
Neva VS Device – Draft Instructions for Use ................................................ 75 
Appendix 4. 
NIH Stroke Scale ............................................................................................ 79 
Appendix 5. 
Investigator’s Qualifications and Responsibilities.......................................... 88 
Appendix 6. 
Sponsor’s Commitments ................................................................................. 91 
 
 

 
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ABBREVIATIONS 
 
ACA 
Anterior Cerebral Artery 
AE 
Adverse Event 
aSAH 
Aneurysmal Subarachnoid Hemorrhage 
ASPECTS 
Alberta Stroke Program Early CT score  
β-HCG 
Beta Human Chorionic Gonadotropin 
BioMDG 
Biologics and Medical Device Consulting Group 
CFR 
Code of Federal Regulations 
CNS 
Central Nervous System 
CRO 
Clinical Research Organization 
CSF 
Cerebrospinal Fluid 
CT 
Computed Tomography 
CV 
Cerebral Vasospasm  
DCI 
Delayed Cerebral Ischemia 
DHHS 
Department of Health and Human Services 
DSA 
Digital Subtraction Angiography 
DSMB 
Data Safety Monitoring Board 
DVT 
Deep Vein Thrombosis 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
HDE 
Humanitarian Device Exemption 
HIPAA 
Health Insurance Portability and Accountability Act 
ICA 
Internal Carotid Artery 
ICH 
Intracranial Hemorrhage 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IVH 
Intraventricular hemorrhage 
LMW 
Low Molecular Weight 
 
MCA 
Middle Cerebral Artery 
mRS 
Modified Rankin Scale 
NCCT 
Non-Contrast CT 
NIH 
National Institutes of Health 
NIHSS 
NIH Stroke Scale 
NO 
Nitric Oxide  
PCA 
Posterior Cerebral Artery 
PI 
Principal Investigator 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RNS 
Reactive Nitrogen Species 
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
TCD 
Transcranial Doppler 
UADE 
Unanticipated Adverse Device Effect 
 
 

 
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PERSONNEL AND FACILITIES 
 
 
STUDY SPONSOR 
Vesalio (dba of Legacy Ventures LLC) 
3200 West End Ave 
Suite 500 
Nashville, TN 37203 
 
MEDICAL MONITOR 
Jonathan J. Ratcliff, MD, MPH Assistant Professor, Department 
of Emergency Medicine, Emory University, School of Medicine 
49 Jesse Hill Jr Dr 
Atlanta, GA 30303 
 
INVESTIGATORS 
Principal Investigator (for entire study): 
Dr. Arthur John Ulm III 
Nashville Neurosurgery Associates 
330 22nd Avenue North  
Nashville, TN 37203 
 
Other Investigators: TBD 
 
IMAGING CORE LAB 
Dr. David Liebeskind, MD, FAAN, FAHA, FANA 
Professor of Neurology and Director, Neurovascular Imaging 
Research Core 
UCLA Department of Neurology 
Neuroscience Research Building 
635 Charles E Young Drive South, Suite 225  
Los Angeles, CA 90095-7334 
 
 
CLINICAL RESEARCH 
ORGANIZATION (CRO) 
Biologics and Medical Device Consulting Group (BioMDG) 
20370 Skyhawk Lane 
Topanga, CA 90290 
Phone: (310) 455-3473 
Fax: (888) 295-1535 
 
 
 
 

 
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1. 
DELAYED CEREBRAL ISCHEMIA DUE TO SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH) 
In the US, the annual incidence of all strokes is 795,000.   Eighty-seven percent (87%) are 
ischemic, 10% are intracranial hemorrhage (ICH) strokes, and 3% are SAH strokes.1  
Eighty-five percent (85%) of SAH is aneurysmal, with the remaining attributed to 
traumatic brain injury, vascular malformations, and to inflammatory and non-inflammatory 
lesions.2  The 24-hour mortality rate for aneurysmal SAH (aSAH) is 20%, with 10% - 15% 
acute mortality before reaching the hospital, and 10% mortality within 24 hours of 
hospitalization.1,3,4  The majority of patients who survive to hospitalization are treated 
using either an endovascular intervention (coiling) or by surgical clipping.  Delayed 
cerebral ischemia (DCI) can occur in up to 45% of patients 3-14 days post-intervention.5-20  
It is thought to be caused by the combined effects of vasospasm, arteriolar constriction and 
thrombosis, cortical spreading ischemia, and neuroinflammatory processes triggered by the 
initial ictus,11,21-23 and accounts for almost 50% of the deaths following aSAH.24-26  
 
1.1. 
PATHOPHYSIOLOGY 
Cerebral vasospasm (CV) is strongly associated with DCI, and, although it is not the 
only contributing factor to poor clinical outcomes, it is the most important and 
potentially treatable cause of morbidity and mortality after aSAH.  As in other body 
systems, (e.g. coronary artery vasospasm), vasospasm of arteries in the brain is 
thought to be precipitated by a confluence of multiple pathological processes that 
result in a reduction of nitric oxide (NO) bioavailability.  NO has a direct 
vasodilation effect and plays a significant role in modulating endogenous 
vasoconstrictive agents (e.g. production and release of endothelin-1 [ET-1] and 
thromboxanes), and in mediating the inflammatory response.27   
 
In the coronary arteries, vasospasm may occur because of ischemic conditions, 
endothelial cell damage, and oxidative stress.  In the brain, the main driver of 
vasospasm is thought to be the release of ferrous hemoglobin and erythrocyte 
contents through hemolysis during the initial ictus.  NO is upregulated in response to 
the insult.  However, the large amount of extracellular hemoglobin and other blood 
products in the subarachnoid space are thought to reduce NO bioavailability by 
acting as an NO “sink”.  Additionally, in the context of this exaggerated 
inflammation, excess NO production can be harmful.  Reactive nitrogen species 
(RNS), especially peroxynitrite, are capable of disrupting cellular metabolism, 
irreversibly damaging DNA, and ultimately causing cell death and damage to the 
adjacent cortex.27-29  Together with the net reduction in bioavailable NO, and the 
continued release of vasoconstrictive agents, voltage gated calcium channels are 
opened causing the smooth muscle in the arteries to contract.30  
 
The severity of the vasospasm is related to volume, density and persistence of the 
initial subarachnoid thrombus, the degree of early brain injury, and to other 
underlying conditions that can reduce brain oxygen.31  Severe vasospasm (> 50% 
narrowing) within the DCI window (at approx. day 7 post ictus) is highly suggestive 
of poor clinical outcomes.15,31,32  Prophylactic treatment with calcium channel 
blockers (both oral and targeted infusion) are often administered with the aim of 

 
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preventing smooth muscle depolarization and subsequent vasospasm.  However, the 
only drug approved for this specific indication, oral nimodipine, is largely 
ineffective,33 perhaps because it does not address the local reduction in bioavailable 
NO or the presence of other vasoactive agents. 
 
 
1.2. 
CURRENT TREATMENT OPTIONS 
Current standard of care for treatment of patients post aSAH is geared towards 
prevention of secondary DCI, particularly by detecting and reducing the incidence of 
vasospasm.15,24,25,34-37 The only FDA approved drug for the treatment of aSAH is oral 
nimodipine (tablet and suspension) and it is a class I recommendation. †24,25,33 
Targeted intraventricular infusion and intravenous nimodipine have been granted 
orphan status (5/28/2015 and 8/10/2017, respectively) and have shown some efficacy, 
but neither approach has been approved.38-40  Use of other vasodilators such as 
verapamil and milrinone have shown some level of success, but are not specifically 
approved for this indication.24,25,41  Although not approved for this use by FDA, its 
use is common and is part of the standard of care guidelines issued over the decades 
by the American Heart Association.24,42,43  Hyperdynamic therapy with induced 
hypertension, and augmentation of cardiac output using inotropic drugs has also 
shown some efficacy.24,25,41  Intra-arterial treatments such as luminal angioplasty are 
conducted using cardiac devices off-label [(Sprinter Legend balloon (Medtronic), 
Maverick (Boston Scientific), Gateway (Boston Scientific) and Scepter XC 
(Microvention)] with some success.44-46  NeuroFlo, a dual aortic balloon device was 
developed specifically for treatment of DCI by diverting blood flow to the brain and 
was approved under HDE H030005, but is no longer available in commercial 
distribution. 
 
 
1.3. 
UNMET CLINICAL NEED  
DCI continues to occur in up to 45% of patients post aSAH despite maximal medical 
care.  It is associated with a substantial burden on health care resources, most of 
which are related to long-term care and loss of productivity, as half of the patients 
affected are under the age of 55.1,2,9,11,47 
 
 
1.4. 
MECHANICAL DILATATION FOR PREVENTION OF VASOSPASM 
Cerebral angioplasty conducted with a variety of endovascular catheters has 
demonstrated improvement, and occasionally, permanent reversal of vasospasm in 
treated vessels.44-46,48-53  Arterial dilatation was first discussed in the peer-reviewed 
literature in 1984,54 and has steadily gained acceptance as a viable treatment option 
for patients that fail maximal medical therapy.  Due to the low incidence of this 
condition, however, cerebral angioplasty has not been studied in an adequately 
powered controlled randomized study.  Nonetheless, the reported neurological 
 
†  
See approved labeling (https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018869s014lbl.pdf  and 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203340lbl.pdf ) 

 
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improvement rates using this treatment strategy are far better than the documented 
natural history of the disease. 
 
Physiological Effect of Mechanical Dilatation.  Circumferential dilation of an 
artery causes a ‘controlled injury.’  The stretch can cause endothelial denudation, 
fracture of the intima, medial thinning and tearing of the adventitia.  These 
mechanical effects alter the connections between the smooth muscle cells in the 
media and their elastic fibers.   
 
 
Figure 1. Arterial anatomy 
 
Several studies have demonstrated that arterial dilatation decreases arterial 
contractility and some have seen arterial paralysis.55  Arterial dilatation may largely 
be efficacious because of the disconnection of the endothelium from the media and 
because of the disruption of connective tissues that proliferate in the vessel wall after 
a subarachnoid hemorrhage.  The effect is both mechanical and biochemical.  The 
mechanical overstretching causes a paralytic injury,56,57 while the disconnection of 
the endothelium eliminates the local release of endothelium derived vasoconstricting 
factors (e.g. ET-1, thromboxanes) and disrupts the calcium channel inputs into the 
media.58  
 
Current Procedural Limitations.  There are no commercially available, FDA-
approved devices available for the treatment of CV, and devices used off-label can 
only be safely deployed in the most proximal vessel segments; internal carotid and 
vertebrobasilar arteries and the first segment of the middle cerebral artery (MCA). 
Accessing and treating vasospasm in the anterior cerebral arteries, M2 MCA and 
Posterior cerebral arteries is more problematic and associated with higher 
complication rates. Fatal arterial ruptures, branch occlusion, displacement of 
aneurysm clip or re-rupture of a treated aneurysm during balloon dilation have been 

 
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reported.26,44,59  In addition, because balloon dilation is an occlusive process, the 
procedure may further harm an already ischemic brain. 
 
Stent Retriever Based Angioplasty - A New Approach for Managing CV.  The use of 
stent retrievers (stentrievers) to cause vasodilation in patients with delayed cerebral 
vasospasm secondary to subarachnoid hemorrhage was recently published.60 The 
small proof of concept case series (4 patients) reported the use of the Solitaire and 
Capture stent retrievers to safely achieve vasodilation with long-lasting therapeutic 
effect (> 24 hours).  In two of the cases, stent angioplasty resulted in a reversal of 
focal neurological symptoms. 
 
The advantages of using a stent retriever over a balloon to dilate spastic cerebral 
arteries post aSAH include: 
 
• better maneuverability and safer deployment into distal and posterior segments;  
• controlled dilation using the intrinsic outward radial force, (as opposed to a fixed 
diameter expansion in balloon angioplasty which is operator dependent and can 
result in vessel rupture); and  
• the intervention is conducted without occluding blood flow to already severely 
compromised ischemic tissues. 
 
 
 
1.5. 
STUDY GOALS 
The objective of this study is to assess the safety and probable benefit of the NeVa 
VS device (a modified stent retriever) in patients presenting with symptomatic 
cerebral vasospasm despite maximal medical management following aSAH. 
 
 
 
 
2. 
NEVA VS DEVICE DESCRIPTION AND PRINCIPLES OF OPERATION 
The Vesalio NeVa™ VS device is a neuro mechanical percutaneously introduced 
transluminal cerebral dilatation device.  The design of the NeVa VS is based on the 
common design for stentrievers (e.g., TREVO Retrievers (DEN150049) and Solitaire 
Revascularization Device (K162539)). 
 
2.1. 
DEVICE DESCRIPTION 
The NeVa VS device has a self-expanding nitinol stent-like scaffolding tip attached 
to a nitinol push wire.  The device can only be delivered through a Trevo Pro 18 
Microcatheter.  
  

 
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Figure 2. NeVa VS device 
 
When deployed at the target treatment area, the tip (which was compressed in the 
microcatheter), expands into its original shape in the artery and applies expansive 
radial forces to the wall of the artery.  The NeVa VS can be deployed in the M1 and 
M2 branches of the middle cerebral artery (MCA), intracranial internal carotid artery 
(ICA), intracranial vertebral artery, basilar artery, and the P1 posterior cerebral artery 
(PCA).  
 
The device is provided sterile and is intended for single-use only. 
 
2.1.1. THE EXPANDABLE TIP 
The expandable tip on the distal end of the NeVa VS is constructed of a tubular 
scaffolding laser cut from Nitinol tube stock.  It has tapered distal and proximal ends 
and a proprietary scaffolding design to optimize expansive radial forces for effective 
dilation force.  Figure 3 depicts the closed cell configuration in its expanded state. 
 
 
Figure 3. NeVa VS Expandable tip 
 
The total length of the NeVa VS tip is 35 mm, the length of the fully expanded 
diameter is 22 mm with 4mm of gradual taper on either side.  The expanded outside 

 
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diameter is 4 mm and the device configuration can be deployed in vessels with a pre-
vasospasm diameter from 2.0 – 4.0 mm. 
 
The design of the expandable tip integrates the following set of key features: 
 
• Radiopaque markers positioned on the structure at proximal and distal ends to 
ensure fluoroscopic visualization during placement; 
• Gradual double ended taper as opposed to a uniform diameter (as seen in other 
stent retrievers) to allow for a more distal deployment in a vessel; 
• Two central twisting tethers in the middle of the tip (see Figure 4).  This feature 
provides enhanced flexibility and maneuverability, particularly if the vasospasm 
is occurring in a branched segment of the vasculature.  
 
 
Figure 4. NeVa VS Central twisting tether design 
 
Two versions of the NeVa VS are available.  They only differ in the configuration of 
radiopaque markers for fluoroscopic visualization on the tip.  Both versions have a 1 
mm radiopaque marker coil (92% Platinum/ 8% Tungsten) at the proximal end.  Both 
also have a radiopaque marker coil on the distal end. The standard NeVa VS has the 
same 1 mm radiopaque marker on the distal end as on the proximal end.  The 
enhanced visualization version has an extended radiopaque marker coil that is 5 mm 
in length (same materials and radial dimensions, only 4 mm longer). An illustration of 
the two (2) distal end marker coils is provided in Figure 5.   
 
 
Figure 5. NeVa VS Distal marker configurations (a) standard (b) extended 
 

 
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Both distal radiopaque markers (standard and extended) provide visual indication 
under fluoroscopy, however, the extended marker is available for clinicians that 
prefer enhanced visualization. 
 
2.1.2. PUSHER ASSEMBLY 
The pusher assembly is comprised of an introducer and delivery pusher that are used 
to deliver the expandable tip to the treatment site. 
 
 
Figure 6. NeVa VS Pusher Assembly 
 
The introducer consists of a polymer tube that protects the device and distal segment 
of the delivery pusher from damage.  When firmly seated in the hub of the 
microcatheter, the introducer creates an uninterrupted passage for the device to be 
advanced through the microcatheter. 
 
 
 
2.2. 
PROPOSED INDICATIONS FOR USE 
The NeVa VS is intended for the treatment of aneurysmal subarachnoid hemorrhage 
patients who experience symptomatic vasospasm despite maximal medical 
management. 
 
 
2.3. 
PRINCIPLES OF OPERATION 
The NeVa VS is a percutaneously introduced transluminal cerebral artery dilatation 
device that is temporarily inserted into the cerebral vasculature for the dilation of 
targeted vessels to treat SAH induced vasospasm.  The overall operation and 
deployment of the NeVa VS follows the same basic principles and procedures as for 
use of stentrievers.  However, instead of deploying the expandable tip to remove a 
thrombus, deployment of the expandable tip is intended to apply a controlled 
expansive radial force to dilate a spastic artery.  Following is a description of the 
device operation.  A discussion of the scientific rationale for mechanical dilatation 
for the treatment of CV can be found in Section 1.4. 

 
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1) A suitable guide catheter is placed in the vessel close to the targeted site(s). 
Using an appropriate guidewire, a microcatheter is advanced to the target vessel 
and then the catheter tip is positioned distal to the target site with sufficient space 
to deploy the NeVa VS into the target vessel.  The guidewire is retrieved, and the 
position of the catheter is confirmed used angiographic techniques. 
 
Figure 7. Microcatheter Navigation to the Target Vessel 
 
2) The NeVa VS device is transferred into the microcatheter and then advanced 
within the catheter using the push wire.  With aid of fluoroscopic monitoring, the 
NeVa VS expandable tip is advanced until its distal markers line up with the end 
of the catheter. 
 
Figure 8. Advancement of the NeVa VS in a Target Vessel 
 
3) The NeVa VS is deployed by fixing the push wire in place and withdrawing the 
microcatheter in the proximal direction.  The catheter is retracted until the 
catheter tip is just proximal of the proximal marker on the expandable tip. 

 
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Figure 9. Deployment of the NeVa VS in a Target Vessel, including placement in 
artery branch (right) 
 
4) Once deployed in the target vessel, the scaffolding structure of the NeVa VS tip 
intrinsically expands, providing a slow, controlled dilation. 
 
Figure 10. Example of Dilation Forces with the NeVa VS 
 
5) As needed, the stent can be resheathed back into the microcatheter and 
redeployed in the target vessel at additional multiple locations based on the 
judgement of the healthcare provider. 
6) After sufficient deployments of the stent have been performed in the target 
vessel, the device is retrieved into guide catheter as the device is completely 
retracted.  

 
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Figure 11. Serial Segment Vessel Dilation with the NeVa VS 
 
 
2.3.1. 
VASODILATION WITH THE NEVA VS  
The NeVa VS device design is a modification of the stent retrievers currently 
available in commercial distribution (Solitaire, Trevo) which have been safely used 
for a number of years for mechanical thrombectomy in ischemic stroke.  The design 
features of the NeVa VS are compared to these stentrievers in Table 1. 
 
Table 1. Feature Comparison Between the NeVa VS, and the Commercially 
Available Solitaire, and Trevo Stent Retrievers 
Design Features 
NeVa VS 
Solitaire 
Trevo 
Size* 
4-22 
 6-30 
4-20 
4-20  
Expansion diameter 
4.0 mm 
6.0 mm 
4.0 mm 
4.0 mm 
Distal Tip 
tapered 
uniform 
uniform 
uniform 
Compressive radial force 
(N/mm)† 
1.7 – 3.8 
1.9 - 4 
1.13-2.51 
2 - 3.5 
Expansive radial force 
(N/mm) † 
1 – 1.9 
0.6 – 1.4 
0-.058 
0.4 – 1.2 
Segmented design which 
allows deployment at a 
branching point in the 
artery 
yes 
no 
no 
no 
* 
For each device, the first value refers to the nominal diameter, the second value refers to the 
length expressed in mm 
† 
Bench testing results 
 
Unlike other stent retrievers which have a uniform diameter across the stent segment 
that cause a ‘ledge’ effect at the interface with the spastic segment, the NeVa VS’s 
tapered distal end provides a more gentle and anatomically conforming dilatation 
process.   
 
Current stent retrievers also have a high compressive radial force (the force required 
to externally compress the device) and a very low expansive radial force (force of 
stent expanding upon deployment), particularly at diameters over 2mm.  The NeVa 

 
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VS was engineered to have a similar compressive radial force as other stent 
retrievers, but a greater expansive radial force at every diameter of expansion across 
the indicated range.  This allows for more effective dilation force than other 
stentrievers, a stated deficiency in standard stentrievers design noted in the 
feasibility study discussed earlier in this section.60  Further, by limiting the dilation 
force to the intrinsic outward radial force of the device (in contrast to balloon 
catheters which can be expanded to a pre-fixed diameter) and performing the dilation 
over longer periods up to several minutes (as opposed seconds for a balloon 
catheter), the potential for injury to the vessel is reduced.  
 
Finally, two additional design enhancements make the NeVa VS more suitable for 
treating CV: 
 
• The NeVa VS has two large twisting tethers in the middle of the stent which 
allow the device to be deployed into two branch points around bends in the artery 
without causing significant deformation. And,  
• the NeVa VS has a proximal taper which allows the deployed device to be 
withdrawn from a distal position to a more proximal position and to sequentially 
dilate the vessel.  
 
2.3.2. 
PRECLINICAL DATA 
The ability of the NeVa VS to safely dilate vasospastic arteries was demonstrated in 
a small GLP study in the juvenile porcine model.  Three (3) Yorkshire crossbred 
pigs were used as the animal model for the study.  The porcine model was chosen 
because the animals have similar arterial sizes as humans and have similar 
hemodynamic properties that could affect device use.  In addition, the selected 
animal model has similar vessel wall thickness, smooth muscle reactivity, and 
clotting processes to humans.  Two (2) of the animals were used for acute evaluation 
and one (1) for chronic evaluation. 
 
The following test and control devices were tested as part of this study: 
 
• NeVa VS (test article) 
• Trevo XP 4x20 stent retriever (control article) 
• Maverick angioplasty balloon (control article) 
 
Three (3) test articles and three (3) control articles were deployed in separate target 
arteries in each animal.  NeVa VS test articles were deployed in all three (3) animals, 
two (2) for acute and one (1) for chronic evaluation.  The Trevo XP was deployed in 
a single animal for acute comparison to the NeVa VS and the Maverick balloon 
catheter was deployed in two (2) animals for both acute and chronic comparison to 
the NeVa VS. 
 
There were no complications noted during insertion, deployment, or retraction for 
any of the test or control articles deployed.  A total of 54 deployments with the 
NeVa VS test article were performed evenly over 9 arteries (across 3 animals).  For 

 
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the Maverick control article, a total of 36 deployments were performed evenly over 6 
arteries (across 2 animals).  With the Trevo control article, a total of 18 deployments 
were performed over 3 arteries (a single animal).  No mechanical damage was 
observed with any of the test or control articles during the procedure.  There were no 
incidents of vessel perforation.  All three (3) animals remained stable under 
anesthesia without complications and survived to the end of the procedure.   
 
After deployment of each test and control article at the treatment sites, various 
degrees of spasm were observed.  Overall for the NeVa VS, spasm was temporary in 
all cases and recovered to a baseline level (Score = 0) in 7 of 9 treatment sites and to 
a Score = 1 (10% slight narrowing) and Score = 2 (27% moderate narrowing) for the 
two remaining sites.  In comparison, for the Trevo controls all three treatment sites 
only recovered to a Score = 1 (21%, 24%, and 23% narrowing) and for the Maverick 
controls only 1 of 6 recovered to a baseline level, with two (2) of the sites recovering 
to a Score of 1 and the remaining three (3) sites recovering to a Score = 2.  Mean 
vessel scores after 60 minutes were 0.33 for NeVa VS, 1.0 for Trevo, and 1.33 for 
Maverick devices.  Based on these results, the arteries treated with the NeVa VS 
exhibited a lower level of vasospasm.  In general, swine arteries are susceptible to 
vasospasm, and the results seen here are comparable with other thrombectomy 
devices used in swine. This expected result was determined to not pose a significant 
safety risk. 
 
Histological findings did not reveal any significant downstream tissue effects.  In 
addition, observations from the pathological evaluation demonstrate that the NeVa 
VS had lower or similar scores for minor and superficial injuries to treatment vessels 
than the other devices.  Based on the results of the study, the deployment of the 
NeVa VS appears to be safe with no evidence of downstream effects and 
successfully meets the usability criteria for the device. 
 
 
 
 
 
3. 
GOOD CLINICAL PRACTICES (GCP) STATEMENT 
This trial will be conducted in compliance with all applicable federal regulations pertaining 
to investigational drugs and devices including but not limited to: 21 CFR Part 50, Part 54, 
Part 56, Part 812, and GCP standards.  This trial will be conducted in compliance with the 
protocol as approved by an Institutional Review Board (IRB).  Any deviations from the 
protocol that may affect the safety and welfare of study participants will be immediately 
reported to the Sponsor and to the IRB per each institution’s guidelines. 
 
 
 
 
 

 
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4. 
INVESTIGATIONAL PLAN 
 
4.1. 
STUDY OBJECTIVES 
The objective of the VITAL Study is to assess the safety and probable benefit of the 
Neva VS device (a modified stent retriever) in patients presenting with symptomatic 
cerebral vasospasm despite maximal medical management following aSAH. 
 
Outcomes include safety, procedural success and clinical improvement.     
 
 
4.2. 
STUDY DESIGN 
This is an open-label, single-arm, multicenter, 30-day study designed to assess the 
safety and probable benefit of the Neva VS device in patients presenting with 
symptomatic cerebral vasospasm following aSAH.  Up to 150 eligible subjects at up 
to 15 sites will participate in the study. 
 
Test results from routinely performed standard of care assessments in aSAH 
management may be used to determine eligibility.  Therefore, pre-screening without 
obtaining informed consent is allowed.  Due to the emergent nature of vasospasm, all 
patients admitted with SAH secondary to a ruptured aneurysm that was secured with 
surgical clipping or endovascular intervention with a Hunt and Hess Scale grade of 4 
or less will proceed with screening.  
 
The study will be thoroughly explained to the subject or his/her legal representative 
in order to obtain informed consent.  Informed consent can be obtained prior to onset 
of vasospasm.  Screening must be completed within 21 days post SAH ictus.   
 
Screening will include assessment of study eligibility, relevant medical history, vital 
signs, pre-hospital and current modified Rankin Scale (mRS), NIH Stroke Scale 
(NIHSS), non-contrast head CT-scan (NCCT) to determine ICH, concomitant 
medications, coagulation panel, and urine pregnancy test (unless  already conducted 
at hospital admission; women of childbearing potential only).  Laboratory testing 
does not need to be repeated if testing was performed within the past 72 hours.  The 
modified Fisher grade and Hunt-Hess grading system at time of aSAH will be 
documented.  
 
Patients who subsequently experience vasospasm in the ICA, basilar, MCA, ACA or 
PCA territory on TCD and/or clinical signs of symptomatic vasospasm (change in 
level of consciousness, focal neurological deficit) will be eligible to participate in the 
study.   
 
Note, the site will determine eligibility based on the in/exclusion criteria listed 
above.  Although, the core lab will assess specific parameters at Screening that are 
part of the eligibility criteria, the assessment by the Core Lab is for consistency 
across study participants and sites.  
 

 
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On Day 0, (day of the NeVa VS intervention), subjects with confirmed vasospasm 
(defined as > 50% stenosis in the ICA, basilar, MCA, ACA, or PCA territory as 
demonstrated by DSA or CTA) within 21 days post SAH ictus will be eligible to 
undergo the interventional procedure.  All study images will be sent to the Core Lab.  
Eligible subjects will be treated with the appropriate sized NeVa VS device in all 
affected vessels.   
 
The interventional procedure with the NeVa VS device will be performed as 
follows:   
The NeVa VS device is a percutaneously introduced transluminal cerebral 
vasodilatation device that is temporarily inserted into the cerebral vasculature for the 
dilation of targeted spastic vessels with controlled expansive radial force.  The Neva 
VS device will be navigated to the most distal size compatible location of the 
affected area.  It will be deployed from distal location to proximal location by 
unsheathing and re-sheathing the device, retracting the microcatheter and 
unsheathing and re-sheathing more proximally until the entire size compatible 
affected area has been treated.  A final DSA will be performed at the end of the 
procedure to characterize the degree of narrowing in the treated segment(s) of the 
target vessel. Procedural complications and procedural success will be documented. 
 
At 24-hours (± 6 hours) post intervention, imaging to determine ICH (NCCT), TCD 
and NIHSS will be obtained.  Vital signs, concomitant medications, and adverse 
events (AEs) will also be assessed.  
 
If vasospasm recurs in a previously treated segment or in another (different) vessel / 
or a previously treated vessel segment or territory after treatment of the initial 
vasospasm but prior to hospital discharge, treatment with the NeVa VS is allowed if 
the subject still meets all study entry criteria.  If a subject is retreated, he or she will 
be followed up for 30 more days per the retreatment schedule in Appendix 1.  All 
treated areas will be imaged accordingly. 
 
At Day 21 (± 2 days) post aSAH or hospital discharge (whichever occurs first), 
imaging to determine ICH (NCCT), TCD, NIHSS, mRS will be obtained.  
Concomitant medications, and adverse events will be assessed. 
 
At Day 30 (± 7 days) post intervention (initial treatment with NeVa VS), mRS, and 
adverse events will be assessed. 
 
Note, all non-contrast CT or MRI (if obtained), CTA and DSA acquired during the 
index hospitalization will be transmitted to the core lab for review. 
 
A summary of the schedule of evaluations and visits can be found in Appendix 1. 
 
 
 
 

 
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4.3. 
SUBJECT POPULATION 
Up to 150 subjects with aSAH meeting the following study entry criteria will be 
enrolled and treated.  
 
4.3.1. 
INCLUSION CRITERIA 
Subjects must satisfy all inclusion criteria to be included in the study: 
 
1. 
Age ≥ 18 years. 
2. 
Subarachnoid hemorrhage secondary to ruptured aneurysm. 
3. 
Ruptured aneurysm secured with surgical clipping or endovascular 
intervention. 
4. 
Baseline digital subtraction angiography (DSA) or CT angiography at the time 
of aSAH clinical presentation or  aSAH intervention with well-visualized 
intra-cerebral vessels is available for review.  
5. 
Vasospasm in one or more of the following: the internal carotid artery (ICA), 
basilar, middle cerebral artery (MCA), anterior cerebral artery (ACA), or 
posterior cerebral artery (PCA) territory on transcranial Doppler (TCD), 
and/or CT angiography, and/or clinical signs of symptomatic vasospasm 
(change in level of consciousness, focal neurological deficit) confirmed by > 
50% narrowing in these territories on DSA. 
6. 
Vasospasm despite maximized medical management defined as oral 
Nimodipine (unless contraindicated), systemic hypertension with SBP greater 
than 130 mmHg and euvolemia. 
7. 
Target vessel pre-vasospasm diameter ≥ 2.0 mm and ≤ 4.0 mm. 
8. 
Subject or legal representative is able and willing to give informed consent. 
 
 
4.3.2. 
EXCLUSION CRITERIA 
Subjects will not be eligible for the study if any of the following criteria are present: 
 
1. 
The presence of an unsecured ruptured aneurysm.  Note unsecured unruptured 
aneurysms remote to the site of treated aSAH are not an exclusionary.  
2. 
Symptoms attributable to other causes (e.g., hydrocephalus, metabolic, 
infection). 
3. 
Hunt and Hess Grade of 5 
4. 
Large infarct on CT scan defined as ASPECTS 0-5. 
5. 
Intracranial hemorrhage not caused by aneurysm rupture. 
6. 
History of bleeding disorders. 
7. 
Baseline platelets < 30,000 
8. 
International normalized ratio (INR) > 1.7. 
9. 
Any known contraindications to mechanical dilation of vasospastic vessels 
including but not limited to: 
 
• Excessive vessel tortuosity that prevents the placement of the device 
• Evidence of rapidly improving neurological signs of stroke 

 
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• Large territory completed cerebral infarction, edema with mass effect and 
intra-parenchymal hemorrhage in vascular territory to be treated, or 
• any other vascular anatomic variants or anomalies  
10. 
Pre-existing neurological or psychiatric disease that would confound the 
neurological or functional evaluations, e.g. dementia with prescribed anti-
cholinesterase inhibitor (e.g. Aricept). 
11. 
History of severe allergy to contrast medium. 
12. 
Known allergy to NeVa materials (nitinol, stainless steel). 
13. 
Suspected or confirmed septic embolus, or bacterial endocarditis. 
14. 
Septic shock or central nervous system (CNS) infection confirmed via 
cerebrospinal fluid (CSF) sampling. 
15. 
Known current or recent use of illicit drugs or alcohol abuse.  
16. 
Females who are pregnant or breastfeeding. 
17. 
Any other condition that, in the opinion of the investigator, precludes an 
endovascular procedure or poses a significant hazard to the subject if an 
endovascular procedure is performed. 
 
 
4.4. 
STUDY PROCEDURES 
Prior to recruitment of any subjects into the study, written approval of the protocol 
and informed consent must be obtained from the IRB. 
 
4.4.1. 
INFORMED CONSENT 
The investigator will explain the study purpose, procedures, and subject’s 
responsibilities to the potential participant and/or legal representative.  The subject's 
willingness and ability to meet the follow-up requirements will be determined and 
written informed consent will be obtained (Appendix 2).  The subject or legal 
representative will sign and date the informed consent form.  The investigator will 
also sign and date the consent form.  The original informed consent form will be 
retained with the subject records; a copy will be provided to the subject or legal 
representative.   
 
Following is a detailed list of study visits from screening to final follow-up and the 
required procedures/tests.  Methodologies for specific tests/ procedures are described 
in Section 4. 
 
4.4.2. 
SUBJECT IDENTIFICATION 
To maintain confidentiality, the subject’s name should not be recorded on any study 
document other than the informed consent form.  A subject is considered enrolled 
after informed consent has been obtained.  Each enrolled subject will be assigned a 
unique identifier in the following format: XX-YY-0.  XX is the 2-digit assigned site 
number, YY is the 2-digit sequential subject ID number starting with 01, and “0” 
defines the initial treatment.  If retreatment is needed, the subject is assigned the 
same site and subject number but now with treatment type “A” for the first 
retreatment, “B” for the second, etc.  For example, the first treatment of the first 
subject at site 04 will be assigned 04-01-0; if this subject requires retreatment, the 

 
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subject ID will be 04-01-A.  Subject ID numbers will not be re-used (e.g., if the 
subject is determined to be a screen failure).    
 
4.4.3. 
SCREENING (DAY 0 TO DAY 21 POST ASAH) 
Due to the emergent nature of vasospasm, all patients admitted with subarachnoid 
hemorrhage secondary to a ruptured aneurysm that was secured with surgical 
clipping or endovascular intervention with a Hunt and Hess Scale grade of 4 or less 
will proceed with screening. 
 
Prior to screening, the subject/legal representative will provide informed consent.  
Screening should be completed between Day 0 to Day 21 following aSAH.  Test 
results from routinely performed standard assessments may be used to determine 
eligibility including a DSA or CTA at time of aSAH presentation or aSAH 
intervention which must be available for review.  
 
Screening to determine eligibility will be assessed sequentially, starting with the 
least invasive and least expensive tests as follows.  Results from each test / 
screening activity should be reviewed prior to proceeding to the next step. 
 
• Evaluation of eligibility  
• Medical history (including modified Fisher scale and Hunt-Hess grading at time 
of aSAH) 
• Concomitant medications 
• Vital signs 
• Pre-hospital and current modified Rankin Scale (mRS) 
• NIH Stroke Scale (NIHSS) 
• Coagulation panel 
• Urine pregnancy test (women of childbearing potential only), Pregnancy test 
does not need to be repeated if obtained at current hospital admission.   
o Note, laboratory testing does not need to be repeated if testing was 
performed within the past 72 hours of the NeVa VS procedure and results 
are available.   
• Non-contrast head CT-scan to determine ICH. 
 
Patients who subsequently experience vasospasm in the ICA, basilar, MCA, ACA or 
PCA territory on TCD and/or clinical signs of symptomatic vasospasm (change in 
level of consciousness, focal neurological deficit) will be eligible to participate in the 
study.   
 
 
4.4.3.1. 
SCREEN FAILURES 
Subjects not meeting all study entry criteria will be designated as screen failures.  
End of study procedures will not be performed for these subjects, but their reason for 
ineligibility will be recorded on the Screening Log.  Screen failures are not counted 
towards total study enrollment.   
 

 
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4.4.4. 
DAY 0 – NEVA VS INTERVENTION 
 
4.4.4.1. 
DIGITAL SUBTRACTION ANGIOGRAPHY (DSA) 
DSA including AP and LAT views with late arterial phase in lateral view, will be 
obtained at the beginning of the intervention, and at the end of the procedure.  Take 
all necessary precautions to limit X-radiation doses to patients and themselves by 
using sufficient shielding, reducing fluoroscopy times, and modifying X-ray 
technical factors where possible. 
 
The DSAimaging study will be reviewed and assessed by an independent core 
laboratory after the procedure.   
 
4.4.4.2. 
ENDOVASCULAR TREATMENT 
Administer intravenous sedation or general anesthesia, as appropriate, to ensure 
subject safety and comfort.   
 
Systemic anticoagulation with heparin may be used during the procedure at the 
discretion of the neurointerventionist.  Use of IV or IA antiplatelets is strongly 
discouraged. 
 
The Neva VS device is a percutaneously introduced into the cerebral vasculature for 
the dilation of targeted spastic vessels with controlled expansive radial force.  The 
Neva VS device will be navigated to the most distal size compatible (≥ 2.0mm and ≤ 
4.0mm diameter on baseline DSA) location of the affected area.  The Neva VS 
device will be deployed from distal location to proximal location by unsheathing, 
controlled dilation, and re-sheathing the device, retracting the microcatheter and 
unsheathing, dilation and re-sheathing more proximally until the entire affected 
vascular territory has been treated.  Do not to advance or withdraw the device 
against resistance or significant vasospasm as moving or torqueing of the device 
against resistance or significant vasospasm may result in damage to the vessel or 
device. 
 
A final DSA will be performed at the end of the procedure to characterize the degree 
of narrowing in the treated segment(s) of the target vessel.  Procedural complications 
will be documented. 
 
Vesalio acknowledges that it may be your practice and / or your institution’s policy 
to use intra-arterial calcium channel blockers in treating patients that have 
experienced subarachnoid hemorrhage. We understand that this is done as a 
neuroprotective measure for these patients. This is consistent with and recommended 
by the American Heart Association as part of the standard of care. Please note, 
however, that this method and dose of administration has not been reviewed or 
approved by FDA for commercial use. 
 
Do not proceed with use of the NeVa VS device if the primary vasospasm is 
resolved post-intra-arterial administration of calcium channel blockers. We urge you 

 
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to continue to follow and comply with your institution’s policies and to document 
the type, time, dosage, and route of administration for this type of intervention (if 
used) in the Concomitant Medications form. 
 
Use of any balloon angioplasty intervention as a rescue therapy is off-label and 
prohibited in this study. 
 
4.4.5. 
24 HRS ± 6 HOURS POST TREATMENT WITH NEVA VS 
The following procedures will be performed: 
• Vital signs 
• Determine ICH as indicated by NCCT 
• TCD 
• NIHSS 
• Concomitant medications 
• AE assessment 
 
4.4.6. 
DAY 21 ± 2 DAYS POST ASAH OR DISCHARGE (WHICHEVER OCCURS 
FIRST) 
The following procedures will be performed on Day 21 post aSAH or at discharge 
(whichever occurs first): 
• Determine ICH as indicated by NCCT 
• TCD 
• NIHSS 
• mRS  
• Concomitant medications  
• AE assessment 
 
4.4.7. 
DAY 30 ± 7 DAYS POST INITIAL TREATMENT WITH NEVA VS 
• mRS  
• AE assessment  
 
4.4.8. 
ADDITIONAL TREATMENT OR RETREATMENT AFTER INITIAL 
INTERVENTION 
If vasospasm recurs in a previously treated segment or in another (different) vessel / 
vessel segment or territory after treatment of the initial vasospasm but prior to 
hospital discharge, treatment with the NeVa VS is allowed if the subject still meets 
all study entry criteria.  If a subject is retreated, he or she will be followed up for 30 
more days per the retreatment schedule in Appendix 1.  All treated areas will be 
imaged accordingly. 
 
4.4.9. 
UNSCHEDULED VISITS 
As clinically indicated, and corresponding data must be documented. 
 
 
 

 
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4.5. 
STUDY COMPLETION 
 
4.5.1. 
COMPLETED SUBJECTS 
Each subject in the study will be considered completed when all assessments through 
the Day 30 visit have been performed in accordance with the study protocol. 
 
4.5.2. 
DISCONTINUED SUBJECTS 
Any subject may voluntarily discontinue the study at any time without prejudice.  
The investigator may discontinue a subject from the study at any time if (s)he 
considers that remaining in the study compromises the subject’s health or the subject 
is not sufficiently cooperative.  In either event, reason(s) for discontinuation should 
be recorded. 
 
Possible reasons for study discontinuation include the following: 
 
• Adverse events (AEs) necessitating discontinuation from the study. 
• Subject decision (specify). 
• Investigator decision (specify). 
• Other reason (specify). 
 
The reasons for any subject discontinuation will be recorded on the study completion 
form of the study worksheets. If possible, subjects who withdraw prior to study 
completion will undergo the following: 
 
• 
NIHSS 
• 
mRS 
• 
AE assessment 
 
Lost to follow-up will only be considered at the 30-day visit.  All other visits will be 
considered missed visits if the subject is unable to attend.  Every attempt must be 
made to have subjects complete the study.  The investigator/designee must do his/her 
best to contact the subject by phone at least twice, followed by a certified letter if 
unsuccessful.  If no response is obtained from the subject, the investigator/designee 
is encouraged to contact one of the subject’s relatives or his/her general practitioner.  
Documentation of these contacts must be recorded in the subject’s source.  In cases 
where the subject cannot be contacted by phone or letter, the site must attempt to 
review the death registry, if possible, and gather death certificates.   
 
4.5.3. 
PREMATURE STUDY TERMINATION 
The Sponsor reserves the right to discontinue the study for any safety, ethical or 
administrative reason at any time. 
 
 
 

 
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4.6. 
INVESTIGATIONAL DEVICE ACCOUNTABILITY 
Documentation of receipt, use and return of all NeVa VS devices must be 
maintained by the Principal Investigator (PI) or his/her designee.  Investigational 
NeVa VS devices are to be used only in accordance with this protocol and under 
supervision of the PI or a duly designated person.  It is the PI’s responsibility to 
ensure that all study devices are kept in a secure location, with access limited to 
individuals authorized by the investigator.  A record of all study devices received, 
used and returned must be maintained by the site until the conclusion of the study.  
Following accountability of the study devices by the Sponsor or its designee, all 
unused study devices will be returned to the Sponsor/Designee as directed in writing 
by the Sponsor or designee for gross reconciliation. 
 
 
 
 

 
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4.7. 
CONCOMITANT MEDICATION 
Systemic anticoagulation with heparin may be used during the procedure at the 
discretion of the neurointerventionist.  Use of IV or IA antiplatelets is strongly 
discouraged. The use of oral antiplatelets as per local protocols is acceptable.  
 
Subcutaneous low molecular weight (LMW) heparin is allowed for deep vein 
thrombosis (DVT) prophylaxis per the center’s standard of care. Oral Nimodipine 
treatment (60mg PO Q6hours) starting at presentation through post aSAH day 21 is 
strongly encouraged except when contra-indicated.   
 
Vesalio acknowledges that it may be your practice and / or your institution’s policy 
to use intra-arterial calcium channel blockers in treating patients that have 
experienced subarachnoid hemorrhage.  We understand that this is done as a 
neuroprotective measure for these patients.  This is consistent with and 
recommended by the American Heart Association as part of the standard of care.  
Please note, however, that this method and dose of administration has not been 
reviewed or approved by FDA for commercial use.  Do not proceed with use of the 
NeVa VS device if the primary vasospasm is resolved post-intra-arterial 
administration of calcium channel blockers.  We urge you to continue to follow 
and comply with your institution’s policies and to document the, type, time, dosage, 
and route of administration for this type of intervention (if used) in the Concomitant 
Medications form. 
 
Concomitant medications will be recorded at Screening, 24 hours and Day 21 post 
aSAH or discharge (whichever occurs first).  For each medication taken, the 
following information will be collected:  
 
• Medication trade or generic name; 
• Indication for which the medication was given; 
• Dose/strength, route, and frequency of administration; 
• Date started and date stopped (or continuation at Day 21 post SAH or discharge 
[whichever occurs first]). 
 
 
 
 
 
5. 
EXAMINATIONS AND EVALUATIONS 
 
5.1. 
EVALUATIONS CONDUCTED AT SCREENING ONLY 
 
5.1.1. 
MEDICAL HISTORY 
A medical history will be obtained at Screening.  All positive and negative findings 
will be carefully documented on the study worksheets.  Any new finding discovered 
during the Screening evaluation and prior to the index procedure will be considered 
to be part of the medical history and will not be recorded as an AE. 

 
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5.1.2. 
LABORATORY TESTING  
Laboratory testing will be conducted by a local laboratory at each site at Screening.  
Laboratory testing does not need to be repeated if testing was performed within the 
past 72 hours and results are available.   A coagulation panel including partial 
thromboplastin time (PTT), prothrombin time (PT) and international normalized 
ratio (INR) will be conducted.  
 
5.1.3. 
PREGNANCY TEST (WOMEN OF CHILDBEARING POTENTIAL ONLY) 
For women of childbearing potential, a urine beta human chorionic gonadotropin (β-
HCG) test will be confirmed negative at time of current hospitalization or performed 
at Screening.  Results of the test must be negative.  Confirmed menopause is defined 
the absence of menses for at least 12 months prior to screening. 
 
5.1.4. 
MODIFIED FISHER SCALE 
The modified Fisher scale at the time of aSAH diagnosis will be recorded (Table 2). 
 
Table 2. Modified Fisher Scale 
Score 
Description 
0 
No SAH, no intraventricular hemorrhage (IVH) 
1 
Focal or diffuse thin SAH, no IVH 
2 
Focal or diffuse thin SAH with IVH 
3 
Thick focal or diffuse SAH, no IVH 
4 
Thick focal or diffuse SAH with IVH 
Note: thin SAH is 1 mm thick and thick SAH is ≥ 1mm in depth 
 
5.1.5. 
HUNT-HESS GRADING SYSTEM 
The Hunt-Hess grade at the time of aSAH diagnosis will be recorded (Table 3).  
Only patients with a Hunt and Hess Scale grade of 4 or less are eligible for study 
participation. 
 
Table 3. Hunt Hess Grading System 
Score 
Description 
0 
Unruptured aneurysm 
1 
Asymptomatic or minimal headache and slight neck stiffness 
2 
Moderate to severe headache, neck stiffness, no neurological 
deficit except cranial nerve palsy 
3 
Drowsy, minimal neurologic deficits 
4 
Stuporous, moderate to severe hemiparesis, possible early 
decerebrate rigidity and vegetative disturbances 
5 
Deep coma, decerebrate rigidity, moribund appearance 
 
 
 

 
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5.2. 
EVALUATIONS CONDUCTED DURING THE STUDY 
 
5.2.1. 
VITAL SIGNS 
Vital signs consisting of blood pressure (supine), temperature, weight (at Screening 
only), heart rate, and respiratory rate will be recorded at Screening and 24 hours.   
 
5.2.2. 
IMAGING TO DETERMINE INTRACRANIAL HEMORRHAGE 
NCCT will be performed at Screening, 24 hours and Day 21 post aSAH or discharge 
to assess intracranial hemorrhage.  The Alberta Stroke Program Early CT score 
(ASPECTS) will be determined.  The ASPECTS score is a 10-point quantitative 
topographic CT scan score, determined from evaluation of two standardized regions 
of the MCA territory: the basal ganglia level, where the thalamus, basal ganglia, and 
caudate are visible, and the supraganglionic level, which includes the corona radiata 
and centrum semiovale.  All cuts with basal ganglionic or supraganglionic structures 
visible are required to determine if an area is involved.  The abnormality should be 
visible on at least two consecutive cuts to ensure that it is truly abnormal rather than 
a volume averaging effect.  To compute the ASPECTS, 1 point is subtracted from 10 
for any evidence of early ischemic change for each of the defined regions (Figure 
12).   
 
 
Figure 12. ASPECTS score 
 
M4, M5, M6 are the anterior, lateral and posterior MCA territories immediately 
superior to M1, M2 and M3, rostral to basal ganglia.  Subcortical structures are 
allotted 3 points (C, L, and IC).  MCA cortex is allotted 7 points (insular cortex, M1, 
M2, M3, M4, M5and M6.  A normal CT scan receives ASPECTS of 10 points.  A 

 
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score of 0 indicates diffuse involvement throughout the MCA territory.  In order to 
be eligible for study participation, ASPECTS must be > 5 at Screening. 
 
5.2.3. 
TRANSCRANIAL DOPPLER (TCD) 
AHA/ASA guidelines indicate that it is reasonable to monitor for the development of 
arterial vasospasm following aSAH.25 Transcranial Doppler provides a noninvasive 
method for recording blood flow velocity (and indirectly, diameter) in the basal 
cerebral arteries and therefore is especially useful in detecting vasospasm following 
subarachnoid hemorrhage.  Vasospasm most commonly involves the basal arteries, 
where the changes in vessel diameter will be inversely proportional to the mean 
velocity measurements.  Examination of patients requires that the examiner be 
experienced and familiar with the vascular anatomy and the various TCD indicators 
of vasospasm.  For example, normal mean velocity for the MCA is 62 +/- 12 cm/sec. 
Significant spasm on angiogram of the MCA corresponds to a mean velocity of 120 
cm/sec.  Mean velocities of the MCA of 200 cm/sec or greater indicate severe spasm 
and correlate with 50% or greater narrowing on angiogram.61 
 
It is expected that participating centers will monitor aSAH patients with TCD as part 
of standard of care.  Patients with suspected vasospasm on TCD will be asked to 
participate in the study.  Vasospasm of > 50% for study eligibility can only be 
confirmed by DSA.  Following the index procedure, TCD will be performed at 24 
hours and on the Day 21 post aSAH or discharge visit.  TCD will not be assessed by 
the Core lab. 
 
5.2.4. 
CT ANGIOGRAPHY 
CT Angiography has been increasingly used as a noninvasive tool to diagnostic 
vasospasm with a relatively high degree of accuracy and may be used a study 
screening tool. However, for purposes of study eligibility, vasospasm of > 50% must 
be confirmed by DSA. 
 
5.2.5. 
DIGITAL SUBTRACTION ANGIOGRAPHY (DSA) 
DSA will be performed at Screening to determine the extent of stenosis in the ICA, 
basilar, MCA, ACA or PCA territories.  Only subjects with > 50% in any of these 
territories will undergo the index procedure. 
 
At the intervention, DSA including AP and LAT views with late arterial phase in 
lateral view, will be obtained at the beginning of the intervention, and at the end of 
the procedure and will be assessed by the treating interventionalist.  The 
DSAimaging study will subsequently be reviewed and assessed by an independent 
core laboratory.   
 
5.2.6. 
MODIFIED RANKIN SCALE (MRS) 
The mRS is provided in Table 4.  The mRS measures the degree of disability or 
dependence in daily activities.62  At screening, a pre-hospital (historic) mRS and 
current mRS will be obtained by the site.  At Day 21 post aSAH or discharge 
(whichever occurs first) and Day 30 visits, mRS will be determined.   

 
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Table 4. mRS 
Score 
Description 
0 
No symptoms at all 
1 
No significant disability despite symptoms; able to carry out all 
usual duties and activities 
2 
Slight disability; unable to carry out all previous activities, but able 
to look after own affairs without assistance 
3 
Moderate disability; requiring some help, but able to walk without 
assistance 
4 
Moderately severe disability; unable to walk without assistance and 
unable to attend to own bodily needs without assistance 
5 
Severe disability; bedridden, incontinent and requiring constant 
nursing care and attention 
6 
Death 
 
5.2.7. 
NIH STROKE SCALE (NIHSS) 
NIHSS (Appendix 4) is 15-item examination that measure stroke-related 
neurological deficits.  Each specific ability is scored between a 0 and 4 (some 
elements have a scale from 0 to 2 or 0 to 3).  For each item, a score of 0 typically 
indicates normal function, while a higher score is indicative of some level of 
impairment.  The individual scores from each item are summed in order to calculate 
a subject's total NIHSS score.  NIHSS must be conducted by certified study 
personnel at Screening, 24 hours (+6/-6hours), and at Day 21 post aSAH or 
discharge (whichever occurs first).  The interpretation of the NIHSS score is 
provided in Table 5. 
 
Table 5. NIHSS 
Score 
Stroke Severity 
1-4 
Minor stroke 
5-15 
Moderate stroke 
16-20 
Moderate to severe stroke 
21-42 
Severe stroke 
 
5.2.8. 
CONCOMITANT MEDICATIONS 
Concomitant medications will be documented at Screening, 24 hours and Day 21 
days post aSAH or discharge (whichever occurs first) as described in Section 3.7.   
 
 
 
 
 
6. 
EVALUATION OF ADVERSE EVENTS 
 

 
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6.1. 
DEFINITIONS 
An adverse event (AE) is the development of an untoward medical occurrence or 
the deterioration of a pre-existing medical condition following or during exposure to 
an investigational medical device, whether or not considered causally related to the 
investigational medical device.   
 
An untoward medical condition can be symptoms (e.g., nausea, chest pain), signs 
(e.g., tachycardia, enlarged liver) or clinically significant abnormal results of an 
investigation (e.g., laboratory findings, electrocardiogram). 
 
Conditions or diseases that are chronic but stable should not be recorded as an AE.  
Changes in a chronic condition or disease that are consistent with natural disease 
progression are NOT considered AEs and should not be recorded on AE worksheets.  
These medical conditions should be adequately documented on the appropriate page 
of the study worksheet (relevant medical history).  However, medical conditions 
present at enrollment that worsens in intensity or frequency in a manner inconsistent 
with the natural course of the disease during the treatment or post-treatment periods 
should be reported and recorded as AEs. 
 
A serious adverse event (SAE) is any untoward medical occurrence which: 
• Results in death; 
• Is life-threatening; 
• Requires inpatient hospitalization (admission to hospital with a stay > 24 hours) 
or prolongation of hospitalization which is not specifically required by the 
protocol or is elective; 
• Results in permanent impairment of a body function or permanent damage to a 
body structure; or 
• Requires medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure. 
 
Additionally, important medical events that may not result in death, be life-
threatening or require hospitalization may be considered SAEs when they jeopardize 
the subject or require medical or surgical intervention to prevent one of the serious 
outcomes listed above.   
 
An unanticipated adverse device effect (UADE) is defined as any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in predicate devices, or any 
other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
 
 
6.2. 
ASSESSMENT OF ADVERSE EVENTS (AES) 
The need to capture AEs is not dependent upon whether or not the clinical event is 
associated with the use of the study device or procedure.  All AEs, regardless of 

 
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severity, occurring at Neva VS intervention through the Day 30 visit must be 
recorded.  Events occurring prior to the endovascular (Neva VS) procedure must be 
listed in the medical history. 
 
The following information should be obtained for each AE: 
 
1. Event description.  Every effort must be made to report the underlying condition 
or unifying diagnosis for the event.  To avoid vague, ambiguous or colloquial 
expressions, the AE should be recorded in standard medical terminology rather than 
the subject’s own words when possible.  Signs and symptoms that are considered 
unrelated to an encountered syndrome or disease should be recorded as individual 
AEs on the CRF (e.g., if congestive heart failure and severe headache are observed at 
the same time, each event should be recorded as an individual AE).   
 
In addition, AEs occurring secondary to other events (e.g., sequelae) should be 
identified by the primary cause (i.e., a "primary" AE, if clearly identifiable, generally 
represents the most accurate clinical term to record on AE CRF; events occurring 
secondary to the primary event should be described in the narrative description of 
the case [e.g., example: orthostatic hypotension → fainting and fall to floor → head 
trauma →neck pain; the primary AE is orthostatic hypotension]). 
 
2. Duration: The date of onset and date of resolution should be reported.  Every 
effort should be made to capture the exact dates. 
 
3. Outcome: The final status of the event should be reported as resolved, ongoing, 
or if it resulted in death.  If the event is present at the final study visit, the ongoing 
box must be marked.  
 
4. Severity: The worst severity of the event must be reported as mild, moderate, or 
severe using the following definitions: 
 
- Mild: Aware of sign or symptom, but easily tolerated 
- Moderate: Discomfort enough to cause interference with usual activity 
- Severe: Incapacitating with inability to work or do usual activity 
 
5. Action taken: Treatment of the event may be reported as none, medical and/or 
surgical.  
 
6. Seriousness: Determined by using the criteria in Section 5.1. 
 
7. Relationship to device (study device or ancillary i device), and procedure/ 
treatment.  The relationship to device and study procedure will be assessed using 
the following criteria. 
 
 
i Ancillary device includes microcatheter, guide catheter, or another device that is not the study device (Neva 
VS device) 

 
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Definitely Not 
Related 
Evidence exists that the adverse event definitely has a cause other than 
the device/procedure under investigation (e.g. pre-existing condition 
or underlying disease, intercurrent illness, or concomitant medication) 
and does not meet any other criteria listed. 
Possibly Related 
A temporal relationship exists between the event onset and the 
device/procedure under investigation.  Although the adverse event 
may appear unlikely to be related to the device/procedure under 
investigation, it cannot be ruled out with certainty; and/or the event 
cannot be readily explained by the subject’s clinical state or 
concomitant therapies. 
Definitely Related 
Strong evidence exists that the device/procedure under investigation 
caused the adverse event.  There is a temporal relationship between 
the event onset and the device/procedure under investigation.  There is 
strong therapeutic evidence that the event was caused by the 
device/procedure under investigation. The subject’s clinical state and 
concomitant therapies have been ruled out as a cause. 
Unknown 
Unable to make a determination on causality of the event. 
 
 
6.3. 
REPORTING/RECORDING OF AES 
Throughout the course of the study, all efforts will be made by the investigator to 
remain alert to possible AEs.  The first concern will be the safety of the subject, and 
for providing appropriate medical intervention.  The period of observation for 
collection of AEs starts at index (Neva VS) procedure until the Day 30 follow-up 
visit.  Any AE should be recorded on the appropriate study worksheet. 
 
 
6.4. 
SAES REQUIRING EXPEDITED REPORTING 
Serious adverse events (SAEs) that occur within 24 hours of the NeVa VS 
intervention require expedited reporting to the Sponsor or designee regardless of 
relationship to study device or study procedure.  In addition, UADEs require 
expedited reporting. 
 
All SAEs that occur within 24 hours of the index procedure, including death, 
and suspected UADEs must be reported within 3 working days to the study 
Sponsor/Designee, by: 
 
• Completing the AE information in the Electronic Data Capture (EDC) 
system and selecting appropriate criteria that classifies the AE as serious.   
• Completing and uploading the SAE form in the EDC.   
 
In order to have the Investigator’s signature on file, the signed SAE form needs to be 
uploaded to the EDC at the time of initial data entry.   
 
In case of death, the site will provide a copy of the death certificate and autopsy 
report, if applicable, to the Sponsor/Designee.  If no such documents are available, 

 
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the Investigator will describe the circumstances of the subject’s death in the source 
document. 
   
The investigator must follow their local IRB policy for SAE reporting. 
 
The Sponsor/Designee will review all SAEs and suspected UADEs and determine if 
the SAE constitutes a UADE.  All UADEs will be reported to all reviewing IRBs 
and participating investigators within 10 days after the Sponsor first receives notice 
of the effect. 
 
 
6.5. 
ANTICIPATED COMPLICATIONS/AES 
Anticipated complications/AEs are defined as complications/events that can be 
reasonably associated with aSAH or the use of the Neva VS device.  
 
Potential procedural complications include, but are not limited to: 
 
• Hematoma and hemorrhage at the puncture site 
• Perforation or dissection of the vessel 
• Vasoconstriction (vasospasm) 
• Change in mental status 
• COMA/Persistent Vegetative State 
• Persistent neurological deficits 
• Neurological deterioration including stroke progression, stroke in a new vascular 
territory and death 
• Transient ischemic attack 
• Brain edema 
• Ischemia 
• Infection 
• Allergic reaction/adverse reaction to device materials, procedure medications or 
contrast media 
• Air embolism 
• Intracranial hemorrhage 
• Vascular occlusion 
• Pseudoaneurysm formation 
• Post procedural bleeding 
• Peripheral nerve damage (e.g., femoral nerve) 
• Distal embolization including to a previously uninvolved territory 
• Device(s) deformation, collapse, fracture or malfunction 
• Thrombosis (acute and subacute0 
• Arteriovenous fistula 
• General discomfort, tenderness, pain 
• Nausea and/or vomiting 
• Radiation effects, including, but not limited to: alopecia, burns ranging in 
severity from skin reddening to ulcers, cataracts, and delayed neoplasia 

 
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• Death 
 
Anticipated AEs include, but are not limited to: 
• Blood and lymphatic system disorders 
o Anemia 
o Thrombocytopenia 
• Cardiac disorders 
o Atrial fibrillation 
o Bradycardia 
o Cardiac arrest 
o Congestive heart failure 
o Tachycardia 
• Death 
• Eye disorders 
o Retinal artery embolism 
• Gastrointestinal disorders 
o Abdominal pain 
o Dysphagia 
o Gastrointestinal hemorrhage 
o Hematochezia 
o Nausea 
o Upper gastrointestinal hemorrhage 
o Vomiting 
• General disorders 
o Catheter site hematoma 
o Pyrexia 
• Infections and Infestations 
o Bacteremia 
o Clostridia infection 
o Pneumonia 
o Sepsis 
o Urinary tract infection 
• Injury, poisoning and procedural complications 
o Traumatic pneumothorax 
o Vascular access complication 
• Investigations 
o Abnormal echocardiogram 
o Increased international normalized ratio 
• Metabolism and nutrition disorders 
o Diabetes 
o Electrolyte imbalance 
o Hyperglycemia 
o Hypoglycemia 
o Hypokalemia 
• Musculoskeletal and connective tissue disorders 
o Compartment syndrome 

 
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o Musculoskeletal pain 
• Nervous system disorders 
o Brain edema 
o Carotid artery dissection 
o Cerebral gas embolism 
o Cerebral hematoma 
o Cerebrovascular accident 
o Cerebrovascular spasm 
o Clonus 
o COMA 
o Convulsion 
o Depressed level of consciousness 
o Hemorrhagic cerebral infarction 
o Headache 
o Increased intracranial pressure 
o Intraventricular hemorrhage 
o Ischemic stroke 
o Persistent Vegetative State 
o Subarachnoid hemorrhage 
• Psychiatric disorder 
o Agitation 
• Respiratory and thoracic mediastinal disorders 
o Atelectasis 
o Dyspnea 
o Hypoxia 
o Pleural effusion 
o Pneumonia aspiration 
o Pneumothorax 
o Pulmonary edema 
o Respiratory distress 
o Respiratory failure 
o Vascular disorders 
• Vascular disorders 
o Deep vein thrombosis 
o Hypertension 
o Hypotension 
o Vasospasm  
o Vessel perforation 
 
 
 
6.6. 
DEVICE MALFUNCTION 
Device malfunction is defined as failure of the device to perform in accordance with 
its intended purpose when used in accordance with the Instructions for Use (IFU) or 
clinical investigational plan.   
 

 
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Device failure may or may not result in an AE/SAE.  All AEs/SAEs associated with 
a device failure are by definition device-related. 
 
 
 
 
7. 
STATISTICAL METHODS 
The primary goal of this study is to assess the safety and probable benefit of the Neva VS 
device in patients presenting with symptomatic cerebral vasospasm despite maximal 
medical management following aSAH.  Sample size estimations were not based on formal 
statistical hypotheses testing because the patent population and annual incidence of 
symptomatic cerebral vasospasm after aSAH is less than 8000 cases / year.  Hypothesis 
testing will not be performed on any endpoint.  
 
7.1. 
PATIENT CATEGORIZATION 
Screen Failure - Any patient who was consented and entered into the screening 
process appropriately, but subsequently did not meet the entry criteria in order to be 
treated.  Patients who fail screening will not be followed for safety or feasibility 
assessment, and no other study procedures will be performed. 
 
Evaluable Patient - Any patient who in whom the Neva VS procedure was started, 
defined as introduction of a Neva VS device into the vasculature (regardless of the 
ability to reach the target vessel.   
 
Lost to follow-up - A patient deemed to be lost to follow-up is any patient who 
underwent the Neva VS procedure, but who does not complete scheduled study 
visits.  This includes those patients who withdraw consent and refuse further study 
participation and all attempts to contact the patient are deemed unsuccessful. 
 
 
7.2. 
STUDY OUTCOMES 
The following study outcomes will be determined in evaluable patients: 
 
• Procedural Success - defined as 50% or greater vessel caliber on DSA compared 
to baseline, as determined by the core laboratory. 
• Retreatment / additional treatment – the rate of retreatment or treatment of 
additional territories will be quantified.  
• Symptomatic Improvement - for clinically symptomatic patients, a decrease at 
24 hours of ≥ 3-points from Screening as measured by NIHSS and/or resolution 
of pre-procedural clinical deficits.  
• Change in ASPECT Score –change in ASPECT score on NCCT from Screening 
to Day 21 or discharge, whichever occurs first  
• Clinical Status – Change in modified Rankin Scale score from Screening at Day 
30 
 

 
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7.3. 
SAFETY 
All evaluable patients will be included in the safety analyses.  Adverse events and 
serious adverse events will be summarized using descriptive statistics. 
 
 
7.4. 
STATISTICAL ANALYSES 
Descriptive statistics will be performed.  Categorical variables will be summarized 
by the number and percentage of patients in each category.  Continuous variables 
will be summarized using n, mean, SD, median, minimum, and maximum values.  
No statistical testing will be performed. 
 
 
 
 
 
8. 
IMAGING CORE LABORATORY 
The goal of the core lab is to provide unbiased assessment of DSA/CTA imaging obtained 
at the time of aSAH presentation or intervention and DSA obtained during the Neva VS 
procedure.  Specifically, DSA including AP and LAT views with late arterial phase in 
lateral view, will be obtained at the beginning of the intervention with the Neva VS device, 
and at the end of the procedure.  These images will be sent to the core laboratory post-
procedure. 
 
The imaging procedures will be defined in the Core Lab Manual.  De-identified images will 
be sent directly from the site to the core lab. 
 
 
 
9. 
DATA SAFETY MONITORING BOARD (DSMB) 
The independent data safety monitoring board (DSMB) will periodically review a limited 
set of tables and/or listings, including all reported SAEs.  The objectives of the DSMB 
meetings are to review the safety outcomes of the study and provide guidance to Sponsor 
regarding the safety of the NeVa VS system.  There will be no adjustment for multiple 
testing due to the DSMB data review.  Further details of DSMB responsibilities are 
included in the DSMB Charter. 
 
 
 
10. ACCESS TO STUDY DOCUMENTS AND STUDY MONITORING 
The Sponsor has designated BioMDG to monitor the progress of this study.  The clinical 
monitor, as a representative of the Sponsor, has the obligation to follow this study closely.   
 

 
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The Sponsor or its designee may meet with investigators prior to the initiation of the study 
in order to review the adequacy of the subject population, facilities, and equipment with 
respect to the needs of the study, and to familiarize the investigator with the study protocol.   
 
During the study, the clinical monitor will visit the study facilities regularly, and utilize 
telephone and written communications on an ongoing basis to maintain current knowledge 
of the study.  During periodic visits to the study site, the monitor will review the source 
documents used for data entry in the EDC system to verify the accuracy and completeness 
of the information contained in those reports in preparation for retrieval.  Source 
documents must contain all data entered in the EDC system.  All data generated during this 
study and the source documents from which they originated are subject to inspection by the 
Sponsor or its representatives, the FDA and other regulatory agencies. 
 
Upon completion of the study, the clinical monitor will conduct a final visit (close-out) to 
the site.  The objectives of this visit are to ascertain that all regulatory records and reports 
are complete, verify that study drug and other supplies have been accounted for and ensure 
that the investigator is aware of his/her responsibilities post-study. 
 
 
 
11. QUALITY CONTROL AND ASSURANCE 
The Sponsor and/or its contracted representatives utilize Standard Operating Procedures 
(SOPs) designed to ensure that research procedures and documentation are consistently 
conducted/prepared to the highest quality standards.  These SOPs also require compliance 
with Health Authority regulations and Good Clinical Practice guidance. 
 
A quality assurance audit may be conducted by the Sponsor or its designee at any time 
during or after completion of a study.  The Investigator will be given adequate notice if 
he/she is selected for an audit.  The audit will include, but is not limited to, a review of all 
informed consent forms, source documents, medical records, regulatory documentation, an 
assessment of study conduct and protocol compliance, and a review of the investigational 
drug accountability.  At the conclusion of an audit, the auditor will conduct a brief meeting 
with the Investigator to review the findings of the audit. 
 
11.1. TRAINING 
Each site will be trained to the investigational plan prior to performing any study-
related procedures.  Procedure training will be completed by an experienced 
Procedural/Clinical Specialist in both a classroom and simulated environment and 
may include use of an in-vitro or in-vivo model.    
 
 
 
 
12. INSTITUTIONAL REVIEW BOARD (IRB) 
Prior to the initiation of the study, the protocol, and the informed consent form will be 
submitted to the IRB for approval.  By signing the clinical trial agreement, the investigator 

 
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is assuring that an IRB which complies with the requirements set forth in 21 CFR Part 56, 
will be responsible for the initial and continuing review of the proposed clinical study.  A 
copy of the IRB approval letter for the protocol, the informed consent, and the protocol 
signature page must be submitted to the Sponsor or its designee, prior to release of 
investigational supplies to the study site.  The approval letter must refer to the specific 
protocol and the informed consent form.  The study site must maintain an accurate and 
complete record of all reports, documents and other submissions made to the IRB 
concerning this protocol.  A list of the IRB members, their titles or occupations, and their 
institutional affiliation, or an IRB assurance number must be provided to the Sponsor or its 
designee prior to release of study supplies. 
 
The investigator is responsible for notifying the IRB of any SAEs and UADE as required 
by the IRB.  A copy of the notification must be forwarded to BioMDG.   
 
Status reports must be submitted to the IRB at least once a year (or more frequently as 
required by the IRB) and the IRB must be notified of completion or termination of the 
study.  A final report must be provided to the IRB and the Sponsor within 2 months of 
study completion or termination.  This report should include: any deviations from the 
protocol, the number of participants evaluated, the number of participants who withdrew or 
were withdrawn and the reasons for withdrawal, any significant AEs and the investigator's 
summation of the study. 
 
 
 
13. INFORMED CONSENT PROCESS 
It is the responsibility of the investigator to inform each subject or his/her legal 
representative, prior to the screening evaluation, of the purpose of this clinical trial, 
including possible risks and benefits and document the informed consent process in the 
subject’s chart.  A sample informed consent form containing the required elements of 
informed consent is provided in Appendix 2.  Any changes made to this sample must be 
approved by the Sponsor or its designee, prior to submission to an IRB.  After approval by 
the Sponsor or its designee, the informed consent must be submitted to and approved by an 
IRB.  Prior to entry into the study or initiation of any study-related procedures, the subject 
or his/her legal representative must read, sign and date the informed consent form.  The 
person executing the consent must also sign and date the IRB-approved consent form.  One 
original informed consent form is to be retained by the study site and a copy is to be given 
to the subject or his/her legal representative.  The informed consent process must be 
documented in the subject’s source/medical record. 
 
The informed consent must be written in a language in which the subject or his/her legal 
representative is fluent.  If a foreign language translation is required, a statement of 
certification of the translation must be issued.  Regulations require that foreign language 
informed consent forms be submitted to the IRB for approval.  The investigator must 
forward a copy of the consent form, the certified foreign language translation and an IRB 
approval letter to the Sponsor or its designee. 
 

 
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14. CONFIDENTIALITY 
In accordance with GCP and with the national data protection laws, all information 
concerning the subjects in the study must be treated as strictly confidential by all persons 
involved in the study. 
 
The investigator acknowledges that all information acquired from the Sponsor or its 
designee or developed or acquired in connection with the study are strictly confidential.  
The investigator will not disclose any confidential information to any third party nor use 
confidential information for any purpose without first obtaining the consent of Sponsor in 
writing.  Such consent shall be deemed to have been given for disclosure to any person for 
whom the investigator is responsible at his/her center, but only so far as required for the 
purposes of the study, and, in the case of disclosures to staff, only if such staff are bound by 
obligations of confidentiality no less strict than those set out herein. 
 
 
 
15. PROTOCOL AMENDMENTS 
The Sponsor will document modifications to the protocol in the form of a written 
amendment.  Protocol modifications that impact subject safety or the validity of the study 
must be approved by the IRB before implementation.  In the case of a medical emergency, 
to remove immediate apparent hazard to subjects, a change may be made preferably after 
discussion with the Sponsor or its designee.  In these instances, the IRB and FDA will be 
notified as soon as possible.  
 
 
 
16. DATA MANAGEMENT 
Electronic data capture (EDC) will be utilized for this study.  Study worksheets will be 
provided by the Sponsor or its designee to the site before data collection.  To facilitate data 
entry, the worksheets will coincide with the data entry pages in the EDC system to insure 
minimal issues during data entry.  If the site elects to use the worksheets, appropriate 
worksheets will be completed and initialed or signed where indicated at each examination.  
All worksheets will be completed in a legible manner in black/blue ink.  Alternatively, the 
site may elect to use their own source documents.  It is expected that there will be source 
data for all entries in the EDC. 
 
Any corrections to the worksheets will be made by drawing a single line through the 
incorrect entry, recording the correct information, and initialing and dating the change.  
The study worksheets and data entered in the EDC system will be audited by the Study 
Monitor. 
 
Once the data is ready to be entered into the EDC System, then the site will begin entering 
the data into the system.  The monitor will review data entered into the EDC against the 
source documents and/or worksheets and either approve the data records or create queries 

 
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to the site for further review.  If the data records are deemed “clean” with the approval of 
the monitor, then the investigator can e-sign the records.  Finally, when the data records are 
ready to be locked, the data manager will perform the interim lock in the system.  However, 
the data manager also has the right to unlock the data record if any updates to the data are 
necessary.  
 
Data are protected by preventing unauthorized users from accessing the system with the 
use of username and password combination.  In addition, each individual user will be 
assigned a specific role in the EDC System which will grant that user the right to enter, 
view, edit and/or delete the data.  Furthermore, any changes to the data are captured in the 
EDC System’s audit trail where a reason for change is required.   
 
All clinical data generated in the study will be submitted to the Sponsor or designated CRO 
for quality assurance review and statistical analysis.  All worksheets and data entered into 
the EDC system will be reviewed for completeness and evident recording errors will be 
rectified by contact with the appropriate clinical site.  Computerized data checks will be 
used to identify unusual data entries for verification prior to statistical analysis. 
 
To minimize the amount of missing data, investigators will be trained on the deleterious 
effect that missing data have on trial integrity and credibility and that missing data could 
diminish the scientific value of all subjects' altruistic contributions.  
 
 
 
17. RECORD KEEPING AND RETENTION 
Data generated for the study should be stored in a limited-access file area and be accessible 
only to representatives of the study site, the Sponsor and its representatives and 
FDA/relevant health authorities/regulatory agencies.  All reports and communications 
relating to study subjects will identify subjects only by initials and subject identification 
number.  Complete subject identification will be kept by the investigator.  This information 
will be treated with strict adherence to professional standards of confidentiality. 
 
An investigator must in reasonable time, upon request from any properly authorized officer 
or employee of FDA/relevant health authority or regulatory agency, permit such officer or 
employee to have access to requested records and reports, and copy and verify any records 
or reports made by the investigator.  Upon notification of a visit by the FDA/relevant health 
authority or regulatory agency, the investigator will contact the Sponsor or its designee 
immediately.  The investigator will also grant Sponsor representatives the same privileges 
offered to FDA/relevant health authority or regulatory agents/officers/employees. 
 
The Investigator must provide the Sponsor/Designee with the following documents prior to 
study initiation and retain a copy in the study file: 
 
• 
Current signed curriculum vitae (within 2 years prior to study initiation) and current 
medical licenses for the Principal Investigator and all co-investigators listed on the 
clinical trial agreement. 

 
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• 
A copy of the original approval for conducting the study by the IRB.  Renewals, with 
continuance of the study, must be submitted at yearly intervals or as required by IRB 
policy. 
• 
A copy of the IRB approved informed consent form. 
• 
IRB member list and/or DHHS General Assurance Number (if IRB has an Assurance 
number). 
• 
Signed Financial Disclosure Form for the Principal Investigator and all co-
investigators listed on the clinical trial agreement,   
• 
The signature page of this protocol signed and dated by the Principal Investigator. 
 
In addition to the documents listed above, the study site will also retain the following 
items: 
 
• Certifications and laboratory reference ranges for all local laboratories used for this 
study. 
• Delegation of authority log. 
• All original informed consent forms with required signatures. 
• All IRB correspondence. 
• Study monitoring log. 
• Screening/enrollment log. 
• Device accountability records. 
• Copies of all pertinent correspondence pertaining to the study (except budget issues) 
between the Sponsor or the CRO and the site. 
• Copies of all SAEs forms/supporting documentation submitted to the Sponsor or its 
designee. 
 
All study-related records must be maintained for at least 5 years after study completion.   
The Sponsor will notify the principal investigator when records are no longer needed.  The 
investigator will not discard any records without notifying the Sponsor.  If the principal 
investigator moves from the current investigational site, the Sponsor should be notified of 
the name of the person who will assume responsibility for maintenance of the records at the 
investigational site or the new address at which the records will be stored.  The investigator 
will notify the Sponsor as soon as possible in the event of accidental loss or destruction of 
any study documentation. 
 
 
 
18. INVESTIGATOR FINAL REPORT 
The investigator shall provide the IRB and the Sponsor with an accurate final report within 
2 months after completion, termination or discontinuation of the study.  The final report 
may not precede final data submission which has not been monitored. 
 
 
 
19. STUDY REPORT AND PUBLICATION 

 
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The data resulting from this study will be the proprietary information of the Sponsor and 
may be made public after all data have been analyzed and the study results are available.  
None of the data resulting from this study will be allowed to be presented or published in 
any form, by the investigator or any other person, without the prior written approval of the 
Sponsor.  At the end of the study, a clinical study report will be written by the Sponsor or 
its designee.   
 
 

 
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constricted cerebral arteries after aneurysmal SAH. Acta Neurochir (Wien) 1984;70:65-79. 
55. 
Consigny PM, Tulenko TN, Nicosia RF. Immediate and long-term effects of angioplasty-
balloon dilation on normal rabbit iliac artery. Arteriosclerosis 1986;6:265-76. 
56. 
Yamamoto Y, Smith RR, Bernanke DH. Mechanism of action of balloon angioplasty in 
cerebral vasospasm. Neurosurgery 1992;30:1-5; discussion -6. 
57. 
Grande A, Nichols C, Khan U, et al. Treatment of post-hemorrhagic cerebral vasospasm: 
role of endovascular therapy. Acta Neurochir Suppl 2011;110:127-32. 
58. 
Chan PD, Findlay JM, Vollrath B, et al. Pharmacological and morphological effects of in 
vitro transluminal balloon angioplasty on normal and vasospastic canine basilar arteries. J 
Neurosurg 1995;83:522-30. 
59. 
Linskey ME, Horton JA, Rao GR, Yonas H. Fatal rupture of the intracranial carotid 
artery during transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. 
Case report. J Neurosurg 1991;74:985-90. 
60. 
Bhogal P, Loh Y, Brouwer P, Andersson T, Soderman M. Treatment of cerebral 
vasospasm with self-expandable retrievable stents: proof of concept. J Neurointerv Surg 
2017;9:52-9. 
61. 
Newell DW, Winn HR. Transcranial Doppler in cerebral vasospasm. Neurosurg Clin N 
Am 1990;1:319-28. 
62. 
van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver 
agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-7. 
 
 
 

 
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APPENDICES 
 
 
 
 

 
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TABLE OF APPENDICES 
 
 
Appendix 1. 
Schedule of Evaluations and Visits................................................................. 59 
Appendix 2. 
Sample Informed Consent............................................................................... 62 
Appendix 3. 
Neva VS Device – Draft Instructions for Use ................................................ 75 
Appendix 4. 
NIH Stroke Scale ............................................................................................ 79 
Appendix 5. 
Investigator’s Qualifications and Responsibilities.......................................... 88 
Appendix 6. 
Sponsor’s Commitments ................................................................................. 91 
 
 
 

 
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Appendix 1. 
Schedule of Evaluations and Visits 
 
 
 

 
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SCHEDULE OF EVALUATIONS AND VISITS – INITIAL INTERVENTION 
PROCEDURE 
SCREENING 
(DAY 0-21 
POST ASAH) 
INTERVENTION 
DAY 0 (WITHIN 21 
DAYS POST ASAH)f 
24 HRS ± 6 
HRS (POST 
DAY 0) 
DAY 21 ± 2 DAYS 
POST ASAH OR 
DISCHARGE 
(WHICHEVER 
OCCURS FIRST) 
DAY 30 ± 7 
DAYS (POST 
DAY 0)  
EARLY 
WITHDRAWAL 
Visit Number 
1 
2 
3 
4 
5 
6 
Baseline Evaluations 
 
 
 
 
 
 
Informed Consent 
 
 
 
 
 
 
Medical History 
 
 
 
 
 
 
     Modified Fisher scale a 
 
 
 
 
 
 
     Hunt-Hess grading system a 
 
 
 
 
 
 
Coagulation panel 
 
 
 
 
 
 
Urine pregnancy test (women of childbearing 
potential only) 
 
 
 
 
 
 
Feasibility and Safety Parameters 
 
 
 
 
 
 
Vital signs 
 
 
 
 
 
 
Imaging to determine ICH, non-contrast head 
CT scan (NCCT) 
 
 
 
 
 
 
Presentation of vasospasm b 
 
 
 
 
 
 
Transcranial Doppler (TCD), and/or CT 
angiography 
 
 
 
 
 
 
Confirmation of vasospasm  DSAc  
 
 
 
 
 
 
Procedural success d 
 
 
 
 
 
 
NIHSS 
 
 
 
 
 
 
Modified Rankin Scale (mRS) 
 e 
 
 
 
 
 
Concomitant Medications 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
a. 
At the time of aSAH diagnosis 
b. 
Documentation of vasospasm on TCD and/or clinical presentation 
c. 
Vasospasm confirmed by DSA (greater than 50% stenosis in the ICA, Basilar, MCA, ACA or PCA territory)  
d. 
Procedural success is defined as a reduction in vessel narrowing of 50% or greater in the treated segment when compared to baseline  DSA or CTA.  
e. 
Pre-hospital and current mRS 
f. 
If another (different) vessel / territory experiences vasospasm after treatment of the initial vasospasm but prior to hospital discharge, treatment with the 
NeVa VS is allowed if the subject still meets all study entry criteria.  See Schedule of Evaluations and Visits – Repeat Intervention.  All treated areas will 
be imaged accordingly.  
 

 
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SCHEDULE OF EVALUATIONS AND VISITS – REPEAT INTERVENTION 
PROCEDURE 
SCREENING 
(DAY 0-21 
POST ASAH) 
INTERVENTION 
DAY 0 (WITHIN 21 
DAYS POST ASAH)f 
24 HRS ± 6 
HRS (POST 
DAY 0) 
DAY 21 ± 2 DAYS 
POST ASAH OR 
DISCHARGE 
(WHICHEVER 
OCCURS FIRST) 
DAY 30 ± 7 
DAYS (POST 
DAY 0)  
EARLY 
WITHDRAWAL 
Visit Number 
1 
2 
3 
4 
5 
6 
Feasibility and Safety Parameters 
 
 
 
 
 
 
Vital signs 
 
 
 
 
 
 
Coagulation panel 
 
 
 
 
 
 
Eligibility determination 
 
 
 
 
 
 
Imaging to determine ICH, non-contrast head 
CT scan (NCCT) 
 
 
 
 
 
 
Presentation of vasospasm a 
 
 
 
 
 
 
Transcranial Doppler (TCD), and/or CT 
angiography 
 
 
 
 
 
 
Confirmation of vasospasm  DSAb  
 
 
 
 
 
 
Procedural success c 
 
 
 
 
 
 
NIHSS 
 
 
 
 
 
 
Modified Rankin Scale (mRS) 
 
 
 
 
 
 
Concomitant Medications 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
a. 
Documentation of vasospasm on TCD and/or clinical presentation 
b. Vasospasm confirmed by DSA (greater than 50% stenosis in the ICA, Basilar, MCA, ACA or PCA territory)  
c. 
Procedural success is defined as a reduction in vessel narrowing of 50% or greater in the treated segment when compared to baseline DSA or CTA.  
 

 
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Appendix 2. 
Sample Informed Consent 
 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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SAMPLE SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM / HIPAA 
AUTHORIZATION 
 
TITLE: 
The VesalioTM Neva VS for the Treatment of Symptomatic 
Cerebral Vasospasm Following Aneurysmal Subarachnoid 
Hemorrhage (aSAH) (The VITAL Study) 
 
PROTOCOL NO.: 
VS-002 
 
 
SPONSOR: 
Vesalio 
 
INVESTIGATOR: 
Name 
 
Address 
 
City, State Zip 
 
Country 
 
SITE(S): 
Name 
 
Address 
 
City, State Zip 
 
Country 
 
STUDY RELATED 
PHONE NUMBER(S): 
Name 
 
Phone number(s) 
 
 
Subject Initials: 
[_______________________] 
 
Subject Number: 
[_______________________] 
 
 
WHY AM I BEING ASKED TO VOLUNTEER? 
You are being asked to participate in a research study sponsored by Vesalio.  Before you decide 
whether to participate, it is important for you to know why the research is being done, and what 
it will involve.  Please take your time to read the following information carefully, and feel free to 
discuss your decision with your family, friends, and your primary care doctor.  Please ask your 
study doctor to explain if there is anything that is not clear or if you would like more 
information.  If you agree to take part in this study, you need to sign this consent form.  Your 
signature on this form means that you have been told about and understand the purpose of the 
study, procedures to be followed, and any benefits or risks.  Your signature on this form also 
means that you want to take part in this study if you meet the criteria, based on the results of 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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Page 64 of 92 
your medical tests, which must be done before you are asked to continue your participation in the 
study.  After you agree, you will be provided with a copy of this signed form for your records.   
 
DO I HAVE TO TAKE PART? 
Taking part in this study is entirely voluntary, and you may refuse to participate or withdraw 
from the study at any time without influencing your regular medical treatment and without 
giving a reason.  A decision to withdraw at any time, or a decision not to take part, will not affect 
the standard of care you receive.  Regardless of your decision, you will still be treated for your 
medical condition.   
 
WHY IS THE PURPOSE OF THIS? 
The purpose of this research study is to find out if a medical device, the NeVa VS device, is able 
to treat vasospasms (abnormal narrowing of blood vessels in your brain) that developed after you 
experienced a subarachnoid hemorrhage (bleeding into the space surrounding your brain) caused 
by a ruptured aneurysm (large bulge of the blood vessel wall caused by weakening of the blood 
vessel wall) – hereinafter referred to as aneurysmal subarachnoid hemorrhage (aSAH). 
 
This study is designed to assess the safety and probable benefit of using the Neva VS device.   
The Neva VS device is an investigational (experimental) device which means that the Neva VS 
device has not been approved by the US Food and Drug Administration (FDA).    
 
WHO IS IN CHARGE OF THIS STUDY? 
This study is sponsored and funded by Vesalio Co., Ltd.  The Principal Investigator is being paid 
by Vesalio Co., Ltd. to conduct this study.  Together with your doctor, Vesalio Co., Ltd. will also 
use a specialized research company, called a contract research organization, in addition to a 
specialized laboratory to manage some of the requirements of the study.   
 
HOW MANY PEOPLE WILL TAKE PART IN THIS RESEARCH STUDY? 
Up to 150 patients will take part in this study at up to 15 hospitals.   
 
WHAT HAPPENS IF I AGREE TO BE IN THIS RESEARCH STUDY? 
After you sign this consent form indicating you want to participate in this study, you will need to 
undergo some tests to see if you qualify for the study.  If you do not meet all of the study entry 
criteria, you will not be able to participate in the study and your study doctor will discuss with 
you other options that you may have for treatment of your medical condition.   
 
This study is a prospective, open-label, single-arm clinical study.  If you agree and are eligible to 
participate, you will be treated with the Neva VS device.  
 
WHAT TESTS, PROCEDURES, AND DIAGNOSTIC STUDIES WILL BE DONE 
DURING THIS STUDY?  
Most tests are routine, standard of care following aSAH.  If you sign this consent form, you 
allow the results to be shared with the Sponsor of the study and its representatives. 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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Page 65 of 92 
 
Medical history: the study doctor and/or research team will examine your available medical 
records and ask you questions about your health, your medical history and hospitalizations 
including assessments performed when you were originally admitted for your aSAH. 
 
Vital signs: blood pressure, temperature, weight, heart rate, and breathing rate. 
 
Medication review: the study doctor and/or research team will ask you what medications you are 
taking.   
 
Blood test: you will give a blood sample (about 2-3 tablespoons) for routine blood tests.  
 
Urine test: if you are a woman who can get pregnant, a urine pregnancy test will be performed if 
it wasn’t already performed at hospital admission. 
 
NIH Stroke Scale (NIHSS): a non-invasive examination that measures stroke-related 
neurological deficits. 
 
Modified Rankin Score (mRS): a non-invasive examination that measures the degree of 
disability or dependence in daily activities. 
 
Hunt and Hess Scale: a non-invasive examination that measures stroke-related neurological 
deficits. 
 
Modified Fisher Scale: a non-invasive examination that measures the amount of blood seen 
from the images of your brain after your aneurysm rupture. 
 
Brain imaging: brain imaging such as a non-contrast head CT scan will be performed to assess 
for bleeding.   
 
Angiographic imaging: imaging of your brain vessels will be performed for confirmation and 
location of the vasospasm and to determine access to the blood vessel. 
 
Transcranial Doppler: a non-invasive ultrasound imaging method that measures the velocity of 
blood flow through your blood vessels in your brain. 
 
Intervention: After applying a local anesthetic (numbing medication), the interventional surgeon 
will make two small incisions in your groin area and introduce small plastic tubes (called access 
sheaths) through the incisions.  Through the access sheaths, the interventional surgeon can 
introduce a longer tube (called catheter) to inject dye (contrast medium) and use x-rays 
(fluoroscopy) to see your blood vessels on a monitor.  The interventional surgeon will look at 
your blood vessels to see if you are a good candidate for the Neva VS procedure.  If you qualify, 
the NeVa VS device is advanced through the tube into your blood vessel to the location of the 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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vasospasm(s).  The device will be temporarily expanded for few minutes and then moved along 
the blood vessel to other location(s) for temporarily expansion.  After all locations are treated, 
the device and the tubes (catheters and access sheaths) will be removed.  The entire procedure 
should take approximately one hour.   
 
Assessment of adverse events – Assessment of any unpleasant medical experiences, side effects, 
or discomforts that may happen to you.   
 
Visit # 1: Screening 
Screening will involve the following procedures: medical history, Hunt and Hess Grade, 
modified Fisher Scale, NIHSS, mRS, vital signs, blood test, urine pregnancy test (if applicable), 
transcranial Doppler, and medication review.  
 
Visit # 2: Intervention/Procedure (Day 0) 
After angiographic imaging to confirm your eligibility, the intervention with the Neva VS device 
and assessment of adverse events will be performed. 
  
Visit # 3 – 24 hours  
At this time, vital signs, brain imaging, transcranial Doppler, NIHSS, mRS, and assessment of 
adverse events will be performed. 
 
Visit # 4 – 21 Days after aSAH or Discharge (whichever occurs first) 
At this time, brain imaging, medication review, transcranial Doppler, NIHSS, mRS and 
assessment of adverse events will be performed. 
 
Visit # 5 – 30 Days 
At this time, mRS and assessment of adverse events will be performed. 
 
Additional Treatment for New or Recurring Vasospasm Before Hospital Discharge 
If vasospasm recurs or you experience vasospasm in other areas of your brain before you are 
discharged from the hospital, you may receive additional treatment with the NeVa VS.   
 
HOW LONG WILL I BE IN THIS RESEARCH STUDY? 
Your last follow up visit will be approximately 30 days after your last treatment with NeVa VS.  
After this visit, you will have completed this study. 
 
WHAT DO I HAVE TO DO AS A PARTICIPANT IN THIS STUDY? 
Participation in this study requires you to attend all your scheduled visits.  During your 
participation in the study you will be asked to report any unpleasant medical experiences that 
you may have.  You also must not participate in any other clinical trial while participating in this 
study.   
 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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WHAT ABOUT MY RIGHTS TO DECLINE PARTICIPATION OR WITHDRAW 
FROM THE STUDY? 
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw 
from the study at any time.  If you withdraw from the study, no new data about you will be 
collected for study purposes unless the data pertain to a side effect related to the study.  If such 
an event occurs, we may need to review your entire medical record.   
 
Your decision not to participate or to withdraw from the study will not involve any penalty or 
loss of benefits to which you are entitled and will not affect your access to health care.  If you do 
decide to stop your participation in the study, you should talk to your doctor immediately, so 
he/she can advise you of any additional tests that may be needed for your safety.  Your doctor 
may decide to take you off this study if your condition gets worse, if you have serious side 
effects, or if he/she determines that it is no longer in your best interest to continue.  The Sponsor 
or regulatory agencies may stop this study at any time without your consent.  If this occurs, you 
will be notified and your study doctor will discuss with you other options you may have.   
 
WHAT ARE THE RISKS OF THIS RESEARCH STUDY? 
Below is a description of these risks.   Your doctor will discuss the risks and procedures with you 
before you start in the study.   
 
Risks from NeVa VS Intervention  
As described above, the interventional surgeon will make two small incisions in your groin area 
and introduce small plastic tubes through the incisions.  These tubes (called access sheaths and 
catheters) are placed in your blood vessels to establish access for Neva VS procedure.  There 
may be pain or discomfort at the insertion sites and risk of infection. There is also a small risk of 
nerve damage that may cause pain and/or tingling at the sheath insertion site or down the leg.  
There is risk of damage to the artery or vein resulting in swelling, bruising, bleeding, or 
hematoma (collection of blood in the soft tissue) at the insertion site or deeper in the 
pelvis/abdomen. Bleeding complications may result in decreased blood pressure, increased heart 
rate, and, in severe cases, need for transfusion. There is some risk that introducing instruments 
will cause the artery or vein to spasm or narrow (stenosis) and require treatment. There is a risk 
that a blood clot will form in the blood vessel that requires treatment.  Additional treatments for 
these risks may include, medications, an additional procedure, or in rare cases surgery. When the 
sheaths and catheters are removed, manual compression is used to stop bleeding which may also 
cause discomfort or pain. The introduction of devices in the brain blood vessels may cause local 
injury including brain bleeding and/or strokes. Brain bleeding and/or strokes can cause 
permanent paralysis and/or loss of sensation in of one or more limbs and/or face as well as 
speech and/or visual problems, and even coma or death. 
 
Possible risks from the use of X-rays (fluoroscopy) and dye (contrast medium):  X-rays 
(fluoroscopy) will be used during sheath/ catheter placement and to visualize your blood vessels.  
The total fluoroscopy time and radiation exposure is estimated at several minutes and delivers 
approximately the same amount of radiation as a regular chest X-ray. Rare but possible effects of 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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Page 68 of 92 
radiation include: alopecia, (hair loss) burns ranging in severity from skin reddening to ulcers, 
cataracts, and delayed neoplasia (cancer). The interventional surgeon will also use dye (contrast 
medium) to better see your blood vessels during fluoroscopy.  Contrast medium may cause a 
sensation of warmth or occasionally nausea which lasts a few minutes.  In rare cases, contrast 
medium causes a mild reaction such as hives or skin redness.  More serious reactions have been 
known to occur (rarely) including damage to your kidneys, and inflammation (swelling) of the 
blood vessels, or (very rarely) a life-threatening problem with breathing or blood flow.    
 
Risks from Non-Contrast Head CT scan 
There is always a slight chance of cancer from excessive exposure to radiation. However, the 
benefit of an accurate diagnosis far outweighs the risk.   
 
Women should always inform their physician and x-ray or CT technologist if there is any 
possibility that they are pregnant. CT scanning is, in general, not recommended for pregnant 
women unless medically necessary because of potential risk to the baby. 
 
Risks from Blood Tests 
You will have routine blood samples taken from a vein in your arm by a needle stick.  Risks 
associated with drawing blood from your arm include slight discomfort and/or bruising.  
Infection, bleeding, clotting, or fainting are also possible, although unlikely.   
 
Unknown risks 
In addition to the risks already described, there may be other discomforts or risks from this study 
agent and/or procedures that we do not know about.  You will be watched for signs and 
symptoms of any side effects and you should tell your doctor if you do not feel well or 
experience any unusual symptoms.   
 
In the event of your death, an autopsy will be requested. It would be done to provide additional 
information about the research. Your family and your “legally authorized representatives” have 
the right to refuse the autopsy even if you sign this consent form. 
 
ARE THERE BENEFITS TO TAKING PART IN THIS RESEARCH STUDY? 
There may be no direct benefit to you by participating in this study.  However, it is possible that 
the Neva VS device diminishes or eliminates the vasospasms in your brain which may result in 
subjects experiencing less severe ischemic brain injury and less final disability, but there are no 
guarantees. 
 
Knowledge from this study may help us better understand how to treat people with vasospasm.     
 
WHAT IF NEW INFORMATION BECOMES AVAILABLE? 
If additional data regarding potential safety risks become available during the study, your 
research doctor will tell you about it and discuss with you whether you want to continue in the 
study.  If you decide to withdraw from the study, your research doctor will make arrangements 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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Page 69 of 92 
for your care to continue.  If you decide to continue in the study, you may be asked to sign an 
updated consent form which will explain the new information clearly.   
 
Also, on receiving new information your research doctor might consider it to be in your best 
interests to withdraw you from the study.  He/she will explain the reasons and arrange for your 
care to continue.   
 
WILL I NEED TO PAY FOR THE TESTS AND PROCEDURES? 
Participation in this study will be of no cost to you.  All medical exams, urine and blood tests, 
and study evaluations and procedures that are specifically required for this research study only 
are provided to you at no cost to you.  You will also not need to pay for the NeVa VS device.  
Vesalio Co., Ltd. pays for this research.  However, if taking part in this study leads to procedures 
or care not included in this study, it may lead to added costs for you or your insurance company.   
 
WILL I BE PAID TO TAKE PART?  
You will not receive any payment for taking part in this research study. 
 
WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THIS RESEARCH 
STUDY? 
In the event of an injury resulting from your participation in this study, you will be provided with 
appropriate medical care.  However, the costs incurred may, ultimately, be borne by your 
medical insurance.  Further information concerning this and your rights as a research subject can 
be obtained from [NAME OF PRINCIPAL INVESTIGATOR] or by phone [PHONE 
NUMBER] or by mail: 
 
[MAILING ADDRESS] 
 
WHAT ARE MY RIGHTS IF I TAKE PART IN THIS RESEARCH STUDY? 
You have the right to refuse to sign this consent.  Taking part in this research study does not take 
away any other rights or benefits you might have if you did not take part in the study.  Taking 
part in this study does not give you any special privileges.  You will not be penalized in any way 
if you decide not to take part or if you stop after you start the study.  Specifically, you do not 
have to be in this study to receive or continue to receive medical care from your doctor.  If you 
stop the study, you would still receive medical care for your condition although you would not 
be able to be treated with the Neva System. 
   
 
WHAT ABOUT CONFIDENTIALITY? 
The personal information obtained about you during the course of this study will remain 
confidential.  When recording the results of the study you will be referred to only by a unique 
subject identifier code number and your initials.  Except when required by law, you will not be 
identified by name, social security number, address, telephone number, or any other direct 
personal identifier in study records.   

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
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Page 70 of 92 
 
Your records may be reviewed in order to meet Federal Food and Drug Administration (US 
FDA) regulations, or other national and/or local health regulatory authorities.  Your records may 
be copied by, or for these groups.  If your research record is reviewed by any of these groups, 
they may also need to review your entire medical record.  Copies of the study records that do not 
include your name but may be traced back to you may also be given to the groups listed below.  
The Sponsor may send a copy of the records to the FDA or other regulatory agencies.   
 
By agreeing to participate in this research study, you consent to give representatives of the 
following entities access to your research-related medical records to ensure the proper conduct of 
the research and to verify the accuracy of the collected data.   
 
Clinical monitors, auditors, IRB members, and regulatory authorities will be granted access to 
your original medical records for verification of clinical trial procedures and/or data, without 
violating your confidentiality, to the extent permitted by the applicable laws and regulations.   
 
Reviewers for the study may include the Sponsor (Vesalio Co., Ltd.), or its representatives such 
as members of the Data Safety Monitoring Board, the Contract Research Organization identified 
as BioMDG, Inc., and the IRB or other Research Committee(s) that approve and oversee 
research in the hospitals and clinics.  Additionally, representatives of national regulatory 
authorities (for example the Food and Drug Administration in the USA), representatives of the 
central laboratory facilities appointed by the Sponsor responsible for analyzing the blood tests, 
and other representatives as designated by the Sponsor who will have a role in the handling and 
analysis of the study data or in trial operations.   
 
Complete confidentiality cannot be promised because information needs to be shared as 
described.  However, information will be collected and shared following professional standards 
of confidentiality.   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
WHAT WILL HAPPEN TO THE RESULTS OF THIS STUDY? 
The results of this research study will be used to support an application to regulatory agencies 
that approve medical devices.  In addition, the results may be used in scientific publications or 
presented at medical meetings.  Your identity as a participant will not be revealed.   
 
WHO HAS REVIEWED THIS STUDY? 
The study has been reviewed by the FDA and an IRB (research ethics committee). 
 
WHO CAN ANSWER MY QUESTIONS? 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
Protocol VS-002/E 
CONFIDENTIAL 
Vesalio 
 
 
Page 71 of 92 
If you have any questions, concerns, or complaints about this research study, you may call the 
study site.  If you think you have an injury or illness from the study agent, contact the study 
doctor listed on the first page of the consent form.  
 
You should contact the study doctor first if you have questions, complaints, or concerns about 
the study. 
 
Please call [Name] IRB at [Phone number] if: 
 
• You want to talk to someone other than the study doctor or study staff. 
• You have a hard time reaching the study doctor or study staff. 
• You have questions about your rights as a research subject. 
 
WHAT ALTERNATIVES ARE THERE TO PARTICIPATION IN THIS STUDY?   
If you choose not to take part in this study, other treatment for vasospasm such as endovascular 
therapy with vasodilators and angioplasty balloons is available to you.  You do not have to take 
part in this study to receive treatment for your condition.   
 
 
 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
Protocol VS-002/E 
CONFIDENTIAL 
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Page 72 of 92 
STATEMENT OF CONSENT 
 
I confirm that I have read and understand this consent form.  I confirm that the purpose of this 
study, procedures to be followed, and risks and benefits have been explained to me.  I have been 
allowed to ask questions, and my questions have been answered to my satisfaction.  I have 
decided of my own free will to agree to take part in this study.   
 
I understand that my participation is voluntary and that I am free to withdraw at any time, 
without giving any reason, and without my medical care or legal rights being affected.   
 
I understand that sections of any or all of my medical records may be reviewed by 
representatives of the Sponsor, Vesalio, its subcontractors, or by regulatory authorities where it is 
relevant to my taking part in this research.  I understand that I will not be referred to by name in 
any report concerning the study.  I agree to disclosure of such records and any results to the 
regulatory authorities.  I understand that I will be provided clinically-appropriate medical care 
and that I have access to my doctor in case of any injury or deterioration in my health or well-
being caused directly by my participation in this study.   
 
 
 
 
 
 
 
Printed Name of Participating Subject 
 
 
 
 
 
 
 
 
 
 
 
Signature of Participating Subject 
 
Date 
 
Time 
 
 
 
 
 
 
 
Printed Name of Legal Authorized Representative (if subject in unable to sign) 
 
 
 
 
 
 
 
 
 
Signature of Legal Authorized Representative 
 
Date 
 
Time 
Signature of Physician or his/her Representative 
Obtaining Consent 
 
Date 
 
Time 
 
 
 
 
 
 
 
 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
Protocol VS-002/E 
CONFIDENTIAL 
Vesalio 
 
 
Page 73 of 92 
HEALTH INSURANCE PORTABILITY AND ACCOUNTABILITY ACT  
(HIPAA) AUTHORIZATION 
 
Federal regulations give you certain rights related to your health information.  These include the 
right to know who will receive the information and how it will be used.  The study doctor must 
obtain your authorization (permission) to use or release any health information that might 
identify you. 
 
What information may be used and shared? 
The study doctor and study staff will use and share your health information as part of this 
research study. This may include your name, address, telephone number or other facts that could 
identify the health information as yours.   
Examples of the information that may be used are: 
• Medical records (from any doctor, hospital or other healthcare provider) 
• Information created or collected during the research.  This could include your medical 
history, and dates or results from any physical exams, laboratory tests or other tests. 
 
Who will receive information about you? 
The study doctor and study staff will share your personal health information with: 
• the sponsor, including persons or companies working for or with the sponsor 
• [Name] Independent Review Board  
• the U.S. Food and Drug Administration (FDA) 
• Department of Health and Human Services (DHHS) agencies 
• other regulatory agencies  
 
Why will this information be used and/or given to others? 
The sponsor and the groups above will use your health information: 
• to complete this research 
• to evaluate the results of the study 
• to check that the study is being done properly 
• to obtain marketing approval for new products resulting from this research 
 
Is my health information protected after it has been given to others? 
Your health information may be further shared by the groups above. If shared by them, the 
information will no longer be covered by this Authorization.  These groups are committed to 
keeping your health information confidential.  
 
What if I decide not to allow the use of my health information? 
You do not have to sign this form.  If you do not sign this form, you cannot take part in this 
research study.  
 
May I withdraw or revoke (cancel) my permission? 

SUBJECT INFORMATION SHEET / INFORMED CONSENT FORM 
 
A THE VESALIOTM NEVA VS FOR THE TREATMENT OF SYMPTOMATIC CEREBRAL VASOSPASM 
FOLLOWING ANEURYSMAL SUBARACHNOID HEMORRHAGE (ASAH)  
( THE VITAL STUDY PROTOCOL VS-002) 
 
Protocol VS-002/E 
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Page 74 of 92 
YES.  You may withdraw your permission to use and disclose your health information at any 
time.  You can do this by sending written notice to the study doctor.  If you withdraw your 
permission, you will not be able to continue being in the research study. 
 
What happens if I want to withdraw my authorization? 
Information that has already been gathered may still be used and given to others.  If you 
withdraw your permission, no new health information will be gathered unless you have a side 
effect related to the study.  If you withdraw from the study but do not withdraw your 
Authorization, new health information may be collected until this study ends.   
 
Will my authorization expire? 
If you do not withdraw this Authorization in writing, it will remain in effect. 
 
This Authorization [does not have an expiration date. If you do not withdraw this Authorization 
in writing, it will remain in effect indefinitely.] ***OR [will expire December 31, 2060, unless 
you withdraw it in writing before then.]  (FOR CA, WA, WI, IN SITES)*** 
 
The study doctor will keep this Authorization for at least 6 years. 
 
May I review or copy the information obtained or created about me? 
YES. You have the right to review and copy your health information.  However, your access to 
this information may be delayed until the study is complete. 
 
Your decision to withdraw your Authorization or not to participate will not involve any penalty 
or loss of access to treatment or other benefits to which you are entitled.   
 
AUTHORIZATION 
By signing this form, I allow the use or disclosure of my health information.  I will receive a 
signed and dated copy of this Authorization. 
 
 
 
Printed Name of Subject 
 
 
 
Signature of Subject 
Date 
 
 
 
Printed Name of Legal Authorized Representative (if subject is unable to sign) 
 
 
 
Signature of Legal Authorized Representative 
Date 
 

 
Protocol VS-002/E 
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Appendix 3. 
Neva VS Device – Draft Instructions for Use 
 

  
Vesalio NeVa VS System : Instructions for Use 
P/N 100043LV Rev. 02 
Revised 12/2018 
Confidential  
 
 
Page 76 of 92 
 
CAUTION Investigational device.  Limited by Federal (or United States) law to investigational use. 
Caution: This device is restricted to use by or on the order of a physician. 
 
As with any medical treatment, it is the responsibility of the surgeon/physician to use his or her judgment in utilizing the procedures best suited to the needs of the patient.  Only physicians trained in neuro-
interventional procedures should utilize the Vesalio NeVa VS (Vasospasm) System. 
The Vesalio VS System contains (1) NeVa vessel dilation device. 
 
INDICATION FOR USE 
The  NeVa VS System is indicated for the treatment of cerebral ischemia resulting from symptomatic vasospasm following subarachnoid hemorrhage (aSAH), secured by either surgical or endovascular 
intervention for patients who have failed maximal medical management. The NeVa VS System is temporarily deployed within the vasospastic vessel segment where the intrinsic outward radial force of the 
nitinol tip expands the vessel.   
The Vesalio NeVa VS System is indicated for: 
• 
Endovascular temporary use in patients with acute cerebral ischemia related to aSAH induced cerebral vasospasm 
• 
Endovascular temporary use to increase vessel diameter and blood flow in patients who are experiencing symptoms of acute ischemia related to aSAH associated vasospasm. 
 
CAUTION: Evaluate the risks associated with acute endovascular vasospasm therapy (see complications below) and the possible benefits of intravascular vessel dilation prior to use of the Vesalio NeVa 
VS System. Take all necessary precautions to limit X-radiation doses to patients and themselves by using sufficient shielding, reducing fluoroscopy times, and modifying X-ray technical factors where 
possible. 
 
CONTRAINDICATIONS 
• 
Presence of an unsecured, ruptured intracranial aneurysm 
• 
Patient allergy to NeVa VS components (nickel). 
• 
Patients with suspected or known allergies to contrast media  
• 
Pregnancy 
• 
Excessive vessel tortuosity that prevents the placement of the device 
 
• 
Known hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant 
therapy with INR>1.7 
• 
Patient has baseline platelets <30,000 
• 
Evidence of rapidly improving neurological signs of stroke 
• 
Large territory completed cerebral infarction, edema with mass effect and intra-
parenchymal hemorrhage in vascular territory to be treated 
 
WARNINGS AND PRECAUTIONS 
 
The Vesalio NeVa VS System should only be used by physicians who have received appropriate training in cerebral endovascular techniques.  
 
The Vesalio NeVa VS System family of products, as noted in the Recommended Sizing Guideline Table, is designed for use in vessels with a pre-vasospasm diameter ≥ 2.0mm and ≤ 4.0mm 
in diameter. Use of the device in vessel diameters outside the recommendation can produce vessel injury.   
 
The NeVa VS should only be used with the Trevo Pro 18 Microcatheter 
 
The device is provided STERILE for single patient use only.  Reusing the device could result in compromised device performance, cross-infection and other safety related hazards.  
 
Store in a cool, dry place. 
 
Do not re-sterilize. After use, dispose in accordance with hospital, administrative and/or local government policy. 
 
Use the device prior to the ‘Use By Date’ date printed on the package. 
 
Carefully inspect the sterile package and device prior to use to verify that neither has been damaged during shipment.  Do not use kinked or damaged components. 
 
The Vesalio NeVa VS System has not been shown to be MRI compatible.   
 
Tighten the Rotating Hemostasis Valves sufficiently to create an adequate hemostasis seal without crushing the introducer sheath and Vesalio NeVa VS System shaft.  Inadequately tightening 
the Rotating Hemostasis Valves my lead to premature deployment of the device. 
 
After deployment, the distal tip of the device may foreshorten. 
 
COMPLICATIONS 
Possible complications of the use of the Vesalio NeVa VS System include but are not limited to: 
• 
Perforation or dissection of the vessel 
• 
Air embolism 
• 
Arterial perforation with guidewire 
• 
Subarachnoid/interventricular hemorrhage due to vessel perforation from 
guidewire placement or device microcatheter placement. 
• 
Vascular spasm or vascular occlusion 
• 
Neurologic deterioration including stroke and death 
• 
Distal embolization including to a previously uninvolved territory 
• 
Pseudo aneurysm formation 
• 
Device(s) deformation, collapse, fracture or malfunction 
• 
Displacement of coils or clips used to secure an aneurysm 
Complications of routine endovascular revascularization include: 
• 
Cerebral ischemia 
• 
Coagulopathy 
• 
Confusion 
• 
Death 
• 
Embolic stroke 
• 
Hematoma, pain, and/or infection at access site 
• 
Intracerebral/intracranial hemorrhage 
• 
Post-procedure bleeding 
• 
Pseudoaneurysm formation 
• 
Renal failure 
• 
Vessel thrombosis 

  
Vesalio NeVa VS System : Instructions for Use 
P/N 100043LV Rev. 02 
Revised 12/2018 
Confidential  
 
Page 77 of 92 
 
PROCEDURE 
The Vesalio NeVa VS System is delivered endovascularly under fluoroscopic guidance in a manner consistent with other neurovascular catheter-based devices. 
Antiplatelet and anticoagulation regimen used for interventional intracranial procedures is to be performed at the discretion of the treating physician. 
Procedure Steps: 
Angiographic Assessment of Vessel and Device Selection 
1. 
Using angiography, determine the location of the vasospastic vessel segment 
2. 
Review the patient’s pre-vasospasm digital subtraction angiogram or equivalent vascular study (CT angiogram) to confirm that the segment to be treated has a 
diameter of at least 2.0mm prior to deployment. Recommended vessel diameter for the fully expanded portion of NeVa VS is a pre-vasospasm diameter of 2mm. 
The distal tapered portion and marker coil extend 10mm beyond the fully expanded segment. No more than 6 device interventions per vessel should be 
attempted. 
 
Table 1: Vesalio NeVa VS System 
Product Name Numbers and Recommend Sizing Guidelines 
Product 
Number 
Product Name 
Labeled 
Device 
Diameter 
(mm) 
Labeled 
Device Length 
(mm) 
Self Expanded 
Device Diameter 
(mm) 
Recommended Pre-
vasospasm Vessel 
Diameter 
(mm) 
Pusher 
Length 
Introducer 
Microcatheter  
Max. Guidewire 
Diameter 
30050V-VS 
NeVa VS 
4.0 
22 
4.0 
≥ 2.0 and ≤ 4.0 
180cm 
Trevo Pro 18 
NA 
 
Vesalio NeVa VS System Preparation and Procedure 
Preparation  
1. 
Administer anti-coagulation and anti-platelet medications per standard institutional guidelines.  
2. 
Aided by angiographic radiography and reviewing the pre-vasospasm vascular imaging determine the location and size of the area to be revascularized.  
3. 
To achieve optimal performance of the Vesalio NeVa VS System and to reduce the risk of thromboembolic complications, maintain continuous flushing action 
between a) the femoral arterial sheath and the guide catheter, b) the microcatheter and the guide catheter and c) the microcatheter and the push wire and the Vesalio 
NeVa VS System.  Check all connections to make sure that during the continuous flush that no air enters the guide catheter or the microcatheter. 
4. 
Position a suitable guide catheter employing a standard method.  The guide catheter should be appropriately sized to allow for angiography around the microcatheter.  
Connect a RHV to the fitting of the guide catheter, and then connect a tube to the continuous flush. 
5. 
With the aid of Table 1, select a microcatheter suitable for advancing the Vesalio NeVa VS System. 
6. 
Connect a second RHV to the fitting of the microcatheter and then connect a tube to the continuous flush.  
7. 
Set the flush rate per standard institutional guidelines. 
8. 
With the aid of a suitable guide wire, advance the microcatheter until the end of the microcatheter is positioned as distal as possible within the treatable segment of 
the vasospastic vessel.  The treatable segment is determined by reviewing the pre-vasospasm angiographic imaging to ensure that the segment is at least 2.0mm 
in diameter. Remove the guidewire and perform a microcatheter angiogram to ensure proper intra-vascular positioning of the microcatheter prior to deployment. 
Delivering the Vesalio NeVa VS System 
9. 
Insert the distal end of the introducer sheath partially into the RHV connected to the microcatheter. Tighten the RHV and verify that fluid exits the proximal end of 
the introducer sheath. 
10. 
Loosen the RHV and advance the introducer sheath until it is firmly seated in the hub of the microcatheter. Tighten the RHV around the introducer sheath to prevent 
back flow of blood, but not so tight as to damage the Vesalio NeVa VS System during its introduction into the microcatheter. Confirm that there are no air bubbles 
trapped anywhere in the system.  
11. 
Transfer the Vesalio NeVa VS System into the microcatheter by advancing the push wire in a smooth, continuous manner. Once the flexible portion of the push wire 
has entered the microcatheter shaft, loosen the RHV and remove the introducer sheath over the proximal end of the push wire. Once completed, tighten the RHV 
around the push wire. Leaving the introducer sheath in place will interrupt normal infusion of flushing solution and allow back flow of blood into the microcatheter.  
12. 
Visually verify that the flushing solution is infusing normally. Once confirmed, loosen the RHV to advance the push wire.  
13. 
With the aid of fluoroscopic monitoring, carefully advance the Vesalio NeVa VS System until its distal marker lines up at the end of the microcatheter.     
WARNING: IF EXCESSIVE RESISTANCE IS ENCOUNTERED DURING THE DELIVERY OF THE VESALIO NEVA VS SYSTEM, DISCONTINUE THE DELIVERY 
AND IDENTIFY THE CAUSE OF THE RESISTANCE. ADVANCEMENT OF THE VESALIO NEVA VS SYSTEM AGAINST RESISTANCE MAY RESULT IN DEVICE 
DAMAGE AND/OR PATIENT INJURY. 
Deploying the Vesalio NeVa VS System 
14. 
Loosen the RHV around the microcatheter. To deploy the Vesalio NeVa VS System, fix the pusher wire to maintain the position of the device while carefully 
withdrawing the microcatheter in the proximal direction. Do not advance the NeVa VS System beyond the distal tip of the microcatheter, doing so risks damage to 
the vessel and/or the device. 
15. 
Retract the microcatheter until it is proximal to the proximal marker of the Vesalio NeVa VS System. Tighten the RHV to prevent any movement of the push wire.    
16. 
Allow the NeVa VS to remain in place for up to 10 minutes, frequent spot fluoroscopy and angiographic imaging is encouraged to evaluate device expansion and to 
evaluate for any complications such as thrombus formation. 
17. 
Do not advance or withdraw the device against resistance or significant vasospasm as moving or torqueing of the device against resistance or significant vasospasm 
 
may result in damage to the vessel or device 
18. 
After complete expansion or 10 minutes, re-capture the NeVa VS System into the microcatheter using the following steps:  Loosen the RHV around the microcatheter 
and around the push wire. With the aid of fluoroscopic monitoring, hold the push wire firmly in its position to prevent the Vesalio NeVa VS System from moving. 
Carefully re-sheath the Vesalio NeVa VS System by advancing the microcatheter over the Vesalio NeVa VS System until the distal markers of the Vesalio NeVa VS 
System line up at the end of the microcatheter. 
19. 
Once re-captured in the microcatheter, the catheter can be withdrawn to a more proximal segment and the device re-deployed to treat proximal vasospasm following 
steps 15-17 above.  
  
WARNING:  IF EXCESSIVE RESISTANCE IS ENCOUNTERED DURING MICROCATHETER RE-CAPTURE OF THE VESALIO NEVA VS SYSTEM, 
DISCONTINUE THE RE-CAPTURE AND IDENTIFY THE CAUSE OF THE RESISTANCE. IF THERE IS CONTINUED RESISTANCE, WITHDRAW THE 
MICROCATHETER AND NEVA VS SYSTEM TOGETHER AND RE-CAPTURE INTO THE GUIDE CATHETER. DO NOT PERFORM MORE THAN SIX 
DEPLOYMENTS AND MICROCATHETER RE-SHEATHING ATTEMPTS USING A SINGLE VESALIO NEVA VS SYSTEM. 
20. 
After the last deployment, re-capture the device into the microcatheter following the steps above and withdraw the microcatheter and NeVa VS System through the 
guide catheter. Open the guide catheter RHV to allow the microcatheter and the Vesalio NeVa VS System to exit without resistance. Use care to prevent air from 
entering the system. 
21. 
If additional vessel dilation attempts are desired with: 
a new Vesalio NeVa VS System, then repeat the steps described above starting with the “Preparation” section. 

  
Vesalio NeVa VS System : Instructions for Use 
P/N 100043LV Rev. 02 
Revised 12/2018 
Confidential  
 
Page 78 of 92 
 
the same Vesalio NeVa VS System, then:  
 
a. 
Clean the device with saline solution. Do not use solvents or autoclave.  
b. 
Carefully inspect the device for damage.  If there is any damage, do not use the device and use a new Vesalio NeVa VS System for subsequent vasodilation 
attempts following the steps described above starting with the “Preparation” section.  Use of a damaged device could result in additional device damage or 
patient injury. 
 
WARNING:  DO NOT USE EACH VESALIO NEVA VS SYSTEM FOR MORE THAN SIX DEPLOYMENTS AND MICROCATHETER 
RETRIEVALS. 
   
HOW SUPPLIED 
Each Vesalio NeVa VS System contains one device positioned in an introducer sheath. All are supplied STERILE (Gamma) and FOR SINGLE USE ONLY.  All components 
should be handled carefully to avoid damaging the device.   
STORAGE AND HANDLING 
Handle with care.  Packages should be stored in a manner that protects the integrity of the package; packages should be stored at a controlled room temperature in a dry place. 
WARRANTY AND LIMITATION OF WARRANTY 
Vesalio LLC warrants that reasonable care was used in the design and manufacture of this product. Because Vesalio LLC has no control over the conditions of use, patient 
selection or handling of the device after it leaves its possession, Vesalio LLC does not warrant either a good effect or against an ill effect following its use. Vesalio LLC. shall not 
be directly or indirectly responsible for any incidental or consequential loss, damage or expenses directly or indirectly arising from the use of this product. Vesalio LLC sole 
responsibility in the event Vesalio LLC determines the product was defective when shipped by Vesalio LLC, shall be the replacement of the product. This warranty is in lieu of 
and excludes all other warranties not expressly set forth herein, whether expressed or implied by operation of law or otherwise, including but not limited to any implied warranties 
of merchantability or fitness for use. 
 
Symbols Glossary 
 
Lot number 
 
Do not reuse 
 
Model number 
 
Keep dry 
 
Sterile (Gamma Radiation) 
 
Manufacturer 
 
Use -by date 
 
Do Not use if package is 
damaged 
 
Warning 
 
 
Read the documentation 
21MC 
For use only with Trevo Pro 18 
microcatheter 
Rx Only 
Prescription 
 
Do not re-sterilize 
 
 
 
 
Manufacturer: 
Vesalio LLC 
105 North Pointe Drive 
Lake Forest, CA  92630 USA 
Telephone: +615-206-7788 
 
 
  
Patents www.vesalio.com/patent 
 

 
Protocol VS-002/E 
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Appendix 4. 
NIH Stroke Scale 
 
 
 

 
Protocol VS-002/E 
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Vesalio 
 
 
Page 80 of 92 
Date of Exam:  
 
 
 
Time of exam: ___ ____ : ___ ___ am / pm 
 
Person Administering Scale:________________________________________ 
 
Administer stroke scale items in the order listed.  Record performance in each category after each subscale 
exam. Do not go back and change scores. Follow directions provided for each exam technique. Scores 
should reflect what the patient does, not what the clinician thinks the patient can do.  The clinician should 
record answers while administering the exam and work quickly.  Except where indicated, the patient should 
not be coached (i.e., repeated requests to patient to make a special effort). 
 
 Instructions  
Scale Definition  
Score  
1a. Level of Consciousness: The investigator must choose a 
response if a full evaluation is prevented by such obstacles as an 
endotracheal tube, language barrier, orotracheal trauma/bandages. 
A 3 is scored only if the patient makes no movement (other than 
reflexive posturing) in response to noxious stimulation.  
0 = Alert; keenly responsive.  
 
1 = Not alert; but arousable by minor 
stimulation to obey, answer, or respond.  
 
2 = Not alert; requires repeated stimulation to 
attend, or is obtunded and requires strong or 
painful stimulation to make movements (not 
stereotyped).  
 
3 = Responds only with reflex motor or 
autonomic effects or totally unresponsive, 
flaccid, and areflexic.  
______  
1b. LOC Questions: The patient is asked the month and his/her 
age. The answer must be correct - there is no partial credit for being 
close. Aphasic and stuporous patients who do not comprehend the 
questions will score 2. Patients unable to speak because of 
endotracheal intubation, orotracheal trauma, severe dysarthria from 
any cause, language barrier, or any other problem not secondary to 
aphasia are given a 1. It is important that only the initial answer be 
graded and that the examiner not "help" the patient with verbal or 
non-verbal cues.  
0 = Answers both questions correctly.  
 
1 = Answers one question correctly.  
 
2 = Answers neither question correctly.  
______  
1c. LOC Commands: The patient is asked to open and close the 
eyes and then to grip and release the non-paretic hand. Substitute 
another one step command if the hands cannot be used. Credit is 
given if an unequivocal attempt is made but not completed due to 
weakness. If the patient does not respond to command, the task 
should be demonstrated to him or her (pantomime), and the result 
scored (i.e., follows none, one or two commands). Patients with 
trauma, amputation, or other physical impediments should be given 
suitable one-step commands. Only the first attempt is scored.  
0 = Performs both tasks correctly.  
 
1 = Performs one task correctly.  
 
2 = Performs neither task correctly.  
______  
2. Best Gaze: Only horizontal eye movements will be tested. 
Voluntary or reflexive (oculocephalic) eye movements will be 
scored, but caloric testing is not done. If the patient has a conjugate 
deviation of the eyes that can be overcome by voluntary or reflexive 
activity, the score will be 1. If a patient has an isolated peripheral 
nerve paresis (CN III, IV or VI), score a 1. Gaze is testable in all 
aphasic patients. Patients with ocular trauma, bandages, pre-
existing blindness, or other disorder of visual acuity or fields should 
be tested with reflexive movements, and a choice made by the 
investigator. Establishing eye contact and then moving about the 
patient from side to side will occasionally clarify the presence of a 
partial gaze palsy.  
0 = Normal.  
 
1 = Partial gaze palsy; gaze is abnormal in one 
or both eyes, but forced deviation or total gaze 
paresis is not present.  
 
2 = Forced deviation, or total gaze paresis not 
overcome by the oculocephalic maneuver.  
______  
 
 

 
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Page 81 of 92 
3. Visual: Visual fields (upper and lower quadrants) are tested by 
confrontation, using finger counting or visual threat, as appropriate. 
Patients may be encouraged, but if they look at the side of the 
moving fingers appropriately, this can be scored as normal. If there 
is unilateral blindness or enucleation, visual fields in the remaining 
eye are scored. Score 1 only if a clear-cut asymmetry, including 
quadrantanopia, is found. If patient is blind from any cause, score 
3. Double simultaneous stimulation is performed at this point. If 
there is extinction, patient receives a 1, and the results are used to 
respond to item 11.  
0 = No visual loss.  
 
1 = Partial hemianopia.  
 
2 = Complete hemianopia.  
 
3 = Bilateral hemianopia (blind including 
cortical blindness).  
______  
4. Facial Palsy: Ask – or use pantomime to encourage – the patient 
to show teeth or raise eyebrows and close eyes. Score symmetry 
of grimace in response to noxious stimuli in the poorly responsive 
or 
non-comprehending 
patient. 
If 
facial 
trauma/bandages, 
orotracheal tube, tape or other physical barriers obscure the face, 
these should be removed to the extent possible.  
0 = Normal symmetrical movements.  
 
1 = Minor paralysis (flattened nasolabial fold, 
asymmetry on smiling).  
 
2 = Partial paralysis (total or near-total 
paralysis of lower face).  
 
3 = Complete paralysis of one or both sides 
(absence of facial movement in the upper and 
lower face).  
______  
5. Motor Arm: The limb is placed in the appropriate position: extend 
the arms (palms down) 90 degrees (if sitting) or 45 degrees (if 
supine). Drift is scored if the arm falls before 10 seconds. The 
aphasic patient is encouraged using urgency in the voice and 
pantomime, but not noxious stimulation. Each limb is tested in turn, 
beginning with the non-paretic arm. Only in the case of amputation 
or joint fusion at the shoulder, the examiner should record the score 
as untestable (UN), and clearly write the explanation for this choice.  
0 = No drift; limb holds 90 (or 45) degrees for 
full 10 seconds.  
 
1 = Drift; limb holds 90 (or 45) degrees, but 
drifts down before full 10 seconds; does not hit 
bed or other support.  
 
2 = Some effort against gravity; limb cannot 
get to or maintain (if cued) 90 (or 45) degrees, 
drifts down to bed, but has some effort against 
gravity.  
 
3 = No effort against gravity; limb falls.  
 
4 = No movement.  
UN = Amputation or joint fusion, explain: 
_____________________  
 
5a. Left Arm  
 
5b. Right Arm  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______  
 
______  
6. Motor Leg: The limb is placed in the appropriate position: hold 
the leg at 30 degrees (always tested supine). Drift is scored if the 
leg falls before 5 seconds. The aphasic patient is encouraged using 
urgency in the voice and pantomime, but not noxious stimulation. 
Each limb is tested in turn, beginning with the non-paretic leg. Only 
in the case of amputation or joint fusion at the hip, the examiner 
should record the score as untestable (UN), and clearly write the 
explanation for this choice.  
0 = No drift; leg holds 30-degree position for 
full 5 seconds.  
 
1 = Drift; leg falls by the end of the 5-second 
period but does not hit bed.  
 
2 = Some effort against gravity; leg falls to 
bed by 5 seconds, but has some effort against 
gravity.  
 
3 = No effort against gravity; leg falls to bed 
immediately.  
 
4 = No movement.  
UN = Amputation or joint fusion, explain: 
________________  
 
6a. Left Leg  
 
6b. Right Leg  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______  
 
 
______ 
 
 

 
Protocol VS-002/E 
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7. Limb Ataxia: This item is aimed at finding evidence of a 
unilateral cerebellar lesion. Test with eyes open. In case of visual 
defect, ensure testing is done in intact visual field. The finger-nose-
finger and heel-shin tests are performed on both sides, and ataxia 
is scored only if present out of proportion to weakness. Ataxia is 
absent in the patient who cannot understand or is paralyzed. Only 
in the case of amputation or joint fusion, the examiner should record 
the score as untestable (UN), and clearly write the explanation for 
this choice. In case of blindness, test by having the patient touch 
nose from extended arm position.  
0 = Absent.  
 
1 = Present in one limb.  
 
2 = Present in two limbs.  
 
UN = Amputation or joint fusion, explain: 
________________  
______  
8. Sensory: Sensation or grimace to pinprick when tested, or 
withdrawal from noxious stimulus in the obtunded or aphasic 
patient. Only sensory loss attributed to stroke is scored as abnormal 
and the examiner should test as many body areas (arms [not 
hands], legs, trunk, face) as needed to accurately check for 
hemisensory loss. A score of 2, “severe or total sensory loss,” 
should only be given when a severe or total loss of sensation can 
be clearly demonstrated. Stuporous and aphasic patients will, 
therefore, probably score 1 or 0. The patient with brainstem stroke 
who has bilateral loss of sensation is scored 2. If the patient does 
not respond and is quadriplegic, score 2. Patients in a coma (item 
1a=3) are automatically given a 2 on this item.  
0 = Normal; no sensory loss.  
 
1 = Mild-to-moderate sensory loss; patient 
feels pinprick is less sharp or is dull on the 
affected side; or there is a loss of superficial pain 
with pinprick, but patient is aware of being 
touched.  
 
2 = Severe to total sensory loss; patient is not 
aware of being touched in the face, arm, and leg.  
______  
9. Best Language: A great deal of information about 
comprehension will be obtained during the preceding sections of 
the examination. For this scale item, the patient is asked to describe 
what is happening in the attached picture, to name the items on the 
attached naming sheet and to read from the attached list of 
sentences. Comprehension is judged from responses here, as well 
as to all of the commands in the preceding general neurological 
exam. If visual loss interferes with the tests, ask the patient to 
identify objects placed in the hand, repeat, and produce speech. 
The intubated patient should be asked to write. The patient in a 
coma (item 1a=3) will automatically score 3 on this item. The 
examiner must choose a score for the patient with stupor or limited 
cooperation, but a score of 3 should be used only if the patient is 
mute and follows no one-step commands.  
0 = No aphasia; normal.  
 
1 = Mild-to-moderate aphasia; some obvious 
loss of fluency or facility of comprehension, 
without significant limitation on ideas expressed 
or form of expression. Reduction of speech 
and/or comprehension, however, makes 
conversation about provided materials difficult or 
impossible. For example, in conversation about 
provided materials, examiner can identify picture 
or naming card content from patient’s response.  
 
2 = Severe aphasia; all communication is 
through fragmentary expression; great need for 
inference, questioning, and guessing by the 
listener. Range of information that can be 
exchanged is limited; listener carries burden of 
communication. Examiner cannot identify 
materials provided from patient response.  
 
3 = Mute, global aphasia; no usable speech or 
auditory comprehension.  
______  
10. Dysarthria: If patient is thought to be normal, an adequate 
sample of speech must be obtained by asking patient to read or 
repeat words from the attached list. If the patient has severe 
aphasia, the clarity of articulation of spontaneous speech can be 
rated. Only if the patient is intubated or has other physical barriers 
to producing speech, the examiner should record the score as 
untestable (UN), and clearly write an explanation for this choice. Do 
not tell the patient why he or she is being tested.  
0 = Normal.  
 
1 = Mild-to-moderate dysarthria; patient slurs 
at least some words and, at worst, can be 
understood with some difficulty.  
 
2 = Severe dysarthria; patient's speech is so 
slurred as to be unintelligible in the absence of 
or out of proportion to any dysphasia, or is 
mute/anarthric.  
 
UN = Intubated or other physical barrier, 
explain:_____________________________  
______  
 
 

 
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11. Extinction and Inattention (formerly Neglect): Sufficient 
information to identify neglect may be obtained during the prior 
testing. If the patient has a severe visual loss preventing visual 
double simultaneous stimulation, and the cutaneous stimuli are 
normal, the score is normal. If the patient has aphasia but does 
appear to attend to both sides, the score is normal. The presence 
of visual spatial neglect or anosagnosia may also be taken as 
evidence of abnormality. Since the abnormality is scored only if 
present, the item is never untestable.  
0 = No abnormality.  
 
1 = Visual, tactile, auditory, spatial, or 
personal inattention or extinction to bilateral 
simultaneous stimulation in one of the sensory 
modalities.  
 
2 = Profound hemi-inattention or extinction to 
more than one modality; does not recognize 
own hand or orients to only one side of space.  
______  
 
 
 

 
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Appendix 5. 
Investigator’s Qualifications and Responsibilities 
 
 

 
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The investigators have the following responsibilities: 
 
1. 
Subject Selection 
The investigator is responsible for assuring that all subjects entering the study conform to the 
subject selection criteria. 
 
2. 
Informed Consent 
The investigator is responsible for fully reviewing the nature of the study, the possible risks, and 
alternative treatments with the prospective subject/legal representative prior to their enrollment 
in the study.  The investigator is responsible for obtaining written Informed Consent in 
compliance with 21 CFR 50 for each subject or his/her legal representative, prior to enrollment 
in the trial.  A copy of the signed Informed Consent Form will be maintained in the subject's 
medical record. 
 
3. 
Institutional Review Board (IRB) Approval 
The investigator must obtain approval for his participation in this protocol from the IRB for the 
institution at which the procedure will be performed, prior to entering any subjects in the study.  
The Informed Consent document to be used will also be submitted by the Investigator to the IRB 
for approval prior to initiation of the study.  Assurance that the IRB approval of the study 
protocol and Informed Consent has been obtained will be provided to the Sponsor/Designee prior 
to initiation of the study. 
 
4.  
Subject Evaluations and Data Reporting 
The investigator, or trained designee, is responsible for performing the subject assessments as 
described in the study protocol.  Information generated by these evaluations will be recorded on 
the CRFs provided by the Sponsor/Designee or entered into the electronic data capture system 
(EDC) with access provided by the Sponsor/Designee.   
 
Following each subject visit, the CRFs will be completed in a timely manner, e.g., within 48 
hours.  Original reports from the subject assessments (source documents) will be retained as part 
of the subject’s study file. 
 
Investigator(s) will not deviate from the study protocol without prior approval of the 
Sponsor/Designee unless protection of the health, safety or welfare of study subjects requires 
prompt action. 
 
5. 
Record Retention 
In accordance with Commission Directive 2005/28/EC, the investigator shall retain the essential 
documents relating to a clinical trial for at least five years after its completion.   
 
The investigator shall retain the documents for a longer period, where so required by other 
applicable requirements or by an agreement between the Sponsor and the investigator.  
 
Essential documents shall be archived in a way that ensures that they are readily available, upon 
request, to the competent authorities.   

 
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The medical files of trial subjects shall be retained in accordance with national legislation and in 
accordance with the maximum period of time permitted by the hospital, institution or private 
practice. 
 
6. 
Investigational Material Accountability 
The investigator must maintain accurate records of the receipt of investigational material shipped 
by the Sponsor/Designee, including the date and lot numbers received.  In addition, accurate 
records must be kept on the amount and date that investigational material, by lot number, was 
used or returned for each subject in the trial.  The investigator must assure that study supplies be 
used only in subjects enrolled in the study and under the direct supervision of the investigator or 
co-investigators. 
 
Records of all investigational supplies received, used and returned must be kept by the principal 
investigator or his/her designee.  All unused investigational supplies will be returned to the 
Sponsor/Designee as soon as practical upon completion of enrollment.  Investigational material 
accounting procedures must be completed before the study is considered terminated. 
 
 

 
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Appendix 6. 
Sponsor’s Commitments 
 
 
 
 
 

 
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Vesalio is committed to: 
 
1. 
Complying with the Declaration of Helsinki, and all applicable health authority regulations 
governing the conduct of clinical research studies. 
 
2. 
Protecting the rights, health, safety, and welfare of study subjects. 
 
3. 
Informing the clinical investigators of any new information about the study, which may 
affect the health, safety or welfare of the subjects, or may influence their decision to 
continue participation in the study. 
 
4. 
Providing the clinical investigators with the study protocol, and a full set of / access to 
CRFs on which to document the study evaluation variables for each subject entered into the 
study. 
 
5. 
Providing the statistical analysis and study report writing resources necessary to complete 
reporting of the study results. 
 
6. 
Ensuring equity of consideration among all investigators in multicenter studies in all 
matters of publications, meeting presentations, etc. 
 
7. 
Certifying that IRB approval of the protocol and completion of the Investigator’s 
Agreement will occur prior to treatment at any investigational site.