ExtracorPoreal FILtration of Subarachnoid Hemorrhage Via SpinaL CAtheteR EXTension
Phase: NA
Conditions: Subarachnoid Hemorrhage
Sponsor: Minnetronix

 
 
 
ExtracorPoreal FILtration of Subarachnoid Hemorrhage via 
SpinaL CAtheteR EXTension 
 
PILLAR-XT 
 
 
 
Clinical Protocol 
IDE #G150184 
NCT03607825 
 
Revision Date: March 11, 2020 

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TABLE OF CONTENTS 
1. 
SYNOPSIS ............................................................................................................................................. 5 
2. 
INTRODUCTION .............................................................................................................................. 10 
2.1 
PREVIOUS CLINICAL DATA .................................................................................................... 12 
2.2 
CURRENT CLINICAL DATA ..................................................................................................... 14 
3. 
DEVICE / SYSTEM DESCRIPTION ............................................................................................... 15 
3.1 
INTENDED USE ..................................................................................................................... 15 
3.1.1 
Indications for Use ................................................................................................................ 15 
3.2 
COMPONENT SUMMARY ....................................................................................................... 16 
3.3 
DISPOSABLE COMPONENT-CATHETER .................................................................................. 16 
3.4 
OTB DISPOSABLE COMPONENT-FILTER AND FLOW ASSEMBLIES ............................................ 17 
3.5 
NON-DISPOSABLE COMPONENT-DATA ACQUISITION SYSTEM ................................................. 18 
3.6 
SHIPPING AND DEVICE ACCOUNTABILITY OF THE INVESTIGATIONAL SYSTEM ........................... 18 
3.6.1 
Required Disposable Component Return .............................................................................. 18 
4. 
STUDY DESIGN ................................................................................................................................ 19 
4.1 
OBJECTIVE .......................................................................................................................... 19 
4.2 
SCALE AND DURATION ......................................................................................................... 19 
4.3 
STUDY ENDPOINTS .............................................................................................................. 19 
4.4 
JUSTIFICATION FOR STUDY AND DESIGN................................................................................ 20 
5. 
SUBJECT SELECTION .................................................................................................................... 20 
5.1 
STUDY POPULATION AND ELIGIBILITY .................................................................................... 20 
5.2 
SCREENING AND SUBJECT ENROLLMENT ............................................................................... 20 
5.3 
INSTITUTIONAL STANDARD OF CARE TREATMENT................................................................... 20 
5.4 
INCLUSION CRITERIA ............................................................................................................ 21 
5.5 
EXCLUSION CRITERIA ........................................................................................................... 21 
5.6 
INFORMED CONSENT ............................................................................................................ 22 
5.7 
SUBJECT ID ASSIGNMENT AND ENROLLMENT NOTIFICATION................................................... 23 
5.7.1 
Subject Enrollment Classifications ....................................................................................... 23 
6. 
RISKS AND POTENTIAL BENEFITS ............................................................................................ 24 
6.1 
RISKS ASSOCIATED WITH THE DEVICE, COMPONENTS OR PROCEDURE ................................... 24 
6.2 
POTENTIAL BENEFITS ........................................................................................................... 24 
7. 
STUDY REQUIREMENTS ............................................................................................................... 25 
7.1 
SCREENING REQUIREMENTS ................................................................................................ 26 
7.2 
PRE-NEURAPHERESIS IMAGING (CT) REQUIREMENTS ............................................................ 26 
7.3 
HEPARINIZATION/ANTI-PLATELET GUIDANCE/ANEURYSM STABILITY ....................................... 27 
7.4 
CATHETER INSERTION .......................................................................................................... 27 
7.4.1 
Catheter Insertion Highlights ................................................................................................ 28 
7.4.2 
Guidance-Securing the Catheter/Dressing the Wound .......................................................... 29 
7.4.3 
OTB System Disposables Replacement ................................................................................ 31 
7.5 
NEURAPHERESIS THERAPY ................................................................................................... 31 
7.5.1 
Neurapheresis Therapy Rates ................................................................................................ 32 
7.5.2 
Neurapheresis Termination Criteria ...................................................................................... 32 
7.5.3 
Role of the MNeuro Clinical Field Specialist (CFS) ............................................................ 33 
7.5.4 
CSF Pressure Guidance During Neurapheresis ..................................................................... 33 
7.5.5 
Neurologic Assessments During Neurapheresis ................................................................... 34 
7.5.6 
Neurologic Assessments for Intubated Subjects ................................................................... 35 
7.5.7 
CSF Sampling During Neurapheresis ................................................................................... 35 
7.5.8 
Additional Testing Requirements During Neurapheresis ..................................................... 37 
7.5.9 
Patient Transport during Neurapheresis ................................................................................ 37 
7.5.10 
Catheter Removal.................................................................................................................. 37 

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7.6 
POST-NEURAPHERESIS SURVEILLANCE SCHEDULE................................................................ 38 
7.6.1 
2 Day (±1 day) Follow-up Data ............................................................................................ 38 
7.6.2 
Neuro ICU Discharge Follow-up Data ................................................................................. 39 
7.6.3 
30 Day (±3 day) Follow-up Data .......................................................................................... 39 
8. 
ADVERSE EVENTS (AES) ............................................................................................................... 41 
8.1 
ADVERSE EVENT DEFINITIONS .............................................................................................. 41 
8.2 
REPORTABLE ADVERSE EVENTS ........................................................................................... 41 
9. 
DEVIATIONS FROM THE PROTOCOL ....................................................................................... 42 
9.1 
AMENDMENTS TO THE PROTOCOL ......................................................................................... 42 
10. DATA ANALYSIS AND MANAGEMENT ..................................................................................... 42 
10.1 
ANALYSIS POPULATIONS ................................................................................................... 42 
10.2 
ENDPOINT ANALYSIS DEFINITIONS ..................................................................................... 43 
10.3 
DATA MANAGEMENT ......................................................................................................... 44 
11. MONITORING ................................................................................................................................... 44 
12. SUSPENSION OR EARLY TERMINATION OF THE INVESTIGATION ................................ 45 
13. COMPLIANCE ................................................................................................................................... 45 
13.1 
STATEMENT OF COMPLIANCE ............................................................................................ 45 
13.2 
INDEPENDENT MEDICAL MONITOR ..................................................................................... 45 
13.3 
DATA SAFETY MONITORING BOARD (DSMB) ..................................................................... 46 
13.4 
RESPONSIBILITIES ............................................................................................................ 46 
13.4.1 
Investigators Delegation of Authority ................................................................................... 47 
13.4.2 
Investigator Reporting Responsibilities ................................................................................ 48 
13.5 
SPONSOR RESPONSIBILITIES ............................................................................................ 49 
13.6 
INSTITUTIONAL REVIEW BOARD APPROVAL ........................................................................ 49 
14. PUBLICATION POLICY .................................................................................................................. 49 
APPENDIX A: PROTOCOL ABBREVIAITONS .................................................................................. 50 
APPENDIX B:  NEUROLOGIC ASSESSMENTS/GRADING INDICIES .......................................... 51 
 
 

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TABLE OF TABLES 
Table 1: Neurapheresis System Component Summary ........................................................................... 16 
Table 2:Neurapheresis System Risks .................................................................................................... 24 
Table 3: Required CSF Samples ........................................................................................................... 36 
Table 4: Data Collection Schedule ....................................................................................................... 40 
Table 5: Reportable Adverse Events ..................................................................................................... 42 
Table 6: Investigator Reporting Responsibilities .................................................................................... 48 
Table 7: Protocol Abbreviations ........................................................................................................... 50 
Table 8: Glasgow Coma Scale ............................................................................................................. 51 
Table 9: Modified Fisher Grade Classifications ..................................................................................... 51 
Table 10: WFNS Grading System for Subarachnoid Hemorrhage ........................................................... 51 
Table 11: Hunt & Hess Scale ............................................................................................................... 51 
Table 12: Glasgow Outcome Scale Extended ........................................................................................ 52 
Table 13: Modified Rankin Scale ......................................................................................................... 52 
Table 14: Peripheral Neurological Assessment ...................................................................................... 53 
Table 15: The Barthel Index ................................................................................................................ 54 
 
 
TABLE OF FIGURES 
Figure 1: Neurapheresis System Medical Cart ....................................................................................... 15 
Figure 2: Lumbar Proximal Inlet Holes 
                    Figure 3: Thoracic Distal Outlet Holes............. 17 
Figure 4: Filter, Flow and Waste Assemblies ........................................................................................ 17 
Figure 5: Neurapheresis System Touch Screen User Interface................................................................. 18 
Figure 6: Expected PILLAR-XT Subject Flow ...................................................................................... 25 
Figure 7: Temporary Connection of the Catheter Male and Female Ends ................................................. 29 
Figure 8: Catheter Positioning within StayFix ....................................................................................... 30 
Figure 9: Catheter Fixation Device and Protective Dressing ................................................................... 31 
 
 

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1. SYNOPSIS 
 Objective 
The objective of this study is to further demonstrate safety and characterize 
effectiveness of the Neurapheresis™ System (extracorporeal system and 
catheter) to remove red blood cells (RBCs) and lysed blood by-products from 
hemorrhagic cerebrospinal fluid (CSF) following aneurysmal subarachnoid 
hemorrhage (aSAH).  
Investigational      
System 
The Neurapheresis System consists of custom and off-the-shelf components 
designed for use in an intensive care setting.  
Intended Use 
The Neurapheresis System is intended for use in the filtration of cerebral spinal 
fluid in order to remove targeted, disease causing agents from the central 
nervous system.   
Study Design 
Prospective, multi-center, non-randomized single arm study. 
Sample Size 
N=30 subjects treated with Neurapheresis (study therapy) are expected to be 
enrolled. 
Centers 
Up to 8 investigative centers within the United States  
Primary 
Endpoint(s)  
Primary endpoints:  
1. Mean reduction of cisternal blood via CT post study therapy 
2. Proportion of subjects with Neurapheresis Catheter, System or Therapy 
related serious adverse events  
Secondary 
Endpoints 
Secondary safety endpoints:  
• Proportion of subjects with successful catheter placement of those attempted 
• Proportion of subjects with study device or therapy related adverse events 
• Proportion of subjects with systemic CNS infection within 5 days of catheter 
removal 
Secondary efficacy endpoints:  
• Mean reduction of RBCs and total protein by CSF sample post study therapy 
• Mean length of Neuro ICU stay 
Exploratory 
Endpoints 
• Proportion of subjects requiring additional CSF management during 
Neurapheresis or on-going CSF management post study therapy 
• Reduction in biomarkers of inflammation as seen in CSF, blood and 
physiologic manifestations post study therapy  
• Proportion of subjects with symptomatic complications from aSAH  
• Analysis of endpoints by the following sub-groups for any groups that have 
at least 5 subjects that meet the criteria for the group; 
o Age: <45, ≥45-<60, 60 – 70 years  
o Gender: male, female 
o Enrollment Modified Fischer grade: 2, 3, 4 
o Baseline cisternal Hijdra score: ≤15, 16-20, 21-25, 26-30 
o Study therapy time: <16hrs, ≥16-32hrs, >32-48hrs, >48hrs 
o Other sub-groups not yet defined 
Enrollment 
Categorization 
All patients who provide written consent to participate in the study will be 
considered enrolled study subjects, however not all subjects will contribute to 

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the enrollment cap of N=30 treated subjects.  Only “Treated” subjects, as 
defined below, will contribute to the enrollment cap. As such, it is expected that 
up to 40 subjects may be enrolled to meet the enrollment cap of N=30 Treated 
Subjects.    
Informed consent may be obtained prior to or after aneurysm securement as able 
based on patient status upon admission and legally authorized representative 
(LAR) availability if needed.  
Intent to Treat Subjects:  
• Subjects who provide written informed consent but do not have placement of 
the study catheter attempted.  This would include placement tools such as 
the epidural needle and guidewire.  Intent to Treat subjects will be exited 
immediately as they have not received any portion of the study catheter or 
study therapy.  They will not count towards the enrollment cap of N=30 
treated subjects. 
Attempt to Treat Subjects: 
• Subjects who provide written informed consent and have any portion of the 
catheter placement procedure attempted (including the epidural needle and 
guidewire) but placement was unsuccessful.  Attempt to Treat subjects will 
be followed through 2 days post-attempt for safety then exited.  They will 
not count towards the enrollment cap of N=30 treated subjects.  They will be 
included in the analysis of safety endpoints but will not be included in the 
analysis of efficacy endpoints. 
 Treated Subjects: 
• Subjects who provide written informed consent, have successful placement 
of the study catheter and have study therapy initiated. These subjects will be 
followed out to 30 days according to the study protocol then exited.  They  
will count towards the enrollment cap of N=30 treated subjects and used in 
all analyses.  
Inclusion 
Criteria 
 
 
 
 
• Male or female patient age: 18 – 70 years  
• Informed consent by the patient or his/her legally authorized representative 
• Modified Fisher Grade 2, 3 or 4  
• Hunt & Hess I-IV  
• First aneurysmal SAH that has been confirmed by CT scan and secured or 
planned securement via clipping or coiling per institutional SOC  
• Patient is ≤ 48 hours post bleeding event 
• World Federation of Neurosurgeons (WFNS) Grades I-IV  
• Patient is indicated for a ventriculostomy 

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Exclusion 
Criteria 
• Pregnancy 
• Patients with a SAH due to mycotic aneurysm or AV malformation 
• Patients who present with an acute MI or unstable angina 
• Patients with uncontrolled diabetes at the time of catheter placement 
• Patients who present with a creatinine > 2.0mg/dl 
• Imaging demonstrates supratentorial mass lesions >15 cc 
• Imaging demonstrates >2 mm of mid-line-shift associated with infarction 
and or edema 
• Imaging demonstrates infratentorial mass lesion ≥10cc 
• Imaging demonstrates presence of any subdural hematoma 
• Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic and 
quadrageminal) 
• Vasospasm on admission as defined by angiographic evidence 
• Patients with a coagulopathy that cannot be reversed per the professional 
discretion of the investigator   
• Patients with a connective tissue disorder that may impact the integrity of 
the dura 
• Thrombocytopenia def. platelet count < 100,000 
• Patients on low molecular weight heparin such as Lovenox 
• Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors 
• Patients with a documented history of cirrhosis  
• Non-communicating Obstructive hydrocephalus  
• Patients with a lumbar or thoracic spinal anatomy (e.g. severe spinal 
stenosis) or history of posterior fusion hardware that would interfere with 
placement or appropriate in-dwelling of the catheter  
• Existing hardware that prevents accurate CT imaging 
• Pre-existing Lumbar Drain  
• Local skin infections or eruptions over the puncture site 
• Signs of CNS systemic infection, sepsis or pneumonia 
• Lumbar puncture within 6 hours  
• Concurrent participation in another study which is not observational or 
retrospective in nature without prior approval from the Sponsor 
Catheter 
Placement 
During catheter placement, an MNeuro clinical field specialist will be available 
to support the accurate assembly, placement, priming and testing of the system 
prior to beginning study therapy.  
Fluoroscopy is required for catheter placement and as such it is expected to be 
performed in an IR/OR with preservative free saline available from the site to 
adequately prime the system.  
Consent may be obtained prior to aneurysm securement to allow for catheter 
placement immediately following clipping or coiling in the same IR/OR session.  
Alternatively, consent may be obtained following aneurysm securement to 
ensure the patient continues to meet I/E criteria prior to enrollment or if 
applicable due to LAR availability.   In this scenario, the subject must be 
brought back to the IR/OR in a separate session.  The catheter must be placed  
≤48 hours from ictus.  
Neurapheresis 
Therapy 
The study catheter can remain in-dwelling for up to 72 hours (± 4hr) in treated 
subjects during which study therapy can be completed.  Neurapheresis therapy 

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will be incrementally extended during the study such that, the first five (n=5) 
treated subjects enrolled under this protocol, will have a maximum of 36 hours 
(± 4hr) of Neurapheresis therapy (pump time) allowed during the 72 hours (± 
4hr) of catheter in-dwelling. 
 
Following positive DSMB review of the safety data from the first five subjects, 
the remaining up to n=9 treated subjects (for a study total of N=30 Treated 
Subjects) will have no limit on maximum therapy time and instead be limited 
only by the maximum catheter in-dwelling time of 72 hours (± 4hr). 
 
If the DSMB does not agree that it is safe to remove the Neurapheresis therapy 
limit after review of data from the first ten subjects, the maximum of 36 hours (± 
4hr) of Neurapheresis therapy (pump time) will remain in place for the 
remaining subjects.  
Neurapheresis 
Surveillance  
Following aneurysm securement and prior to initiating study therapy, a head CT 
is required to establish safety for beginning study therapy as well as provide a 
baseline to which the follow-up CTs may be compared.  This may be done 
following catheter placement but needs to be done in a department scanner.   
Subjects will be monitored regularly during study therapy according to 
institutional SOC for Neuro ICU monitoring with additional protocol 
requirements as defined below.   Protocol required neuro monitoring should 
begin following catheter securement. The catheter can remain in-dwelling for up 
to 72 hours (± 4hr) in Treated Subjects during which study therapy can be 
performed.   
• 
Intracranial pressure (ICP), Glasgow coma score (GCS), Lumbar 
pressure and Peripheral checks performed hourly (± 1hr) while the 
catheter is in-dwelling  
• 
CSF Sampling every 8 hours while the catheter is in-dwelling 
• 
Venous blood sample will be taken at 36 hours and 72 hours or end of 
catheter in-dwelling (± 4hr) 
To ensure the pressures are accurately obtained, the system will be paused 
temporarily for completion of each study-required neuro check.  If the lumbar 
pressure reads below 4.4 mmHg (6.0 cmH2O), the Investigator will be notified 
for review of clinical symptoms and system data prior to re-starting therapy 
unless a pre-defined treatment plan has already been directed by the Investigator. 
If the ICP recorded at a study-required neuro check is higher than the lumbar 
pressure at the same neuro check.  The system should remain paused until the 
ICP is equal to or lower than lumbar pressure for at least two consecutive neuro 
checks and the Investigator has approved restarting the system. 
Additionally, at 36 hours and 72 hours or end of catheter in-dwelling (± 4hr), a 
head CT will be required. The CTs must be taken using a department scanner 
and will be used to compare to the baseline CT and document the amount of 
blood removal from the basal cisterns for the primary endpoint.  
Additional data related to the clinical status of the subjects will be collected 
throughout study therapy such as the development of complications or study 
adverse events.  

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The study therapy may be paused or terminated at any time by the Investigator 
or Subject but will be required to terminate under the following conditions: 
• 
Brainstem herniation  
• 
Lower extremity paralysis  
• 
Subdural spinal hematoma  
• 
Subdural hematoma or hygroma  
• 
Abnormal gram stain  
• 
Re-bleeding event requiring intervention e.g., re-coiling, re-clip  
• 
Subject previously extubated requires new or re-intubation 
• 
ICP is greater than Lumbar pressure at five consecutive study-required 
neuro checks 
• 
Subject requires inversion (such as Trendelenburg position) 
 
If study therapy must be terminated early (prior to 72 hrs of catheter in-
dwelling), a head CT within (± 4hr) of catheter removal must be obtained to 
document the final amount and location of blood within the basal cisterns to 
allow for comparison to baseline.  
 
The subjects’ EVD should be clamped upon beginning study therapy and remain 
closed unless ICP goes above 20 mmHg or is trending in a way that cannot be 
managed with the study therapy and the investigator feels it is in the best interest 
of the subject to open it.  If it is opened, the set pressure should be 20 mmHg.  
Subjects with an EVD will have ICP values recorded at the same time as the 
neuro checks are completed. 
 
As CSF filtration is considered an adjunct to standard of care, subjects will 
continue on the prescribed medical and physical therapy regimen as directed by 
the treating Investigator during the time of enrollment through study exit.   

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Follow-up 
Surveillance 
Schedule 
Following removal of the catheter, subjects will have follow-up assessments at 2 
days, at Neuro ICU discharge and 30 days.  Collection of required study data, 
assessment of adverse events and evaluation of clinical status will be completed 
at these follow-up time points.  After completion of the 30 day follow-up, the 
subject will be exited from the study.      
2 Day Post-Neurapheresis Follow-up Requirements: 
• 
General Clinical and Hospital Data 
• 
Glasgow Coma Scale 
• 
Head CT 
• 
Venous blood sample  
 
Neuro ICU Discharge: 
• 
General Clinical and Hospital Data 
• 
Glasgow Coma Scale 
• 
Modified Rankin Scale 
• 
Copies of all SOC head CTs performed through ICU discharge 
 
30 Day Post-Neurapheresis Follow-up Requirements:  
• 
General Clinical Data 
• 
Hospital Data (if applicable) 
• 
Glasgow Outcome Scale Extended 
• 
Modified Rankin Scale 
• 
Barthel 
• 
MoCA 
Study Duration 
It is estimated that it will take 12-16 months to complete enrollment and protocol 
required data collection, analysis and reporting requirements. 
Sponsor 
Minnetronix Neuro, Inc.  (MNeuro)        Toll-Free: 888-301-1025 
1635 Energy Park Drive                          Phone: 651-917-4060 
St. Paul, MN 55108                                 Fax: 651-917-4066 
Sponsor Contact Julie M Messer  
Director Clinical & Regulatory Affairs 
651-348-3138 
jmesser@minnetronix.com 
2.  Introduction 
Aneurysmal subarachnoid hemorrhage (aSAH) is a catastrophic neurological condition occurring 
as the result of a ruptured cerebral aneurysm. There are roughly 30,000 cases per year in the US, 
with worldwide estimated incidence of 9 people per 100,0001.  After securement of a ruptured 
aneurysm, patients are closely observed in the hospital for an average of 12-14 days to monitor for 
complications.  aSAH patients can develop severe complications post-aneurysm securement, 
 
1 de Rooij, N. K., Linn, F. H. H., van der Plas, J. A., Algra, A. & Rinkel, G. J. E. Incidence of subarachnoid haemorrhage: a systematic 
review with emphasis on region, age, gender and time trends. Journal of Neurology, Neurosurgery & Psychiatry 78, 1365–1372 (2007) 

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ranging from vasospasm2,3,4  and stroke to hydrocephalus5 resulting in the need for permanent 
shunting of cerebrospinal fluid (CSF).  The lasting effects of these complications can be 
devastating, possibly resulting in permanent disability and even death.  Thus, there remains a 
significant unmet need to reduce complications and improve outcomes for these patients. 
Other common complications of SAH include the following;6,7,8 
• 
Re-bleeding of the rupture  
• 
Delayed cerebral ischemia (DCI) 
• 
Delayed ischemic neurological deficit (DIND) 
• 
Seizures and epilepsy 
• 
Cardiac dysfunction 
• 
Systemic inflammatory response syndrome (SIRS) 
• 
Cerebral edema 
The treatment for aSAH has evolved from an established standard of care (SOC) craniotomy to 
clip the aneurysm, to less invasive image guided techniques of endovascular coil placement to 
pack and exclude the aneurysm from circulation.  Despite advancements in technical approaches, 
the cited clinically significant comorbid state remains unchanged regardless of the therapeutic 
technique.  It is posited that this state of transient compromised cerebral circulation, is related to 
spasmogenic substances e.g., cytokines, generated during the lysis of hemorrhagic cells9 that then 
taint the CSF.  Early removal of blood and blood products (e.g. hemoglobin, oxyhemoglobin, and 
downstream inflammatory proteins) from the CSF has been shown to reduce the incidence of 
vasospasm, stroke, hydrocephalus and shunting, and result in a shorter hospital course10.   
The PILLAR-XT study uses an extracorporeal investigational pump and filtration system with an 
investigational double lumen catheter for the rapid removal of red blood cells (RBC’s) post SAH. 
The system removes the hemorrhagic CSF, filters out RBCs and lysed by-products and returns the 
filtered CSF to the subarachnoid space (SAS) via the same catheter.  Minnetronix Neuro 
(MNeuro) calls this tailored process of the filtration and return of CSF “Neurapheresis™” Therapy 
which is based on blood plasma filtration or “Apheresis.” The active removal of degrading RBC’s 
and their released cytotoxic by-products can be accomplished more efficiently with Neurapheresis 
Therapy than with a standard, passive ventricular or lumbar drain (LD) which are often indwelling 
for up to 10 days.  
 
2 Neal F Kassell et al., “Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage,” Stroke 16 (1985): 562–72. 
3 JT Hughes and PM Schianchi, “Cerebral Artery Spasm. A Histological Study at Necrospy of the Blood Vessels in Cases of 
Subarachnoid Hemorrhage,” Journal of Neurosurgery 48 (1978): 515–25. 
4 Paul Klimo Jr et al., “Marked Reduction of Cerebral Vasospasm with Lumbar Drainage of Cerebrospinal Fluid after Subarachnoid 
Hemorrhage,” Journal of Neurosurgery 100, no. 2 (February 2004): 215–24, doi:10.3171/jns.2004.100.2.0215. 
5 Hasan, D., Vermeulen M., Wijdicks EFM., Hijdra A., & van Gijn J. Management problems in acute hydrocephalus after subarachnoid 
hemorrhage, Stroke V 20: no. 6, 747-753 (1989) 
6 de Oliveira Manoel A.L. and Macdonald R.L. Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage. Front. 
Neurol. 9:292. (2018) 
7 Solenski, N.J., Haley, E. Clark JR., Kassell, N.F., Kongable, G.R.N., Germanson, T., Truskowski, L., & Torner, J.C. Medical 
complications of aneurysmal subarachnoid hemorrhage: A report of the multicenter, cooperative aneurysm study. Crit Care Med, 23(6), 
1007-1017. (1995) 
8 Suarez, J.I., Tarr, R.W., and Selman, W.R. Aneurysmal Subarachnoid Hemorrhage. N Engl J Med, 354, 387-396. (2006) 
9 GS Allen, HS Ahn, and Tj Preziosi, “Cerebral Arterial Spasm - a Controlled Trial of Nimodipine in Patients with 
Subarachnoid Hemorrhage,” New England Journal of Medicine 308 (1983): 619–24. 
10 Paul Klimo Jr et al., “Marked Reduction of Cerebral Vasospasm with Lumbar Drainage of Cerebrospinal Fluid after Subarachnoid 
Hemorrhage,” Journal of Neurosurgery 100, no. 2 (February 2004): 215–24, doi:10.3171/jns.2004.100.2.0215 

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2.1 Previous Clinical Data 
In April 2018 the first-in-human cohort of PILLAR subjects (N=15) treated with Neurapheresis 
therapy was completed.  The study was performed at four clinical sites in the U.S. and concluded 
by MNeuro and Data Safety Monitoring Board (DSMB) review the Neurapheresis System and 
associated therapy were safe for continued investigational use.  A summary of the data is provided 
below.  
PILLAR Study Baseline Subject Status 
Status Prior to Neurapheresis  
N=15  
Summary  
Gender % Female (n/N)  
73% (11/15)  
Height (mean [range])  
5’5”  
[5’2” – 6’]  
History of Smoking  
% Yes (n/N)  
40% (6/15)  
History of Hypertension  
% Yes (n/N)  
73.3% (11/15)  
Family History of SAH  
% Yes (n/N)  
26.7% (4/15)  
WFNS  
(Median [range])  
2 [1 – 4]  
Hunt & Hess  
(Median [range])  
3 [1 – 3]  
Glasgow Coma Scale (GCS)  
(Median [range])  
14 [9 – 15]  
Fisher/Modified Fisher Grade  
(Median [range])  
3 [3 – 4]  
 
Considering the typical aSAH population and study inclusion/exclusion criteria, the subject 
baseline profile proved to be as expected.   One subject did not have catheter placement attempted 
and is not included in further tables. 
PILLAR Aneurysm Securement 
Aneurysm Securement Data  
N=14  
Summary  
% Yes (n/N)  
EVD in place  
84.6% (11/13*)  
Aneurysm Type, Saccular  
85.7% (12/14)  
Aneurysm Type, Wide Neck  
42.9% (6/14)  
Coiled 
64.3% (9/14) 
Clipped 
35.7% (5/14) 
*EVD placement not recorded for one subject 
 
Thirteen of Fourteen subjects 92.9% (13/14) in whom catheter placement was attempted had the 
catheter successfully placed.  The one failed attempt was due to the subject being morbidly obese 
with an unusual distribution of fatty tissue over the lumbar spine thus causing the catheter to bend 
in the tissue rather than continue over the guidewire.  This subject is not included in further tables 
as the study therapy was not performed.  

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PILLAR Neurapheresis Summary 
Neurapheresis  
N=13  
Summary  
mean [range]  
Total Pump Time (hrs) 
15:07 hrs  
[5:32 – 24:00]  
Total processed volume (mL)  
632.0 ml  
[180.6 – 1447.6]  
Catheter in-dwelling 
30:23 hrs 
[15:15 – 36:22]  
 
The PILLAR study protocol, under which subjects were enrolled, limited catheter in-dwelling time 
to 36 hours and total pump time (therapy time) to 24 hours.  As can be seen in the table above, the 
average pump time was shorter than anticipated with only one subject receiving the complete 24 
hour allotted time for study therapy.  Despite this, clearance of red blood cells (RBCs) from the 
lumbar cistern was seen as noted in the table below.  Longer pump times will be necessary for 
more complete blood clearance.  Pre and Post-Neurapheresis total protein measures were also 
taken to account for removal of by-products from lysed blood.  
PILLAR Post-Neurapheresis Outcomes 
Outcome Measured  
N=13  
Pre-Neurapheresis  
mean ± STD  
Post-Neurapheresis  
mean ± STD  
Percent Decrease  
of Means  
Concentration of Total 
Protein  
537.36 ± 500.70 
mg/dL  
144.09 ± 188.44 
mg/dL  
73.2%  
Concentration of CSF 
Red Blood Cells 
(RBCs)  
2.78e5 ± 2.43e5 
cells/μL  
1.17e5 ± 1.30e5 
cells/μL  
57.9%  
 
Subjects were followed at 2-weeks and 30-days post-Neurapheresis.  Other notable outcomes 
include; a mean of 12 days to discharge from the Neuro ICU with a range of [6 – 18 days].  By the 
2-week visit, 38.5% (5/13) were discharged home which increased to 69.2% (9/13) by 30 days.  
 
PILLAR Follow-up Outcomes 
Follow-up Status 
N=13 
Two Week  
Median [range] 
30 Day  
Median [range] 
GCS 
15 [11-15] 
NR* 
WFNS 
1 [1-5] 
NR* 
mRS 
2 [1-5] 
1 [0-4] 
GOS 
NR* 
5 [3-5] 
Barthel 
NR* 
100 [20-100] 
*These neuro assessments were not required per protocol  
 
Finally, the primary safety endpoint for the study was the assessment of adverse events associated 
with the placement of the catheter and operation of the system. As there were no (0) adverse 
events associated with the placement of the catheter and minimal, expected, non-serious adverse 

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events (as seen below) during Neurapheresis, the end points of this study were considered to have 
been met.   
 
The adverse events (AEs) reported below is site reported and was also reviewed by the 
independent DSMB.  While the AEs were reported as potentially related to Neurapheresis therapy, 
they are also known AEs for subarachnoid hemorrhage patients. 
PILLAR Device or Procedure Related Adverse Events During Neurapheresis 
Event  
Timeframe 
Serious Adverse 
Event (SAE) 
Related to 
System 
Related to 
Neurapheresis  
n/N (%) 
Headache with 
Vomiting 
Neurapheresis 
No 
No 
Yes 
1/13 (7.7%) 
Vomiting  
Neurapheresis 
No 
No 
Yes 
1/13 (7.7%) 
 
PILLAR Device or Procedure Related Adverse Events After Neurapheresis 
Event  
Timeframe 
Serious Adverse 
Event (SAE) 
Related to 
System 
Related to 
Neurapheresis  
n/N (%) 
Pain (back/leg) 2 Week F/U 
No 
Unknown 
Unknown 
1/13 (7.7%) 
 
Further, no (0) subjects experienced the following:  
• 
No serious adverse events (study device or study procedure related)  
• 
No unanticipated adverse device effects (UADEs) 
• 
No localized infection or systemic CNS infection  
• 
No organisms seen on any gram stain (no abnormal gram stain) 
• 
No growth on CSF culture (including those out to the standard testing of 96 hours)  
• 
No subdural spinal hematomas 
• 
No subdural hematomas 
• 
No brainstem herniation  
• 
No re-bleeding events 
• 
No deaths 
 
Pillar study endpoints were assessed and all were considered to have been met by internal 
(MNeuro) and independent DSMB review.    
2.2 Current Clinical Data 
Please see the 2019 Pillar-XT Annual Report for the most current summary of study progress and 
study data.  There have been 16 subjects enrolled and treated with Neurapheresis under a previous 
version of this protocol.  
As documented in the 2019 annual report, one subject previously enrolled in this study had a 
herniation event.  The event was identified early by the Investigator and resolved with no further 
complication.  Terminating therapy and use of the Trendelenburg position resolved the event.  
Upon investigation, the event was determined to be a result of evolving mass effect in combination 
with the use of the device that created a sustained negative pressure gradient between the 
intracranial and lumbar pressures. 

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PILLAR-XT Adjudicated Adverse Events During Neurapheresis 
Event  
Timeframe 
Serious Adverse 
Event (SAE) 
Resolved 
Unanticipated 
AE 
n/N (%) 
Pain (back/leg) Neurapheresis 
No 
Yes 
No 
1/16 (6.3%) 
Other: 
Diencephalic 
Herniation 
Neurapheresis 
Yes 
Yes 
No 
1/16 (6.3%) 
  
3. DEVICE / SYSTEM DESCRIPTION 
A description of the device herein referred to as the “Neurapheresis System” is comprised of dual 
lumen catheter used in conjunction with a medical cart based extracorporeal pump and filtration 
system (Figure 1 below). The pump and filtration system include custom and off-the-shelf (OTS) 
disposable and non-disposable components, with custom software to run and monitor the systems 
operation.  The system was designed in accordance with all applicable design controls and 
standards.   
 
 
Figure 1: Neurapheresis System Medical Cart 
3.1 Intended Use 
The Neurapheresis System is intended for use in the filtration of cerebral spinal fluid in order to 
remove targeted, disease causing agents from the central nervous system. 
3.1.1 Indications for Use 
The Neurapheresis System is indicated for the treatment of cerebral spinal fluid in order to remove 
red blood cells and lysis byproducts in patient with aneurysmal subarachnoid hemorrhage.  

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3.2 Component Summary 
The Neurapheresis System access tools and accessories are a combination of OTS and custom 
developed tools designed to gain access to the lumbar SAS and to facilitate catheter placement.  A 
summary of the system components can be found below or in the associated Instructions For Use 
(IFU). 
Table 1: Neurapheresis System Component Summary 
Component Name 
Component Description 
Disposable Status 
Neurapheresis Catheter  
Dual lumen spinal catheter 
Disposable 
Flow Assembly  
Blue and red coiled tubing 
with flow sensor 
Disposable 
Filter Assembly  
Tangential flow filters with 
pressure sensors 
Disposable 
Waste Assembly 
Pump tubing and Waste Bag 
connection 
Disposable 
Epidural Needle 
15g straight epidural needle 
Disposable 
Uncoated Guidewire 
0.018 diameter guidewire 
Disposable 
Waste Bag 
Merit Disposal Depot Bag 
and tubing 
Disposable 
Neurapheresis System Enclosure 
Houses pumps, pressure 
sensors and flow sensors 
Non-Disposable 
Main System Pumps 
Two Peristaltic pumps, one 
for main system other for 
waste assembly 
Non-Disposable 
Data Acquisition System 
Fanless medical station PC 
with LabVIEW software 
Non-Disposable 
 
3.3 Disposable Component-Catheter 
The Neurapheresis catheter has not been tested for MRI compatibility.  
The Neurapheresis system catheter follows 510(k) approved predicates in size and length for 
which the intended use is within the lumbar and thoracic spinal spaces. The catheter materials, 
Nylon 12, Pebax® and Polytetrafluoroethylene (PTFE) are well established composites for 
construct of vascular catheters.  The dual-lumen catheter employs a tapered co-axial design that is 
coil reinforced to assist with handling and, to resist kinking or crushing when navigating the spinal 
anatomy.   
There are radiopaque marker bands at both the proximal inlet and distal outlet sections to assist the 
Investigator with positioning the proximal holes in the lumbar cisterns and the distal outlet in the 
thoracic anatomy as seen in the figures below.   

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         Figure 2: Lumbar Proximal Inlet Holes  
                   Figure 3: Thoracic Distal Outlet Holes 
3.4 OTB Disposable Component-Filter and Flow Assemblies  
The Neurapheresis System out-of-the-body (OTB) disposable “Filter Assembly” is pre-configured 
and packaged in a clamshell tray for ease of transfer on to the sterile field.  The Filter Assembly is 
comprised of various lengths of tubing, two (2) OTS 100 kDa Millipore Pellicon™ tangential flow 
filters (TFF), and (4) OTS PendoTECH pressure sensors.  The sensors are not intended to replace 
SOC patient monitoring devices, nor should they be used for making clinical assumptions or 
decisions.   
 
The Neurapheresis System OTB disposable “Flow Assembly”, is pre-configured and packaged in 
a clamshell tray for ease of transfer on to the sterile field.  The disposable Flow Assembly 
connects to the catheter and to the Filter Assembly.  The Flow Assembly contains an OTS flow 
sensor and two (2) 3-way stopcock sample ports on the inlet and outlet hubs of the system catheter. 
The integrated sensor readings are used to facilitate the automated algorithm, to allow for manual 
adjustments to the pump settings or to trouble shoot system issues.  The 3-way stopcocks of the 
Flow Assembly are used to facilitate CSF sampling and priming of the system.   The figure below 
is a diagram of the filter, flow and waste assemblies as appropriately set up for use.  
Figure 4: Filter, Flow and Waste Assemblies 
 
Radiopaque 
Markers 

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3.5 Non-Disposable Component-Data Acquisition System 
The Neurapheresis System utilizes PC and data acquisition system.  The system operates with 
customized software for the user interface, data logging (archive, analysis and data transfer), motor 
control, pressures and flow rate monitoring. This system software is considered investigational and 
is not commercially available.   The figure below provides a visual of the touch screen user 
interface.   
 
Figure 5: Neurapheresis System Touch Screen User Interface 
The system has an integrated battery back-up for use during transport or a systemic power loss at a 
center.  When not in use, the cart shall be connected to a power supply in the identified center 
storage area.  
3.6 Shipping and Device Accountability of the Investigational System  
The investigational catheter and non-disposable components of the Neurapheresis System will be 
shipped and tracked in accordance with 21CFR§812.140 (b)(2) requirements.  and will only be 
shipped to sites and Investigators who have been selected by MNeuro to participate in this study.   
A Device Accountability Log will be maintained to catalogue receipt and disposition of the 
catheter and non-disposable components.  The Sponsor will provide a shipping mechanism or 
instructions for return of the system and individual components as needed through completion of 
the clinical study.   
3.6.1 Required Disposable Component Return 
The Neurapheresis system catheter is the only disposable that is required to be returned to the 
Sponsor.  While the guidewire is considered to be investigational due to their off-label use, they 
may be destroyed at the study site.  The MNeuro Clinical Field Specialist (CSF) (i.e. technical 
representative) has the discretion to request return of other disposable components if there is a 
performance question that could be answered by further analysis.  Catheters or other used 
disposables are to be returned to the Sponsor in the biohazard shipping containers provided.  
Returns of any components will be documented on the Device Accountability Log. 

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4. STUDY DESIGN 
The PILLAR-XT study is a prospective, multi-center, non-randomized single arm study that is an 
extension of the first-in human PILLAR study. 
4.1 Objective 
The objective of this study is to further demonstrate safety and characterize effectiveness of the 
Neurapheresis™ System (extracorporeal system and catheter) to remove red blood cells (RBCs) 
and lysed blood by-products from hemorrhagic cerebrospinal fluid (CSF) following aneurysmal 
subarachnoid hemorrhage (aSAH).  
4.2 Scale and Duration 
The Study will enroll N=30 “Treated” subjects, as defined by the protocol.  The study will be 
performed at up to 8 centers within the United States.  Subjects will have assessments and data 
collection at enrollment, during catheter placement and Neurapheresis procedure, 2 days (±1 
days), at Neuro ICU discharge and 30 days (±3 days) post removal of the catheter.   
Based on the incidence of occurrence of SAH in the US population, it is estimated that it will take 
approximately 12-16 months to complete enrollment and protocol required data collection, 
analysis and reporting requirements.  
4.3 Study Endpoints 
The PILLAR-XT Study does not have a hypothesis based statistical endpoint due to the feasibility 
nature of the investigation. 
 
Primary Endpoints:  
1. Mean reduction of cisternal blood via CT post study therapy  
2. Proportion of subjects with Neurapheresis Catheter, System or Therapy related serious 
adverse events 
 
Secondary Safety Endpoints:  
• 
Proportion of subjects with successful catheter placement of those attempted 
• 
Proportion of subjects with study device or therapy related adverse events 
• 
Proportion of subjects with systemic CNS infection within 5 day of catheter removal 
 
Secondary Efficacy endpoints:  
• 
Mean reduction of RBCs and total protein by CSF sample post study therapy 
• 
Mean length of Neuro ICU stay 
 
Exploratory endpoints: 
• 
Proportion of subjects requiring additional CSF management during study therapy or 
on-going CSF management post study therapy 
• 
Reduction in biomarkers of inflammation as seen in CSF, blood and physiologic 
manifestations post study therapy 
• 
Proportion of subjects with symptomatic complications from aSAH  
• 
Analysis of endpoints by the following sub-groups for any groups that have at least 5 
subjects that meet the criteria for the group; 
o Age: <45, ≥45-<60, 60 – 70 years  

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o Gender: male, female 
o Enrollment Modified Fischer grade: 2, 3, 4 
o Baseline cisternal Hijdra score: ≤15, 16-20, 21-25, 26-30 
o Neurapheresis time: <16hrs, ≥16-28hrs, >28-40hrs, >40hrs 
o Other sub-groups not yet defined  
4.4 Justification for Study and Design 
The previous first-in-human study, PILLAR study, was completed to substantiate the feasibility and 
safety of Neurapheresis in aneurysmal SAH patients.  As described in section 2.1, the study 
endpoints were met.  The PILLAR-XT study is designed to further confirm safety and characterize 
efficacy of Neurapheresis therapy.  Additionally, this study is expected to generate foundational data 
for development of the Neurapheresis treatment curve (e.g. time or volume processed needed to 
clear blood from the subarachnoid cisterns and lumbar spine).  The study works in tandem with the 
current SOC treatments for SAH and does not detract from the established care pathways, or deny 
enrolled subjects proven therapies.  The PILLAR-XT study utilizes the established skill sets of 
chosen Investigators who are already trained in the treatment and care of SAH patients and 
insertion/management of lumbar drains.  
5. SUBJECT SELECTION 
5.1 Study Population and Eligibility 
Subjects considered for the PILLAR-XT study will be identified from a pool of patients, who are 
admitted to the investigational center and have experienced a SAH.  Subjects will be eligible for 
enrollment based on adherence to the inclusion/exclusion criteria outlined below.  The Investigator 
and/or designated site staff is responsible for screening patients to determine the appropriateness of 
the PILLAR-XT study for each patient based on compliance to study criteria and the overall patient 
status. 
5.2 Screening and Subject Enrollment 
Screening for potential study subjects can be done either prior to or after aneurysm securement 
depending on the institutional work flow, IR/OR availability, LAR availability or patient status.  
Inclusion or exclusion criteria that can be assessed by institutional SOC may be done so prior to 
written informed consent, however no study specific procedures may be performed until informed 
consent is obtained.  Informed consent is considered the point of enrollment.  
5.3 Institutional Standard of Care Treatment  
The PILLAR-XT study does not require a uniform method for the treatment to secure the 
aneurysm i.e., Clip vs. Coil.  Additionally, the Investigator may use accepted institutional SOC 
and professional discretion for interventions and treatments which include, but are not limited to: 
• 
SOC neurological assessments  
• 
SOC imaging 
• 
ICP monitoring 
• 
EVD placement 
• 
“Triple H” therapy (hypertension, hypervolemia, hemodilution)  

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• 
Hyperventilation 
• 
Nimodipine 
• 
Seizure prophylaxis 
• 
Antimicrobial prophylaxis 
5.4 Inclusion Criteria 
Subjects who meet all of the following criteria may be given consideration for inclusion in this 
clinical investigation: 
• Age: 18 – 70 years 
• Informed consent by the patient or his/her legally authorized representative 
• Modified Fisher Grade 2, 3 or 4 SAH 
• Hunt & Hess I-IV  
• First aneurysmal SAH that has been confirmed by CT scan and secured or planned securement 
via clipping or coiling per institutional SOC  
• Patient is ≤ 48 hours post bleeding event 
• World Federation of Neurosurgeons (WFNS) Grades I-IV  
• Patient is indicated for a ventriculostomy 
5.5 Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from this clinical investigation: 
• Pregnancy 
• Patients with a SAH due to mycotic aneurysm or AV malformation 
• Patients who present with an acute MI or unstable angina 
• Patients with uncontrolled diabetes at the time of catheter placement 
• Patients who present with a creatinine > 2.0mg/dl 
• Imaging demonstrates supratentorial mass lesions >15 cc 
• Imaging demonstrates >2 mm of mid-line-shift associated with infarction and or edema 
• Imaging demonstrates infratentorial mass lesion ≥10cc 
• Imaging demonstrates presence of any subdural hematoma 
• Effacement of the basilar cisterns (suprasellar, ambient, chiasmatic and quadrageminal) 
• Vasospasm on admission as defined by angiographic evidence 
• Patients with a coagulopathy that cannot be reversed per the professional discretion of the 
investigator 
• Patients with a connective tissue disorder that may impact the integrity of the dura   
• Thrombocytopenia def. platelet count < 100,000 
• Patients on low molecular weight heparin, such as Lovenox 
• Patients on Clopidogrel bisulfate (Plavix) or other chronic platelet inhibitors 
• Patients with a documented history of cirrhosis  
• Non-communicating obstructive hydrocephalus  
• Patients with a lumbar or thoracic spinal anatomy (e.g. severe spinal stenosis) or history of 
posterior fusion hardware that would interfere with placement or appropriate in-dwelling of 
the catheter 
• Existing hardware that prevents accurate CT imaging 
• Pre-existing Lumbar Drain  
• Local skin infections or eruptions over the puncture site 
• Signs of CNS infection, sepsis or pneumonia 
• Lumbar puncture within 6 hours  

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• Concurrent participation in another study which is not observational or retrospective in nature 
without prior approval from the Sponsor 
5.6 Informed Consent 
The Sponsor will provide to each center, an FDA approved Informed Consent Form (ICF) 
template which may be edited to include center specific language or compliance requirements.  
The Sponsor and Institutional Review Board (IRB) must approve any changes to the form prior to 
use for consent of a patient.  A central IRB, Western IRB (WIRB), will be utilized for this study. 
Each enrolled subject must also consent to data transfers affected by HIPAA; the center may use 
their own HIPAA consent form to document this data transfer. 
Informed Consent is a process by which a patient voluntarily confirms their willingness to 
participate in the study after being informed of all risks and requirements.  Informed Consent is 
documented by means of a signed and dated ICF.  Once the patient or their legally authorized 
representative (LAR) signs and dates the ICF, the patient is considered enrolled in the study and 
becomes a study subject.  
Study enrollment without consent must be reported by Minnetronix, to the IRB and the FDA.  Any 
violations of the informed consent process must be reported as deviations to the sponsor and local 
regulatory authorities as appropriate. 
The process of obtaining Informed Consent shall: 
• 
Process of obtaining Informed Consent must be documented in the Subject’s medical record or 
study binder, 
• 
Be conducted by the Principal Investigator or designee authorized to obtain informed consent,  
• 
Include a description of all aspects of the clinical study that are relevant to the patient’s 
decision to participate throughout the clinical study, 
• 
Avoid any coercion of or undue influence of patient to participate, 
• 
Not waive or appear to waive patient’s legal rights, 
• 
Use native language that is non-technical and understandable to the patient or his/her legal 
representative, 
• 
Provide ample time for the patient or LAR to consider participation and ask questions if 
necessary, 
• 
Ensure important new information is provided to new and existing Subjects throughout the 
clinical study. 
The ICF shall always be signed and personally dated by the subject or LAR and by the 
Investigator or an authorized designee responsible for conducting the Informed Consent process.  
If a LAR provides signatory authority, the subject shall be notified of the informed consent and 
study participation as soon as his/her medical condition allows.  The original signed ICF will be 
retained by the center and a copy of the signed and dated document and any other written 
information must be given to the subject or LAR signing the form.  
If new information becomes available that can significantly affect a subject's future health and 
medical care, that information shall be provided to the affected subject(s) in written form via an 
amended informed consent form or other format as requested by the IRB or FDA.  Further, if 
requested by the IRB or FDA, all affected subjects shall be asked to confirm their continuing 
informed consent in writing. 

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Other situations may necessitate revision of the ICF, e.g., amendments to the protocol, a change in 
Principal Investigator, administrative changes or requests following annual review by the IRB.  
The new version of the ICF must be approved by the IRB and Minnetronix before implementation 
at investigative centers. The IRB will determine the subject population to be re-consented, if 
applicable. 
Once the patient or their LAR provides consent, data collection may begin.  The Investigator shall 
continue the institutional SOC for the treatment of SAH while providing the Sponsor with the data 
required for the study.    
5.7 Subject ID Assignment and Enrollment Notification 
Once Centers have identified a study candidate and Informed Consent has been obtained, the 
Sponsor must be notified as soon as possible to ensure rapid deployment of the Sponsor’s 
Technical Personnel.  Specific instructions on the study communication/notification process will 
be covered at site specific training.  Subject ID’s will be assigned via the study database and 
documented on a screening log.   
5.7.1 Subject Enrollment Classifications 
All patients who provide written consent to participate in the study will be considered enrolled 
study subjects, however not all subjects will contribute to the enrollment cap of N=30 Treated 
Subjects.  Only treated subjects, as defined below, will contribute to the enrollment cap. As such, 
it is expected that up to 40 subjects may be enrolled to meet the enrollment cap.  FDA, IRBs and 
Investigational sites will be notified when enrollment is complete.     
 
Intent to Treat Subjects:  
• 
Subjects who provide written informed consent but do not have placement of the study 
catheter attempted.  This would include placement tools such as the epidural needle and 
guidewire.  Intent to Treat subjects will be exited immediately.  They will not count 
towards the enrollment cap of N=30 treated subjects.  Only enrollment and study exit data 
will be collected in the study database.  
Attempt to Treat Subjects: 
• 
Subjects who provide written informed consent and have any portion of the catheter 
placement procedure attempted (including the epidural needle and guidewire) but 
placement was unsuccessful.  Attempt to Treat subjects will be followed through 2 days 
post-attempt for safety then will be exited. They will not count towards the enrollment cap 
of N=30 treated subjects. They will be included in the analysis of safety endpoints but will 
not be included in the analysis of efficacy endpoints.  Enrollment, catheter placement 
attempt, 2 day follow-up and study exit data will be collected along with any adverse 
events or protocol deviations if applicable.  
Treated Subjects: 
Subjects who provide written informed consent, have successful placement of the study 
catheter and had Neurapheresis initiated. These subjects will be followed out to 30 days 
according to the study protocol then exited.  They will count towards the enrollment cap of 

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N=30 treated subjects and used in all analyses.  All study data through the 30 day follow-
up will be collected. 
 
6. RISKS AND POTENTIAL BENEFITS 
Subjects participating in this study are exposed to the same inherent risks shared by all patients 
undergoing treatment for SAH and who receive a lumbar drain as SOC for a number of clinical 
applications.  These risks include but are not limited to headache, nausea/vomiting, transient pain, 
re-bleed, infection, CSF leak, changes in intracranial pressures, cognitive defects or poor 
neurological outcomes, other SAH complications and complications from associated interventions 
(e.g., IA therapy, angiography) and death.   
The Study protocol does not prevent SOC for the management of SAH patients and utilizes well 
established techniques for lumbar puncture for diagnostic purposes, therapeutic applications or 
interventions.  Only Investigators trained in the management of SAH patients, the associated care 
pathways and/or placement and management of lumbar drains are included in this study.  Further, 
Investigators are trained on the Clinical Protocol to further minimize subject risks.  
6.1 Risks Associated with the Device, Components or Procedure 
The table below outlines the risks that are associated with the Neurapheresis System (catheter, 
components and study procedure).  In the event of a catheter or disposable replacement, the risk 
profile remains unchanged.   
Table 2:Neurapheresis System Risks 
Risks 
Additional radiation exposure 
Brainstem herniation 
Headache 
Nausea / Vomiting 
Fluctuation in CSF volume or pressure 
CSF leak 
Retained catheter 
Localized transient pain (back/leg) 
Peripheral neuropathy / Paralysis 
Re-Bleed / Hemorrhage 
Infection / Sepsis 
Subdural spinal hematoma 
Death 
6.2  Potential Benefits 
It is hypothesized that utilizing the Neurapheresis System post SAH could improve neurological 
outcomes by the rapid removal of the CSF contaminants (blood and those generated during the 
lysis of the subarachnoid hemorrhage11). Other potential benefits may include a reduced likelihood 
 
11 Klimo et al., “Marked Reduction of Cerebral Vasospasm with Lumbar Drainage of Cerebrospinal Fluid after 
Subarachnoid Hemorrhage.” 

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of common SAH complications.  These benefits are only theoretical at this time; therefore, 
subjects may receive no direct benefit from participation in this study.  
 
 
  
Figure 6: Expected PILLAR-XT Subject Flow 
7. STUDY REQUIREMENTS 
Once the subject or LAR provide consent, study data collection should begin as the subject is 
considered enrolled. The Investigator shall follow the institutional SOC for the treatment of SAH 
while providing the Sponsor with the data required for the study.    
 
Informed Consent  
≤ 48 hrs of Ictus
Enrolled
Aneurysm 
secured, subject 
meets I/E
Aneurysm secured, 
subjects meets I/E
Informed Consent 
≤ 48hrs of Ictus
Yes
Subject Not Enrolled
No
Intent to Treat 
Subject
Withdrawn 
Immediately
No
Successful Catheter 
Placement
Attempt to Treat 
Subject 
No
2 Day Follow-up
(±1 day)
Study Exit 
Neurapheresis 
Procedure
Up to 72 hrs catheter in-
dwelling
(±4 hours)
Yes
2 Day Follow-up
(±1 day)
Neuro ICU Discharge 
Follow-up
30 Day Follow-up
(±3 day)
Study Exit
Enrolled
Yes

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Outlined in Figure 6 is the PILLAR-XT Subject flow which describes how subjects would move 
through the study and the associated surveillance requirements.  It is expected that subjects will 
participate in the study for a maximum of 36 days from the time of enrollment to the time of exit.  
7.1 Screening Requirements 
Standard of care assessments may be used to screen potential subjects against inclusion/exclusion 
(I/E) criteria for the study.  Testing that is outside of SOC, cannot be performed until after a 
subject has been enrolled (i.e. written informed consent obtained).  Once the subject has been 
enrolled and it has been determined that screening criteria are met, the subject can be prepared for 
catheter placement.  If instead it is determined that a subject no longer meets study criteria after 
completing all screening assessments, they are to be withdrawn immediately and classified as an 
“Intent to Treat” subject.  Enrollment data collected to that point and the reason for study exit 
should be entered into the case report forms for submission to the sponsor. 
 
A screening CT is required to assess I/E criteria and is expected to be a SOC test for the diagnosis 
and treatment planning of aSAH.  If a subject has been transferred from another institution at 
which a CT was obtained, a new screening CT is not required provided that an electronic copy of 
the CT can be obtained from the referring institution.  It is expected that the volume of any 
identified mass lesions as noted in the study exclusion criteria will be calculated using the standard 
of care formula used by most radiologists in practice today. The formula should be based on the 
estimated volume of an ellipsoid (L × W × H × 0.52 (where 0.52 is an approximation for π/6). 
 
Volume = A x B x C / 2 
• 
A = greatest hemorrhage diameter in the axial plane 
• 
B = hemorrhage diameter at 90º to A in the axial plane 
• 
C = originally described as the number of CT slices with hemorrhage multiplied by the 
slice thickness, but can simply be substituted with the craniocaudal diameter of the 
hemorrhage where there is access to multiplanar reformats 
 
A venous blood sample is also required for screening and to establish baseline values for certain 
inflammatory markers (platelets and white blood cells including neutrophils and lymphocytes).  
Sample amounts should be based on site specific laboratory requirements for completion of tests 
including a Complete Blood Count (CBC) with Differentials and a Comprehensive Metabolic 
Panel (CMP).   Current laboratory certificates are required by the sponsor with laboratory 
processes to be made available upon request.  
7.2 Pre-Neurapheresis Imaging (CT) Requirements 
As aneurysm securement (especially clipping) may change the amount of blood in the 
subarachnoid space, a CT is required following aneurysm securement but prior to beginning 
Neurapheresis.  This CT will serve as the Baseline CT (pre-Neurapheresis CT) which, along with 
the screening CTs, will be compared to the post-Neurapheresis CTs.   The Baseline CT is expected 
to be taken in a department scanner using optimal metal artifact reduction settings at the 
conclusion of aneurysm securement or following catheter insertion but prior to initiation of 
Neurapheresis therapy.  The baseline CT must be reviewed to determine safety, via intracranial 

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stability, prior to beginning Neurapheresis therapy.  In particular, the Investigator must assess the 
CT for the following criteria:  
• 
no evidence of re-bleeding;  
• 
no increasing mass effect;  
• 
no effacement of the basilar cisterns;  
• 
continued communication between the ventricles and subarachnoid space 
 
In addition to the CT requirements above, study therapy cannot begin for at least 8 hours following 
aneurysm securement for subjects who underwent a clipping procedure. 
 
If the subject meets these criteria, study therapy can be initiated.  If the subject does not meet these 
criteria, either the subject can be exited, or another CT can be taken to determine baseline stability.  
If the subject still does not meet the safety criteria to begin study therapy after the second baseline 
CT, the subject is to be exited.   If the study catheter was not placed prior to the baseline CT, the 
subject should be exited as an Intent to Treat Subject and no further follow-up is required.  If 
however the study catheter was placed prior to the baseline CT, a 2-day follow-up is to be 
completed and the subject exited as an Attempt to Treat Subject.  
7.3 Heparinization/Anti-Platelet Guidance/Aneurysm Stability 
If Heparin is to be administered as a center SOC for a coiling procedure, study subjects must have 
a baseline Activated Clotting Time (ACT) drawn prior to administration of the initial heparin 
bolus.  An additional ACT must be checked prior to the Neurapheresis catheter insertion. When 
the ACT reads baseline ±10 sec it is deemed safe to proceed.  ACT’s must be recorded on the case 
report form and are considered to be source documentation if not captured elsewhere in the 
medical record.     
If a subject requires an additional platelet aggregation inhibitor e.g., Integrilin as part of the coiling 
procedure, the Investigator may wait to insert the Neurapheresis catheter but must initiate catheter 
insertion within the window of 48hours post ictus and, coagulation is deemed safe to proceed.  
Subjects who are enrolled and do not meet these criteria of time or coagulation should be 
withdrawn and are classified as “Intent to Treat subjects”.  Documentation of adequate coagulation 
metrics is a protocol requirement regardless of method used to secure the aneurysm. 
 
Prior to proceeding with catheter insertion, the Investigator uses professional judgement to 
determine if the Subject and aneurysm is stable.  If stability is in question, the Investigator may 
wait to insert the catheter but insertion must still fall within the 48 hour from ictus time frame.   
7.4 Catheter Insertion 
The Investigator should be mindful of a history of lumbar or thoracic stenosis or any existing 
spinal instrumentation when placing the catheter.  Initial insertion of the investigational catheter is 
to be timed to be as close as possible to completion of the initial treatment/securement of the SAH 
but no later than 48 hours post-bleeding event.  Ideally, the catheter should be inserted 
immediately after the coiling or clipping procedure; see the previous Section for guidance 
concerning Heparin and anti-platelet administration.  Insertion of the Neurapheresis catheter is 
expected to have a similar pain profile as that of lumbar drain insertion and should be treated 

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accordingly.  It is recommended that adequate local anesthetic and sedation/analgesia is in place at 
the time of catheter insertion.  An MNeuro CFS will be onsite to support the catheter placement 
and system prep. 
 
The Investigator may choose the position which affords the most technical comfort level for 
insertion e.g., lateral decubitus or prone; there is no protocol requirement for positioning, but the 
position of the subject must be documented on the Neurapheresis CRF.  If the catheter placement 
occurs immediately following a clipping procedure, a C-arm and an OR table that can 
accommodate portable fluoroscopy will be needed.  Continuous lateral fluoroscopy is 
recommended during guidewire insertion to ensure that there is no looping of guidewire and that 
catheter follows the guidewire appropriately and tracks dorsally.  Elapsed time to place the 
catheter is a required data item. 
Catheter insertion and system set up are to be performed according to the Instructions For Use 
(IFU).  While highlights of the insertion are included in this protocol, the current IFU should be 
referenced prior to and/or during each procedure.  Investigators delegated to perform catheter 
placement are required to acknowledge their review and understanding of the IFU prior to being 
approved to place the catheter.  The investigational catheter is expected to be inserted under 
fluoroscopic guidance using the tools provided by the Sponsor, however if the subject anatomy is 
unusual, use of different delivery tools e.g., guidewires, and access needles may be allowed.    
Documentation on the case report forms will be required. 
To minimize the risk of infection and nerve damage, insertion and placement of the catheter is 
limited to two (2) discrete events.  If the catheter ceases to function effectively e.g., positional 
migration, kink or clot, the Investigator may remove the catheter once and replace it with another 
catheter.  Subjects must be transported to an interventional procedure room for catheter 
replacement; re-insertion may not be facilitated at the bedside with a C-arm.  The catheter change-
out is be performed according to the IFU.  If a catheter change out is needed, it is required that the 
system disposables are also replaced to mitigate the risk of infection e.g., meningitis.  
Reconnecting to an existing system would result in a protocol deviation.    
7.4.1 Catheter Insertion Highlights 
• 
Soak and flush catheter in preservative free saline prior to insertion 
• 
SOC patient prep, positioning and anesthesia for lumbar puncture 
• 
Insert epidural needle through intervertebral spinous processes to the dural level (skin nick 
or pilot hole may be used to help with passage of the needle 
• 
Remove the needle stylet and observe for CSF drainage, advance slowly until CSF is 
returned 
 
• 
A 5ml CSF sample to be taken from the needle 
o 3ml submitted for Cell counts with Differential and Chemistries 
o 2ml for biomarkers (cytokines) which must be stored in a -80o freezer until 
shipped to the core lab 
• 
An additional level or re-positioned attempt can be made if no CSF is returned 
• 
Do not perform excessive attempts to avoid potential complications such as CSF leakage, 
spinal headache or nerve root damage 
• 
Insert guidewire and advance to low-mid thoracic spine, tracking dorsally 

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• 
Remove epidural needle and leave guidewire in place 
• 
Using an OTW technique, advance catheter over the guidewire (with tension on the end of 
the guidewire to prevent further advancement 
• 
Upon reaching the guidewire tip, advance both the wire and catheter together until the 
catheter proximal inlet holes rest within the lumbar cistern (approximately L2-L3) 
• 
When the catheter is in position remove the guidewire 
   
If there is significant difficulty in gaining access, placing or positioning the catheter, abort the 
procedure and dress the wound per SOC.  Those Subjects who have the procedure aborted due to 
an inability to gain access or obtain an acceptable position are classified as an “Attempt to Treat” 
subject and are followed according to the protocol through 2 day follow-up to assess the wound 
and potential adverse events related to the attempted access or catheter insertion.  Subjects in the 
Attempt category are exited from the study after the protocol required 2 day follow-up visit.  
 
It is highly recommended to have the Neurapheresis System assembled and prepped either prior to 
or while the catheter is being placed to minimize IR/OR time for the subject.  However, if the 
system is not prepped completely by the time of catheter securement is complete, Investigators or 
center staff should carefully join the male and female ends of the catheter together to form a sterile 
loop to avoid CSF leakage while waiting to connect the catheter to the system.  Do not overtighten 
the catheter hubs. The figure below demonstrates how to properly connect the catheter to maintain 
sterility of the catheter hubs.   
 
Figure 7: Temporary Connection of the Catheter Male and Female Ends 
Upon connection of the catheter to the system a flow test is required to ensure the connections are 
secure, the system has been appropriately set up and a flow loop has been established (refer to the 
IFU for proper system assembly and details on the required flow test).  Following completion of a 
successful flow test, the catheter can be externally secured to the subject.  
7.4.2 Guidance-Securing the Catheter/Dressing the Wound 
Investigators are required to use a fixation device to secure the catheter to the subject to eliminate 
catheter movement and pullout.  Commercially available devices (StayFix by Merit Medical) will 
be provided by the Sponsor to ensure availability.  The fixation device contains a dressing but the 
choice of a topical antibiotic ointment is discretionary per the Investigator.  Center personnel may 
also shave any excess hair from around the insertion site to assist with skin preparation for the 
application of the fixation device.  Other institutional SOC surgical tape may be placed over the 
StayFix if preferred, however not underneath the StayFix. 

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The catheter is designed with extra length such that the pressure points can be avoided and that 
access to the system ports can easily be facilitated.  Avoid positioning the extra catheter length 
over a bony prominence by taping the catheter to the Subject’s abdomen or torso for easy access.   
 
An ongoing dialogue with the MNeuro CFS will assure that the exteriorized catheter is properly 
positioned to optimize system functionality, however, guidance is provided below.  
 
• 
Use the protocol required Stay-Fix device to dress the puncture wound site.  Ensure that 
the orientation of the catheter and application of the dressing afford the least amount of 
bend/stress on the catheter (see Figure 8). The catheter should be positioning snugly over 
the blue support pad before securement. 
 
 
 
 
Figure 8: Catheter Positioning within StayFix 
 
• 
On smaller patients, a single coil with the catheter is to be created and may be secured 
with surgical tape. 
o While not required, previous Investigators preferred to cover the StayFix and 
single catheter coil with Tegaderm™ or OpSite™. 
• 
For proper oversight of system functionality, it is imperative that the bifurcation (Y joint) 
and catheter luer hubs are visible at all times. 
o As such, they should not be hidden under the bed sheets or taped to bed rails   
• 
It is necessary and appropriate to have a lengthy “tail” on the catheter.   
o When positioning the tail, it is recommended to tape the catheter to the torso, with 
a loop of coiled tubing to act as strain relief (see Figure 9).   
o Ensure placement of the catheter does not create a pressure point if the subject 
should roll over or move. Chux or gauze may be placed beneath the catheter hubs 
to further protect the connections. 
• 
A second StayFix device may be used to further secure the coiled tubing to the patient’s 
abdomen (Figure 9). 
 
 
 
Required:  
Stay-Fix 

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Figure 9: Catheter Fixation Device and Protective Dressing 
 
7.4.3 OTB System Disposables Replacement 
It is possible that a change of the OTB system disposables i.e., Filter and Flow Assemblies, Luer 
fill set and the waste bag, may be required during the Neurapheresis procedure.  Change-out of the 
OTB system disposables can be driven by physical causes e.g., accidental cutting/crush of tubing 
or, driven by system data e.g., suspicious component behavior etc.     
The Sponsor will track change outs of the disposables and the rationale for each action.  Change-
outs dictated by a component behavior may require return of the affected component to the 
Sponsor for analysis for product development purposes.   
Change out of the OTB system disposables may be facilitated at the bedside; it is not necessary to 
return to the IR/OR, subject transfer is left to the discretion of the Investigator.  
When changing the system disposables, Investigator will disconnect the catheter from the system 
and join the two ends (male→female) forming a sterile loop that maintains the sterility of the 
catheter ends (Figure 7).  A sterile field should be established to connect the filter and flow 
assemblies and to facilitate priming of the system.  The MNeuro CFS will guide center personnel 
in the catheter disconnection, component assembly, handing, and reconnection as needed based on 
the components being replaced.   The IFU should also be referenced during this time for detailed 
instructions on disposable component replacement. 
7.5 Neurapheresis Therapy 
As this is an investigational system, Investigators and study staff expected to place, use or monitor 
the system will be trained in the applicable information, techniques and troubleshooting.  Despite 
training, Investigators and applicable site staff should refrain from making medical decisions 
based on any data point or trend displayed on the Neurapheresis system interface and instead 
continue to reply on SOC devices or data.  
The study catheter may remain in-dwelling for up to 72 hours (± 4hr) in treated subjects during 
which study therapy can be completed.  Neurapheresis therapy will be incrementally extended 
during the study such that, the first five (n=5) treated subjects enrolled under this protocol will 
have a maximum of 36 hours (± 4hr) of Neurapheresis therapy (pump time) allowed during the 72 
hours (± 4hr) of catheter in-dwelling. 
Optional: 
Tegaderm™/OpSite™ 
Catheter Tail
Optional: 
Single Catheter Coil 
Optional: 
Stay-Fix 

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Following positive DSMB review of the data from the first five subjects, the remaining up to n=9 
treated subjects (for a study total of N=30 Treated Subjects) will have no limit on maximum 
therapy time and instead be limited only by the maximum catheter in-dwelling time of 72 hours (± 
4hr). 
If the DSMB does not agree that it is safe to remove the Neurapheresis therapy limit after review 
of data from the first five subjects enrolled under this protocol, the maximum of 36 hours (± 4hr) 
of Neurapheresis therapy (pump time) will remain in place for the remaining subjects. s.   
The sponsor will notify FDA, the IRB and clinical sites of the results from the DSMB review.   
The start of catheter indwelling time is the time of catheter securement completion.  The end of 
catheter indwelling time is marked by catheter removal and is not to exceed a total of 72-hours 
(±4hrs).  Center personnel must document required catheter times in the case report forms and 
medical record source as applicable.   
Neurapheresis therapy start time is documented when study therapy is initiated.  Therapy end is 
captured as the time the pump is stopped to allow for catheter removal.  Study therapy will not be 
continuous for the 72-hours of catheter in-dwelling.  Pausing of therapy may be required for SOC 
activities and potential fluctuations in the clinical status of the subject.  The protocol also requires 
pausing of study therapy at the study required neuro checks and for study required CTs. 
7.5.1 Neurapheresis Therapy Rates  
Neurapheresis therapy will commence slowly at a nominal flow rate of 0.5mL/min. to 
accommodate the volume of hemorrhagic CSF pooled in the lumbar cistern.  An increase of flow 
shall not occur until 1 hour of aggregate pump time has elapsed to optimize the system operation 
during the initial access of the pooled hemorrhage.  At this time, a baseline CSF sample will be 
taken, see Section 7.5.7.  
After the CSF sample has been taken, the MNeuro CFS will transition the system to auto mode.  In 
this mode, an automated algorithm will adjust the flow rates to continuously optimize the 
Neurapheresis therapy based on system pressures.  The MNeuro CFS will be present while the 
system is in auto mode for system oversight.  During study therapy, the waste rate will be 
generally maintained within a range of 12-15 mL/hr as determined by the Investigator.  However, 
at any time the Investigator may choose to manually adjust the system waste rate based on subject 
status. 
7.5.2 Neurapheresis Termination Criteria 
Investigators should engage in an ongoing dialogue with the MNeuro CFS to address starting and 
stopping the pump for CSF sampling, change in clinical status, emergent situations and SOC 
concerns e.g., transport, extubation, physical therapy, study-required neuro checks or other.  If a 
subject meets any of the criteria below, Neurapheresis should be stopped immediately (if not 
previously stopped) and the subject should be scheduled for catheter removal. 
Change(s) in Subject conditions that require Neurapheresis termination are: 
• 
Brainstem herniation  
• 
Lower extremity paralysis  
• 
Subdural spinal hematoma 

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• 
Subdural hematoma or hygroma  
• 
Abnormal gram stain  
• 
Re-bleeding event requiring intervention e.g., re-coiling, re-clip  
• 
Subject previously non-intubated/extubated requires new or re-intubation  
• 
ICP is greater than Lumbar pressure at five consecutive study-required neuro checks 
• 
Subject requires inversion (such as Trendelenburg position) 
As the MNeuro CFS will be on site during Neurapheresis therapy, the sponsor will be notified 
immediately if any subject has the Neurapheresis procedure terminated due to reasons above.  
Source documents may be requested for the Sponsor to adequately review the termination. 
The Investigator may pause the system or terminate the procedure at any time.  The Subject also 
has the right to terminate the procedure at any time.  If study therapy must be terminated early, a 
head CT within (± 4hr) of catheter removal must be obtained to document the final amount and 
location of blood within the basal cisterns to allow for comparison to baseline.  
7.5.3 Role of the MNeuro Clinical Field Specialist (CFS)  
MNeuro clinical field specialists or their trained representatives are responsible for training and 
directing the applicable site staff in the placement, assembly, priming, replacement and removal of 
all components of the Neurapheresis System. The MNeuro CFS is also responsible for the general 
operation and trouble-shooting of the investigational system under guidance from Investigators 
and site staff to confirm the system does not present any care concerns and is functioning properly. 
The attending MNeuro CFS or representative will not practice medicine, alter data or make any 
clinical suggestions based on collected data or observed data trends.  
During the Neurapheresis procedure, the MNeuro CFS is also responsible for addressing any 
system alert states.  System data includes but is not limited to, inlet and return pressure(s), flow 
and waste rates, processed volume etc.  System data collected during a Neurapheresis procedure 
will be recorded on the LabView Software and is saved to the PC hard drive and retrieved to USB 
pen drives.  The MNeuro CFS will also help the site staff document the lumbar pressure from the 
system during the study-required neuro checks.  
If the system experiences an issue e.g., pump failure, filter clot, catheter kink or obstruction, 
breach of sterility etc.., MNeuro CFS or representative will facilitate replacement or removal of 
the affected component after discussing “next steps” with the Investigator.  
7.5.4 CSF Pressure Guidance During Neurapheresis  
Subjects must have an EVD as part of the SOC for post SAH intracranial pressure management.  
Study Investigators should consult with the MNeuro CFS to coordinate the EVD maintenance with 
the Neurapheresis System waste control rate.  Investigators are asked to clamp the EVD and open 
if ICP goes to ≥20mmHg while the Neurapheresis system is operating.  The Investigator has the 
medical discretion to open the EVD at a lower pressure limit as clinical status for a specific subject 
may require.  Alternatively, the Investigator may increase the therapy waste rate to manage an 
increasing trend in ICP with the Neurapheresis system rather than open the EVD.  If the EVD is 
opened, it should be set to a pressure of 20 mmHg.  Also, the Investigator may reduce the system 
waste rate or pause the system if unusually low ICP or clinical symptoms indicate continued 
drainage at the current rate may be unsafe.  

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Brain herniation is a known risk for intracranial hemorrhage patients, including aneurysmal 
subarachnoid hemorrhage, as the blood can create excess pressure in the brain. Likewise, 
herniation is a known risk of lumbar drainage as it may lead to cranial pressure changes.  
SAH patients with increased risk for herniation may include those with:  
• 
CNS infection or abscess;  
• 
Excessive cranial edema/swelling that increases mass effect; 
• 
Hydrocephalus or other complication that could compromise CSF communication; 
• 
Other mass effect (tumor, hematoma, etc.) that may lead to high intracranial pressure 
(ICP); 
• 
A sustained negative pressure change between intracranial and lumbar pressure due to 
high ICP or low lumbar pressure. 
During Neurapheresis therapy, the protocol requires measurement of both lumbar pressure and 
ICP for assessment of subject status administered hourly (±1hr).  This should be performed at the 
same time as the study required neurological assessments. Centers will not be deviated for 
obtaining ICP measurements at a greater frequency if that is the center SOC.  ICP is to be captured 
on the applicable CRF.  It is acceptable to have the attending critical nursing staff obtain the 
measurements if that is the SOC of the center’s critical care unit.  
 
To ensure accurate pressure measurements, the system will be paused, and the inlet pressure 
sensor will be leveled to the lumbar region of the subject.  The lumbar pressure will then be 
recorded.  The site staff will use their normal process for leveling and recording the ICP 
measurement. The system will remain paused if the lumbar pressure falls below 4.4 mmHg (6.0 
cmH2O), and the Investigator will be notified to review clinical symptoms and system data prior 
to restarting.  Alternatively, if the Investigator has pre-defined and documented a treatment plan, 
the system may be re-started according to the plan and on-going communication with the 
Investigator maintained to ensure adequate oversight of subject safety.  
 
If during any pressure check the ICP recorded is higher than the lumbar pressure taken at the same 
neuro check, the system will remain paused until the ICP is equal to or lower than the lumbar CSF 
pressure for at least two consecutive neuro checks AND the Investigator has approved restarting 
the system.   If the ICP remains higher than the lumbar pressure for five consecutive study-
required neuro checks, then therapy will be terminated, and the site should prepare to gather the 
end of treatment data.  
 
In cases where the Neurapheresis procedure is terminated early, the protocol required ICP 
measurements are to be continued until the catheter has been removed.   
7.5.5 Neurologic Assessments During Neurapheresis 
During Neurapheresis therapy, the protocol requires neurological assessments including GCS and 
Peripheral neurological checks for assessment of subject status to be administered hourly (±1 hr).    
Peripheral neurological checks will include assessment of leg strength and sensory changes to 
identify potential adverse events such as subdural spinal hematoma. Centers will not be deviated 
for performing assessments at a greater frequency if that is the center SOC or if additional 
assessments are administered.  Assessments are to be captured on the applicable CRF.   It is 

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acceptable to have the attending critical nursing staff conduct the assessments if that is the SOC of 
the center’s critical care unit.  The Investigator may reduce the system waste rate or pause the 
system if clinical symptoms indicate continued drainage at the current rate may be unsafe. 
 
In cases where the Neurapheresis procedure is terminated early, the protocol required neurological 
assessments are to be continued until the catheter has been removed.  
Neurological monitoring is required hourly during study therapy  and similar to standard practice, 
this monitoring is intended to identify changes to neurological status that may be suggestive of 
neurological decline. Note that the protocol requires that study therapy be stopped if herniation is 
identified, regardless of whether the Investigator believes the herniation to be related to study 
therapy.   
7.5.6 Neurologic Assessments for Intubated Subjects 
To ensure the identification of deterioration in intubated subjects, the following data collection and 
criteria related to the GCS are established to pause the Neurapheresis procedure and allow for 
adequate assessment of the subject’s status.  Specifically, GCS will be captured each hour while 
the subject is intubated.   
 
GCS should be captured noting that the subject is intubated (t) and it would be expected that the 
highest score for an intubated subject will be 10(t) due to inability to provide a verbal response.  
Further, Neurapheresis is required to be paused in an intubated subject if the motor component of 
the GCS drops below 6.  Neurapheresis can begin upon improvement in the motor component 
score back to 6 or at a motor component of 5 that is stable for at least 4 consecutive hours during 
which a cause for the deficiency is identified such that the investigator concludes is not related to 
Neurapheresis.  If the motor component or total GCS score continues to decline Neurapheresis 
should be terminated and the subject scheduled for catheter removal.  
 
Finally, if a subject who was previously extubated/non-intubated requires new or re-intubation, 
Neurapheresis is to be terminated.  
7.5.7 CSF Sampling During Neurapheresis 
During catheter in-dwelling and Neurapheresis therapy, CSF samples will be obtained at regular 
intervals until the catheter is removed. A maximum of 11 CSF samples total per subject will be 
taken.  Ten of those during catheter indwelling, though fewer may be taken if the catheter must be 
removed early.   
Samples will be taken according to the schedule in Table 10 below.  The initial CSF sample will 
be taken during catheter placement however, the first sample taken during catheter in-dwelling 
will be considered the Baseline CSF sample (pre-Neurapheresis sample) to which the later samples 
will be compared.  The last CSF sample taken will be considered the Final sample or (post-
Neurapheresis sample) which will be compared to the Baseline sample for applicable endpoint 
analyses.  To account for different assay requirements, CSF sample volumes are different for the 
initial and seventh (40 hr) sample than those in between.    
It is allowable to collect less CSF sample volume for completion of the Cell counts with 
Differentials based on site specific laboratory requirements.   Current laboratory certificates are 

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required by the sponsor with laboratory processes to be made available upon request.  Care should 
be taken to ensure laboratory samples are handled and processed consistently for accurate data 
reporting.   
During catheter in-dwelling, the first sample (#2 on Table 10 below) should be taken after 1 hour 
(±30min) of Neurapheresis therapy.  The MNeuro CFS will assist in monitoring the therapy time 
in order to prepare for the sample.  The next CSF sample should be taken at 8 hours (±2hr) from 
catheter securement (8 hours of catheter in-dwelling) then each subsequent sample taken every 8 
hours (±1hr) from the previous scheduled sample (i.e. every 8 hours during catheter in-dwelling).  
 
 
 
Table 3: Required CSF Samples 
Sample # 
Sample Metric 
Required Assay 
CSF Sample 
Volume 
1 
During Catheter 
Placement 
(needle stick) 
Cell counts with Differential: RBC, WBC, neutrophils, 
lymphocytes, etc.  
Chemistries: Total protein, Glucose, Culture 
3ml 
CSF Biomarkers (requires -80o storage until shipped)β 
2ml β 
2 
1hr (±30min) of 
Neurapheresis  
Cell counts with Differential and Chemistries  
3ml 
3 
8hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
4 
16hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
5 
24hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
6 
32hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
7 
40hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
CSF Biomarkers (requires -80o storage until shipped) 
2ml 
8 
48hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
9 
56hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
10 
64hr (±2hr)* 
Cell counts with Differential and Chemistries  
3ml 
11 
72hr (±2hr)*¥ 
Cell counts with Differential and Chemistries  
3ml 
*time measured from catheter securement (beginning of indwelling time) 
βif a CSF sample for biomarkers was not obtained during catheter placement (sample #1), it can be done with sample #2 
¥if the catheter is removed prior to reaching the 72hr indwelling limit, a final CSF sample should be taken just prior to 
catheter removal 
 
Center personnel shall work with the MNeuro CFS to time the CSF sampling as to not interfere 
with SOC patient care.  To ensure sample consistency and minimize subject impact, samples are to 
be taken using the automated sampling process within the system.  The system is switched to 
“sample mode” then using sterile technique, a syringe is inserted into the three-way sample 
stopcock.  Sample mode should be set at the nominal flow rate of 0.5ml/minute.  The system will 
automatically fill the syringe.  Once the appropriate amount of CSF has been retrieved, sample 

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mode can be stopped and the syringe removed.  The MNeuro CFS will pause the system prior to 
the sample acquisition, and will leave the system paused for a short period post sampling e.g., 
approx. 15 min, to allow for the CSF fluid balance to recover.   
Also reference the IFU for additional details in regard to CSF sampling.  A de-identified 
laboratory print-out of the required CSF assay analyses must be provided to the Sponsor.  The 
original laboratory results must be available for monitoring.  
7.5.8 Additional Testing Requirements During Neurapheresis 
At 36 hours (±4hr) and 72 hours (±4hr) or end of catheter in-dwelling (whichever comes first), a 
venous blood sample and CT are required.  Timing should be aligned with a study require neuro 
check for efficiency.  The 36 hour CT and the 72 hour (end of catheter in-dwelling) CT must be 
obtained using a department scanner at optimal metal artifact reduction settings as it will be used 
for primary endpoint analysis.   The 72 hours (±4hr) or end of catheter in-dwelling CT can be 
obtained after catheter removal to minimize the risk of compromising sterility of the fluid loop.  
However, if it obtained prior to catheter removal, steps to maintain sterility during patient transport 
should be followed as described in 7.5.9 below.  
The venous blood sample should be submitted for a Complete Blood Count (CBC) with 
Differentials and a Comprehensive Metabolic Panel (CMP) to allow for comparison to pre-therapy 
values.   
7.5.9 Patient Transport during Neurapheresis  
If it is necessary to transport the study subject during the Neurapheresis procedure, ensure that the 
Sponsor’s representative is present and the system is stopped for transport.  Care should be taken 
to protect the integrity of tubing connections during transport.  If possible, transport the system 
connected to the Subject, keeping the fluid loop intact or, remove the tubing and filters from the 
mounting bracket and place the components on the bed.  If a system disconnect is required, 
connect the two catheter ends to one another (male→female) keeping the catheter sterile, see 
Figure 7.  If sterility is compromised when connecting, the ends of catheter should be cleansed 
with Betadine for three minutes per AANA guidelines or SOC at center for sterile line technique 
when reconnecting to the Neurapheresis System.  
 
The patient may sit up, stand, or move from their hospital bed as permitted or recommended by 
SOC. Center personnel should work with the MNeuro CFS to position the system cart in such a 
way to minimize strain on the catheter and tubing and allow proper movement of the patient. The 
system should remain connected to the patient, and depending on the type of movement, the 
system may continue running. 
7.5.10 Catheter Removal 
As described in Section 7.5.8, above, it is a protocol requirement to obtain a CT scan of the head 
within 4 hours of catheter removal (± 4hr from catheter removal) to document the post-therapy 
status.  This post-Neurapheresis CT will be compared to the pre-Neurapheresis CT (Baseline CT) 
to analyze applicable study endpoints.  This CT cannot be obtained bedside.   
 

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An image of the catheter position prior to removal is required showing proximal (lumbar cistern) 
and distal catheter (thoracic anatomy) locations.  It is preferable that this is captured by fluoro to 
be consistent with the intra-procedural images captured during catheter placement, but X-ray 
capture of the image is acceptable it better accommodates work flow at the center.   
 
It is recommended that the Investigator employ the following steps for catheter removal and be 
mindful of any analgesic requirements for catheter removal. It is likely that removal of the 
Neurapheresis catheter will have the same pain profile as the removal of lumbar drains so the 
Investigator may want to consider analgesic coverage per their professional discretion. The steps 
to removing the catheter are outlined below and are not exclusive of the SOC for spinal catheter 
removal at each study site.  The IFU should also be referenced for more detailed information on 
catheter removal. 
 
• 
Stop pump 
• 
Turn flow assembly stopcocks such that the flat aspect of the stop-cock is toward the 
subject.  
• 
Disengage catheter from the flow assembly stopcock  
• 
Join male and female catheter ends together to form a sterile loop 
• 
Obtain image of final catheter position  
• 
Remove dressings and any sutures or fixation mechanisms used to retain catheter 
• 
Gently pull catheter until it exits the subject 
• 
Hold pressure on site until dressing and/or stitch is applied 
• 
Have Subject lie flat or on their side for 30 minutes 
• 
Watch for signs of headache or Dural CSF leak.  If a headache occurs or a blood patch is 
required to seal a leak, complete an Adverse Event CRF. 
Upon removal, follow the steps to return the investigational catheter to the Sponsor.  Confer with 
the MNeuro CFS to ensure proper packaging and documentation for return, in addition to making 
the appropriate annotations in the study Device Accountability Log.  
 
In the event of a Subject death during Neurapheresis, the Technical Representative will work with 
the center to obtain the catheter in a timely fashion.  
7.6 Post-Neurapheresis Surveillance Schedule 
7.6.1 2 Day (±1 day) Follow-up Data 
The first surveillance metric will occur at 2 days (±1 day) according to Table 11. It is expected that 
the Subject will still be in the Neuro ICU at this point.  Along with the clinical status and hospital 
data on the CRF, requirements for this visit include a CT, venous blood sample, GCS and de-
identified laboratory and other applicable SOC source documents. Data should be collected from 
SOC source documents and transferred to the CRFs however, if source documents are not 
available, completed study worksheets can be signed by the investigator and maintained in the 
study file as source documents for monitoring. 
 
A protocol required CT is requested at this follow-up to document the status of any subarachnoid 
blood remaining following Neurapheresis.  Care should be taken to obtain the CT at the same 

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angle as those previously completed to improve the comparability of the data.  The CT can be 
obtained bedside for appropriately equipped investigational sites. 
 
Additionally, a protocol required venous blood sample is to be taken at the 2 day follow-up and 
sent for analysis. (CBC with Differentials/CMP) with associated laboratory reports provided to the 
sponsor. As CSF cultures should be followed for 96 hours from the last sample, it is expected that 
additional CSF analysis laboratory reports would be included with the 2 day follow-up data. Any 
SOC imaging studies (CTs, TCD, etc.) and associated reports completed since catheter removal 
should be submitted. The medical record and clinical status should be reviewed for adverse events 
and reported on the appropriate case report form as applicable. Finally, non-adherence to the visit 
requirements will result in a protocol deviation.  
7.6.2 Neuro ICU Discharge Follow-up Data 
Subjects are expected to be discharged on average 10-14 days post aneurysm securement from the 
Neuro ICU (critical care unit). Discharge may be a change in location (i.e. to a stepdown unit, 
main hospital floor, rehabilitation facility or home) as dictated by clinical status and institutional 
SOC.  Alternatively, Neuro ICU discharge may be based only on clinical status (i.e. the point at 
which the subject no longer meets the institutional definition for critical care monitoring).  If the 
date of discharge from clinical status is different than the date of change to physical location, sites 
are expected to use the earlier of the two dates for the discharge date.  Sites are asked to discuss 
institutional discharge criteria with a sponsor representative to ensure discharge data is collected at 
the appropriate time.  
Data should be collected at the time of discharge and include the following assessments that may 
not be SOC are required.  See Table 11 for detailed requirements; GCS and Modified Rankin 
Scale (mRS).  
As CSF cultures should be followed for 96 hours from the last sample, it is expected that 
laboratory reports after the 2 day follow-up will be submitted with this discharge follow-up data.  
Additionally, any SOC imaging studies (CTs, TCD, etc.) and associated reports completed since 
the last study visit should be submitted. The medical record and clinical status since the last study 
visit should be reviewed for adverse events and reported on the appropriate case report form as 
applicable. Finally, non-adherence to the visit requirements will result in a protocol deviation.  
 
7.6.3 30 Day (±3 day) Follow-up Data 
The final surveillance metric will occur at 30 days (±3 days) post removal of the Neurapheresis 
System catheter according to Table 11.  It is highly likely that the Subject will not be hospitalized 
at this follow-up and as such a return to the clinic is recommended to properly perform the 
required neurological assessments. (GOSE, mRS, Barthel, MoCA).  If the subject refuses to or is 
unable to return, this follow-up may also be completed as able by phone however that should be a 
last option.   
The medical record and clinical status should be reviewed for adverse events and reported on the 
appropriate case report form as applicable. Finally, non-adherence to the visit requirements will 
result in a protocol deviation. 

Table 4: Data Collection Schedule 
Data Items 
Screening / 
Enrollment 
Catheter 
Placement 
Neurapheresis 
Procedure 
 
2-Day Post-
Neurapheresis 
(±1-day)  
Discharge from 
Neuro ICU  
30 Days Post- 
Neurapheresis 
(±3 days) 
Demographics, Medical Hx, SAH 
Symptomology 
√ 
 
 
 
 
 
Aneurysm data; location, measurements, 
securement, etc.  
√ 
 
 
 
 
 
Modified Fisher Grade 
√ 
 
 
 
 
 
WFNS 
√ 
 
 
 
 
 
Hunt & Hess 
√ 
 
 
 
 
 
Glasgow Coma Scale (GCS) 
√ 
 
√¥ 
√ 
√ 
 
Peripheral Check 
 
 
√¥ 
 
 
 
Glasgow Outcome Scale Extended (GOSE) 
 
 
 
 
 
√ 
Modified Rankin Scale (mRS) 
 
 
 
 
√ 
√ 
Barthel Index 
 
 
 
 
 
√ 
Montreal Cognitive Assessment (MoCA) 
 
 
 
 
 
√ 
Activated Clotting Time Data 
(if applicable) 
 
√ 
 
 
 
 
Catheter/System data 
 
√ 
√ 
 
 
 
CSF Sampling and Laboratory Reports 
 
√ 
√ 
√β 
√β 
 
CBC with Differential/CMP Blood Test and 
Laboratory Reports 
√ 
 
√** 
√ 
 
 
Protocol Required CTs Scans 
 
√* 
√*** 
√ 
 
 
SOC CT Scans  
√ 
 
√ 
√ 
√ 
 
Fluoroscopy or X-ray Image of Catheter 
 
√ 
√₾ 
 
 
 
ICP Data (if applicable) 
 
 
√¥ 
√ 
√ 
 
Clinical and Hospital Data 
e.g., LOS, location, vital signs, complications 
√ 
 
√ 
√ 
√ 
√ 
Protocol Deviations 
√ 
√ 
√ 
√ 
√ 
√ 
Adverse Events 
 
√ 
√ 
√ 
√ 
√ 
* CT is required after aneurysm securement but prior to Neurapheresis initiation and must be assessed to ensure intracranial stability prior to beginning therapy 
** Blood sample is required at 36 hrs (± 4hr) and at the end of catheter indwelling or 72 hours (± 4hr) whichever is earlier  
*** CT is required at 36 hrs (± 4hr) and at the end of catheter indwelling or 72 hours (± 4hr) whichever is earlier [cannot be bedside CT] 
¥ ICP (for subjects with EVD), Lumbar Pressure GCS and peripheral checks are required every 1 hours (± 1hr) during catheter in-dwelling  
β Reports for CSF cultures should be followed through 96 hours from the last sample taken prior to catheter removal 
₾ Catheter image to document final catheter placement post-Neurapheresis therapy 
 

8. ADVERSE EVENTS (AEs) 
The Study will not track all-cause AEs or AEs related to SOC or the SAH clinical pathway e.g., 
re-bleed, deep vein thrombosis, skin breakdown etc.  Study required event reporting is limited to 
AEs directly related to the investigational catheter, investigational system or Neurapheresis 
procedure, or study required element (such as CSF sampling).   In cases where the event may have 
an attributable dual causality i.e., SAH clinical path or the Neurapheresis procedure, the center 
should report the event.   
8.1 Adverse Event Definitions  
Adverse Event (AE): Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs in subjects, users or other persons, deemed related to the investigational 
device (catheter and/or placement accessories), Neurapheresis procedure, or study required 
element (such as CSF sampling). 
Serious Adverse Event (SAE): Adverse event as defined above that 
a) led to death,  
b) led to serious deterioration in the health of the subject, that either resulted in: 
1) a life-threatening illness or injury, or,  
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body function,  
c) led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Unanticipated Adverse Device Effect (UADE):  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 the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare 
of subjects” (21 CFR§ 812.3(s)). 
 
Unanticipated Adverse Device Effects (UADE) that occur in subjects enrolled in the clinical trial 
should be reported under the IDE program (812.150) to FDA and all reviewing institutional review 
boards (IRBs) and investigators within 10 working days after you first receive notice of the 
adverse effect(s).  
8.2 Reportable Adverse Events  
The table below outlines the protocol required reportable Adverse Events.  Other events should 
also be reported if they are deemed by the investigator to be related to the investigational catheter, 
investigational system or Neurapheresis procedure, or study required element (such as CSF 
sampling). 
 
 
 
 

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Table 5: Reportable Adverse Events 
Adverse Event 
Spinal headache with or without intervention 
Systemic CNS infection/sepsis 
Localized insertion site infection 
Dural dissection  
Meningitis  
Paralysis  
Brainstem herniation in the absence of re-bleed 
Localized pain  
Hematoma at insertion site 
Peripheral neuropathy  
Nausea/vomiting  
Death 
9. DEVIATIONS FROM THE PROTOCOL 
An Investigator must not make any changes to or deviate from the protocol, except to protect the 
life and physical well-being of a subject in an emergency. An Investigator shall notify the Sponsor 
and the reviewing IRB of any deviation from the protocol to protect the life or physical well-being 
of a subject in an emergency, and those deviations which affect the scientific integrity of the 
clinical investigation.  Such notice shall be given as soon as possible, but no later than 5 working 
days after the emergency occurred, or per prevailing local requirements, if sooner than 5 working 
days.  
All deviations from the protocol, with the reason for the deviation and the date of occurrence, must 
be documented and reported to the Sponsor using the appropriate case report form.  Sites are also 
required to report deviations to the IRB per local requirements.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, center re-training, or discontinuation) 
will be put into place by the Sponsor. 
9.1 Amendments to the Protocol 
If a revision to the protocol is necessary which affects the rights, safety or welfare of the Subject 
or scientific integrity of the data, an amendment by the Sponsor is required.  Appropriate 
approvals of the revised protocol must be obtained prior to implementation.  Centers will be 
notified of any protocol amendment that is to be implemented.  Communication from the Sponsor 
will apprise the center if an enrollment stop is required during the revision processes.  
10. DATA ANALYSIS AND MANAGEMENT 
The PILLAR-XT Study does not have a hypothesis based statistical endpoint due to the feasibility 
nature of the investigation.  The following analysis populations and definitions will be used to 
analyze the PILLAR-XT data.  
10.1 Analysis Populations 
The following analysis populations will be used to perform the endpoint analyses.   
 
Safety Population: 
This population includes only subjects that were classified as Attempt to Treat or Treated Subjects 
and will be used to analyze all pre-defined safety endpoints.  
Treated Population: 
This population includes only subjects classified as Treated Subjects and will be used to analyze 
all pre-defined efficacy endpoints, including exploratory endpoints.  

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10.2 Endpoint Analysis Definitions 
Enrollment will be stopped when 30 subjects have been enrolled and treated with Neurapheresis 
for at least 16 hours, however, this amount of therapy time is not considered a complete treatment 
as absolute blood clearance would not be expected.  This study is expected to generate 
foundational data for development of the Neurapheresis treatment curve (e.g. time or volume 
needed to clear blood from the subarachnoid cisterns and lumbar spine). 
 
Primary Endpoints:  
1. Mean reduction of cisternal blood via CT post study therapy  
a. Pre, 36 hour and post-Neurapheresis CTs will be evaluated by an independent 
neuroradiology core laboratory for quantification of blood volume.  The core lab 
will utilize a three (3) member team for independent review of the primary 
endpoint with agreement of at least two (2) reviewers required.  
b. Mean volumes will be compared using a paired t-test with an alpha level of .05. 
Pre blood volume will be compared to both the 36-hour and post-Neurapheresis 
blood volumes separately to support creation of the therapy curve.  However, the 
Pre to Post Neurapheresis comparison will be the primary endpoint measure.  
c. An analysis of variance may be considered based on results from exploratory sub-
groups analyses  
2. Proportion of subjects with Neurapheresis Catheter, System or Therapy related serious 
adverse events 
a. Events will be reviewed by an independent medical monitor for relatedness and 
will be used to calculate this endpoint (Number of subjects with related 
SAEs/Number of subjects in the Safety Population) 
 
Secondary Safety Endpoints:  
• 
Proportion of subjects with successful catheter placement 
o This only includes the subjects in whom catheter placement was attempted 
(Number of subjects with catheter attempted/Number of subjects in the Safety 
Population) 
• 
Proportion of subjects with device or study therapy related adverse events 
o Events will be reviewed by an independent medical monitor for relatedness and 
will be used to calculate this endpoint (Number of subjects with related 
AEs/Number of subjects in the Safety Population) 
• 
Proportion of subjects with systemic CNS infection within 5 day of catheter removal 
o In order to be considered a CNS infection, the following must be true; abnormal 
growth was identified on CSF culture within 5 days of catheter removal, subject 
has physiologic symptoms of infection and treatment was administered 
specifically for that infection. 
o CNS infection events will be reviewed by an independent medical monitor for 
whether or not the event meets the criteria above and will be used to calculate this 
endpoint (Number of subjects meeting CNS infection definition/Number of 
subjects in the Safety Population) 
 
Secondary Efficacy endpoints:  
• 
Mean reduction of RBCs and total protein by CSF sample post study therapy 
o This calculation utilizes the pre-Neurapheresis sample (first CSF sample taken 
either at the time of needle insertion or after catheter placement, whichever 
laboratory value is greater) as compared to the post-Neurapheresis sample (last 
CSF sample taken prior to catheter removal) 

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• 
Mean length of Neuro ICU stay 
o Mean length of Neuro ICU stay will be calculated by two different methods, one 
using physical location change, the second using criteria for critical care 
monitoring.  
 
Exploratory endpoints: 
• 
Proportion of subjects requiring additional CSF management during study therapy or 
on-going CSF management post study therapy 
• 
Reduction in biomarkers of inflammation as seen in CSF, blood and physiologic 
manifestations post study therapy  
o Such as cytokines, white blood cell counts, neutrophil/lymphocyte ratio, SIRS 
• 
Proportion of subjects with symptomatic complications from aSAH  
o Such as hydrocephalus, clinical vasospasm and delayed cerebral ischemia 
• 
Analysis of endpoints by the following sub-groups for any groups that have at least 5 
subjects that meet the criteria for the group; 
o Age: <45, ≥45-<60, 60 – 70 years  
o Gender: male, female 
o Enrollment Modified Fischer grade: 2, 3, 4 
o Baseline cisternal Hijdra score: ≤15, 16-20, 21-25, 26-30 
o Neurapheresis time: <16hrs, ≥16-32hrs, >32-48hrs, >48hrs 
o Other sub-groups not yet defined 
10.3 Data Management 
A 21 CFR Part 11 compliant electronic data capture platform will be used for this clinical study 
and as such, subject clinical data will be entered into the study database by investigational site 
staff.  All changes made to the clinical data will be captured in an audit trail and available for 
review by MNeuro or its Monitoring representative.  
Unique user ID and password will be provided to each database user by MNeuro or the database 
vendor as determined by contract. Investigators will be required to review and sign off on the data 
entered for each of their study Subjects.  Sites will not have visibility to study data for any other 
site participating in the study.  
Manual and automatic queries will be issued to the site for appropriate response and clarification 
of data.  Site staff will be responsible for resolving all queries generated by the Sponsor and 
making source documentation available for each change as applicable.  
11. MONITORING 
A study initiation visit shall be conducted by the Sponsor and/or their representative to ensure but 
not limited to: 
• 
Current and completed required study documents are on file; 
• 
Training and associated documentation is complete; 
• 
Site staff understand the requirements of this study protocol; 
• 
The site is prepared for study enrollment 
 
MNeuro will provide notification to the site once they have been approved to enroll subjects.  IRB 
approval is a required element for enrollment approval however sites are not authorized to begin 
enrollment until they receive notification from MNeuro, regardless of having IRB approval in 
place.   

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Clinical monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations.  In addition, the Clinical Monitor will verify that study records 
are adequately maintained, that data are reported in a satisfactory manner with respect to 
timeliness, adequacy and accuracy, and that the Investigator continues to have sufficient staff and 
facilities to conduct the study safely and effectively.  The Investigator/institution guarantees direct 
access to original source documents by MNeuro personnel, their designees, and appropriate 
regulatory authorities.  It is important that the Investigator and relevant study personnel are 
available during on-site monitoring visits or audits and that sufficient time is devoted to the 
process. 
12. SUSPENSION OR EARLY TERMINATION OF THE INVESTIGATION 
MNeuro reserves the right to terminate the study at any stage.  MNeuro will exercise this right 
only for valid scientific, safety or administrative reasons and, reasons related to protection of 
Subjects.  Investigators and their associated IRB will be notified in writing in the event of study 
termination. 
Possible reasons for premature study termination include, but are not limited to:  
• 
The occurrence rates of AE/ UADE that present a significant or unreasonable risk to subjects 
enrolled in the study 
• 
An enrollment rate far below expectation that prejudices the conclusion of the study 
• 
A decision on the part of Minnetronix to suspend or discontinue development of the device or 
therapy application. 
13. COMPLIANCE 
13.1 Statement of Compliance 
This study will be conducted in accordance with 21CFR§ 812, International Conference on 
Harmonisation (ICH) E6 Guidelines for Good Clinical Practice (GCP), ethical principles that have 
their origins in the Declaration of Helsinki, and pertinent individual country laws and regulations. 
The study shall not begin until the required approval/favorable opinion from the FDA and the IRB 
has been obtained.  Any additional requirements imposed by the IRB shall be followed.  
13.2 Independent Medical Monitor 
An independent medical monitor will be utilized for review and adjudication of study reported 
adverse events.  The primary focus of adjudication will be whether the event is anticipated and 
relatedness to study device or procedure. The medical monitor will be provided available 
information related to each event such as data from case report forms and copies of de-identified 
source documents including medical records and imaging studies as applicable.  Details related to 
the responsibilities of the Medical Monitor will be documented in a charter.  
 
Medical monitor adjudication data will be provided to the DSMB for review.  

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13.3 Data Safety Monitoring Board (DSMB) 
Following recommendations outlined in guidance documents on data monitoring committees, the 
Sponsor has chosen to establish a DSMB safety oversight committee for the PILLAR-XT study.  
Details related to the responsibilities of the DSMB will be documented in a charter.  
 
The DSMB will be responsible for assessing study stopping (enrollment hold) rules related to the 
occurrence of the following events: 
• 
Brainstem herniation  
• 
Death 
• 
Early termination of Neurapheresis due to neurological decline in subjects presenting as 
Hunt & Hess IV 
• 
CSF leak due to device failure 
Enrollment will be temporarily placed on hold under the following circumstances; 
• 
if there are two separate occurrences of an individual event listed above or;  
o however, if two separate occurrences of the “early termination of Neurapheresis 
due to neurological decline in subjects presenting as Hunt & Hess IV” is met, only 
enrollment of Hunt & Hess IV subjects will be placed on hold. 
• 
if one of the events above is determined by the DSMB to be an unanticipated adverse 
device effect 
The Sponsor will perform an investigation of the event(s) and report to appropriate regulatory 
authorities.  Enrollment may be re-initiated following Sponsor, DSMB and regulatory authority 
approval.  Additionally, the DSMB will review any events determined by the medical monitor to 
be unanticipated adverse device effects. 
13.4 Responsibilities 
The Investigator is responsible for ensuring complete oversight of the study and, that the study is 
conducted in accordance with 21 CFR§ 812, the Clinical Study Agreement, the Clinical Protocol, 
ethical principles that have their origins in the Declaration of Helsinki, any conditions of approval 
imposed by the reviewing IRB, and prevailing local laws and/or regulations, whichever affords the 
greater protection to the subject. 
The Investigator’s responsibilities include, but are not limited to, the following:  
• 
Prior to beginning the study, sign the Investigator Agreement documenting his/her agreement 
to conduct the study in accordance with the Clinical Protocol 
• 
Provide his/her qualifications and experience to assume responsibility for the proper conduct 
of the study and that of key members of the center team, signed up-to-date curriculum vitae or 
other relevant documentation and disclose potential conflicts of interest, including financial, 
that may interfere with the conduct of the clinical study or interpretation of results 
• 
Ensure that adequate investigation site personnel and facilities are in place and site personnel 
are trained 
• 
Make no changes in or deviate from this Clinical Protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any deviation from 
the approved plan that occurred during the course of the clinical investigation 

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• 
Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per regulatory requirements 
• 
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports 
• 
Record, report, and assess (seriousness and relationship to the device/procedure) every adverse 
event  
• 
Report to MNeuro, per the protocol requirements, all SAEs and device deficiencies 
• 
Report to MNeuro all UADE’s 
• 
Supply Minnetronix with any additional requested information related to the safety reporting 
of a particular event 
• 
Maintain the device/system accountability logs and control of the device/system, ensuring that 
the investigational device/system and the accessories are used only by authorized/designated 
users and in accordance with this Clinical Protocol and the IFU  
• 
Allow the Sponsor or its representative to perform monitoring and auditing activities, and be 
accessible to the monitor and respond to questions during monitoring visits 
• 
Allow and support regulatory authorities and the IRB when performing auditing activities 
• 
Ensure that informed consent is obtained in accordance with this Clinical Protocol and 
reviewing IRB requirements 
• 
Provide adequate medical care to a subject during a subject’s participation in a clinical study 
in the case of adverse events, as described in the ICF 
• 
Inform the subject of the nature and possible cause of any adverse events experienced 
• 
Inform the subject of any new significant findings occurring during the clinical investigation, 
including the need for additional medical care that may be required 
• 
Provide the subject with well-defined procedures for possible emergency situations related to 
the clinical study, and make the necessary arrangements for emergency treatment 
• 
Ensure that clinical medical records are clearly marked to indicate that the subject is enrolled 
in this clinical study 
• 
Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided with 
some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided) 
• 
Inform, with the subject’s approval or when required by national regulations, the subject’s 
personal physician about the subject’s participation in the clinical investigation 
• 
Ensure that maintenance and calibration of the equipment relevant for the assessment of the 
clinical investigation is appropriately performed and documented, where applicable. 
13.4.1 Investigators Delegation of Authority 
When specific tasks are delegated by an Investigator, included but not limited to conducting the 
informed consent process, the Investigator is responsible for providing appropriate training and 
documentation thereof, and adequate supervision of those to whom tasks are delegated.  The 
Investigator is accountable for regulatory violations resulting from failure to adequately supervise 
the conduct of the clinical study.  

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13.4.2 Investigator Reporting Responsibilities 
Table 13 below outlines the Investigators Reporting responsibilities as prescribed in 21 CFR§ 
812.150 and required by the sponsor.  
Table 6: Investigator Reporting Responsibilities 
Event 
Classification 
Communication Method 
Communication Timeline 
UADE 
• 
Complete AE CRF with all available new and 
updated information 
• Within 5 business days of first 
becoming aware of the event 
SAE  
• Complete AE CRF with all available new and 
updated information 
• Within 5 business days of first 
becoming aware of the event or as 
per local/regional regulations 
• Reporting required through the end 
of the study 
• Provide all relevant source documentation 
(unidentified) for reported event 
• When documentation is available 
Adverse Event 
Complete AE CRF, which contains such 
information as date of AE, treatment of AE 
resolution, assessment of seriousness and 
relationship to the device 
• No later than 10 working days after 
becoming aware of the information 
• Reporting required through 30 day 
follow-up  
Withdrawal of 
IRB approval 
Notification to Sponsor 
• Within 5 working days 
Progress Report 
Provide to Sponsor 
• Per annum based on date of IRB 
approval 
Non-consent of 
Subject 
Notification to Sponsor 
• Sponsor and IRB notification within 
5 business days of device being used 
Final Report 
Provide to Sponsor and IRB 
• Within 3 months after study 
termination or completion of the 
Investigators part of the 
investigation.  
 
 
 

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13.5 Sponsor Responsibilities 
MNeuro shall adhere to all Sponsor responsibilities outlined in 21 CFR§ 812. 
All information and data sent to MNeuro or its delegate concerning subjects or their participation 
in this study will be considered confidential.  Only authorized MNeuro personnel or a designated 
representative will have access to these confidential records. Authorized regulatory personnel have 
the right to inspect and copy all records pertinent to this study.  Study data collected during this 
study may be used by MNeuro for the purposes of this study, publication, and to support future 
research and/or other business purposes.  All data used in the analysis and reporting of this study 
will be without identifiable reference to specific subject name. 
MNeuro will keep subjects’ health information confidential in accordance with all applicable laws 
and regulations.  MNeuro may use subjects’ health information to conduct this research, as well as 
for additional purposes, such as overseeing and improving the performance or design of its device, 
new medical research and proposals for developing new medical products or procedures, and other 
business purposes.  
13.6 Institutional Review Board Approval 
Prior to gaining Approval-to-Enroll status, the investigational center will provide to the Sponsor or 
their delegate documentation verifying that their IRB is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory requirements.   
A copy of the written IRB approval of the protocol (or permission to conduct the study), Informed 
Consent Form and applicable signed agreements, must be received by the sponsor or their delegate 
before recruitment of subjects into the study.  Prior approval must also be obtained for other 
materials related to subject recruitment or which will be provided to the subject. 
Annual IRB renewals will be obtained throughout the duration of the study as required by 
local/country or IRB requirements.  Copies of the Investigator’s reports and the IRB continuance 
of approval must be provided to the sponsor or their delegate. 
14. PUBLICATION POLICY 
MNeuro shall adhere to the Uniform Requirements of the International Committee of Medical 
Journal Editors (ICMJE; http://www.icmje.org).  In order to ensure the public disclosure of study 
results in a timely manner, while maintaining an unbiased presentation of study outcomes, 
MNeuro personnel may assist authors and Investigators in publication preparation provided the 
following guidelines are followed. 
• 
MNeuro involvement in the publication preparation should be discussed with the Coordinating 
Principal Investigator(s) at the onset of the project 
• 
The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  These authors are determined by enrollment status 
and/or overall contribution to the study.  Study non-compliance may be taken into account for 
authorship determination. 
 
 

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APPENDIX A: PROTOCOL ABBREVIAITONS 
Table 7: Protocol Abbreviations 
Abbreviation 
Term 
AE 
Adverse Event 
CRF 
Case Report Form 
CFS 
Clinical Field Specialist 
CSF 
Cerebrospinal Fluid 
CT 
Computed Tomography 
CTA 
Computed Tomography Angiogram 
DSMB 
Data Safety Monitoring Board 
GCP 
Good Clinical Practice 
GCS 
Glasgow Coma Scale 
GOSE 
Glasgow Outcome Scale Extended 
EVD 
External Ventricular Drain 
H&H  
Hunt and Hess 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICP 
Intracranial Pressure 
ICU 
Intensive Care Unit 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISO 
International Standards Organization 
IVH 
Intraventricular Hemorrhage 
LAR 
Legally Authorizes Representative 
LOS 
Length of Stay 
MRA 
Magnetic Resonance Angiogram 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 
OTB 
Outside-the-body 
OTS 
Off-The-Shelf 
OTW 
Over-The-Wire 
RBC 
Red Blood Cell 
SAE 
Serious Adverse Event 
SAH 
Subarachnoid Hemorrhage 
SAS 
Subarachnoid Space 
SNF 
Skilled Nursing Facility 
SOC 
Standard of care 
TCD 
Transcranial Doppler 
TCU 
Transitional Care Unit 
UADE 
Unanticipated Adverse Device Effect 
WFNS 
World Federation of Neurosurgeons 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX B:  NEUROLOGIC ASSESSMENTS/GRADING INDICIES 
Table 8: Glasgow Coma Scale 
Activity 
Rating                                                                                           Score 
EYE OPENING 
 
1= Even to supra-orbital pressure 
2= Pain from sternum/limb/supra-orbital pressure 
3= Non-specific response, not necessarily to command 
4= Eyes open, not necessarily aware 
  Never 
  To pain 
  To verbal stimuli 
  Spontaneously 
                                                                                              Eye Score (         ) 
MOTOR RESPONSE 
 
1= No response 
2= Extension(decerebrate rigidity) 
3= Abnormal flexion(discorticate rigidity) 
4= Flexion withdrawal 
5= Arm attempts to remove supra-orbital/chest pressure 
6= Follows simple commands 
  None 
  Extension 
  Flexor response 
  Withdrawal 
  Localizes pain 
  Obeys commands 
                                                                                            Motor Score (         ) 
VERBAL RESPONSE 
 
1= No response 
2= Incomprehensible sounds 
3= Inappropriate words 
4= Disoriented and converses 
5= Oriented and converses 
  None 
  Incomprehensible 
  Inappropriate 
  Confused 
  Oriented 
                                                                                Verbal Score (         ) 
                                                                                Total (3-15): 
 
Table 9: Modified Fisher Grade Classifications 
Grade 
Appearance of Hemorrhage 
0 
No SAH, or IVH 
1 
Thin diffuse or focal SAH, no IVH  
2 
Thin diffuse or local SAH, with IVH 
3 
Thick focal or diffuse SAH, no IVH 
4 
Thick local or diffuse SAH with IVH 
 
 
Table 10: WFNS Grading System for Subarachnoid Hemorrhage 
Glasgow Coma Scale 
Motor Deficit 
Grade 
15 
Absent 
1 
13-14 
Absent 
2 
13-14 
Present 
3 
7-12 
Present or Absent 
4 
3-6 
Present or Absent 
5 
 
Table 11: Hunt & Hess Scale  
Description 
Grade 
Asymptomatic, mild headache, slight nuchal rigidity 
1 
Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy 
2 
Drowsiness/confusion, mild focal neurologic deficit 
3 
Stupor, moderate-sever hemiparesis 
4 
Coma, decerebrate posturing 
5 
                                                                                                                                  Grade (1-5) 
 

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Table 12: Glasgow Outcome Scale Extended  
Score 
Description 
1 
DEATH 
2 
VEGETATIVE STATE 
Unable to obey commands or say words with only reflex responses but with periods of spontaneous 
eye opening 
3 
SEVERE DISABILITY - Lower 
Patient fully dependent for all activities of daily living.  Requires assistance to be available 
constantly.  Unable to be left alone at night.  
4 
SEVERE DISABILITY - Upper 
Can be left alone for up to 8 hours but remains dependent. Unable to use public transport or shop by 
themselves 
5 
MODERATE DISABILITY - Lower 
Able to return to work in sheltered workshop or noncompetitive job.  Rarely participates in social and 
leisure activities. Ongoing daily psychological problems (quick temper, anxiety, mood swings, 
depression) 
6 
MODERATE DISABILITY - Upper 
Able to return to work but at a reduced capacity.  Participates in social and leisure activities less than 
half as often.  Weekly psychological problems.  
7 
GOOD RECOVERY - Lower 
Return to work.  Participates in social and leisure activities a little less and has occasional 
psychological problems 
8 
GOOD RECOVERY - Upper 
Full recovery with no current problems relating to the injury 
                                                                                                                                             Total (1-5)_________ 
Table 13: Modified Rankin Scale 
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 
Moderate 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 
Dead 
                                                                                                                                             Total (0-6)  ________ 
 
 
 
 
 
 

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Table 14: Peripheral Neurological Assessment 
Leg Strength 
Scale 
Score 
(0-10) 
RIGHT 
+5 Full ROM, Full Strength 
+4 Full ROM, Less than normal Strength 
+3–Can raise extremity but not  against 
resistance 
+2-Can move extremity but not lift it 
+1-Slight movement 
0-No movement 
 
 
 
 
(           ) 
LEFT 
+5 Full ROM, Full Strength 
+4 Full ROM, Less than normal Strength 
+3–Can raise extremity but not  against 
resistance 
+2-Can move extremity but not lift it 
+1-Slight movement 
0-No movement 
 
 
 
 
(            ) 
Drift-Leg 
Scale 
Score 
(0-2) 
RIGHT 
Present:  Yes (0) or No (+1) 
 
LEFT 
Present:  Yes (0) or No (+1) 
 
Sensory-Leg 
Scale 
Score 
(0-8) 
RIGHT 
+2 Intact 
+1 Decreased to light touch 
0 Absent 
 
LEFT 
+2 Intact 
+1 Decreased to light touch 
0 Absent 
 
Chest 
+2 Intact 
+1 Decreased to light touch 
0 Absent 
 
Umbilicus 
+2 Intact 
+1 Decreased to light touch 
0 Absent 
 
Sensory-
Proprioception 
Scale 
Score 
(2-4) 
Right Leg 
+2 Intact 
+1 Decreased 
 
Left Leg 
+2 Intact 
+1 Decreased 
 
Total Score 
Total Score 
(2-24) 
 
 
 
 
 
 
 
 
 
 

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Table 15: The Barthel Index 
Activity 
Score 
Feeding 
0=unable 
5=needs help cutting, spreading butter, etc, or requires modified diet 
10=independent 
 
Bathing 
0=dependent 
5=independent (or in shower) 
 
Grooming 
0=needs help with personal care 
5=independent face/hair/teeth/shaving (implements provided) 
 
Dressing 
0=dependent 
5=needs help but can do about half unaided 
10=independent (including buttons, zips, laces, etc.) 
 
Bowels 
0=incontinent (or needs to be given enemas) 
5=occasional accident 
10=continent 
 
Bladder 
0=incontinent, or catheterized and unable to manage alone 
5=occasional accident 
10=continent 
 
Toilet Use 
0=dependent  
5=needs some help, but can do so something alone 
10=independent (on and off, dressing, wiping) 
 
Transfers (Bed to Chair and Back) 
0=unable, no siting balance 
5=major help (one or two people, physical) can sit 
10=minor help (verbal or physical) 
15=independent 
 
Mobility(On Level Surfaces) 
0=immobile or < 50 yards 
5=wheelchair independent, including coroners, > 50 yards 
10=walks with help of one person (verbal or physical) 
15=independent (but may use any aid; for example, stick) > 50 yards 
 
Stairs 
0=unable 
5=needs help (verbal, physical, carrying aid) 
10=independent 
 
                                                                                        Total (0-100)