Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas With TRUFILL® n-BCA
Phase: NA
Conditions: Chronic Subdural Hematoma
Sponsor: Cerenovus, Part of DePuy Synthes Products, Inc.

  Cerenovus 
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CLINICAL STUDY PROTOCOL 
Middle Meningeal Artery EMbolization for the Treatment of 
SuBduRal HemAtomas with TRUFILL® n-BCA 
MEMBRANE STUDY
Protocol Number:  CNV_2020_01 
Version: 4.0 
September 25, 2024 
History of Changes 
Version Date 
Description 
Version 1.0— January 25, 2021 
Original Document  
Version 2.0 – December 12, 2022
Amendment 1
Version 3.0 – January 17, 2024 
Amendment 2 
Version 4.0 – September 25, 2024 
Amendment 3 
Sponsor:  Cerenovus, part of DePuy Synthes Products, Inc. 
   31 Technology Dr.  
   Irvine, CA  92618 USA 
This document is a confidential communication of Cerenovus.  The recipient agrees that no information 
contained herein will be published or disclosed without written approval of Cerenovus.  This document may be 
disclosed to appropriate institutional review boards or duly authorized representatives of regulatory 
authorities as appropriate; under the condition that confidentiality is requested. 
NCT04816591

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Table of Contents 
1. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE.................................................. 20 
1.1  
Background Information ............................................................................................................ 20 
1.2  
Current Treatment Options ....................................................................................................... 20 
1.2.1.  
Conservative Medical Management.......................................................................................... 20 
1.2.2.  
Surgical Intervention ................................................................................................................. 21 
1.3. 
 Neurovascular Embolization .................................................................................................... 22 
1.4.  
Rationale ................................................................................................................................... 24 
1.5.   
Previous Experience ................................................................................................................. 24 
1.5.1.  
Bench and Animal Validation .................................................................................................... 24 
1.5.2.  
Study Product ............................................................................................................................ 25 
1.6.  
Potential Risks and Benefits ..................................................................................................... 26 
1.6.1.  
Known Potential Risks .............................................................................................................. 26 
1.6.2.  
Minimization of Risks ................................................................................................................ 27 
1.6.3.  
Potential Benefits ...................................................................................................................... 28 
1.6.4.  
Risk-Benefit Rationale .............................................................................................................. 28 
2.  
OBJECTIVES AND PURPOSE ............................................................................................................. 28 
2.1. Objectives ............................................................................................................................................ 28 
3.  
STUDY DESIGN AND ENDPOINTS .................................................................................................... 28 
3.1. Description of the Study Design .......................................................................................................... 29 
3.1.1. Primary Endpoint .............................................................................................................................. 29 
3.1.2. 
Secondary Endpoints – Effectiveness ...................................................................................... 29 
 
SUBJECTS REQUIRING A SURGICAL PROCEDURE ON THE CSDH WITHIN 12 MONTHS ................................. 30 
 
MEAN CHANGE IN HEMATOMA VOLUME AT 6 MONTHS COMPARED TO BASELINE, AS ASSESSED BY AN 
INDEPENDENT CORE LABORATORY ..................................................................................................................... 30 
3.1.1.  
Secondary Endpoints – Safety .................................................................................................. 30 
3.1.4.   
Secondary Endpoints – Health Economics ............................................................................... 30 
4.  
STUDY POPULATION ........................................................................................................................... 30 
4.1 
Participant Inclusion Criteria ..................................................................................................... 31 
4.2.  
Participant Exclusion Criteria .................................................................................................... 31 
4.3. 
Study Duration .......................................................................................................................... 32 
4.4. Number of Subjects ............................................................................................................................. 33 
4.5. Number of Sites ................................................................................................................................... 33 
4.6. Participant Withdrawal or Termination ................................................................................................ 33 
4.6.1. Reasons for Withdrawal or Termination ........................................................................................... 33 
4.6.2. Handling of Participant Withdrawals or Termination ........................................................................ 33 
5. STUDY DEVICE .......................................................................................................................................... 33 
5.1. Study Device Description .................................................................................................................... 33 
5.1.1. Device Acquisition ............................................................................................................................ 33 
5.1.2. Device Appearance, Packaging, and Labeling Description ............................................................. 34 
5.1.3. 
Device Training Requirements and Investigator Experience .................................................... 35 
5.1.4. Device Storage and Stability, Preparation and Instructions for Use ................................................ 35 
5.1.5. Device Returns ................................................................................................................................. 35 
6.  
STUDY PROCEDURES .......................................................................................................................... 36 
6.1.  Independent Imaging Core Lab for Image Evaluation ....................................................................... 36 
6.2.  Concomitant Medications, Treatments, and Procedures ................................................................... 37 
6.3.   Neurological and Cognitive Evaluations ............................................................................................ 37 
6.4.   Medical Resource Utilization and Health Economics ........................................................................ 38 
6.5   Viz RECRUIT...................................................................................................................................... 38 

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7.  
STUDY SCHEDULE ............................................................................................................................... 38 
7.1.  
Screening (0-30 days prior to randomization) ........................................................................... 38 
7.2. Pre-randomization through Discharge ................................................................................................ 40 
7.2.1. Surgical Cohort ................................................................................................................................. 40 
7.2.1.1.  
Surgery ...................................................................................................................................... 40 
7.2.1.2. 
Pre-Randomization ................................................................................................................... 40 
7.2.1.3.  
Randomization .......................................................................................................................... 41 
7.2.1.4. 
Day 0 (within 10 days of surgery): ............................................................................................ 41 
7.2.1.4.1 eMMA Arm  Study Embolization Procedure (within 10 days of surgery) .................................. 41 
7.2.1.4.2. Surgery Alone Arm: Telephone or In-person Visit (within 10 days of surgery) ......................... 42 
7.2.1.5. 
Discharge .................................................................................................................................. 43 
7.2.2. 
Non-Surgical Cohort ................................................................................................................. 43 
7.2.2.1. 
Pre-Randomization ................................................................................................................... 43 
7.2.2.2. 
Randomization .......................................................................................................................... 44 
7.2.2.3. 
Day 0: (within 10 days of randomization) .................................................................................. 44 
7.2.2.3.2. NSMM Arm Only: Follow-up Visit (within 10 days of randomization ......................................... 45 
7.2.2.4. 
Discharge (eMMA arm only) ..................................................................................................... 45 
7.3. 
Follow-up – All Subjects ............................................................................................................ 45 
7.3.1. 
1 Month Follow-up (±14 days) – Clinic or Phone/Telehealth Visit ............................................ 46 
7.3.2. 
3 Months Follow-up (±14 days) – Clinic or Phone/Telehealth Visit .......................................... 46 
7.3.3. 
6 Months Follow-up (±30 days) – Clinic Visit ............................................................................ 47 
7.3.4. 
1 Year Follow-up (± 60 days) – Clinic or Phone/Telehealth Visit ............................................. 47 
7.4. 
Unscheduled Visit ..................................................................................................................... 48 
7.5. 
Post-Randomization Surgical Procedure/ Re-Operation .......................................................... 48 
7.6. 
Early Termination ...................................................................................................................... 49 
7.7. 
Lost to Follow-up ....................................................................................................................... 50 
7.8. 
Schematic of Study Design  ...................................................................................................... 51 
7.9. 
Schedule of Assessments ......................................................................................................... 53 
8. 
ASSESSMENT OF SAFETY .................................................................................................................. 55 
8.1. 
Specific Safety Parameters ....................................................................................................... 55 
8.1.1. 
Adverse Event (AE) .................................................................................................................. 55 
8.1.2. 
Serious Adverse Event (SAE) ................................................................................................... 55 
8.1.3. 
Adverse Device Effect (ADE) .................................................................................................... 56 
8.1.4. 
Serious Adverse Device Effect (SADE) .................................................................................... 56 
8.1.5. 
Unanticipated Serious Adverse Device Effect (USADE) .......................................................... 56 
8.1.6. 
Unanticipated Adverse Device Effect (UADE) .......................................................................... 56 
8.1.7. 
Device Deficiency, Device Malfunction, and Use Error ............................................................ 56 
8.2 
Classification of an Adverse Event ........................................................................................... 57 
8.2.1. 
Severity of Event ....................................................................................................................... 57 
8.2.2. 
Relationship to Study Device and/or Procedure ....................................................................... 58 
Note: Related events are defined as those with causal, probable and possible relationship to the event. 59 
8.2.3. 
Outcome .................................................................................................................................... 59 
8.3. 
Time Period and Frequency for Adverse Event Assessment and Follow-up ........................... 59 
8.4. 
Reporting Procedures ............................................................................................................... 60 
8.4.1. 
Adverse Event Documentation and Reporting Requirements .................................................. 60 
8.4.2. 
Unanticipated Adverse Device Effect Reporting ....................................................................... 61 
8.5. 
Device Complaints, Failures, Deficiencies, and Malfunctions .................................................. 61 
8.6. 
Clinical Events Committee ........................................................................................................ 61 
8.7. 
Data Monitoring Committee ...................................................................................................... 62 
9. 
CLINICAL MONITORING ................................................................................................................... 62 
9.1 
Site Selection ............................................................................................................................ 63 
10.0 STATISTICAL METHODOLOGY ....................................................................................................... 63 
10.1 
Analysis Sets ............................................................................................................................. 63 

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10.2 
Randomization and Blinding Procedures .................................................................................. 64 
10.3 
Levels of Significance ............................................................................................................... 64 
10.4 
Sample Size Justification .......................................................................................................... 64 
10.5 
Analyses to be Conducted ........................................................................................................ 65 
10.5.1. 
General Conventions ................................................................................................................ 65 
10.5.2. 
Disposition of Study Subjects ................................................................................................... 65 
10.5.3. 
Demographics and Baseline Characteristics ............................................................................ 66 
10.5.4. 
Procedural and Post-Procedural Characteristics ...................................................................... 66 
10.5.5. 
Primary Endpoint and Secondary Endpoint Analyses and Associated Hypotheses ................ 66 
10.5.5.1. Primary Endpoint and Associated Hypotheses ......................................................................... 66 
10.5.5.2. Secondary Endpoints and Associated Hypotheses .................................................................. 67 
10.5.5.3. Other Secondary Endpoint Analyses – Effectiveness .............................................................. 68 
10.5.5.4. Secondary Endpoint Analyses – Safety .................................................................................... 69 
10.5.5.5. Secondary Endpoint Analyses – Health Economics ................................................................. 70 
10.5.5.6. Safety Analyses ........................................................................................................................ 70 
10.5.5.7. Plans for Interim Analyses ........................................................................................................ 71 
10.5.5.8. Handling of Missing Data .......................................................................................................... 71 
10.5.5.9. Sensitivity Analyses .................................................................................................................. 72 
10.5.5.10. Subgroup Analyses ................................................................................................................... 72 
10.5.5.11. Sex Specific Analyses ............................................................................................................... 72 
10.5.5.12. Assessment of Site/Region Homogeneity ................................................................................ 72 
11. ETHICS AND PROTECTION OF HUMAN SUBJECTS ................................................................... 72 
11.1 
Ethical Standard ........................................................................................................................ 73 
11.2. 
Institutional Review Board / Ethics Committee ......................................................................... 74 
11.3. 
Informed Consent Process ....................................................................................................... 74 
11.3.1. 
Consent and Other Informational Documents Provided to Participants ................................... 74 
11.3.2. 
Consent Procedures and Documentation ................................................................................. 74 
11.3.3. 
Participant and Data Confidentiality .......................................................................................... 75 
12. QUALITY ASSURANCE AND QUALITY CONTROL ..................................................................... 75 
13. DATA HANDLING AND RECORD KEEPING .................................................................................. 76 
13.1 
Data Collection and Management Responsibility ..................................................................... 76 
13.1.1. 
Electronic Case Report Forms .................................................................................................. 76 
13.1.2. 
Source Documentation ............................................................................................................. 76 
13.1.3. 
Study Records ........................................................................................................................... 77 
13.1.4. 
Health Economic Data .............................................................................................................. 77 
13.1.5. 
Data Reporting .......................................................................................................................... 78 
13.1.6. 
Data Verification and Review .................................................................................................... 78 
13.1.7. 
Final Data Analysis ................................................................................................................... 78 
13.2. 
Study Record Retention and Archiving ..................................................................................... 78 
14. PROTOCOL DEVIATIONS ................................................................................................................... 79 
15. DATA AND PUBLICATION POLICY ................................................................................................. 79 
16. STUDY ADMINISTRATION ................................................................................................................. 79 
16.1 
Study Registration ..................................................................................................................... 79 
16.2. 
Steering Committee .................................................................................................................. 79 
17. CONFLICT OF INTEREST ................................................................................................................... 80 
18. BIBLIOGRAPHY .................................................................................................................................... 81 
 

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List of Figures and Tables 
54TFIGURE 1 – TRUFILL® N-BUTYL CYANOACRYLATE  (N-BCA) LIQUID EMBOLIC SYSTEM ... 34 
54TTABLE 1 - INTENSITY OR SEVERITY DEFINITIONS ........................................................................... 57 
54TTABLE 2 - ADVERSE EVENT CAUSALITY CLASSIFICATIONS ......................................................... 58 
54TTABLE 3 - ADVERSE EVENT OUTCOME CLASSIFICATIONS ........................................................... 59 
54TTABLE 4 - ADVERSE EVENT REPORTING REQUIREMENTS ............................................................ 60 
54TTABLE 5 – ASSUMPTIONS OF EVENT PROBABILITY OF PRIMARY ENDPOINT IN SURGICAL 
COHORT ........................................................................................................................................................... 65 
54TTABLE 6 - ASSUMPTIONS OF EVENT PROBABILITY OF PRIMARY ENDPOINT IN NON-
SURGICAL MEDICAL MANAGEMENT COHORT ................................................................................. 65 
 
54TLIST OF ABBREVIATIONS ............................................................................................................................ 6 
 
 

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LIST OF ABBREVIATIONS  
 
ADE  
Adverse Device Effect  
ADP  
Adenosine Diphosphate 
AE 
 
Adverse Event 
AEDs  
Antiepileptic Drugs 
AI 
 
Artificial Intelligence 
ASADE 
Anticipated Serious Adverse Device Effect 
AT 
 
As Treated  
AVMs  
Arteriovenous Malformations 
CEC 
 
Clinical Events Committee 
CFR 
 
Code of Federal Regulations 
CMH  
Cochran–Mantel–Haenszel 
cSDH  
Chronic Subdural Hematoma 
CT 
 
Computed Tomography 
DMC  
Data Monitoring Committee 
DSA  
Digital Subtraction Angiography 
EC 
 
Ethics Committee 
eCRF   
Electronic Case Report Form 
ECA  
External Carotid Artery 
EDC  
Electronic Data Capture 
eMMA 
Middle Meningeal Artery Embolization 
EVOH  
Ethylene-Vinyl Alcohol 
FDA  
Food and Drug Administration 
GCP 
 
Good Clinical Practice 
GCS 
 
Glasgow Coma Scale 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
 
Informed Consent Form 
ICU 
 
Intensive Care Unit 
IDE 
 
Investigational Device Exemption  
IFU 
 
Instructions for Use 
IRB 
 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGS  
Markwalder Neurological Grading Scale 
ITT 
 
Intent-to-Treat 
MM 
 
Medical Management 
MMA  
Middle Meningeal Artery 
MMSE 
Mini-Mental State Exam 
MRI 
 
Magnetic Resonance Imaging 
mRS  
Modified Rankin Scale 
MRU  
Medical Resource Utilization  
n-BCA  
n-Butyl Cyanoacrylate 
NSMM 
Non-Surgical Medical Management 
OUS  
Outside of the United States 
PHI 
 
Protected Health Information 
PI 
 
Principal Investigator  
PP 
 
Per Protocol 
PVA  
Polyvinyl Alcohol 

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QA 
 
Quality Assurance 
QC 
 
Quality Control 
SADE  
Serious Adverse Device Effect  
SAE 
 
Serious Adverse Event 
SAP 
 
Statistical Analysis Plan 
SAS 
 
Statistical Analysis Software 
SDH  
Subdural Hematoma 
SDV  
Source Data Verification 
SEPS  
Subdural Evacuating Port System 
SOC 
 
Standard of Care 
SOP 
 
Standard Operating Procedure 
UADE  
Unanticipated Adverse Device Effect 

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PROTOCOL AGREEMENT AND STATEMENT OF COMPLIANCE FORM 
  STUDY NAME AND NUMBER: MEMBRANE – CNV_2020_01 
 
  STUDY TITLE: A Prospective, Multi-Center, Randomized Controlled Pivotal Study to Evaluate the 
Safety and Effectiveness of TRUFILL® n-BCA Embolization of the Middle Meningeal Artery for 
the Treatment of Subdural Hematoma 
 
VERSION NUMBER: 4.0 
 
VERSION DATE: September 25, 2024 
 
I have read this protocol and agree to conduct this clinical study in accordance with the design and specific 
provisions outlined herein. I understand the protocol, and I understand I am solely responsible to ensure the 
investigation is conducted in accordance with Good Clinical Practice (GCP), the ethical principles that have their 
origin in the Declaration of Helsinki, ISO 14155 requirements, applicable FDA regulations (21 CFR Parts 812, 11, 
50, 54 and 56), local regulations, the signed clinical study contract with Sponsor, and with the protocol outlined 
herein. I will conduct this study as outlined herein and will make reasonable effort to complete the study within the 
time period designated by the Sponsor.    
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who will assist 
in the conduct of this study. I will discuss this material with them to ensure they are fully informed regarding the 
device and the conduct of the study. I will ensure delegation to qualified individuals. 
I will fulfill the requirements of my Institutional Review Board (IRB), or other oversight committee, to ensure 
complete and continual oversight of this clinical investigation. I will use an Informed Consent Document approved 
by the Sponsor and my reviewing IRB/EC.  
I agree to report all information or data in accordance with the protocol and I agree to report adverse events as 
defined in this protocol to the Sponsor, and comply with all adverse event reporting requirements of my reviewing 
IRB/EC and local regulations.  I agree to permit the Sponsor, its authorized representatives, my reviewing IRB/EC, 
the FDA, and any regulatory authority/body access to all records relating to the clinical investigation. 
The below signature confirms I have read and understood this protocol and its associated amendments or 
attachments, and will accept respective revisions or amendments provided by the Sponsor. 
     
 
 
 
 
 
Principal Investigator (PI) 
Name (PRINT) 
 
 
 
 
Signature 
 
Date 
   
 
 
 
Site Name 
 
  
 
 
 
Address 
 
 

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PROTOCOL SUMMARY 
Full Title & Protocol Number Middle Meningeal Artery EMbolization for the Treatment of 
SuBduRal HemAtomas with TRUFILL® n-BCA (Protocol #: 
CNV_2020_01) 
Short Title 
MEMBRANE  
IDE number  
G200310 
Sponsor 
CERENOVUS, part of DePuy Synthes Products, Inc.  
31 Technology Drive  
Irvine, CA 92618 
Study Device 
TRUFILL n-BCA Liquid Embolic System (TRUFILL n-BCA) 
Indication 
TRUFILL n-BCA Liquid Embolic System is intended for 
embolization in the neurovasculature for the treatment of chronic 
subdural hematoma (cSDH). 
 
Study Device Description 
The TRUFILL n-Butyl Cyanoacrylate Liquid Embolic  
System is an artificial embolization device, comprised of  
TRUFILL n-BCA, TRUFILL Ethiodized Oil and TRUFILL 
Tantalum Powder. The TRUFILL System is used under fluoroscopic 
guidance via superselective catheter delivery to obstruct or reduce 
blood flow. Upon contact with body fluids or tissue, the mixture 
polymerizes into a solid material. The n-BCA is a clear, free- flowing 
liquid that polymerizes via an anionic mechanism. Ethiodized oil is 
used as a radiopaque polymerizing retardant. Radiopacity of the n-
BCA mixture is accomplished by adding ethiodized oil and tantalum 
powder to the n-BCA. 
 
Study Design 
This is a prospective, multi-center, open-label, randomized 
controlled study in which up to 376 subjects will be randomized to 
receive standard of care (SOC) alone or SOC and TRUFILL n-BCA 
MMA embolization for the treatment of cSDH. Subjects will be 
followed at 1 month, 3 months, 6 months, and 1 year post-procedure.  
The primary endpoint will be evaluated at 6 months post-procedure. 
The study is designed to evaluate the effectiveness and safety of 
MMA in two cohorts – a surgical cohort and a non-surgical cohort. 
 
Sample Size 
Up to 376 randomized subjects at up to 35 sites 
Study Population 
Patients presenting with a previously untreated symptomatic chronic 
subdural hematoma not requiring emergent surgery/decompression 
Study Duration 
Start date:   Q1, 2021 
End date: Q3, 2025 
Procedure(s) description 
Patients presenting with a cSDH will be assessed by the treating 
neurosurgeon to determine whether the patient will undergo either 
surgery or non-surgical management. Patients will then be screened 
for trial enrollment based on the protocol inclusion and exclusion 
criteria. Patients who meet all eligibility criteria and consent to 

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participate in the MEMBRANE trial will be randomized 1:1 to 
undergo embolization of the MMA plus standard of care vs SOC 
alone (either surgery or non-surgical management). A computed 
tomography (CT) scan must be performed within 36 hours prior to 
the randomization to demonstrate stability of the hematoma.  
Stability is defined as no worsening of midline shift or increase in 
the size of the cSDH from the screening image that results in new or 
worsening clinical symptoms.   
 
Surgery Cohort: 
All patients will undergo the surgical procedure for SDH 
decompression prior to randomization. Post the surgical procedure 
patients will be randomized to MMA embolization (eMMA) or 
surgery alone.  
Surgery + MMA Embolization  
For subjects randomized to surgery and MMA embolization, the 
MMA embolization will occur using TRUFILL n-BCA.  The MMA 
embolization procedure will occur within 10 days after the surgery 
and within the same hospital admission*. A CT scan to demonstrate 
stability of the hematoma must be performed within 36 hours prior 
to randomization.   
Surgery alone  
Subjects randomized to surgery alone will receive no further 
intervention.  
*Subjects may be transferred within the same hospital network for 
the study MMA embolization procedure.  
Non-Surgical Cohort: 
Patients assigned to the Non-Surgical cohort will be randomized to 
non-surgical 
medical 
management 
(NSMM) 
plus 
MMA 
embolization or non-surgical medical management alone. 
Non-Surgical 
Medical 
Management 
(NSMM) 
+ 
MMA 
Embolization 
For subjects randomized to NSMM and MMA embolization, the 
MMA embolization will occur using TRUFILL n-BCA.  The MMA 
embolization procedure may occur up to 10 days after 
randomization. A CT scan must be performed within 36 hours prior 
to randomization.  
Non-Surgical Medical Management 
Subjects randomized to NSMM will be managed per non-surgical 
medical management SOC including: modifying/stopping oral 
anticoagulation therapy, initiation of medication i.e. statins (if 
applicable), observation, repeat imaging, and life-style modification. 

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NOTE: Subjects randomized to the non-embolization SOC groups, 
either surgery alone or NSMM, CANNOT undergo MMA 
embolization during the follow up period (i.e. crossover). 
Primary Objective 
The objective of this study is to evaluate the safety and 
effectiveness of TRUFILL n-BCA for MMA embolization in 
patients presenting with a cSDH compared to patients treated with 
standard of care management. 
Primary Endpoints 
Primary effectiveness endpoint: Residual or re-accumulation of the 
cSDH (>10 mm) at 6 months as assessed by an independent core 
laboratory OR re-operation or surgical procedure on the cSDH 
within 6 months post randomization. 
 
Primary safety endpoint: Occurrence of all adverse events (AEs) 
through 6 months 
 
Secondary Endpoints 
Secondary Effectiveness Endpoints –  
1. Mean change in hematoma volume at 3 and 12 months 
compared to baseline, as assessed by an independent core 
laboratory 
2. Reduction >50% in hematoma volume at 3, 6 and 12 
months as assessed by an independent core laboratory 
3. Complete resolution of the cSDH at 3, 6 and 12 months as 
assessed by an independent core laboratory 
4. Median time to achieve complete resolution of the cSDH 
5. Subjects that develop an acute component of their existing 
cSDH or a new cSDH at 3, 6 and 12 months as assessed by 
an independent core laboratory 
6. Subjects requiring a surgical procedure on the cSDH within 
3 and 6 months post randomization 
7. Subjects requiring more than one surgery on the cSDH 
within 3, 6 and 12 months post randomization 
 
NOTE: The following secondary endpoints will be tested for 
statistical significance for the purpose of supporting labeling 
claims: 
- 
Good functional outcome at 3 months (mRS 0-2 or no 
worsening from baseline if baseline mRS> 3)  
- 
Subjects requiring a surgical procedure on the cSDH 
within 12 months  

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- 
Mean change in hematoma volume at 6 months compared 
to baseline, as assessed by an independent core laboratory 
 
Secondary Safety Endpoints – 
1. mRS distribution change at 3, 6 and 12 months  
2. Death, stroke, myocardial infarction or thromboembolic 
complications within 3, 6 and 12 months as assessed by the 
Clinical Events Committee (CEC) 
3. Development of new onset of seizures within 3, 6 and 12 
months as assessed by the CEC  
4. 4. Change in Markwalder Grading Scale at 3, 6 and 12 months 
compared to baseline  
5. 5. Change in Mini-Mental State Exam (MMSE) score at 6 
months compared to baseline 
Secondary Health Economics Endpoints-  
1. Hospital days and intensive care unit (ICU) days 
2. Change in EQ-5D-5L score at 6 months compared to baseline  
Follow-up Intervals 
 Hospital Discharge 
 A follow up will occur for Surgery Alone and NSMM groups in 
the same timeframe as the study embolization procedure occurs 
in the embolization treatment groups to ensure equal treatment 
(e.g., number of subject contacts) across study randomization 
arms 
 1 Month Follow-up (Clinic or Phone/Telehealth Visit and CT 
Scan)  
 3 Month Follow-up (Clinic or Phone/Telehealth Visit and CT 
Scan) 
 6 Month Follow-up (Clinic Visit and CT Scan) 
 1 Year Follow-up (Clinic or Phone/Telehealth Visit  and CT 
Scan) 
Inclusion Criteria 
1. Subject is between 18 and 90 years of age (inclusive) at the 
time of consent 
2. Subject has a diagnosis of chronic subdural hematoma with 
mass effect determined by brain imaging (CT or MRI) and 
correlated clinical symptoms  
3. Pre-randomization modified Rankin Score (mRS) < 3 
a. Surgical Cohort: Assessment should reflect the 
subject’s condition just prior to undergoing surgery.  
Assessment may be performed post-surgery using 
pre-surgical data. 

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4. Subdural Hematoma Size  
a. Non-Surgical Medical Management Cohort:  
i. Midline shift < 10mm and hematoma 
thickness > 10 mm as measured on coronal 
imaging perpendicular to the skull.  
ii. No focal deficit related to the chronic 
subdural hematoma 
b. Surgical Cohort:  
i. No requirement 
5. A CT performed within 36 hours prior to randomization that 
demonstrates stability of the hematoma. Stability is defined as 
no worsening of midline shift or increase in the size of the 
cSDH from the screening image that results in new or 
worsening clinical symptoms 
6. Patient or designated Legal Authorized Representative, 
confirms the patient has the mental capacity, willingness and 
ability to comply with protocol and follow-up requirements 
7. In the opinion of the treating physician, treatment with 
TRUFILL n-BCA is technically feasible (e.g., no significant 
vessel tortuosity, stenosis, occlusion or variation in vascular 
anatomy to prohibit safe endovascular access)  
Exclusion Criteria 
1. Patients presenting with an acute SDH (e.g. patient presenting 
with a SDH due to trauma); mixed density is permitted  
2. Subject has a prior history of craniotomy/burr hole/Subdural 
Evacuating Port System (SEPS) ipsilateral to the cSDH prior to 
the baseline procedure treatment   
3. Subject presents with bilateral cSDHs (contralateral cSDH 
<5mm and not requiring treatment is permitted) 
4. Subject presents with Glasgow Coma Scale < 9 
5. Markwalder assessment > 3 
6. cSDH that developed with underlying conditions such as 
vascular lesions, brain tumor, arachnoid cyst, spontaneous 
intracranial hypotension, end stage renal disease (ESRD) on 
hemodialysis, end stage liver disease or other comorbidities 
causing a coagulopathy   
7. Prior carotid stent placement that crosses the origin of the 
External Carotid Artery (ECA) ipsilateral to the subdural 
hematoma 
8. Selective angiography demonstrates opacification of a 
potentially dangerous anastomosis or dangerous anatomic 
variation that could lead to increased procedural risk 
9. Presumed septic embolus, or suspicion of microbial 
superinfection 

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10. CT or MRI evidence of intra-cranial tumor or mass lesion 
11. Significant contraindication to angiography (e.g., kidney 
failure) 
12. Life expectancy of less than 1 year 
13. Women who are pregnant, lactating, or of childbearing age and 
plan on becoming pregnant during the course of the clinical 
investigation 
14. Current involvement in an investigational (drug, device, etc.) 
clinical trial that may confound study endpoints. Subjects in 
observational, natural history, and/or epidemiological studies 
not involving intervention are eligible. Sponsor approval is 
required prior to randomization. 
15. Patient unwilling to follow SOC recommendations (e.g. refuses 
surgery or lifestyle modifications) 
Safety Assessments 
All adverse events occurring from the time of randomization through 
the one year follow up visit will be captured. Subjects’ follow up 
assessments will follow the schedule of assessment tables (see 
below). 
Sample Size and Power 
Calculation 
Cochran–Mantel–Haenszel (CMH) statistic will be used to test 
superiority in the primary effectiveness endpoint of SOC with 
eMMA over SOC alone. The CMH test will be performed with 
stratification of the cohorts (surgery vs. NSMM). Subjects within 
each cohort will be randomized 1:1 to SOC alone or SOC with 
eMMA.  Assuming a common odds ratio of 0.34, a total sample size 
of 376 subjects after accounting for 10% attrition will provide at least 
80% power for the primary effectiveness endpoint at a one-sided 
significance level of 0.05. 
 
For the primary safety endpoint, we expect at least an 80% 
probability of observing AEs that occur at an incidence of at least 
1% within each treatment group. This expectation pertains to 
approximately 188 participants receiving eMMA (surgery + eMMA 
and NSMM + eMMA) and 188 participants receiving standard of 
care (surgery alone and NSMM alone). 
Statistical Analysis  
The primary effectiveness endpoint will be evaluated in subjects who 
are randomized (ITT analysis set). This endpoint will be considered 
successful if the p-value from the continuity corrected CMH test is 
less than 0.05. Study success will be based on successful 
demonstration of the primary effectiveness endpoint. 
Tests of hypotheses of the secondary endpoints will be performed at 
0.05 significance level using a gatekeeping strategy for multiplicity 
control.  
The primary safety endpoint will be evaluated using the As Treated 

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analysis set.  
Descriptive summary statistics will be presented for other study 
endpoints. The number and percentages of subjects will be presented 
for categorical endpoints. Descriptive statistics for continuous 
variables will include the number of subjects, mean, standard 
deviation, median, minimum and maximum. The study will be 
deemed a success if the primary effectiveness endpoint criterion is 
met. 

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Schedule of Assessments 
 
Surgical Cohort 
 
Screening 
(0‐30 days prior to 
Randomization ) 
Surgical Procedure 
Pre‐Randomization1 
Randomization  
 
Day 0 (within 10 days of 
surgery) 
 
Embolization Arm Only: 
Embolization Procedure  
 
Surgery Alone Arm Only: 
Phone/In person Follow up  
Discharge5 
1 Month Follow‐up  
(+/‐14 days) Clinic or 
Phone/Telehealth + CT Exam 
3 Months Follow‐up   
(+/‐ 14 days) Clinic or 
Phone/Telehealth + CT Exam 
6 Months Follow‐up   
(+/‐ 30 days) Clinic Visit 
1 Year Follow‐up  
(+/‐ 60 days) Clinic Visits or 
Phone /Telehealth/ + CT exam 
 
Unscheduled Visit 
Re‐Operation 
Table Legend: 
X = Required 
O = Optional, to be collected if 
performed during standard of 
care 
 
Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
CT ExamP2 
X7 
 
X 
(≤36 hrs before 
randomization) 
 
 
 
X 
X 
X 
X 
O 
X 
Surgical Procedure  
 
X 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
Embolization Procedure (Embolization Arm Only) 
 
 
 
 
X 
(DSA for eMMA) 
 
 
 
 
 
 
 
Glasgow Coma Scale (GCS) 
 
 
X 
 
 
 
 
 
 
 
O 
 
Markwalder Grading Scale (MGS) 
XP3 
 
 
X 
X 
XP4 
XP4,6 
XP4 
O 
 
Modified Rankin Score (mRS) 
XP3 
 
 
X 
X 
XP4 
XP4,6 
XP4 
O 
 
Mini‐Mental State Exam (MMSE) 
 
 
X 
 
 
X 
 
 
X 
 
O 
 
Quality of Life (EQ‐5D‐5L) 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adherence to SOC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Review of Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical Resource Utilization 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 Pre-Randomization assessments may occur on the day of randomization, prior to the subject being randomized.  
2 An external CT scan (not performed by the site) is acceptable as long as the scan is provided to the site investigator and the core laboratory. 
3 Assessment should reflect the subject’s condition just prior to undergoing surgery.  Assessment may be performed post-surgery using pre-surgical data.  
4Assessment must be performed by a qualified independent evaluator who is not part of the interventional (embolization) treating team, not involved in patient care or data entry, and is blinded to study treatment 
assignment. The evaluator does not need to be a physician. 
5Discharge assessments may be performed when subject is medically ready to be discharged OR at the time of discharge. 
6 mRS and MGS may be completed via phone/telehealth by blinded assessor. 
7 MRI at screening is acceptable. Pre-randomization imaging must be CT scan 
 

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Non‐Surgical Cohort 
 
Screening 
(0‐30 days prior to 
Randomization) 
Pre‐Randomization1 
Randomization    
 
Day 0 (within 10 days of 
randomization) 
 
Embolization Arm Only: 
Embolization Procedure  
 
NSMM Arm Only: 
Phone/In person Follow up  
Discharge4 
Embolization Arm Only 
1 Month Follow‐up  
(+/‐14 days) Clinic or 
Phone/Telehealth + CT Exam 
3 Months Follow‐up  
(+/‐ 14 days) Clinic or 
Phone/Telehealth + CT Exam 
6 Months Follow‐up  
(+/‐ 30 days) Clinic Visit 
1 Year Follow‐up  
(+/‐ 60 days) Clinic Visit or 
Phone/Telehealth + CT Exam 
Unscheduled Visit 
Surgical Procedure   
Table Legend: 
X = Required 
O = Optional, to be collected if performed 
during standard of care 
 
Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
CT ExamP2 
X6 
X 
(≤36 hrs 
before 
randomizati
on) 
 
 
 
X 
X 
X 
X 
O 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
Embolization Procedure (Embolization Arm 
Only) 
 
 
 
X 
(DSA for eMMA) 
 
 
 
 
 
 
Glasgow Coma Scale (GCS) 
X 
 
 
 
 
 
 
 
O 
 
Markwalder Grading Scale (MGS) 
X 
 
 
X 
X 
XP3 
XP3,5 
XP3 
O 
 
Modified Rankin Score (mRS)P  
X 
 
 
X 
X 
XP3 
XP3,5 
XP3 
O 
 
Mini‐Mental State Exam (MMSE) 
 
X 
 
 
X 
 
 
X 
 
O 
 
Quality of Life (EQ‐5D‐5L) 
 
X 
 
 
 
 
 
X 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adherence to SOC 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Review of Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical Resource Utilization 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
P1 PPre-Randomization assessments may occur on the day of randomization, prior to the subject being randomized.  
P2P An external CT scan (not performed by the site) is acceptable as long as the scan is provided to the site investigator and core laboratory. 
P3 PAssessment must be performed by a qualified independent evaluator who is not part of the interventional (embolization) treating team and not involved in patient care or data entry and is blinded to study 
treatment assignment. The evaluator does not need to be a physician 
4 The discharge assessments may be performed when subject is medically ready to be discharged OR at the time of discharge. 
5 mRS and MGS may be completed via phone/telehealth by blinded assessor. 
6 MRI at screening is acceptable. Pre-randomization imaging must be CT scan 
 

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1. Background Information and Scientific Rationale 
1.1  
Background Information 
Subdural hematoma is an accumulation of blood between the dura and arachnoid layers of 
the meninges surrounding the brain that can cause symptoms including headache, seizures, 
memory or other neurological (including motor) impairment, and confusion. SDH can 
occur in an acute (emergent) fashion, often becoming symptomatic within 72 hours and 
requiring immediate surgical intervention, or develop chronically over a period of 3 or 
more weeks (Sahyouni et al., 2017). The most common cause of chronic SDH is thought 
to be a combination of direct or indirect head trauma and chronic inflammation. Other 
known causes or risk factors include alcoholism, liver cirrhosis, chronic renal failure, 
hematologic disease, and anticoagulant or antiplatelet therapy (Sim et al., 2012). Given 
these risk factors, cSDH has a predilection towards the elderly: the estimated annual 
incidence of cSDH is 1-5.3 cases per 100,000 population, but the incidence among 
individuals > 65 years has been reported as high as 48.0-80.1 per 100,000 per year (Kudo 
et al., 1992; Karibe et al., 2011; Adhiyaman et al., 2017). Moreover, recent data suggest 
that cases of cSDH are on the rise due to population aging and the increased use of 
antithrombotic medications (Sim et al., 2012; Adhiyaman et al., 2017).  
The clinical diagnosis of cSDH is based on symptomatic presentation and the presence of 
risk factors such as recurrent falls, increased confusion, and decreased mobility. cSDH is 
confirmed on brain imaging with CT without contrast enhancement (Soleman et al., 2014) 
and typically quantified in terms of hematoma size or volume and the presence or absence 
of cerebral compression, whereas clinical assessment and treatment response are measured 
using the Markwalder grading system for the classification of cSDH or non-specific scales 
such as the modified Rankin Scale and Glasgow Coma Scale. 
The primary goal of cSDH treatment is to relieve intracranial pressure and drain 
accumulated blood and fluids in order to alleviate patient symptoms. The current standard 
of care is somewhat variable but generally utilizes pharmacological and/or surgical 
interventions to accomplish this aim. 
 
1.2  
Current Treatment Options  
Current treatments for cSDH can be divided into conservative medical management (MM) 
and surgical intervention. Of note, there is a dearth of class I evidence supporting the 
efficacy of any pharmacological treatment for cSDH, such that current MM options are 
largely based on theoretical efficacy and physician experience. 
 
1.2.1.  Conservative Medical Management 
Conservative MM is indicated in patients who are asymptomatic or have only mild 
symptoms and none or mild clinical or imaging signs of cerebral compression. MM can 
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observation approach (Lee, 2019). Antiplatelet therapy is typically discontinued, and 
anticoagulant therapy is converted with vitamin K (Soleman et al., 2014). A survey of 
practice in the United Kingdom and Ireland found that while conservative management 
was used in less than 25% of cases, more than half of medical management utilized a 
steroid (Santarius et al., 2009). An international survey that included the United States and 
Europe similarly found that almost half of respondents used steroid monotherapy with 
dexamethasone when electing for conservative treatment, whereas ACE inhibitors and 
statins were rarely (~10% of respondents) prescribed (Laldjising et al., 2020). 
Unfortunately, few studies have provided rigorous evidence for the efficacy of MM alone 
for cSDH. Jiang et al. (2018) evaluated atorvastatin monotherapy (8 weeks, 20 mg) versus 
placebo for cSDH in a Chinese population and reported a reduction in hematoma volume 
of 12.55 mL compared to the placebo group, as well as a significant improvement in 
neurological function. Conversion to surgery was necessary in 11.2% in the atorvastatin 
group compared to 23.5% in the placebo group. Fountas et al. (2019) similarly compared 
dexamethasone monotherapy to surgical therapy or a combination thereof; in this study, 
surgery (burr hole craniotomy) plus dexamethasone resulted in the lowest rate of 
recurrence (4%) followed by a rate of 7.3% in the surgery only group and 30% in the 
dexamethasone monotherapy group. The recently completed SUCRE trial compared 
methylprednisolone to placebo in cSDH using a double-blind, randomized controlled 
design (Hénaux et al., 2017), but the results are not yet available. 
1.2.2.  Surgical Intervention 
Surgical evacuation of cSDH is a common neurosurgical procedure that alleviates 
intracranial pressure and cerebral compression in order to ameliorate patient symptoms. 
Surgical options typically include single or double burr hole evacuation and craniotomy. 
The majority of published studies on surgical management of SDH use a threshold of 10 
mm for patient inclusion and/or outcome assessment, and refer to the established surgical 
guidelines (Bullock et al., 2006 “…acute SDH with a thickness greater than 10 mm or a 
midline shift greater than 5 mm on computed tomographic [CT] scan should be surgically 
evacuated..”), which are in turn based on the mortality rates associated with increased 
hematoma thickness (up to 10% for ≤10 mm, 50% for 18 mm and ≥90 % for thickness 30 
mm and higher; Bullock et al., 2006; Zumkeller et al, 1996). A prospective observational 
cohort study in United Kingdom and Ireland found that burr hole craniotomy was the most 
common procedure for cSDH (89%) and moreover that 96% of all patients underwent some 
form of surgery (Brennan et al., 2017). Despite the widespread use of surgical evacuation 
for cSDH, these procedures are associated with important risks in the target population due 
to advanced age and comorbidities and furthermore do not address the cause of hematoma 
formation. To this end, surgical evacuation is associated with a recurrence rate of roughly 
5-30% depending on the specific surgical technique (Oh et al., 2010). Rovlias et al. (2015) 
found that age, neurological status on admission, and antiplatelet or anticoagulant therapy 
were significant predictors of outcome after burr hole evacuation with closed system 
drainage in a cohort of 986 patients. This study reported a recurrence rate of 11.8% and a 
postoperative complication rate of 22.7%. Knopman et al. (2018) examined rates of 
reoperation after craniotomy for isolated nontraumatic SDH in two separate cohorts and 
reported reoperation rates of 5-10% and mortality of 8-18%. 

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Several studies indicate that drain insertion (subdural or subperiosteal) may decrease the 
rate of recurrence and improve patient outcomes. A meta-analysis of 10 studies comparing 
subdural versus subperiosteal drain placement after burr hole evacuation of cSDH 
demonstrated that subdural drain placement significantly decreased the rate of recurrence 
(odds ratio, 0.73; 95% confidence interval, 0.58-0.92). Brennan and colleagues (2017) 
similarly found that failure to insert a subdural drain significantly predicted reoperation 
and unfavorable outcome. Sanitarius et al. (2009) reported a recurrence rate of 9.3% with 
subdural drain placement versus 24.0% without drain placement at 6 months follow-up, 
indicating a noteworthy benefit. 
1.3. 
 Neurovascular Embolization 
Given the nature of cSDH as a disease of the elderly that can occur secondary to serious 
comorbidities, there is a need for effective treatment options that minimize or circumvent 
surgical risk and decrease the probability of recurrence. Endovascular embolization of the 
MMA with embolic materials including n-BCA, polyvinyl alcohol (PVA) particles, 
ethylene vinyl alcohol (EVOH) copolymers, and coils/gelatin sponges is an increasingly 
attractive option. In cSDH, the MMA and neovascular vessels in the outer membrane 
anastomose via the dura mater, leading to intermittent bleeding of weak or vulnerable blood 
vessels and an increase in cSDH volume. Theoretically, embolization of the MMA reduces 
the recurrence of cSDHs by disrupting blood flow to the outer membrane of the hematoma 
(Saito et al., 2019). On this premise, endovascular embolization of the MMA not only 
provides a minimally invasive alternative to surgery, but also addresses a root cause of 
hematoma formation. 
Several studies have demonstrated the efficacy of endovascular treatment in cSDH, with 
early studies focusing on the treatment of recurrent cSDH. Saito et al. performed 
embolization of the MMA using 12-24% n-BCA for recurrence after single burr hole 
evacuation with irrigation (cohort recurrence rate, 11.8%) in 8 patients and reported only 
1 recurrence 3 months after surgery with no complications (Saito et al., 2019). The authors 
attributed recurrence after MMA embolization to neovascularization of the inner 
membrane and septum. In a similar study, Ishihara et al. performed MMA embolization 
with 20% n-BCA in 7 patients with intractable cSDH after burr hole evacuation and 
reported no cases of further recurrence at 15 months follow-up (Ishihara et al., 2007). In a 
case study, MMA embolization with n-BCA was successfully used to treat iatrogenic dural 
arteriovenous fistula associated with recurrent cSDH in an 82-year-old woman (Mewada 
et al., 2016). Okuma et al. reported a case series of 17 patients which involved three patients 
treated with gelatin microspheres and one patient treated with coils alone, resulting in 
recurrence-free survival in all patients at a mean follow-up of 26.3 ± 17.4 months (Okuma 
et al., 2019). Another case report involving a 13-year-old male patient treated with coil-
based MMA embolization for recurrent cSDH showed no neurological complications or 
recurrence at 5-year follow-up (Kang et al., 2015). Several studies have demonstrated 
successful MMA embolization using PVA for recurrent cSDH, typically resulting in low 
recurrence rate (Mandai et al., 2000;Tsukamoto et al., 2011;Kim, 2017;Ban et al., 
2018;Sirh et al., 2018;Link et al., 2019). In addition, Tempaku et al. reported a case series 
of five patients with repeated recurrence of cSDH that were successfully treated with MMA 

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embolization using PVA particles, each showing no further recurrence at follow-up ranging 
from 4 to 60 weeks (Tempaku et al., 2015).  
Other studies have proposed the use of embolization as an adjuvant to surgical therapy in 
high-risk or intractable cases. In a cohort of 17 patients with multiple intractable risk factors 
to standard treatment, MMA embolization with 20% n-BCA or trisacryl gelatin 
microspheres followed by burr hole craniotomy and irrigation led to no complications or 
recurrence during a mean follow-up of 26.3 months (Okuma et al., 2019). A prospective 
cohort study performed MMA embolization for cSDH using gelatin sponges and Guglielmi 
detachable coils as an adjunct treatment to closed-system drainage or irrigation with 
drainage in 4 patients, resulting in no observed recurrence at 6 months (Mino et al., 2010). 
PVA-based MMA embolization has also been used as a successful adjuvant to surgical 
therapy in several studies, including case reports, case series, and prospective and 
retrospective cohort studies (Tempaku et al., 2015;Sirh et al., 2018;Link et al., 2019;Arham 
and Zaragita, 2020). One pilot study examined MMA embolization with PVA as an 
adjuvant to surgery for symptomatic cSDH and identified superior volume resorption 
(mean difference, 17.5 mL) compared to a surgery control group (Ng et al., 2020). An 
ongoing non-randomized clinical trial also seeks to investigate the efficacy of PVA as 
adjuvant therapy and PVA as a stand-alone therapy relative to burr hole 
drainage/craniotomy (NCT04065113).   
More recently, MMA embolization has been explored as a stand-alone therapy for cSDH. 
A case series which included a 63-year-old female at risk of recurrent cSDH that was 
treated with MMA embolization (16% n-BCA) at the first sign of recurrence demonstrated 
complete disappearance of the hematoma at 4-months (Hashimoto et al., 2013). Another 
prospective investigation of MMA embolization with PVA for cSDH achieved 
spontaneous hematoma resolution in all of 27 asymptomatic patients, whereas 1 of 45 
symptomatic patients experienced hematoma re-accumulation after treatment. In this 
study, a recurrence rate of 1.4% was significantly lower than 27.5% (129/469) in the 
conventional treatment group (Ban et al., 2018). Similarly, Link et al. (2019) performed 
MMA embolization with PVA particles (150-250 microns) as new treatment in 42 patients 
plus treatment for recurrence in 8 patients and reported a recurrence rate of 8.9% (4 
patients) (Link et al., 2019). Overall, 91% of patients were stable or showed a decrease in 
hematoma size and avoided surgery through follow-up. There were no differences in 
treatment-related complications. Shotar et al. compared 104 MMA embolization 
procedures (triacryl gelatin microspheres in 81 cases, n-BCA in 5 cases) performed in 89 
patients to 174 historic controls and identified recurrence rates of 4% and 14%, respectively 
(odds ratio, 0.28; 95% confidence interval, 0.07-0.86) (Shotar et al., 2020).  
Despite advances and rapid adoption of new devices and techniques, significant unmet 
clinical needs still exist, creating a demand for innovation and new devices for MMA 
embolization. The use of PVA particles for MMA embolization is significantly limited by 
a tendency for particle aggregation (Sharma et al., 2016), which can result in poor 
penetration, vessel occlusion proximal to the intended target, and concerns for distal 
embolization. These issues are in part avoidable through sufficient particle dilution and 
slow infusion, the latter of which increases procedure times. Moreover, the long-term 

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efficacy of PVA is not well examined in the literature. While EVOH copolymers offer 
better penetration compared to PVA, these agents also require slow infusion to avoid issues 
related to DMSO toxicity: EVOH copolymers are prepared in DMSO solvent, which 
diffuses away on contact with blood to permit EVOH polymerization. Rapid injection of 
DMSO can lead to vasospasm and necrosis, making slow infusion necessary to limit the 
rate of DMSO diffusion (Vaidya et al., 2008). These liquid embolic agents commonly 
require microcatheters that are larger than ideal, which can hamper distal access and put 
patients at higher risk for other complications (Arafa et al., 1999;Righini et al., 2004).  
n-BCA resolves some of the shortcomings of the other embolic agents being used to treat 
chronic subdural hematomas. Unlike PVA and EVOH, n-BCA is supplied as a clear, free-
flowing monomer that undergoes rapid polymerization upon exposure to an anionic 
environment (e.g. blood, water), the speed of which depends on the concentration of n-
BCA (Pollak and White, 2001). n-BCA can be delivered through a smaller microcatheter 
than other liquid embolic agents to facilitate distal access and decrease likelihood of other 
complications. Compared to the alternatives, n-BCA may be optimal for procedures 
performed under conscious sedation because of its quick action, pain-free nature of the 
injection, and lower associated fluoroscopy exposure (Velat et al., 2008). Accordingly, the 
use of n-BCA for MMA embolization is expected to maximize the safety and efficacy of a 
minimally invasive protocol for treatment of cSDH and warrants evaluation against both 
surgical and MM interventions that represent the current standard of care for cSDH.  
1.4.  
Rationale 
The use of liquid embolic agents for the minimally invasive treatment of cSDH offers a 
solution that both circumvents the risk of surgical complications and addresses the source 
of fluid accumulation, thereby decreasing the likelihood of recurrence. There are currently 
no endovascular embolic agents approved in the US for treating chronic subdural 
hematomas. Despite the promising preliminary findings summarized above, there is a need 
for high-quality evidence from prospective randomized controlled studies to support MMA 
embolization as a primary treatment option for cSDH. TRUFILL n-BCA provides a 
minimally invasive option for stand-alone treatment as well as, as an adjunct to surgical 
treatment of cSDHs and offers several potential advantages to other current embolic agents.  
The aim of the present study is to assess the safety and effectiveness of MMA embolization 
with TRUFILL n-BCA Liquid Embolic System in both non-surgical and surgical patient 
populations relative to standard management without MMA embolization  in a prospective, 
multicenter, pivotal clinical trial. Data generated will be used to support a Pre-market 
Approval Application to expand the indication of TRUFILL n-BCA to include treatment 
of subdural hematomas. 
1.5.   Previous Experience  
1.5.1.  Bench and Animal Validation 
The safety and effectiveness of TRUFILL n-BCA Liquid Embolic System for its currently 
approved use in embolization of cerebrovascular AVMs, is supported by extensive pre-
clinical bench and animal testing. The same pre-clinical bench and animal data set also 

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support the reasonable safety of the use of TRUFILL n-BCA in embolization of MMA in 
treatment of SDH. Pre-clinical bench and animal testing include the following: 
 
Polymerization Rate for a range of nBCA and Ethiodized Oil mixture ratios 
o In vitro evaluation with pre-determined objective acceptance criteria 
o In vivo evaluation by physicians to qualitatively assess polymerization 
 
Viscosity of individual components: nBCA, Ethiodized Oil  
 
Tantalum Powder particle size and suspension in ethiodized oil 
 
Radiopacity of liquid embolic 
 
Microcatheter Compatibility  
 
USP Physicochemical Testing – n-BCA, Ta Powder 
 
Evaluation of Hydrolytic Degradation of implant 
 
Evaluation of Elution of Ethiodized Oil from implant 
 
Verification that product meets sterility requirements (SAL 10-6) 
 
Package & Sterile Barrier Integrity  
 
Self Piercing Luer Cap performance testing 
 
Shelf Life – Real Time Studies confirming minimum 2-year shelf-life 
 
Biocompatibility of liquid embolic system per ISO 10993  
o 
In vitro evaluations of cytotoxicity, genotoxicity, hemocompatibility per    
            applicable chapters of ISO 10993  
o 
In vivo evaluations of hemolysis, intramuscular implantation for 7 and 30  
            days, systemic and sub-chronic toxicity, pyrogenicity, intracutaneous           
            reactivity/toxicity, and delayed contact sensitization per applicable chapters   
            of ISO 10993 
 
Cerenovus has undertaken all necessary steps to apply standard techniques in designing, 
pre-clinically evaluating, and manufacturing the devices to ensure they are safe and 
perform as intended.  
 
  
1.5.2.  Study Product  
  
 
TRUFILL n-BCA Liquid Embolic System has been commercially available in the US since 
2000 and in select countries (Belarus, Russia) globally since 2012. TRUFILL n-BCA 
Liquid Embolic System may be considered Investigational for certain countries and will 
be tracked as an investigational product as applicable. 
 

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An Investigational Device Exemption (IDE) Instructions for Use (IFU) will be provided to 
the sites separately for instructions on use of the device for the study. 
 
1.6.  
Potential Risks and Benefits  
Risks that may be associated with the use of the TRUFILL n-BCA and the procedure are 
described in this section. 
 
1.6.1.  Known Potential Risks 
 
The following AEs associated with endovascular embolization of the MMA have been 
identified as possible (anticipated) AEs associated with the use of the TRUFILL n-BCA or 
with the procedure.   
 
Access site injury (including bleeding, bruising, infection, pain) 
 
Allergic reaction / anaphylactic shock 
 
Catheter glued inside vessel 
 
Cerebral infarction  
 
Death 
 
Early polymerization 
 
Embolism, including pulmonary and thromboembolism 
 
Headache 
 
Hematoma 
 
Hemorrhage 
 
Infection/inflammation 
 
Late polymerization 
 
Myocardial infarction  
 
Nausea / vomiting 
 
Neurological deficits  
 
Non-target embolization (passage of embolic material into normal vessels adjacent 
to the target) which may cause but not limited to blindness, dysesthesias of the face 
(increased or decreased sensitivity), facial weakness, or deafness 
 
Occluded catheter  
 
Renal failure 
 
Seizure  

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Stroke  
 
SDH hematoma recurrence 
 
Vasospasm  
 
Vessel dissection, perforation and injury  
 
Use of the device requires fluoroscopy which presents potential risks to physicians and patients 
associated with x-ray exposure.  Possible risks include, but are not limited to, the following: 
 
Alopecia 
 
Burns ranging in severity from skin reddening to ulcers 
 
Cataracts 
 
Delayed neoplasia 
 
1.6.2.  Minimization of Risks 
Efforts will be made to minimize the potential risks through the following: 
1. Treating investigators who participate in the study will have extensive experience 
using TRUFILL n-BCA or similar device (e.g., other n-BCA) in neurovascular 
embolization procedures. 
2. Investigators will have experience performing embolizations through the middle 
meningeal artery. 
3. All sites will have a neurosurgical program capable of treating subdural 
hematomas. 
4. All sites will be required to have adequate resources to conduct the clinical study 
and assure compliance.  
5. Each investigator will ensure oversight and approval of the study by the IRB/EC 
prior to initiation of the study at the investigation site.   
6. The investigator and study personnel will be trained on the study protocol. 
7. An IDE IFU will be provided to the sites for instructions on use of the device for 
the study. 
8. Subjects will be carefully evaluated against the pre-defined inclusion/exclusion 
criteria prior to being enrolled in the study to ensure that their diagnosis and medical 
status are appropriate for participation.  
9. Each investigator will be required to commit to follow all subjects per protocol, 
including preforming the required CT scans. 
10. Subjects will be monitored closely as part of the study to allow for detection of 
adverse events.  This should allow for early treatment, if necessary.     

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11. Data from all investigation sites will be monitored by the sponsor throughout the 
study to evaluate protocol compliance and identify any issues that may affect the 
safety and welfare of the subjects.  
12. All safety endpoints for the study will be reviewed and adjudicated by an 
independent CEC. 
13. All imaging based endpoints for the study will be assessed by an independent core 
laboratory.  
14. An Independent Data Monitoring Committee (DMC) will be responsible for 
assessing and monitoring the accumulated AEs and interim data on a periodic basis 
as the study progresses to ensure subject safety. 
 
1.6.3.  Potential Benefits 
 
 
The potential benefits of TRUFILL n-BCA are that it may decrease or stop the blood flow 
into the MMA and thus decrease or eliminate the outflow of blood that may be contributing 
to the formation and/or growth of the cSDH, which may help decrease or eliminate the 
hematoma, potentially reducing symptoms, the need for surgical treatment, as well as the 
risk of future complications or death. Although there may be no direct benefits of study 
participation, subject participants will undergo an enhanced level of clinical scrutiny 
compared to routine clinical care, which may provide some indirect health benefits.  
1.6.4.  Risk-Benefit Rationale 
Extensive commercial experience with TRUFILL n-BCA supports the reasonable safety of 
the device, and available data on MMA embolization for the treatment of SDH further 
support the safety of the procedure.  Published literature also suggests that the rates of 
surgical treatment following MMA embolization may be lower than those associated with 
standard of care alone. Multiple steps will be taken to ensure risks to the subject are 
minimized including selecting only sites experienced with endovascular MMA treatment, 
monitoring subject closely thorough follow-up evaluations as required by the protocol and 
independent oversight of the study through a DMC.  Cerenovus considers the potential 
benefits of MMA embolization with TRUFILL n-BCA to outweigh the potential risks in 
the defined subject population. 
 
 
2.  
Objectives and Purpose  
2.1. Objectives 
The objective of this study is to evaluate the safety and effectiveness of TRUFILL n-BCA 
for MMA embolization in patients presenting with a cSDH compared to patients treated 
with standard of care management. 
 
 
3.  
Study Design and Endpoints 

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3.1. Description of the Study Design 
This is a prospective, multi-center, open-label, randomized controlled study in which up to 
376 subjects will be enrolled and randomized to receive standard of care alone or standard 
of care and TRUFILL n-BCA MMA embolization for the treatment of cSDH. Pre-planned 
treatment should be TRUFILL n-BCA as the only liquid embolic agent. The subjects will 
be followed at 1 month, 3 months, 6 months, and 1 year post-procedure.  The primary 
endpoint will be evaluated at 6 months post-procedure.  The study is designed to evaluate 
the effectiveness and safety of MMA in two cohorts – a surgical cohort and a non-surgical 
cohort. 
 
3.1.1. Primary Endpoint 
 Primary effectiveness endpoint: Residual or re-accumulation of the cSDH (>10 
mm) at 6 months as assessed by an independent core laboratory OR re-operation or 
surgical procedure on the cSDH within 6 months post randomization. 
 
Re-operation and surgical procedures will be reported by the site.  Hematoma size 
will be assessed by the independent core laboratory. 
Primary safety endpoint: Occurrence of all AEs through 6 month 
3.1.2. Secondary Endpoints – Effectiveness  
 
1. Mean change in hematoma volume at 3 and 12 months compared to baseline, 
as assessed by an independent core laboratory  
2. Reduction> 50% in hematoma volume at 3, 6 and 12 months as assessed by an 
independent core laboratory 
3. Complete resolution of the cSDH at 3, 6 and 12 months as assessed by an 
independent core laboratory  
4. Median time to achieve complete resolution of the cSDH 
5. Subjects that develop an acute component of their existing cSDH or a new 
cSDH at 3, 6 and 12 months as assessed by an independent core laboratory  
6. Subjects requiring a surgical procedure on the cSDH within 3 and 6 months 
post randomization 
7. Subjects requiring more than one surgical procedure on the cSDH within 3, 6 
and 12 months post randomization 
Re-operation and surgical procedures will be reported by the site. Hematoma volume and 
resolution, as well as identification of an acute component of the cSDH or a new cSDH 
will be assessed by the independent core laboratory. 
 

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NOTE: The following secondary endpoints will be tested for statistical significance for 
the purpose of supporting labeling claims: 
 
Good functional outcome at 3 months (mRS 0-2 or no worsening from baseline if 
baseline mRS > 3) 
 
Subjects requiring a surgical procedure on the cSDH within 12 months  
 
Mean change in hematoma volume at 6 months compared to baseline, as assessed by an 
independent core laboratory 
3.1.1.  Secondary Endpoints – Safety  
 
1. mRS distribution change at 3, 6 and 12 months 
2. Death, stroke, myocardial infarction or thromboembolic complications within 3, 6 and 12 
months as assessed by the Clinical Events Committee (CEC) 
3. Development of new onset of seizures within 3, 6 and 12 months as assessed by the CEC 
4. Change in Markwalder Grading Scale at 3, 6 and 12 months compared to baseline   
5. Change in Mini-Mental State Exam MMSE score at 6 months compared to baseline 
Death, stroke, myocardial infarction, thromboembolic complications and new onset seizures 
will be adjudicated by the CEC. Markwalder and mRS used in secondary endpoints will be 
assessed by a qualified independent evaluator who is not part of the interventional 
(embolization) treating team and not involved in patient care or data entry and is blinded to 
study treatment assignment. 
 
3.1.4.   Secondary Endpoints – Health Economics 
 
1. Hospital days and intensive care unit (ICU) days  
2. Change in EQ-5D-5L score at 6 months compared to baseline 
 
 
4.  
Study Population 
Study population will be patients presenting with a previously untreated chronic subdural 
hematoma not requiring emergent surgery/decompression. 
Investigators will assess potential subjects who are candidates for the study. Patients will 
be assessed by the site physicians to determine whether the patient will undergo either 
surgery or non-surgical management of the hematoma, per standard of care. Patients will 
then be screened for trial enrollment based on the protocol inclusion and exclusion criteria. 
Patients who meet all eligibility criteria and consent to participate in the MEMBRANE 
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Older age is shown to be a factor in developing cSDH: the estimated annual incidence of 
cSDH is 1-5.3 cases per 100,000 population, but the incidence among individuals > 65 
years has been reported as high as 48.0-80.1 per 100,000 per year (Kudo et al., 1992; Karibe 
et al., 2011; Adhiyaman et al., 2017). Based on the age profile of cSDH patients, the 
Medicare population would benefit most from the study treatment. The results of this study 
are expected to be generalizable to the Medicare population based on age requirement >=65 
for enrollment. 
 
4.1 
Participant Inclusion Criteria 
Candidates for this study must meet ALL of the following criteria: 
1. Subject is between 18 and 90 years of age (inclusive) at the time of consent 
2. Subject has a diagnosis of chronic subdural hematoma with mass effect 
determined by brain imaging (CT or MRI) and correlated clinical symptoms   
3. Pre-randomization modified Rankin Score (mRS) < 3 
a. Surgical Cohort: Assessment should reflect the subject’s condition just 
prior to undergoing surgery.  Assessment may be performed post-
surgery using pre-surgical data. 
4. Subdural Hematoma Size  
Non-Surgical Medical Management Cohort:  
 Midline shift < 10mm and hematoma thickness > 10 mm as measured on 
coronal imaging perpendicular to the skull   
 No focal deficit related to the chronic subdural hematoma 
Surgical Cohort:  
 No requirement 
5. A CT performed within 36 hours prior to randomization demonstrates stability 
of the hematoma. Stability is defined as no worsening of midline shift or 
increase in the size of the cSDH from the screening image that results in new 
or worsening clinical symptoms.  
6. Patient or designated Legal Authorized Representative, confirms the patient 
has the mental capacity, willingness and ability to comply with protocol and 
follow-up requirements  
7. In the opinion of the treating physician, treatment with TRUFILL n-BCA is 
technically feasible (e.g., no significant vessel tortuosity, stenosis, occlusion or 
variation in vascular anatomy to prohibit safe endovascular access)  
 
4.2.  
Participant Exclusion Criteria 

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Candidates will be excluded from participation if ANY of the following apply: 
1. Patients presenting with an acute SDH (e.g. patient with presenting with a SDH 
due to trauma); mixed density is permitted  
2. Subject has a prior history of craniotomy/burr hole/SEPs ipsilateral to the cSDH 
prior to the baseline procedure treatment   
3. Subject presents with bilateral cSDHs (contralateral cSDH <5mm and not requiring 
treatment is permitted) 
4. Subject presents with Glasgow Coma Scale < 9 
5. Markwalder assessment > 3 
6. cSDH that developed with underlying conditions such as vascular lesions, brain 
tumor, arachnoid cyst, spontaneous intracranial hypotension, end stage renal 
disease (ESRD) on hemodialysis, end stage liver disease or other comorbidities 
causing a coagulopathy   
7. Prior carotid stent placement that crosses the origin of the External Carotid Artery 
(ECA) ipsilateral to the subdural hematoma 
8. Selective angiography demonstrates opacification of a potentially dangerous 
anastomosis or dangerous anatomic variation that could lead to increased 
procedural risk 
9. Presumed septic embolus, or suspicion of microbial superinfection 
10. CT or MRI evidence of intra-cranial tumor or mass lesion 
11. Significant contraindication to angiography (eg. kidney failure). 
12. Life expectancy of less than 1-year 
13. Women who are pregnant, lactating, or who are of childbearing age and plan on 
becoming pregnant during the course of the clinical investigation 
14. Current involvement in an investigational (drug, device, etc.) clinical trial that may 
confound study endpoints. Subjects in observational, natural history, and/or 
epidemiological studies not involving intervention are eligible. Sponsor approval is 
required prior to randomization 
15. Patient unwilling to follow SOC recommendations (e.g. refuses surgery or lifestyle 
modifications) 
 
4.3. 
Study Duration 
The duration of the study is expected to be approximately 3 years. This includes an 
enrollment period of approximately 2 years and a post-treatment follow-up evaluation of 1 
year. 
 

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4.4. Number of Subjects  
A target of 376 subjects will be randomized into this study. Each cohort will have a 
maximum enrollment of 276 subjects (approximately 70%) and a minimum of 100 
subjects. To ensure generalizability of the results and minimize the influence of any single 
site, no more than approximately 15% of the total 376 randomized subjects will be allowed 
at a single site, with limits on individual strata (i.e., a maximum of 38 subjects per cohort 
with a combined limit of 56 subjects randomized across both cohorts per site). 
The study will be conducted in up to 475 enrolled (consented) subjects to achieve 376 
subjects randomized at up to 35 sites in the United States (US). It may later be determined 
that approximately 50 of the 376 randomized subjects in approximately 5 of these 35 sites 
and will be in geographies outside of the US. Randomization will be stratified by site within 
cohort.  
 
4.5. Number of Sites 
The study will be conducted at up to 35 sites.  
 
4.6. Participant Withdrawal or Termination 
4.6.1. Reasons for Withdrawal or Termination 
Subjects are free to withdraw from participation in the study at any time by notifying the 
investigator.  The investigator may terminate participation in the study if any adverse event 
or other medical condition or situation occurs such that continued participation would not 
be in the best interest of the participant.   
4.6.2. Handling of Participant Withdrawals or Termination 
Subjects that withdraw consent after treatment are not required to undergo study-related 
follow-up after withdrawal. They will not be replaced and will be considered part of the 
subject cohort.  The reason for early withdrawal will be documented in the source 
documents and case report forms.   
In the event a subject withdraws from the study, their data will be excluded from the data 
analysis from the time of withdrawal going forward. All data collected prior to withdrawal 
will be included in the data analysis. 
 
 
5. Study Device  
5.1. Study Device Description 
5.1.1. Device Acquisition 
The TRUFILL n-BCA System is commercially available in the US, and considered an 
investigational device in other regions with sites participating in this study.  The device is 
manufactured for Medos International SARL by Cerenovus, Inc. US and CE Marked 

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catalog codes are identical in all aspects of design, chemical composition, and packaging 
configuration, and only the labeling is different to account for differences in US and EU 
medical device labelling requirements. The devices that will be used at US study sites will 
be the US commercial devices and contain commercial labeling and instructions for use as 
approved by FDA (PMA# P990040). Devices used at study sites at all regions outside the 
US (OUS) will be those labeled with the European CE Mark.  
Due to commercial availability in the US, shipments and device accountability will not be 
tracked in the US for this study. However, devices will be fully traceable though the 
company’s 21 CFR 820 and ISO 13485 complaint quality system. Device accountability 
will be tracked in regions where TRUFILL n-BCA is considered an investigational device. 
5.1.2. Device Appearance, Packaging, and Labeling Description 
The TRUFILL n-Butyl Cyanoacrylate (n-BCA) Liquid Embolic System is an artificial 
embolization device, comprised of TRUFILL n-BCA, TRUFILL Ethiodized Oil and 
TRUFILL Tantalum Powder. These components must be used as a system. They are not 
intended for use as individual components. 
TRUFILL n-BCA is a clear, free- flowing liquid that polymerizes via an anionic 
mechanism. Ethiodized oil is a straw-to-amber colored, oily fluid containing iodinated 
poppy seed oil and is used as a radiopaque polymerizing retardant. Tantalum powder is a 
finely ground, irregularly shaped, dark gray metal that can be used with ethiodized oil to 
make the n-BCA radiopaque. 
The families of compatible microcatheters, and recommended accessories for use with the 
TRUFILL n-BCA system are listed in the IFU. 
 
 
 
Figure 1 – TRUFILL® n-Butyl Cyanoacrylate  (n-BCA) Liquid Embolic System 
 
 
                

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5.1.3. Device Training Requirements and Investigator Experience 
In addition to the clinical protocol training, all investigators who will be performing 
procedures for this study will be trained on the study IDE IFU and will be required to 
undergo didactic training on use of TRUFILL n-BCA for MMA embolization. Treating 
investigators not already experienced with TRUFILL n-BCA are required to undergo 
training via a device in-service, which includes detailed reviews of the device 
(specifications, indications for use, procedural components, etc.). 
 A physician proctor may be provided to provide support for the first few cases that each 
investigator uses the TRUFILL n-BCA for MMA embolization.  The combination of the 
didactic and hands-on portions of the device training will be documented and along with 
any physician proctoring to provide the investigator with the experience necessary to 
perform the protocol specified procedures for the study. 
TRUFILL n-BCA for MMA embolization should only be used by investigators who have 
endovascular training and thorough knowledge of angiographic techniques and the 
treatment of cSDH.   
There must be at least one physician at each site experienced in standard of care surgical 
evacuation of SDH via burr hole, craniotomy. 
 
5.1.4. Device Storage and Stability, Preparation and Instructions for Use 
 
The TRUFILL n-BCA System device should be stored in a cool, dark, dry place, in 
accordance with the IFU. 
 
The n-BCA mixture polymerizes into a solid material upon contact with body fluids or 
tissue. Recommended ratios of n-BCA to ethiodized oil and tantalum powder vary 
depending on the location, diameters and tortuosity/linearity of the target, and flow rates. 
Higher concentrations of ethiodized oil increase the polymerization time, which allows the 
physician to embolize the target more distally. Higher concentrations of n-BCA result in a 
faster polymerization rate, which will allow the physician to embolize the target more 
proximally. Radiopacity of the n-BCA mixture is accomplished by adding ethiodized oil 
and tantalum powder to the n-BCA. These additives will also extend the polymerization 
time of the n-BCA. Guidelines for recommended mixtures and approximate 
polymerization times are listed in the IFU. 
 
5.1.5. Device Returns 
Any suspected device malfunction, treatment failure or device associated with an adverse 
event will undergo a thorough complaint analysis and must be properly documented on the 
electronic Case Report Forms (eCRFs).  In the event of a suspected malfunction or device 
observation, the device shall be returned to Cerenovus for analysis if the device was not 
implanted.  All returned devices must be properly decontaminated per hospital policy and 

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properly labeled with the subject identification number, date of event, identified as a 
defective return, non-defective return, or adverse event. Retain tracking information. All 
study devices should be returned to: 
  
 
 
 
 
 
 
C.G. Laboratories,Inc. 
 
 
 
2449 Bob White Dr. 
 
 
 
Granbury, TX 76049 USA 
 
 
6.  
Study Procedures 
Some of the procedures completed as part of this study are standard of care which may vary 
from site to site. For the purpose of the MEMBRANE Study, “Standard of Care” is defined 
as the best care for the individual subject including guideline-based care where clinical 
guidelines are available.  Patients should be evaluated by the physician, in accordance with 
their institutional practice, to establish an appropriate treatment plan based on the subject’s 
medical condition and available diagnostic screening procedures prior to enrollment in the 
study. 
 
6.1.  Independent Imaging Core Lab for Image Evaluation 
An independent Imaging Core Lab shall be utilized to provide an unbiased and 
standardized assessment of study imaging. All subject Protected Health Information (PHI) 
will be redacted by the site before an image is uploaded to the Core Lab for evaluation.  
The Imaging Core Lab assessors will be blinded to subjects’ previous medical history. The 
Imaging Core Lab will evaluate all primary and secondary endpoints that are based on 
imaging, specified in the list below, as well as other parameters of interest specified in the 
Core Lab Reading Guidelines.  
 Subdural hematoma volume 
 Subdural hematoma thickness 
 Presence of a new cSDH or an acute component 
 
The study endpoints parameters will be independently read by two Imaging Core Lab 
assessors. In the event of discordance between the two reviewers, a third independent 
assessor will evaluate the image. This independent assessor will be a blinded evaluator and 
will not have access to assessments of other reviewers. The interpretation identified by 2 
out of the 3 reviewers will be used. 
 
All imaging (DSA and CT) shall be performed in accordance to the Oculus Imaging 
Guideline  recommended protocol provided to the sites. A copy of the study DSA and CT 
scans will be submitted to the core lab. De-identified images may be sent via DICOM 

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format on a CD (that contains the subject ID, study visit, Sponsor name, and protocol 
number), or uploaded electronically to the Imaging Core Lab website. An external CT scan 
(not performed by the site) is acceptable as long as the scan is provided to the site 
investigator and the core laboratory. 
 
6.2.  Concomitant Medications, Treatments, and Procedures 
The following will be recorded throughout the study on the eCRF:  
 
Antithrombotic medications (i.e., antiplatelet, anticoagulant, fibrinolytics)  
 
Statins 
 
Steroids 
 
Antiepileptic drugs (AEDs)  
 
Medications used during the study embolization procedure, excluding anesthesia  
 
Medications to treat adverse events 
 
Any additional surgeries (e.g. Endovascular/Neurovascular Surgery, Percutaneous   
            Endoscopic Gastrostomy, Tracheostomy, Shunt) performed throughout the study  
            period related to the treatment of the cSDH  
 
6.3.   Neurological and Cognitive Evaluations 
The following neurological and cognitive evaluations will be used in this study:  
 
Glasgow Coma Scale (GCS) - The Glasgow Comma Score is a tool used 
by healthcare providers to objectively quantify the degree of impairment in patients 
presenting with neurological symptoms. It is composed of 3 categories scored 
between 3-6 for normal response and 1 for no response. The individual scores from 
each category are summed in order to calculate a subject's total GCS score. The 
maximum possible score is 15, indicating normal function, with the minimum score 
being a 3, indicating unresponsive patient. 
 
The modified Rankin Scale (mRS) - The mRS is a scale commonly used 
to measure the degree of disability or dependence in the daily activities in subjects 
following stroke or other neurologic events. It is a scale with seven categories 
ranging from no symptoms (=0) to severe disability (=5) and death (=6).  
The mRS assessments used in a secondary endpoint will be performed by a 
qualified independent evaluator who is not part of the interventional (embolization) 
treating team and not involved in patient care or data entry and is blinded to study 
treatment assignment.  The evaluator does not need to be a physician. 
 
Markwalder Neurological Grading Scale (MGS) - Markwalder 
Neurological Grading Scale is a grading system developed to evaluate neurological 
performance in patients presenting with cSDH. It is a 5 point scale ranging from 0 

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(patient neurologically normal), through 1-3 (mild to severe neurological deficit), 
to 4 (patient comatose). 
The MGS assessment used in a secondary endpoint will be performed by a qualified 
independent evaluator who is not part of the interventional (embolization) treating 
team and not involved in patient care or data entry and is blinded to study treatment 
assignment.  The evaluator does not need to be a physician. 
 
Mini Mental State Exam (MMSE) - The Mini Mental State Exam is a 
standardized tool widely used by healthcare providers to assess mental state in 
elderly patients or those who may be cognitively impaired. It includes tests of 
orientation, attention, memory, language, and visual-spatial skills. It is comprised 
of questions (e.g. “What is the year?”) and tasks (e.g. “Make up and write a sentence 
about anything.”). The examiner asks questions and gives directions to perform 
tasks and scores the response according to MMSE instructions. Scores 0-17 indicate 
severe cognitive impairment, scores 18-23 indicate mild impairment, and scores 
24-30 are considered normal. 
All study personnel assigning the MMSE score will have training available in 
performing of the MMSE assessment. 
6.4.   Medical Resource Utilization and Health Economics  
Medical resource utilization associated with the study procedure will be collected in the 
eCRF by the investigator and study-site personnel for all subjects throughout the study. 
Procedure and post-procedure healthcare resource utilization will be assessed at hospital 
discharge. Healthcare resource utilization will include length of hospitalization and number 
of ICU days. 
The study will also utilize the EQ-5D-5L questionnaire to assess subjects’ quality of life. 
The EQ-5D-5L measures self-assessed health-related quality of life based on 5 categories: 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each area is 
rated on a scale that describes the degree of problems in that area (i.e. I have no problems 
walking about, slight problems, moderate problems, severe problems, or unable to walk).  
This tool also has an overall health scale where the rater selects a number between 1-100 
to describe the condition of their health, 100 being the best imaginable. 
6.5   Viz RECRUIT 
All MEMBRANE study sites will have the option to utilize the Viz Recruit system. Viz 
RECRUIT is Viz.ai, Inc.’s commercial software application designed to support subject 
screening in research studies. Viz RECRUIT can interface with and incorporate 
commercial products and artificial intelligence (AI)-based algorithms to assist clinicians in 
identifying potential candidates who may meet study criteria.  
 
 
7.  
Study Schedule 
7.1.  
Screening (0-30 days prior to randomization) 

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Patients presenting with a chronic subdural hematoma will be assessed by the institution’s 
site physicians to determine the appropriate standard of care treatment regardless of the 
research study, either surgery or non-surgical management. Patients will then be screened 
for trial enrollment based on the protocol inclusion and exclusion criteria. During the initial 
screening phase, the investigator will perform an initial evaluation of potential study 
subjects for study eligibility.  This initial screening phase may include review of existing 
patient information (e.g. previously performed CT, laboratory studies, medical history, 
physical examination, etc.)  A Pre-screening Log will be utilized at enrolling centers and 
will capture all patients with presenting with a diagnosis of cSDH, as well as the reason for 
non-eligibility, including detailed reasons for cases when eMMA was not deemed 
technically feasible.  
Informed consent must be obtained from all subjects prior to any study-specific 
evaluations. The informed consent process is detailed further in Section 11.3.  
A patient is considered enrolled in the study upon signing the informed consent form.  
All Subjects who provide written informed consent will be entered into Electronic Data 
Capture (EDC) regardless of whether or not they undergo randomization.  
The following screening data will be collected after subject provides a signed informed 
consent and is confirmed to meet eligibility criteria, prior to the randomization: 
 Relevant medical history will be collected from a subject interview and a review 
of the subject’s medical records with specific attention to neurological 
deficits/sequelae, bleeding disorders, cardiac conditions that carry a high risk of 
neurological events, or conditions that may compromise survival or ability to 
complete follow-up. 
 Relevant medication history will be collected from a subject interview and a 
review of the subject’s medical records.  The following relevant medications taken 
within 30 days prior to  randomization will be recorded.  
 Antithrombotic medications (i.e., antiplatelet, anticoagulant, fibrinolytics)  
 Statins 
 Steroids 
 Antiepileptic drugs (AEDs)  
 A pregnancy test will be done according to the treating institutions SOC (e.g., 
blood or urine test).  Pregnancy may also be ruled out by documented medical 
history (e.g. menopause, surgical sterility). 
 CT exam (MRI allowed only at screening)– a standard CT or MRI exam will be 
performed as part of the screening process. 
All screening tests should be completed within 30 days prior to randomization. 

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In the event that greater than 30 calendar days has elapsed prior to randomization, screening 
tests and procedures are to be repeated, as needed to ensure all are performed within 30 
days of the randomization.  
 
7.2. Pre-randomization through Discharge 
 
This section is presented separately for the surgical and non-surgical cohorts, based on their 
respective treatments. 
 
7.2.1. Surgical Cohort 
7.2.1.1.  
Surgery 
 
Patients assigned to surgery as determined by the institution’s site physicians will undergo 
surgical cSDH decompression, per the institution’s standard of care. All patients will 
undergo surgery prior to randomization. The type of surgery will be captured in the eCRF. 
7.2.1.2. 
Pre-Randomization 
 
After surgery and prior to randomization, the assessments listed below will be performed, 
and data collected on the eCRF.  Pre-randomization assessments may occur post-surgery 
on the day of randomization, prior to the subject being randomized. 
 CT 
The CT scan must demonstrate stability of the hematoma. Stability is defined as 
no worsening of midline shift or increase in the size of the cSDH from the 
screening image that result in new or worsening clinical symptoms.   
 GCS 
If any worsening of the subject’s GCS post the pre-randomization CT is noted, a 
new CT scan is required to demonstrate stability of the hematoma. 
  mRS 
 
For the surgical cohort, mRS should reflect status prior to surgery 
 MGS 
For the surgical cohort, MGS should reflect status prior to surgery.   
 MMSE 
 Quality of Life (EQ-5D-5L) 
 Concomitant medications 
 Medical resource utilization 

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Subjects determined to be ineligible for the study prior to randomization will only require 
the reason for the eligibility failure and study exit to be recorded in the eCRF.  No further 
follow-up or data collection in the eCRFs are required. 
7.2.1.3.  
Randomization 
 
Post the surgical procedure, patients who meet all eligibility criteria and consent to 
participate in the  MEMBRANE trial will be randomized 1:1 to undergo surgery and 
embolization of the MMA vs. surgery alone (SOC). 
 
For subjects randomized to surgery and eMMA, the MMA embolization procedure will 
occur up to 10 days after the surgery (but within the same hospital admission). 
Embolization is defined as injection of TRUFILL n-BCA into a blood vessel beyond the 
tip of the microcatheter. 
 
Subjects randomized to surgery alone will receive no further intervention. 
 
NOTE: Subjects randomized to the surgery alone group CANNOT undergo MMA 
embolization during the follow up period (i.e. no crossover). 
 
7.2.1.4. 
Day 0 (within 10 days of surgery):  
7.2.1.4.1 
eMMA Arm  Study Embolization Procedure (within 10 days of 
surgery) 
The subject should be prepared for the planned study embolization procedure according to 
standard hospital procedures for MMA embolization.  Medications appropriate for 
anesthesia will be administered using standard hospital practice. Immediately prior to 
TRUFILL n-BCA placement, the physician will perform a digital subtraction angiography 
(DSA) of the MMA.  Selection of the target artery segment and angiography will be done 
using standard techniques and images will be submitted to the core lab.  
Clinical sites will be responsible for providing ancillary devices (e.g., guidewires, guide 
catheters, sheaths) during the procedure.  
Pre-planned treatment should be TRUFILL n-BCA as the only liquid embolic agent. The 
treating investigator will utilize the TRUFILL n-BCA device to embolize the MMA per 
the IDE IFU.  
 
The following data should be captured during the procedure and recorded on the eCRF.: 
 Procedure date 
 Name of the implanting physician 
 Ancillary devices used to gain access and deliver the study device (e.g., 
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 Procedure start and end times (arterial puncture through last catheter withdrawal) 
 Total cumulative fluoroscopy time  
 Presence of vasospasm (vessel and times of onset/resolution).  Vasospasm will be 
captured as an adverse event only if it leads to a subsequent thrombotic or ischemic 
event. 
 Embolization technique (all that apply):  
o 
No embolization 
o 
Proximal ligation 
o 
Penetration without reaching midline 
o 
Penetration to midline 
o 
Penetration beyond midline 
 Total number of TRUFILL n-BCA packages opened during the procedure and lot 
numbers of the packages 
 Ratios of TRUFILL n-BCA system component used 
  AEs 
 Medical Resource Utilization 
 All procedure medications except anesthesia 
   Device malfunctions/deficiency 
 
Note: Procedural data collected in this study that is not essential to the study endpoints will 
not be considered a deviation if absent  
 
The timing of all study follow-up visits is relative to the date of the study embolization 
procedure (Day 0). 
 
In the event that the subject is confirmed eligible for the study and randomized for the 
eMMA procedure, but the target artery is not treated with the TRUFILL n-BCA (including 
those subjects who are deemed not to be suitable candidates for eMMA based on pre-
procedure angiograms), the subject will be followed-up per study schedule up to 6 months.  
7.2.1.4.2. 
Surgery Alone Arm: Telephone or In-person Visit (within 10 days of 
surgery) 
 
In order to ensure an equal number of contacts with all subjects, those subjects randomized 
to surgery alone will undergo a Day 0 follow-up visit.  The Day 0 visit should occur within 
10 days of surgery. The purpose of the visit is to ask how the subject is feeling after the 
surgery, review any post-surgery instructions, and to record the following information 
which will then be entered into the eCRF: 

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 AEs 
 Relevant medications taken 
 Medical Resource Utilization 
 
 
The timing of all study follow-up visits is relative to the date of this Day 0 follow-up visit. 
 
In the event that the subject is not discharged within 10 days of surgery, the Day 0 visit 
assessments may be performed inpatient, within 10 days of surgery.  
 
In the event the subject cannot be contacted within 10 days of surgery, the Day 0 visit date 
will be 10 days post surgery and all subsequent follow-up visits will be based on this Day 
0 date.  
 
7.2.1.5. 
Discharge 
 
The following data will be collected upon subject being medically ready for discharge or 
at discharge and entered into the eCRF by the site: 
 
MGS  
 
mRS 
 
MMSE 
 
AEs 
 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical Resource Utilization 
 
7.2.2. Non-Surgical Cohort 
7.2.2.1. 
Pre-Randomization  
 
Prior to randomization, the assessments listed below will be performed, and data 
collected on the eCRF. Pre-randomization assessments may occur on the day of 
randomization, prior to the subject being randomized. 
 
CT 
The CT scan must demonstrate stability of the hematoma. Stability is defined as 
no worsening of midline shift or increase in the size of the cSDH from the 
screening image that results in new or worsening clinical symptoms.   
 
GCS 

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If any worsening of the subject’s GCS post the pre-randomization CT is noted, a 
new CT scan is required to demonstrate stability of the hematoma. 
 
mRS 
 
MGS 
 
MMSE 
 
Quality of Life (EQ-5D-5L) 
 
Concomitant medications 
 
Medical resource utilization 
Subjects determined to be ineligible for the study prior to randomization will only require 
the reason for the eligibility failure and study exit to be recorded in the eCRF.  No further 
follow-up or data collection in the eCRFs are required. 
7.2.2.2. 
Randomization  
 
Patients who meet all eligibility criteria and consent to participate in the MEMBRANE 
trial will be randomized 1:1  to undergo NSMM and embolization of the MMA vs. NSMM 
alone (SOC). 
 
For patients randomized to NSMM and MMA embolization, the MMA embolization will 
occur using TRUFILL n-BCA.  The MMA embolization procedure may occur up to 10 
days after randomization. Patients randomized to NSMM alone will NOT undergo the 
study embolization procedure and will be managed per non-surgical medical management 
standard of care alone including: modifying/stopping oral anticoagulation therapy, 
initiation of medication i.e. statins (if applicable), observation, repeat imaging, and life-
style modification. NOTE: Subjects in the non-surgical cohort may have only one CT scan 
as their screening and randomization. If the CT scan is within 36 hours of randomization, 
an additional CT scan may not be required.   
 
NOTE: Patients randomized to the NSMM alone group CANNOT undergo MMA 
embolization during the follow up period (i.e. no crossover). 
 
7.2.2.3. 
Day 0: (within 10 days of randomization) 
7.2.2.3.1. 
eMMA Arm Only: Study Embolization Procedure (within 10 days of 
randomization)  
 
Subjects in the NSMM cohort who are randomized to the eMMA arm undergo the same 
study embolization procedure and capture the same data on the eCRF as described in 
Section 7.2.1.4. 
 

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7.2.2.3.2. 
NSMM Arm Only: Follow-up Visit (within 10 days of randomization 
 
In order to ensure an equal number of contacts with all subjects, those subjects randomized 
to NSMM alone will undergo a follow-up visit (may be performed via telephone) within 
10 days of randomization.  The purpose of the call is to ask how the subject is feeling, 
remind the subjects to adhere to NSMM guidelines previously provided, and to record the 
following information which will then be entered into the eCRF: 
 
AEs 
 
Relevant medications taken 
 
Medical Resource Utilization 
 
The timing of all study follow-up visits is relative to the date of this Day 0 follow-up visit. 
 
In the event that the subject cannot be contacted within 10 days of randomization, the Day 
0 visit date will be 10 days post randomization and all subsequent follow-up visits will be 
based on this Day 0 date.  
 
 
7.2.2.4. 
Discharge (eMMA arm only) 
 
The following data will be collected upon subject being medically ready for discharge or 
at discharge for the eMMA arm and entered into the eCRF by the site: 
 
 MGS 
 
mRS 
 
MMSE 
 
AEs 
 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical Resource Utilization 
 
For subjects randomized to receive NSMM only (no eMMA), the pre-randomization 
assessments outcomes will be carried forward to the discharge timepoint. These 
assessments do not need to be repeated. 
 
7.3. 
Follow-up – All Subjects 
The follow-up period begins immediately post-treatment (i.e., MMA embolization 
procedure for subjects randomized to receive embolization or telephone visit for subjects 
randomized to SOC). Site personnel will review the follow-up requirements with the 

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subjects to help ensure compliance with the schedule.  Any imaging related to the target 
cSDH conducted post-treatment and prior to the final study visit should be sent to the 
Imaging Core Lab.  
It is important that the follow-up schedule be adhered as closely as possible for all subjects.  
Subjects may not be able to return for visits at exactly the date required therefore, a visit 
window is acceptable.  Visits not completed within the window will be recorded as protocol 
deviations.  A study visit should be scheduled as close as possible to the earlier side of the 
visit window to allow for possible re-scheduling thereby minimizing deviations. 
In order to maximize patient retention and decrease the potential for missing data, all 
follow-up visits, except the 6 month visit, can be either an in person clinic visit or a 
phone/telehealth visit (e.g. video conference or a telephone call). However, a CT exam will 
still be required. An external CT scan (not performed by the site) is acceptable as long as 
the scan is provided to the site investigator and core laboratory. 
Any study subject who does not attend a scheduled follow-up visit should be contacted by 
site personnel to determine the reason for the missed appointment and to reschedule.  The 
reason for the missed visit shall be recorded.  If the missed visit was due to an AE, an AE 
eCRF must be completed and any reporting and assessment requirements must be met. 
 
7.3.1. 1 Month Follow-up (±14 days) – Clinic or Phone/Telehealth Visit 
The following data will be collected and entered into the eCRF by the site: 
 
CT exam is required and must be sent to the independent Imaging Core 
Lab 
 
MGS 
 
mRS 
 
AEs 
 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical resource utilization 
 
7.3.2. 3 Months Follow-up (±14 days) – Clinic or Phone/Telehealth Visit 
The following data will be collected and entered into the eCRF by the site: 
 
CT exam is required and must be sent to the independent Imaging Core 
Lab 
 
MGS* 
 
mRS* 
 
AEs 

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 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical resource utilization 
 
*NOTE: Must be performed by a qualified independent evaluator who is not part 
of the interventional (embolization) treating team and not involved in patient care 
or data entry and is blinded to study treatment assignment. The evaluator does not 
need to be a physician.  Assessments may be completed via phone/telehealth by 
blinded assessor. 
 
7.3.3. 6 Months Follow-up (±30 days) – Clinic Visit 
The following data will be collected and entered into the eCRF by the site: 
 
CT exam is required and must be sent to the independent Imaging Core 
Lab 
 
MGS* 
 
mRS* 
 
MMSE  
 
Quality of Life (EQ-5D-5L) 
 
AEs 
 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical resource utilization 
 
*NOTE: Must be performed by a qualified independent evaluator who is not part 
of the interventional (embolization) treating team and not involved in patient care 
or data entry and is blinded to study treatment assignment. The evaluator does not 
need to be a physician. Assessments may be completed via phone/telehealth by 
blinded assessor. 
 
7.3.4. 1 Year Follow-up (± 60 days) – Clinic or Phone/Telehealth Visit 
The following data will be collected and entered into the eCRF by the site: 
 
CT exam is required and must be sent to the independent Imaging Core 
Lab 
 
MGS* 

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 
mRS* 
 
Quality of Life (EQ-5D-5L) 
 
AEs 
 
Relevant medications taken 
 
Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 
Medical resource utilization 
 
*NOTE: Must be performed by a qualified independent evaluator who is not part 
of the interventional (embolization) treating team and not involved in patient care 
or data entry and is blinded to study treatment assignment. The evaluator does not 
need to be a physician. Assessments may be completed via phone/telehealth by 
blinded assessor. 
 
7.4. 
Unscheduled Visit 
Subjects returning for an unscheduled visit to the study center that is related to the cSDH 
treated in the study or indicating new or unresolved signs and/or symptoms will be 
documented as an unscheduled follow-up.  Information to be collected, at a minimum 
includes: 
 AEs 
 Relevant medications 
 Adherence to SOC recommendations (e.g. MM, lifestyle modifications) 
 Medical resource utilization 
The following assessments will be optional but if performed per standard of care, should 
be entered in the eCRF: 
 CT exam – if performed, must be sent to the independent Imaging Core Lab 
 GCS 
 MGS 
 mRS 
 MMSE 
 
7.5. 
Post-Randomization Surgical Procedure/ Re-Operation 
As determined by the treating physician, subjects in both randomization cohorts may 
require surgical hematoma decompression at any time after randomization. Subjects who 

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undergo re-operation or surgical procedure on the cSDH within 6 months post 
randomization will be considered as failing the primary endpoint. 
In the event a surgical procedure or re-operation is performed post-randomization, the 
following data will be collected and entered into the eCRF by the site: 
 
CT exam is required and must be sent to the independent Imaging Core 
Lab 
 
AEs 
 
Relevant medications taken 
 
Medical resource utilization 
 
Type of surgery 
 
NOTE: After the initial study procedure, TRUFILL n-BCA may NOT be used for 
MMA embolization during the follow up period. 
 
7.6. 
Early Termination 
The study can be discontinued at the discretion of the investigator or study Sponsor for 
reasons including, but not limited to, the following: 
 Per recommendation of the DMC 
 Unanticipated adverse device effect (UADE) presenting an unreasonable risk to 
subjects (Sponsor may terminate the study immediately) 
 Obtaining new scientific knowledge that shows that the study is no longer valid or 
necessary 
 Insufficient recruitment of subjects 
 Persistent non-compliance of a site with the protocol, or IRB/EC regulatory 
requirements 
If the study is discontinued or suspended prematurely at a single clinical site (e.g. due to 
non-compliance or lack of enrollment) or across all study centers, the Sponsor shall inform 
the clinical investigator(s)/investigational center(s) of the termination or suspension in 
enrollment, along with the reason. The Sponsor will also inform site personnel that 
although enrollment will be halted, the currently enrolled subjects will continue to be 
followed per protocol through the one-year follow-up visit and then exited from the study. 
The Sponsor’s communication to the investigator(s)/investigational center(s) will also 
include instructions for the investigator to promptly inform all consented subjects at their 
center(s), as well as the IRB/EC regarding the change in study status, along with the reason 
for termination or suspension.  The Sponsor will notify regulatory authorities in writing of 
the action, per regulations.  The personal physicians of the subjects may also need to be 
informed if deemed necessary.  
 

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7.7. 
Lost to Follow-up 
Every attempt will be made to have all subjects complete the follow-up visit schedule. A 
subject will not be considered lost to follow-up until the last study visit and unless efforts 
to obtain compliance are unsuccessful. At a minimum, the effort to obtain follow-up 
information will include three attempts to make contact via telephone/email and if 
unsuccessful, then a letter from the investigator, sent via FedEx or similar traceable 
method, will be sent to the subject’s last known address. Both contact logs and letter contact 
efforts to obtain follow-up will be recorded in the subject study files and a return receipt is 
filed to document delivery of the letter. 
 
 
 

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7.8. 
Schematic of Study Design 
 

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7.9. 
Schedule of Assessments 
 
Surgical Cohort 
 
Screening 
(0‐30 days prior to 
Randomization ) 
Surgical Procedure 
Pre‐Randomization1 
Randomization  
 
Day 0 (within 10 days of 
surgery) 
 
Embolization Arm Only: 
Embolization Procedure  
 
Surgery Alone Arm Only: 
Phone/In person Follow up  
Discharge5 
1 Month Follow‐up  
(+/‐14 days) Clinic or 
Phone/Telehealth + CT Exam 
3 Months Follow‐up   
(+/‐ 14 days) Clinic or 
Phone/Telehealth + CT Exam 
6 Months Follow‐up   
(+/‐ 30 days) Clinic Visit 
1 Year Follow‐up  
(+/‐ 60 days) Clinic Visits or 
Phone /Telehealth/ + CT 
exam 
Unscheduled Visit 
Re‐Operation 
Table Legend: 
X = Required 
O = Optional, to be collected if 
performed during standard of 
care 
 
Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
CT ExamP2 
X7 
 
X 
(≤36 hrs before 
randomization) 
 
 
X 
X 
X 
X 
O 
X 
Surgical Procedure  
 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
Embolization Procedure (Embolization Arm Only) 
 
 
 
 
X 
(DSA for eMMA) 
 
 
 
 
 
 
 
Glasgow Coma Scale (GCS) 
 
 
X 
 
 
 
 
 
 
O 
 
Markwalder Grading Scale (MGS) 
XP3 
 
 
X 
X 
XP4 
XP4,6 
XP4 
O 
 
Modified Rankin Score (mRS) 
XP3 
 
 
X 
X 
XP4 
XP4,6 
XP4 
O 
 
Mini‐Mental State Exam (MMSE) 
 
 
X 
 
 
X 
 
 
X 
 
O 
 
Quality of Life (EQ‐5D‐5L) 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adherence to SOC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Review of Adverse Events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical Resource Utilization 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 Pre-Randomization assessments may occur on the day of randomization, prior to the subject being randomized. 
2 An external CT scan (not performed by the site) is acceptable as long as the scan is provided to the site investigator and the core laboratory. 
3 Assessment should reflect the subject’s condition just prior to undergoing surgery.  Assessment may be performed post-surgery using pre-surgical data.  
4Assessment must be performed by a qualified independent evaluator who is not part of the interventional (embolization) treating team, not involved in patient care or data entry, and is blinded to study treatment assignment. The evaluator does 
not need to be a physician. 
5Discharge assessments may be performed when subject is medically ready to be discharged OR at the time of discharge. 
6 mRS and MGS may be completed via phone/telehealth by blinded assessor. 
7 MRI at screening is acceptable. Pre-randomization imaging must be CT scan 
 
 

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Non‐Surgical Cohort 
 
Screening 
(0‐30 days prior to 
Randomization) 
Pre‐Randomization1 
Randomization    
 
Day 0 (within 10 days of 
randomization) 
 
Embolization Arm Only: 
Embolization Procedure  
 
NSMM Arm Only: 
Phone/In person Follow up  
Discharge4 
Embolization Arm Only 
1 Month Follow‐up  
(+/‐14 days) Clinic or 
Phone/Telehealth + CT Exam 
3 Months Follow‐up  
(+/‐ 14 days) Clinic or 
Phone/Telehealth + CT Exam 
6 Months Follow‐up  
(+/‐ 30 days) Clinic Visit 
1 Year Follow‐up  
(+/‐ 60 days) Clinic Visit or 
Phone/Telehealth + CT Exam 
Unscheduled Visit 
Surgical Procedure   
Table Legend: 
X = Required 
O = Optional, to be collected if performed 
during standard of care 
 
Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
CT ExamP2 
X6 
X 
(≤36 hrs 
before 
randomizatio
n) 
 
 
 
X 
X 
X 
X 
O 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
Embolization Procedure (Embolization Arm Only) 
 
 
 
X 
(DSA for eMMA) 
 
 
 
 
 
 
Glasgow Coma Scale (GCS) 
X 
 
 
 
 
 
 
 
O 
 
Markwalder Grading Scale (MGS) 
X 
 
 
X 
X 
XP3 
XP3,5 
XP3 
O 
 
Modified Rankin Score (mRS)P  
X 
 
 
X 
X 
XP3 
XP3,5 
XP3 
O 
 
Mini‐Mental State Exam (MMSE) 
 
X 
 
 
X 
 
 
X 
 
O 
 
Quality of Life (EQ‐5D‐5L) 
 
X 
 
 
 
 
 
X 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adherence to SOC 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Review of Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical Resource Utilization 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
P1 PPre-Randomization assessments may occur on the day of randomization, prior to the subject being randomized.  
P2P An external CT scan (not performed by the site) is acceptable as long as the scan is provided to the site investigator and core laboratory. 
P3 PAssessment must be performed by a qualified independent evaluator who is not part of the interventional (embolization) treating team and not involved in patient care or data entry and is blinded to study treatment assignment. The evaluator does not need to be a physician 
4 The discharge assessments may be performed when subject is medically ready to be discharged OR at the time of discharge. 
5 mRS and MGS may be completed via phone/telehealth by blinded assessor. 
6 MRI at screening is acceptable. Pre-randomization imaging must be CT scan 
 

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8. 
Assessment of Safety 
8.1. 
Specific Safety Parameters 
 
To ensure the safety of the subject and provide a complete picture of the safety of the 
device so that important safety events are not missed, all adverse events occurring from 
the time of randomization through the one year follow up visit will be captured at each 
study visit. Progression of disease or subdural hematoma recurrence (e.g. increase in 
midline shift or increase in subdural hematoma size) will not be considered an AE, unless 
symptomatic.  
 
In addition, all mortality will be reported in the study regardless of causality.  
 
The following will be reported by the independent Imaging Core Lab and not reported as 
AEs unless they are symptomatic. 
 
Increased midline shift  
 
Increased subdural hematoma size 
8.1.1. Adverse Event (AE) 
An adverse event (AE) is defined as any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons, whether or not related to the investigational medical device and 
whether anticipated or unanticipated (ISO 14155:2020). 
Note 1: This definition includes events related to the investigational medical device or the 
comparator. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to the 
investigational medical devices or comparators. Any medical condition that is present prior 
to randomization will be considered as baseline and not reported as an AE. Such conditions 
should be added to medical history, if not previously reported.  
 
8.1.2. Serious Adverse Event (SAE) 
A serious adverse event (SAE) is defined (ISO 14155:2020) as an adverse event that: 
 
Led to death 
 
Led to serious deterioration in the health of the subject, users or other 
persons as defined by one or more of the following:  
 
a life-threatening illness or injury, or 
 
a permanent impairment of a body structure or a body  

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            function including chronic diseases, or 
 
in-patient or prolonged hospitalization, or 
 
medical or surgical intervention to prevent life-threatening  
  
illness or injury or permanent impairment to a body structure  
or a body function 
 
Led to fetal distress, fetal death, a congenital abnormality, or birth defect  
including physical or mental impairment  
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
clinical investigation plan, without serious deterioration in health, is not considered a 
serious adverse event. 
8.1.3. Adverse Device Effect (ADE) 
An adverse device effect is defined as an adverse event related to the use of an 
investigational medical device (ISO 14155:2020). 
Note 1: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device 
Note 2: This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device 
8.1.4. Serious Adverse Device Effect (SADE) 
A serious adverse device effect is an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE (ISO 14155:2020). 
8.1.5. Unanticipated Serious Adverse Device Effect (USADE) 
Per ISO 14155:2020, an unanticipated serious adverse device effect is a serious adverse 
device effect which by its nature, incidence, severity or outcome has not been identified in 
the current risk assessment. 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment. 
8.1.6. Unanticipated Adverse Device Effect (UADE) 
Per 21 Code of Federal Regulations (CFR) 812.3(s), an unanticipated adverse device effect 
(UADE) is 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. 
8.1.7. Device Deficiency, Device Malfunction, and Use Error 

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neuroradiology and who are not otherwise involved with the study.  The CEC will review 
all adverse events to adjudicate the safety endpoints (e.g. death, stroke, MI, 
thromboembolic complications, new onset seizure).  The CEC will operate under a CEC 
Charter.  
 
8.7. 
Data Monitoring Committee 
An independent DMC will be responsible for assessing and monitoring the accumulated 
AEs and interim data on a periodic basis as the study progresses to ensure subject safety.  
The DMC will be comprised of representatives from multiple disciplines including but not 
limited to neurosurgery, neurology, interventional neuroradiology and biostatistics. The 
DMC will advise the Sponsor regarding the continuing safety of subjects and those yet to 
be recruited to the study, as well as the continuing validity and scientific merit of the study. 
The DMC will provide recommendations to the Sponsor regarding stopping or continuing 
enrollment in the study. The DMC will operate according to an approved charter.  
 
 
9. 
Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of human 
subjects are protected, that study data are accurate, complete, and verifiable, and that study 
conduct complies with 21 CFR Parts 812, 11, 50, 54, and 56, ISO 14155, the currently 
approved protocol, Good Clinical Practice, and with applicable regulatory requirements. 
Each site will undergo periodic monitoring visits, and subject source documentation, 
including medical records, shall be made available during the visits.   
The monitors for this study will be: 
Johnson and Johnson  
31 Technology Drive 
Irvine CA, 92618  
 
Johnson & Johnson Medical (Shanghai) Ltd.  
Part C F1-3 No 439 Fute West First rd China (Shanghai) Pilot Free Trade Zone, 
Shanghai, P.R. CHINA  
 
Monitoring visits may include but are not limited to the following: 
 
Protocol adherence 
 
Source data verification and accuracy of the eCRFs  
 
Verification that informed consent is being obtained for all subjects screened and 
enrolled in the study in accordance with requirements described in the study 
protocol 
 
Verification of completeness of the Regulatory Binder 

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 
Verification of accuracy of all study logs such as the Delegation of Responsibility 
Authority Log, Pre-Screening Logs, etc.  
 
Device accountability for regions in which the study device is investigational 
 
Compliance with applicable regulations 
 
Identification and action to resolve any issues or challenges with the study. 
Data are to be submitted promptly via eCRF after collection. Missing or unclear data will 
be queried to be corrected as necessary throughout the study. The Sponsor will request 
further documentation such as physician notes, outside hospital records, etc. when further 
documentation is required to understand any adverse events.  Monitoring will be conducted 
in accordance with the monitoring plan. 
 
9.1 
Site Selection  
 
The sites selected to participate in this study will be required to have: 
 Treating investigators who participate in the study will have extensive experience using 
TRUFILL n-BCA or similar device (e.g., or other n-BCA) in neurovascular 
embolization procedures. 
 
All sites will have a neurosurgical program capable of treating subdural hematomas. 
 
Investigators will have experience performing embolizations through the middle 
meningeal artery. 
 
All sites will be required to have adequate resources to conduct the clinical study and 
assure compliance.  
 
Each investigator will be required to commit to follow all subjects per protocol,  
including preforming the required CT scans. 
 
 
 
10.0 Statistical Methodology 
The sponsor will be responsible for the overall analysis of data from this protocol. A 
separate Statistical Analysis Plan (SAP) will be written and approved prior to the database 
lock. The SAP will describe all planned analyses based on the statistical design of this 
study and subsequent data collected. A brief statistical overview of key statistical analyses 
is provided below. 
 
10.1 
Analysis Sets 
The following analysis sets are defined for this study:   
 
Intent-to-Treat (ITT) Analysis Set 
The ITT analysis set consists of all enrolled subjects who are randomized in the study. 
Subjects will be analyzed as randomized regardless of treatment received. 

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 
Per Protocol (PP) Analysis Set   
The PP analysis set is a subset of the ITT analysis set, excluding the subjects with 
significant eligibility deviations, as well as those who did not receive treatment as assigned, 
in addition to other major protocol deviations which will be outlined in the Statistical 
Analysis Plan. 
 
As Treated (AT) Analysis Set   
The As Treated analysis set consists of all randomized in the study who receive study 
treatment. Subjects will be analyzed by actual treatment they received. 
10.2 
Randomization and Blinding Procedures 
This is an open label study. Subjects presenting with a subdural hematoma will be assessed 
by site physicians to determine the appropriate treatment for each subject: surgery or non-
surgical management. Eligible subjects will then be randomized 1:1 to undergo SOC with 
eMMA vs SOC alone. Randomization will be stratified by site within cohort. 
The Sponsor will remain blinded to the summary outcomes by treatment arm until the 
primary endpoint analyses are complete.  
10.3 
Levels of Significance 
The primary effectiveness endpoint will be tested at a one-sided significance level of 0.05. 
Secondary endpoints will be tested using a gatekeeping strategy only if the primary 
effectiveness endpoint is successful. The familywise error-rate for hypotheses tests 
intended for labeling will therefore be controlled at 5%. 
10.4 
Sample Size Justification  
Cochran–Mantel–Haenszel (CMH) statistic will be used to test superiority in the primary 
effectiveness endpoint of SOC with eMMA over SOC alone. The CMH test will be 
performed with stratification of the cohorts (surgical vs. NSMM).  A target of 
approximately up to 70% of subjects are expected to be allocated to the surgical cohort and 
the remaining subjects will be allocated to the NSMM cohort. Subjects within each cohort 
will be randomized 1:1 to SOC alone or SOC with eMMA. Assuming a common odds ratio 
(Agresti, 1990) of0.34, a total sample size of 376 subjects after accounting for 10% attrition 
will provide at least 80% power for the primary effectiveness endpoint at a one-sided 
significance level of 0.05.  
Anticipated effectiveness rates for the primary effectiveness endpoint were derived from 
the literature (key articles include Rovlias et al., 2015; Kim, 2017; Brennan et al., 2017; 
Ban et al., 2018; Knopman et al., 2018; Fountas et al., 2019; Link et al., 2019; Shotar et 
al., 2020; Ng et al., 2020). The assumptions in Tables 5 and 6 below reflect the consensus 
of the Executive Steering Committee for the study. 
For the secondary endpoint that evaluates a component of the primary effectiveness 
endpoint later in time (12 months), it is anticipated that the effect size will be at least as 
large for the primary effectiveness endpoint assessment. 
 

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Table 5 – Assumptions of event probability of primary effectiveness endpoint in 
surgical cohort 
 
SOC with eMMA 
SOC alone 
Event-free (success) probability 
95.9% 
88.5% 
Event (failure) probability 
4.1% 
11.5% 
Odds ratio  
0.33 
 
 
Note: odds ratio is calculated as the ratio of odds of failure over success in SOC with eMMA versus 
the odds of SOC alone.  
Table 6 - Assumptions of event probability of primary effectiveness endpoint in 
non-surgical medical management cohort 
 
SOC with eMMA 
SOC alone 
Event-free (success) probability 
90.9% 
78.0% 
Event (failure) probability 
9.1% 
22.0% 
Odds ratio 
0.35 
Note: odds ratio is calculated as the ratio of odds of failure over success in SOC with eMMA versus 
the odds of SOC alone. 
 
For the primary safety endpoint, we expect at least an 80% probability of observing 
AEs that occur at an incidence of at least 1% within each treatment group. This expectation 
pertains to approximately 188 participants receiving eMMA (surgery + eMMA and NSMM 
+ eMMA) and 188 participants receiving standard of care (surgery alone and NSMM 
alone). 
 
 
10.5 
Analyses to be Conducted 
10.5.1. General Conventions 
Data will be summarized by treatment arm and cohort, unless instructed otherwise. 
Standard descriptive summaries for continuous data include the number of observations 
with data, number of observations with missing data, mean, standard deviation, median, 
minimum, and maximum values. For categorical data, the count and percent will be 
provided.  
In the event a subject withdraws or discontinues from the study without completing full 
follow-up, unless otherwise specified, observed data up to the date of discontinuation or 
withdrawal will be included in analyses. Unless specified otherwise, percentages will be 
based on the number of subjects without missing data. 
Endpoints will be analyzed by analysis window in the SAP and may differ from the 
protocol defined clinical visit window.   
10.5.2. Disposition of Study Subjects 
Subject disposition will be summarized by treatment arm and cohort in the following 
way: 
 With a summary of the number and percentage of subjects enrolled by site/investigator 

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 With a subject accountability table which indicates the number and percentage of 
subjects in each analysis set, and a summary of subjects who were randomized, 
completed the study, who died or were withdrawn or lost-to-follow-up with associated 
reasons. 
10.5.3. Demographics and Baseline Characteristics 
All demographic and baseline characteristics, will be summarized for each analysis set, 
including but not limited to: age, sex, medical history, prior treatment etc.  
10.5.4. Procedural and Post-Procedural Characteristics 
Procedural and immediate post-operative characteristics will be summarized for each 
analysis set. 
10.5.5. Primary Endpoint and Secondary Endpoint Analyses and Associated 
Hypotheses 
10.5.5.1. 
Primary Endpoint and Associated Hypotheses 
1. Primary effectiveness endpoint: Residual or re-accumulation of the cSDH  (>10 
mm) at 6 months as assessed by an independent core laboratory OR re-operation or 
surgical procedure on the cSDH within 6 months post randomization 
The primary effectiveness endpoint analysis will be conducted on the ITT analysis set as 
the primary analysis; the same analysis will be repeated using the PP and AT analysis sets 
as supportive analyses. 
The null and alternative hypotheses for this endpoint are 
HR0R: 𝜃஼ெு > 1 
HRAR: 𝜃஼ெு < 1 
Where 𝜃஼ெு is the common odds ratio for primary effectiveness endpoint failure. Cochran-
Mantel-Haenzel (Agresti 1990) test with continuity correction, and stratification by cohort 
(surgical or non-surgical) will be used to test the primary effectiveness endpoint at a one-
sided significance level of 5%. 
Subjects are considered as primary effectiveness endpoint failures if they have reported 
any of the following events:  
o Residual or re-accumulation of their subdural hematoma (>10mm) at 6 months 
as assessed by the independent Imaging Core Lab; 
o Any re-operations or surgical procedures on the cSDH within 6 months post-
randomization. 
The number and percentage of subjects with events will be summarized by treatment arm 
and cohort. 
For subjects who didn’t receive any re-operations or surgical procedures on the cSDH, but 
with missing values on the subdural hematoma thickness at 6 months, their missing 
hematoma thickness at 6 months will be imputed, further details refer to section 10.5.5.8. 

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Subjects whose hematoma thickness at 6 months is missing due to death prior to the 6-
month CT scan and the death is due to an AE found by the CEC to be related to the study 
device or underlying disease state (i.e., lack of efficacy in study treatment), will be 
considered failures on this endpoint. 
The endpoint will be considered successful if the p-value the continuity corrected CMH test 
is significant at the 0.05. The study will be considered successful if the primary 
effectiveness endpoint is claimed a success.  
2. Primary safety endpoint: Occurrence of all AEs through 6 months 
All AEs through 6 months will be summarized descriptively using the As Treated analysis 
set in treatment with eMMA (surgery + eMMA and NSMM + eMMA) vs. treatment with 
SOC (surgery alone and NSMM alone). The same analysis will be repeated using the ITT 
and PP analysis sets as supportive analyses. 
 
10.5.5.2. 
Secondary Endpoints and Associated Hypotheses 
Hypotheses on secondary endpoints will only be tested if the primary effectiveness 
endpoint is achieved.  
These hypotheses will be analyzed in the ITT analysis set per the following order. 
1. 
Good functional outcome at 3 months (mRS 0-2 or no worsening from 
baseline if baseline mRS ≥3)  
The null and alternative hypotheses for the non-inferiority test on this endpoint are  
 
HR0R: 𝑃ௌை஼ା௘ெெ஺െ𝑃ௌை஼ ≤ -12% 
HRAR: 𝑃ௌை஼ା௘ெெ஺െ𝑃ௌை஼ > -12% 
 
where 𝑃ௌை஼ା௘ெெ஺ and 𝑃ௌை஼ are the proportions of success in subjects who reported good 
functional outcome at 3 months in the treatment of SOC+ eMMA and SOC alone (across 
both cohorts), respectively. A subject is considered a success for this endpoint if mRS is 0-
2 at 3 months, or there is no worsening from baseline if  baseline mRS is  ≥3.     
Based on the precedent for the same endpoint in the EMBOLISE Study (NCT04402632) 
presented at the International Stroke Conference (Davies et al., 2024) and in agreement 
with the MEMBRANE study Co-Principal Investigators (PIs), the application of the 12% 
non-inferiority margin will not yield a clinically meaningful difference from the treatment 
of standard of care. 
Subjects with missing data at 3 months will be imputed per section 10.5.5.8. The null 
hypothesis will be rejected if the one-sided 95% lower confidence bound is greater than     
-12%.   
 
2. 
Subjects requiring a surgical procedure on the cSDH within 12 months 

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The null and alternative hypotheses for the superiority test on this endpoint are 
HR0R: 𝜃஼ெு·௦௣ > 1 
HRAR: 𝜃஼ெு·௦௣ < 1 
where 𝜃஼ெு·௦௣ is the common odds ratio for surgical procedure endpoint failure. Cochran-
Mantel-Haenzel test with continuity correction, and stratification by cohort (surgery or 
NSMM) at a one-sided significance level of 5% will be performed.  
Subjects are considered as surgical procedure endpoint failures if they experienced any re-
operations or surgical procedures on the cSDH within 12 months. 
The endpoint will be considered successful if the p-value from the continuity corrected 
CMH test is less than at the 0.05. 
3. 
Mean change in hematoma volume at 6 months compared to baseline as 
assessed by an independent core laboratory 
The null and alternative hypotheses for this endpoint are 
HR0R: 𝛥 ≥ 0 
HRAR: 𝛥 < 0 
where 𝛥ൌ µௌை஼ା௘ெெ஺െ µௌை஼ is the difference in mean change in  hematoma volume at 
6 months compared to baseline between treatments of SOC+eMMA vs. SOC alone. 
µௌை஼ା𝒆ெெ஺ is the mean change hematoma volume with SOC and eMMA (6 months – 
baseline); while µௌை஼ similarly is the mean change in hematoma volume in SOC alone. 
Baseline is defined as the pre-randomization image.  
ANOVA (analysis of variance) will be performed to test this secondary endpoint. Change 
in hematoma volume at 6 months will be the outcome variable. Main effects for treatment 
(SOC alone or SOC with eMMA) and cohort (surgery or NSMM) will be included in the 
model. Subjects with missing values on hematoma volume at baseline or 6 months will be 
imputed according to the strategy described in section 10.5.5.8.  The null hypothesis will 
be rejected if the one-sided 95% upper confidence bound on 𝛥 is less than 0. 
 
10.5.5.3. 
Other Secondary Endpoint Analyses – Effectiveness 
Secondary effectiveness endpoints will be summarized by the planned treatment arm and 
cohort using the ITT and PP analysis sets. Missing values on the assessments will be 
excluded.  
1. 
Mean change in hematoma volume at 3 and 12 months compared to baseline 
as assessed by an independent core laboratory 
Mean change in hematoma volume and change from baseline will be summarized at 3and 
12 months. Baseline is defined as the pre-randomization image. 
2. 
Reduction of > 50% hematoma volume at 3, 6 and 12 months as assessed by 
an independent core laboratory 

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Logistic regression will be used to obtain the predicted probability and estimated odds ratios 
for the reduction of >50% in hematoma volume at 3, 6 and 12 months. Details of the logistic 
regression models will be provided in the SAP. The predicted probabilities of reduction 
>50% at 3, 6 and 12 months will be summarized. Baseline is defined as the pre-
randomization image. 
3. 
 Complete resolution of the cSDH at 3, 6 and 12 months assessed by an 
independent  core laboratory 
Logistic regression will be used to obtain the predicted probabilities and the estimated odds 
ratios of complete resolution of cSDH at 3, 6 and 12 months. Details of the logistic 
regression model(s) will be provided in the SAP. The predicted probabilities of complete 
resolution at 3, 6 and 12 months will be summarized.  
4. 
Median time to achieve complete resolution of the cSDH 
Inverse prediction from logistic regression will be used to estimate the median time to 
achieve complete resolution of the cSDH, where the median time is the time corresponding 
to 50% predicted probability of achieving complete resolution of the cSDH. Details of the 
logistic regression model(s) will be provided in the SAP.  
5. 
Subjects that develop an acute component of their existing cSDH or a new    
cSDH at 3, 6 and 12 months as assessed by an independent core laboratory 
Stratified Kaplan-Meier analyses by cohort and treatment will be used to summarize the 
cumulative incidence of  an acute component of the existing cSDH or a new cSDH at 3, 6 
and 12 months. 
6. 
Subjects requiring surgical procedure on the cSDH within 3 and 6 months post 
randomization 
Stratified Kaplan-Meier analyses by cohort and treatment will be used to summarize the 
cumulative incidence of surgical procedures on the cSDH within 3 and 6 months. 
7. 
Subjects requiring more than one surgery on the cSDH within 3, 6 and 12 
months post randomization 
The number and percentage of subjects who require more than one (i.e., two or more) 
surgical procedures or re-operations on the cSDH within 3, 6 and 12 months post 
randomization will be summarized by cohort and treatment. 
10.5.5.4. 
Secondary Endpoint Analyses – Safety 
Secondary safety endpoints will be summarized using ITT, PP and As Treated analysis 
sets. 
1. 
mRS distribution change at 3, 6 and 12 months  
mRS distribution at baseline and post-baseline mRS at 3, 6 and 12 months will be 
summarized across all subjects by treatment and cohort. Subjects with missing mRS scores 
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subjects with missing mRS scores due to reasons other than all-cause death will be excluded 
from the analysis.   
2. 
Death, stroke, myocardial infarction or thromboembolic complications 
within 3, 6 and 12 months as assessed by the Clinical Events Committee 
Death, stroke, myocardial infarction or thromboembolic complications are considered as a 
composite endpoint. Stratified Kaplan-Meier analyses by cohort and treatment will be 
used to summarize the cumulative incidence of the composite endpoint within 3, 6 and 12 
months. 
3. 
Development of new onset of seizures within 3, 6 and 12 months as assessed 
by the Clinical Events Committee 
Stratified Kaplan-Meier analyses by cohort and treatment will be used to summarize of the 
cumulative incidence of  new onset of seizures within 3, 6 and 12 months. 
4. 
Change in Markwalder Grading Scale at 3, 6 and 12 months compared to 
baseline 
Mean Markwalder Grading Scale score at each timepoint and change from baseline at 3, 6 
and 12 months will be summarized. 
5. 
Change in MMSE score at 6 months compared to baseline 
Mean MMSE score and change from baseline at 6 months will be summarized. 
10.5.5.5. 
Secondary Endpoint Analyses – Health Economics 
Health economic endpoints will be summarized in PP analysis set.  
1. 
Hospital days and ICU days 
Index procedure hospitalization for the eMMA treatment will be summarized by 
cohort.  
All-cause hospitalizations during follow-up will be summarized separately by 
treatment arm and cohort. The number of hospitalizations, proportion of subjects 
who are hospitalized, length of stay in ICU, and total length of stay in days 
(including ICU days) will be summarized separately. Subjects who die before 
discharge will be summarized separately. 
2. 
Change in EQ-5D-5L score at 6 months compared to baseline 
Mean EQ-5D-5L score at baseline and follow-up visits and change from baseline 
at 6 months and 1 year; and change between 6 months to 1 year will be summarized 
as well. 
10.5.5.6. 
Safety Analyses 
Safety analyses will be summarized by treatment arm and cohort in As Treated analysis 
set.  

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All AEs collected in the study will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). AEs, SAEs, device or procedure-related AEs, AEs by severity, 
UADEs and deaths will be summarized with frequencies and listed. 
Study device malfunctions will be summarized and listed.  
10.5.5.7. 
Plans for Interim Analyses 
There are no planned interim analyses in the study. 
10.5.5.8. 
Handling of Missing Data 
 
Missing data for primary effectiveness endpoint at 6 months 
For the primary effectiveness endpoint, subjects who did not receive any post-
randomization re-operations or surgical procedures on the cSDH, but with missing values 
on the subdural hematoma thickness at 6 months will be imputed with multiple imputation 
method that will make use of the subject’s own baseline hematoma thickness values and 
other potential auxiliary variables from each cohort.  
The multiple imputation method results in a large collection of imputed datasets. The 
imputed primary effectiveness endpoint value (success or failure) will then be analyzed 
through CMH test. Estimates of common odds ratio from continuity corrected CMH test 
and associated variance will then be computed in each imputed dataset and pooled together 
per Rubin's method (1996). Additional imputation details will be elaborated in the SAP. 
Missing data will be imputed in the primary analysis with ITT analysis set. The supportive 
analysis using PP and AT analysis set will use the observed values, no missing data to be 
imputed.  
 
Secondary endpoint: Good functional outcome at 3 months (mRS 0-2 or no 
worsening from baseline if baseline mRS ≥3)  
Subjects with missing mRS scores due to death prior to 3 months will be considered to 
have a score of 6 in the analysis. Subjects with missing data at 3 months due to reasons 
other than death will be imputed with multiple imputation that will make use of baseline 
mRS and other auxiliary variables. Estimates of risk difference of the treatments and 
associated variance will then be computed in each imputed dataset and pooled together 
per Rubin's method.  
 
Secondary Endpoint: Missing data for surgical procedures on the cSDH within 12  
            months 
Subjects with unknown status on surgical procedures within 12 months due to early 
discontinuation from the study will be imputed with multiple imputation method that will 
make use of the subject’s hematoma thickness values and other potential auxiliary 
variables in each cohort.  The estimates of common odds ratio and associated variance 
from each imputed dataset will then be handled in the same way as the primary 
effectiveness endpoint. 
 
Secondary Endpoint: Missing data for mean change in hematoma  

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            volume at 6 months 
Subjects with missing values on hematoma volume at 6 months will be imputed with 
multiple imputation method that will make use of the subject’s baseline hematoma volume 
and other potential auxiliary variables in each cohort. The imputed hematoma volume at 
6 months will then be used to in the model. Estimates of mean hematoma volume at 6 
months and associated variance from each imputed dataset will then be combined per 
Rubin’s method. 
 
No missing data imputation is planned for the analyses of other secondary  
            endpoints 
 
10.5.5.9. 
Sensitivity Analyses 
The sensitivity analysis for the primary effectiveness endpoint will include a Gail-Simon 
test (1985) for a potential qualitative interaction between the two cohorts at an alpha level 
of 0.15. Additional sensitivity analyses will be detailed in the SAP. 
10.5.5.10. 
Subgroup Analyses 
The primary effectiveness endpoint will be analyzed by subgroups with clinically 
meaningful risk factors using the ITT analysis set. Summary statistics will be presented at 
each subgroup level by cohort. Further details will be detailed in SAP. 
10.5.5.11. 
Sex Specific Analyses 
To investigate the effects by sex on the primary effectiveness endpoint, a logistic regression 
using the ITT analysis set will be performed and a treatment by sex interaction term will 
be included. The binary outcome on the primary effectiveness endpoint will be used as the 
response variable. The interaction term will be tested at an alpha level of 0.15 using Wald 
chi-square test statistic. A non-significant p-value on the interaction term (p-value > 0.15) 
will support poolability of outcomes across females and males. Summary statistics by sex 
will be presented by cohort. 
10.5.5.12. 
Assessment of Site/Region Homogeneity  
Homogeneity of odds ratio of the primary effectiveness endpoint across sites and regions 
(US vs. OUS) will be assessed  at an alpha level of 0.15 using the ITT analysis set. Logistic 
regression will be performed and a region by treatment interaction  test will be included. A 
separate logistic regression will be performed in a similar way testing for site by treatment 
interaction. Then the Holm-Bonferroni multiplicity adjustment method will be used to 
control the family-wise error rate at 15% for the site and region hypothesis tests of 
homogeneity of the primary effectiveness endpoint. Sites with insufficient number of 
subjects will be pooled by geographic region before the actual analyses. The OUS 
enrollment is small (50) and is expected to be distributed between the two treatments and 
two strata. If there are model convergence issues, descriptive statistics by region will be 
provided. 
 
11. Ethics and Protection of Human Subjects 

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11.1 
Ethical Standard 
As the Sponsor of this study, Cerenovus has the overall responsibility for the conduct of 
the study, including assurance that the study is conducted in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, as well as the regulatory 
requirements of the Food and Drug Administration and local government. The Sponsor 
will also maintain compliance with Good Clinical Practice (International Conference on 
Harmonization (ICH) version 4 du 1 May 1996), the European standard EN ISO 
14155:2020 (Clinical Investigation of Medical Devices for Human Subjects), Sponsor 
general responsibilities (21 CFR 812.40), selection of investigators (21 CFR 812.43), 
monitoring (21 CFR 812.46), supplemental applications (21 CFR 812.35 [a] and [b]), 
maintaining records (21 CFR 812.140 [b]), and submitting reports (21 CFR 812.150 [b)]), 
and to local regulations where required. 
 
General Responsibilities   
Sponsor’s general duties consist of submitting the IDE application to FDA, assuring that 
sites have received IRB/EC approvals prior to starting the study, selecting investigators, 
ensuring proper clinical site monitoring and ensuring subject informed consent is obtained.  
Any additional requirements imposed by an IRB/EC or regulatory authority shall be 
followed, if appropriate. 
 
Data Quality and Reporting 
Sponsor is responsible for providing quality data that satisfy federal regulations and 
informing proper authorities of unanticipated adverse effects and deviations from the 
protocol.   
 
Selection of Investigators 
Sponsor will select qualified investigators, obtain a signed Investigator Agreement and 
provide the investigators with the information necessary to conduct the study. 
 
Supplemental Applications—Protocol Amendments  
As appropriate, Sponsor will submit changes in the study protocol to the FDA and 
investigators to obtain IRB/EC re-approval.  A justification for each amendment will be 
documented.   
 
Maintaining Records  
Sponsor will maintain copies of correspondence, signed Investigator Agreements, data, 
adverse device effects, financial disclosure and other records related to the study.  
 
Submitting Reports  
Sponsor will submit any required regulatory reports identified in this section of the 
regulation.  This includes unanticipated adverse device effects, withdrawal of FDA 
approval, current investigators list, annual progress reports, recall information, final reports 
and device use without informed consent. 
 

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11.2. Institutional Review Board / Ethics Committee 
The protocol, ICF, recruitment materials, and all participant materials will be submitted to 
the IRB/EC for review and approval.  IRB/EC approval of both the protocol and the consent 
form must be obtained before any participant is consented.  A stamped copy of the IRB/EC 
approval letter and approved consent form must be submitted to the Sponsor certifying 
study approval prior to subject consent.   
Any amendment to the protocol will require review and approval by the IRB/EC before the 
changes are implemented to the study. The Sponsor and the IRB/EC must approve in 
writing any changes to the protocol that affect the rights safety and/or welfare of the 
subjects or may adversely affect the validity of the study. All changes to the consent form 
will be IRB/EC approved and a determination will be made regarding whether previously 
consented participants need to be re-consented. 
Investigators are responsible for submitting and obtaining initial and continuing review of 
the study by their IRB/EC. 
 
11.3. Informed Consent Process 
11.3.1. Consent and Other Informational Documents Provided to Participants 
Patient’s informed consent must be obtained and documented.  
The IRB/EC must review and approve an ICF specific to this study.  Cerenovus will 
provide each study center with an example ICF.  The clinical center, to meet specific 
IRB/EC requirements, may modify this example ICF; however, the ICF must contain all 
of the informed consent elements required by 21 CFR 50.25 or according to applicable 
local requirements.  Each investigational site will provide sponsor with a copy of the 
IRB/EC approved ICF and renewed approvals and consents as appropriate for the duration 
of the study.  The original, signed and dated ICF should be retained by the investigational 
site for monitoring, and a copy provided to the subject. 
 
11.3.2. Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to an individual agreeing to participate 
in a study and continues throughout the individual’s study participation. Discussion of risks 
and possible benefits of participation will be conducted with the patients and their families. 
The investigator, or designee, will explain the research study to the patient and answer any 
questions that may arise. All patients will receive verbal and written information in 
language at a level of complexity understandable to the patient about the purpose, 
procedures, and potential risks of the study and of their rights as research participants. 
Patients will have ample opportunity to review the written consent form and to ask 
questions prior to signing. The patients should be allowed additional time as desired to 
consider the study prior to agreeing to participate. Prior to participation in the study, the 
ICF will be signed and personally dated by the patient or his/her legal representative. The 
subjects may withdraw consent at any time throughout the course of the study. The rights 

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and welfare of the participants will be protected, and it will be emphasized to them that the 
quality of their medical care will not be adversely affected if they decline to participate in 
this study. A signed and dated copy of the ICF must be collected from each enrolled subject 
and kept in the study subject files.  Subjects will be notified in a timely manner of any 
significant new information that develops over the course of the study that may affect their 
willingness to participate. 
The informed consent will include an authorization for use and disclosure of the subject’s 
PHI, in accordance with the Health Insurance Portability and Accountability Act (HIPAA) 
or as required per local regulations. Subject confidentiality will be maintained throughout 
the clinical study in a way that assures that individual subject data can be tracked back to 
the source data. For this purpose, a unique subject identification code will be used that 
allows identification of all data reported for each subject. Data relating to the study may be 
made available to third parties, provided the data are treated as confidential and with 
compliance with HIPAA and any local privacy regulation and ultimately that the subject’s 
privacy is guaranteed. 
It is not expected that the TRUFILL n-BCA System will be used emergently as eligibility 
confirmation includes a screening process, and subjects requiring emergent hematoma 
evacuation will not be eligible to participate in the study. Therefore, consent under 
emergency circumstances does not apply.  
 
11.3.3. Participant and Data Confidentiality 
During this clinical investigation, all representatives of the Sponsor will comply with all 
in-country privacy laws, including HIPAA and regulations regarding contact with subjects, 
their medical record information, copying of information, and protection of the subject 
identities. 
All information and data sent to Cerenovus concerning subjects or their participation in 
this clinical investigation will be considered confidential. Only authorized Cerenovus 
personnel or representatives (including contracted service providers, i.e. Imaging Core 
Lab, Clinical Research Associate, Central Lab etc.), representatives of regulatory agencies 
will have access to these confidential files upon request (including, but not limited to, 
admissions/discharge summaries for hospital admission occurring during a subject’s study 
participation and autopsy reports for deaths occurring during the clinical investigation).  
All data in the analysis and reporting of this evaluation will be used ensuring security and 
privacy of protected health information in accordance with HIPAA.  
 
12. Quality Assurance and Quality Control 
Quality Control (QC) procedures will be implemented beginning with the data entry system 
and ongoing QC checks will be run on the database. Any missing data or data anomalies 
will be communicated to the site(s) for clarification/resolution.  
Following written (Standard Operating Procedures) SOPs, monitors will verify that the 
clinical study is conducted, and data are generated, documented, and reported in 

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compliance with the protocol, Good Clinical Practice (GCP), and the applicable regulatory 
requirements. If noncompliance is identified, Sponsor is required by regulation to 
implement measures to secure compliance.  
The investigational site will provide direct access to all study related information, source 
data/documents, and reports for the purpose of monitoring and auditing (i.e. Quality 
Assurance (QA) by the Sponsor and its representatives, and inspection by local and 
regulatory authorities.  
 
 
13. Data Handling and Record Keeping 
13.1 
Data Collection and Management Responsibility 
Data collection is the responsibility of the site clinical study staff under the supervision of 
the investigator.  The investigator is responsible for ensuring the accuracy, completeness, 
and timeliness of the data entered.  The Sponsor is responsible for all data management 
activities. These activities include the development of a database, utilizing validated 
database software, into which all study data will be entered by the clinical sites. The 
Sponsor will be responsible for ensuring the overall integrity of the database. 
 
13.1.1. Electronic Case Report Forms 
Electronic CRFs have been developed to capture the information outlined in this study 
protocol. Data on these eCRFs will be monitored, corrected if necessary, and entered into 
a validated database.  All changes made to the data will be tracked in the electronic audit 
trail, recording the current value, previous value, reason for change, date timestamp of data 
entry/change, and the name of the person who changed the data. The investigator will 
electronically sign all subject eCRFs as verification that the data have been reviewed and 
correctly reflects source documentation. Data from these eCRFs will be used to provide 
analysis of this study. 
 
13.1.2. Source Documentation 
Data entered on to the eCRFs will be obtained from source documentation, such as hospital 
procedure reports, admission and discharge summaries, and other hospital or physician 
office/clinic documents. If no standard hospital or clinic document exists to capture 
information required specifically for this clinical investigation, a source worksheet may be 
developed to record this information. Any worksheets shall be signed by the investigator 
at the given site and will serve as the source document for those data parameters. These 
source documents will serve as the basis for monitoring subject specific information 
against the eCRFs. 
Electronic subject records will be considered source documents on the condition that the 
hospital’s database is a validated system. If this is not the case, electronic records will have 

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to be printed and added to the subject’s paper file. A print-out of an eCRF cannot be used 
as source documentation. 
 
13.1.3. Study Records 
Regulations require that investigators maintain information in the subject’s medical 
records, which corroborate data collected on the eCRFs.  The Investigator is responsible 
for maintaining medical and study records for every subject participating in the clinical 
study (including information maintained electronically such as digital imaging).  The 
Investigator will also maintain original source documents from which study-related data 
are derived, which include, but are not limited to: 
 Clinic progress notes recording subject’s medical history and medications 
 Medical charts with operative reports and condition of subject upon discharge 
 Medical records regarding AEs, including treatment and clinical outcome  
 Results of diagnostic examinations 
 Imaging (such as x-rays, MRIs), as well as the report of the radiologist’s     
   reading/interpretation of diagnostic imaging 
 Notes of phone calls and/or correspondence indicating investigational site’s   
attempts to follow study subjects at the required follow-up visits until subject’s      
participation in the study is complete or terminated 
 Records relating to subject death (e.g., death certificate, autopsy report) 
 Print-outs of source data generated by technical equipment (e.g., x-rays, MRIs) 
must be filed with the subject’s records.   
Only authorized Cerenovus personnel or representatives, authorized site personnel, local 
government authorities, or the FDA, acting in their official capacities, will have access to 
these confidential files. 
 
13.1.4. Health Economic Data 
The frequency of health care utilization during hospitalization for the study index 
procedure and any additional hospitalizations during the study period will be collected.  
This data will not be provided to the FDA as part of the IDE reporting because it does not 
support the safety and efficacy of the investigational device.   
The hospitalization health care data to be collected may include, but is not limited to, the 
subject’s admission date, discharge  date, procedure date, ICD-10 and procedure codes and 
DRG assignment (if applicable). 
In addition, the Sponsor will collect health economic data associated with follow up care 
including any additional or necessary procedures/surgeries resulting from the index 

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procedure, ER visits, and/or outpatient visits to address issues related to the target cSDH. 
Data collected may include quality of life data, length of hospital stay, and readmissions. 
 
13.1.5. Data Reporting 
The investigator, or designated individual, is responsible for timely completion of all data 
from the study via the eCRFs supplied by Cerenovus. The investigator/delegated individual 
is required to electronically sign the eCRF on the appropriate pages to verify that he/she 
has reviewed, and attests to the correctness, of the recorded data. Completed eCRFs will 
be reviewed and monitored at the investigational site by Cerenovus, personnel or designee 
at regular intervals throughout the study. To this end, the investigator and institution must 
permit inspection of the study files and subject eCRFs by such representatives and/or 
responsible government agencies.  
Investigators are required to prepare and submit accurate and timely reports on this study 
to the IRB/EC and Cerenovus as applicable. 
 
13.1.6. Data Verification and Review 
Cerenovus will track the amount of missing data and contact sites as appropriate to instruct 
them on steps to minimize missing data and remain compliant with protocol required 
assessments. Missing or unclear data will be queried as necessary throughout the study.  
Cerenovus will request further documentation such as physician and/or radiology reports 
when complications or malfunctions are observed and reported. Cerenovus will be 
responsible for auditing the database and confirming the overall integrity of the data. 
 
13.1.7. Final Data Analysis 
All exported datasets for analyses will undergo a final data review before final database 
lock. Once all critical data are monitored and locked, the final analyses of clinical 
investigation data will be performed. 
 
13.2. Study Record Retention and Archiving 
The investigator will maintain all essential study documents and source documentation that 
support the data collected on the study subjects in compliance with FDA regulations per 
21 CFR 812.140(d).  Documents must be retained for a period of 2 years after the latter of 
the following two dates: The date on which the investigation is terminated or completed, 
or the date that the records are no longer required for purposes of supporting a premarket 
approval application, or as specified per country specific record retention requirements, 
after the study is completed and or terminated.  The investigator will take measures to 
ensure that these essential documents are not accidentally damaged or destroyed. If for any 
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custody must be transferred to an individual who will assume responsibility. Cerenovus 
must receive written notification of this custodial change. 
 
 
14. Protocol Deviations 
The investigator is responsible for ensuring that the clinical investigation is conducted in 
accordance with the procedures described in the protocol, and any conditions required by 
the reviewing IRB/EC.  A protocol deviation is a failure to comply (intentionally or 
unintentionally) with the requirements of the clinical study as specified in the protocol.  
Examples of protocol deviations include late visits, missed visits, required follow-up 
testing not completed, visit out of window, non-adherence to inclusion/exclusion criteria, 
etc. and shall be reported to the Sponsor through the eCRFs.   Deviations will be reviewed 
and assessed by the Sponsor.   
It is the responsibility of the site to use vigilance to identify and report deviations to the 
Sponsor and IRB/EC per regulation and applicable guidelines.  The study monitors shall 
verify that the conduct of the study is in compliance with the approved protocol and 
applicable regulations and shall identify deviations and any issues of noncompliance. 
Corrective and preventative actions will be implemented promptly as necessary and 
significant protocol deviations that raise subject safety concerns or indicate repeat 
noncompliance may be grounds for investigator disqualification. 
The investigator is not allowed to deviate from the protocol except under emergency 
circumstances to protect the rights, safety and well-being of study participants. Under 
emergency circumstances, deviations may proceed without prior approval of the sponsor 
and the IRB/EC. Such deviations shall be documented and reported to the sponsor and 
IRB/EC as soon as possible. 
 
 
15. Data and Publication Policy 
Publications and/or presentation of the clinical investigational results will be coordinated 
between Cerenovus and the clinical investigation author(s).  Authorship will be determined 
prior to development of any manuscript.  All information concerning the study device, 
Sponsor operations, patent application, manufacturing processes, and basic scientific data 
supplied by the Sponsor to the investigator and not previously published, are considered 
confidential and remain the sole property of the Sponsor.   
 
 
16. Study Administration 
16.1 
Study Registration 
This study will be registered on the clinical trial registries and results data banks like, but 
not limited to www.ClinicalTrials.gov. 
16.2. Steering Committee 

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A Steering Committee comprised of physicians with experience in the areas of 
neurosurgery, neurology or interventional neuroradiology has been appointed for this 
study.  The responsibilities of the Steering Committee include: 
 
Consultation on study design, protocol development, subject eligibility 
inquiries, data to be collected, analyses to be performed and investigator training 
 
Review of clinical data and statistical analyses, assist in data interpretation 
and writing 
 
Provide oversight of the study 
 
 
17. Conflict of Interest 
The term “conflict of interest” refers to situations in which financial or other personal 
considerations may compromise or have the appearance of compromising a researcher's 
professional judgment in conducting or reporting research. Cerenovus will make every 
effort to safeguard against conflicts of interest to assure the integrity of the data, subject 
safety and investigator objectivity. 
Clinical investigators will complete financial disclosure forms prior to initiating the study 
and update them annually or when changes occur related to stock and stock options and 
income from salary, honorariums, and consulting fees. 
 
 
 

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