Prospective Evaluation to Characterize the Real-World Performance of the EMBOVAC Aspiration Catheter for Neurothrombectomy: A Post-Market Clinical Follow-up Trial.
Conditions: Acute Ischemic Stroke
Sponsor: Cerenovus, Part of DePuy Synthes Products, Inc.

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
Prospective Evaluation to Characterize the Real-
World PerFormance of the EMBOVACTM 
Aspiration Catheter for Neurothrombectomy:  
A Post-Market Clinical Follow-up Trial  
 
PERFECT 
 
 
Protocol Number:  CNV_2019_01 
Version:  2.0 
5 November 2021 
 
History of Changes 
Version Date 
Description 
Version 1.0— 21NOVEMBER2019 
Original Document  
Version 2.0 – 5 NOVEMBER 2021 
Protocol Revision 
 
 
 
Sponsor:  CERENOVUS 
  
   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.  This document may be disclosed to 
appropriate institutional review boards, independent ethics committees, or duly authorized representatives of 
regulatory authorities as appropriate; under the condition that confidentiality is requested.
ClinicalTrials.gov Identifier: NCT04531904
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Table of Contents 
1. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................................................................... 14 
1.1. 
BACKGROUND INFORMATION..................................................................................................................... 14 
1.2. 
CURRENT TREATMENT OPTIONS ................................................................................................................. 14 
1.3. 
PREVIOUS EXPERIENCE WITH EMBOVACTM ASPIRATION CATHETER ................................................................... 15 
1.3.1. 
Rationale ....................................................................................................................................... 16 
1.4. 
COMMERCIAL PRODUCT ........................................................................................................................... 16 
1.5. 
POTENTIAL RISKS AND BENEFITS ................................................................................................................. 16 
1.5.1. 
Known Potential Risks .................................................................................................................... 16 
1.5.2. 
Minimization of Risk ...................................................................................................................... 17 
1.5.3. 
Known Potential Benefits ............................................................................................................... 17 
2. 
OBJECTIVES AND PURPOSE ......................................................................................................................... 17 
2.1. 
OBJECTIVES ........................................................................................................................................... 17 
3. 
STUDY DESIGN AND ENDPOINTS................................................................................................................. 18 
3.1. 
DESCRIPTION OF THE STUDY DESIGN ............................................................................................................ 18 
3.2. 
STUDY ENDPOINTS .................................................................................................................................. 18 
3.2.1. 
Primary Endpoint ........................................................................................................................... 18 
3.2.2. 
Secondary Effectiveness Endpoints ................................................................................................. 18 
3.2.3. 
Safety Endpoints ............................................................................................................................ 19 
3.2.4. 
Health Economic Endpoints ............................................................................................................ 20 
3.3. 
RESCUE THERAPY .................................................................................................................................... 20 
4. 
STUDY POPULATION ................................................................................................................................... 20 
4.1. 
PARTICIPANT INCLUSION CRITERIA ............................................................................................................... 20 
4.2. 
EXCLUSION CRITERIA ............................................................................................................................... 21 
4.3. 
STRATEGIES FOR RECRUITMENT AND RETENTION ............................................................................................ 22 
4.4 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................................... 23 
4.4.1 
Reasons for Withdrawal or Termination ......................................................................................... 23 
4.4.2 
Handling of Participant Withdrawals or Termination ...................................................................... 23 
5. 
STUDY DEVICE ............................................................................................................................................ 23 
5.1 
STUDY DEVICE DESCRIPTION .......................................................................................................................... 23 
5.1.1 
DEVICE ACQUISITION ............................................................................................................................... 23 
5.1.2 
DEVICE RETURNS .................................................................................................................................... 24 
6. 
STUDY PROCEDURES AND EVALUATIONS ................................................................................................... 24 
6.1. 
STUDY SPECIFIC PROCEDURES .................................................................................................................... 24 
6.1.1. 
Imaging ......................................................................................................................................... 24 
6.1.2. 
Independent Imaging Core Lab for Image Evaluation ...................................................................... 25 
6.1.3. 
Procedural Angiogram Shipment .................................................................................................... 26 
6.1.4. 
Clot Collection and Processing ........................................................................................................ 27 
6.1.5. 
Independent Central Lab for Clot Evaluation ................................................................................... 27 
6.1.6. 
Neurological Evaluations ............................................................................................................... 28 
7. 
STUDY SCHEDULE ....................................................................................................................................... 28 
7.1. 
PRE-SCREENING / SCREENING .................................................................................................................... 28 
7.2. 
BASELINE .............................................................................................................................................. 29 
7.3. 
PROCEDURE .......................................................................................................................................... 29 
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7.4. 
24 HOURS POST PROCEDURE (±12HOURS) ................................................................................................... 30 
7.5. 
DISCHARGE OR 7 DAYS (WHICHEVER OCCURS FIRST) (-1/+7 DAYS) ...................................................................... 31 
7.6. 
90 DAY (±14 DAYS) FOLLOW-UP ............................................................................................................... 31 
7.7. 
UNSCHEDULED VISIT ................................................................................................................................ 31 
7.8. 
EARLY TERMINATION ............................................................................................................................... 31 
7.9. 
LOST TO FOLLOW-UP ............................................................................................................................... 32 
7.10. 
STUDY DESIGN ....................................................................................................................................... 33 
8. 
ASSESSMENT OF SAFETY ............................................................................................................................. 33 
8.1. 
SPECIFIC SAFETY PARAMETERS ................................................................................................................... 34 
8.1.1. 
Adverse Event (AE) ......................................................................................................................... 34 
8.1.2. 
Serious Adverse Event (SAE) ........................................................................................................... 34 
8.1.3. 
Adverse Device Effect (ADE) ........................................................................................................... 35 
8.1.4. 
Serious Adverse Device Effect (SADE).............................................................................................. 35 
8.1.5. 
Unanticipated Serious Adverse Device Effect (USADE)..................................................................... 35 
8.1.6. 
Device Deficiency, Device Malfunction, and Use Error ..................................................................... 35 
8.2. 
CLASSIFICATION OF AN ADVERSE EVENT ........................................................................................................ 36 
8.2.1. 
Severity of Event ............................................................................................................................ 36 
8.2.2. 
Relationship to Study Device .......................................................................................................... 37 
8.2.3. 
Outcome........................................................................................................................................ 38 
8.2.4. 
Time Period and Frequency for Adverse Event Assessment and Follow-up ....................................... 38 
8.2.5. 
Adverse Event and Device Deficiency Documentation and Reporting Requirements ........................ 38 
9. 
CLINICAL MONITORING .............................................................................................................................. 39 
10. 
STATISTICAL METHODS ............................................................................................................................... 40 
10.1. 
STATISTICAL METHODOLOGY ..................................................................................................................... 40 
10.2. 
ANALYSIS SETS ....................................................................................................................................... 40 
10.3. 
LEVELS OF SIGNIFICANCE ........................................................................................................................... 41 
10.4. 
SAMPLE SIZE JUSTIFICATION ...................................................................................................................... 41 
10.5. 
ANALYSES TO BE CONDUCTED .................................................................................................................... 41 
10.5.1. General Conventions ...................................................................................................................... 41 
10.5.2. Disposition of Study Subjects .......................................................................................................... 41 
10.5.3. Demographic, Baseline and Procedural Characteristics ................................................................... 41 
10.5.4. Primary and Secondary Endpoint Analyses ..................................................................................... 42 
10.5.4.1. Primary Endpoint Analysis.............................................................................................................. 42 
10.5.4.2. Secondary Endpoint Analyses ......................................................................................................... 42 
10.5.4.2.1. 
Secondary Effectiveness Endpoints ........................................................................................ 42 
10.5.4.2.2. 
Secondary Safety Endpoints .................................................................................................. 43 
10.5.5. Health Economic Endpoints ............................................................................................................ 43 
10.5.6. Clot Analysis .................................................................................................................................. 44 
10.5.7. Plans for Interim Analyses .............................................................................................................. 44 
10.5.8. Handling of Missing Data ............................................................................................................... 44 
10.6. 
MEASURES TO MINIMIZE BIAS ................................................................................................................... 44 
11. 
ETHICS AND PROTECTION OF HUMAN SUBJECTS ........................................................................................ 45 
11.1. 
ETHICAL STANDARD ................................................................................................................................. 45 
11.2. 
ETHICS COMMITTEE (EC) .......................................................................................................................... 46 
11.3. 
INFORMED CONSENT AND DATA RELEASE FORM PROCESS................................................................................. 47 
11.3.1. Consent and Other Informational Documents Provided to Participants ........................................... 47 
11.3.2. Consent and Data Release Form Procedures and Documentation ................................................... 48 
11.4. 
PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................................... 49 
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11.4.1. Research Use of Stored Human Samples, Specimens and data ........................................................ 49 
11.5. 
FUTURE USE OF STORED SPECIMENS ............................................................................................................ 49 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL........................................................................................... 50 
13. 
DATA HANDLING AND RECORD KEEPING .................................................................................................... 50 
13.1. 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITY ................................................................................... 50 
13.1.1. Electronic Case Report Forms ......................................................................................................... 50 
13.1.2. Source Documentation ................................................................................................................... 51 
13.1.3. Study Records ................................................................................................................................ 51 
13.1.4. Health Economic Data ................................................................................................................... 52 
13.1.5. Data Reporting .............................................................................................................................. 52 
13.1.6. Data Verification and Review ......................................................................................................... 52 
13.1.7. Final Data Analysis......................................................................................................................... 52 
13.1.8. Study Record Retention and Archiving ............................................................................................ 52 
14. 
PROTOCOL DEVIATIONS.............................................................................................................................. 53 
15. 
DATA AND PUBLICATION POLICY ................................................................................................................ 54 
16. 
STUDY ADMINISTRATION ........................................................................................................................... 54 
16.1. 
STUDY REGISTRATION .............................................................................................................................. 54 
16.2. 
STEERING COMMITTEE ............................................................................................................................. 54 
17. 
CONFLICT OF INTEREST ............................................................................................................................... 55 
REFERENCES ......................................................................................................................................................... 56 
 
 
 
List of Figures and Tables 
Figure 1 Schematic of Study Design ..................................................................................................................... 13 
 
Table 1 Schedule of Assessments ......................................................................................................................... 12 
Table 2 Pre-clinical Design Verification and Validation Testing ............................................................................ 15 
Table 3 eTICI Scale ............................................................................................................................................... 25 
Table 4 Intensity or Severity Definitions .............................................................................................................. 37 
Table 5 Adverse Event Causality Classifications ................................................................................................... 37 
Table 6 Adverse Event Outcome Classifications ................................................................................................... 38 
Table 7 Adverse Event Reporting Requirements .................................................................................................. 39 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
ADAPT  
A Direct Aspiration First Pass Technique 
ADE 
 
Adverse Device Effect  
AE 
 
Adverse Event 
AIS 
 
Acute Ischemic Stroke 
ASPECTS 
Alberta Stroke program early CT score 
BA 
 
Basilar Artery  
CEC 
 
Clinical Events Committee 
CT 
 
Computed Tomography 
EC 
 
Ethics Committee  
eCRF   
Electronic Case Report Form 
EDC 
 
Electronic Data Capture 
GCP 
 
Good Clinical Practice 
HIPAA  
Health Insurance Portability and Accountability Act 
ICA 
 
Internal Carotid Artery 
ICF 
 
Informed Consent Form 
ICH 
 
International Council for Harmonization  
IFU 
 
Instructions for Use 
IV 
Intravenous 
IV t-PA  
Intravenous tissue Plasminogen Activator 
LVO 
 
Large Vessel Occlusion 
MCA 
 
Middle Cerebral Artery 
mITT 
 
Modified Intent-to-Treat 
MRI 
 
Magnetic Resonance Imaging 
mRS 
 
Modified Rankin Scale 
mTICI  
modified Thrombolysis in Cerebrovascular Infarction 
NIHSS  
National Institutes of Health Stroke Scale 
PHI 
 
Protected Health Information 
PP 
 
Per Protocol 
PI 
 
Principal Investigator 
PMCF  
Post-Market Clinical Follow-Up 
RBC 
 
Red Blood Cell 
SADE  
Serious Adverse Device Effect  
SAE 
 
Serious Adverse Event 
SAP 
 
Statistical Analysis Plan 
SAS 
 
Statistical Analysis Software 
SDV 
 
Source Data Verification 
SOC 
 
Standard of Care 
SOP 
 
Standard Operating Procedure 
US 
 
United States 
USADE  
Unanticipated Serious Adverse Device Effect 
VA 
 
Vertebral Artery 
WBC 
 
White Blood Cell  
 
 
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KEY ROLES AND RESPONSIBILITIES 
 
 
Sponsor: 
Cerenovus 
31 Technology Dr.  
Irvine, CA  92618 USA  
 
 
Contacts: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coordinating 
Investigator  
Contact: 
 
 
 
 
 
 
Medical Safety 
Contact: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
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PROTOCOL AGREEMENT AND STATEMENT OF COMPLIANCE FORM 
 
STUDY NAME AND NUMBER: PERFECT - CNV_2019_01 
 
STUDY TITLE:  Prospective Evaluation to Characterize the Real-World PerFormance of the 
EMBOVACTM Aspiration Catheter for Neurothrombectomy: A Post-Market 
Clinical Follow-up Trial 
 
 
VERSION NUMBER: 2.0  
 
VERSION DATE:   05 November 2021 
 
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 
study is conducted in accordance with specific provisions of the associated ECs, the current applicable 
version of ISO 14155, the ethical principles that have their origin in the Declaration of Helsinki, and that 
are consistent with Good Clinical Practice (GCP) and the applicable national and regional regulatory 
requirements, the signed agreement with Cerenovus, and with the protocol outlined herein. I will conduct 
this study as outlined therein 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 fulfill the requirements of my Ethics Committee (EC), 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 EC (where required).  
I agree to report all information or data in accordance with the protocol and, in particular, I agree to report 
any required adverse events as defined in this protocol to the Sponsor, and comply with all adverse event 
reporting requirements of my reviewing EC.  I agree to permit the Sponsor, its authorized representatives, 
my reviewing EC, 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 
 
ClinicalTrials.gov Identifier: NCT04531904
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PROTOCOL SUMMARY 
Title of Study 
Prospective 
Evaluation 
to 
Characterize 
the 
Real-World 
PerFormance of the EMBOVACTM Aspiration Catheter for 
Neurothrombectomy: A Post-Market Clinical Follow-up Trial. 
Short Title 
PERFECT 
Study Sponsor 
CERENOVUS                                                                                      
31 Technology Drive                                                                        
Irvine, CA 92618 USA 
Study Device 
EMBOVACTM Aspiration Catheter 
Indication 
The EMBOVACTM Aspiration Catheter is indicated for general 
intravascular use in the neuro vasculature. The catheter can be used 
to facilitate introduction of diagnostic or therapeutic agents and is 
also intended for use in removal/aspiration of emboli and thrombi 
from selected blood vessels in the neuro vasculature. 
Study Design 
Prospective, multi-center, single arm, post-market clinical follow-
up study.    
Sample Size 
Approximately 100 subjects will be enrolled. 
Number of Sites 
Approximately 10 institutions primarily in Europe. 
Study Duration 
Start Date: 2020 
End Date: 2022 
Study Procedures 
EMBOVACTM Aspiration Catheter is used with ADAPT (A Direct 
Aspiration, First Pass Technique) as the first attempted 
device/technique for mechanical thrombectomy in the subject. 
The study evaluation time points follow the site’s standard of care 
and include:  
1. 
Study Procedure 
2. 
24 Hour follow-up (+/- 12 hrs) 
3. 
7 Day / Discharge follow-up (-1/+7 days) (whichever 
comes first)  
4. 
90 Day Follow-up (+/- 14 days) 
Primary Objective 
The primary objective of this Post-Market Clinical Follow-Up 
(PMCF) study is to characterize the performance of the 
EMBOVACTM Aspiration Catheter in the treatment of acute 
ischemic stroke in a real-world clinical setting. 
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Secondary Objective 
The secondary objective is to confirm the benefit of a ‘system 
approach’ using Cerenovus products (e.g., distal access catheter, 
balloon guide catheter) which have been designed for use together  
in the treatment of acute ischemic stroke. 
Primary Endpoint 
Proportion of patients having successful revascularization, defined 
as number of subjects achieving a modified Thrombolysis in 
Cerebral Infarction (mTICI) score of ≥ 2b at the end of the 
procedure, as determined by Core Lab. 
Secondary Effectiveness 
Endpoints 
 Successful Revascularization (final mTICI ≥ 2b) without rescue 
therapy, as determined by Core Lab   
 Complete Revascularization (final mTICI ≥ 2c), as determined 
by Core Lab 
 First Pass Effect (mTICI ≥ 2c without rescue), as determined by 
Core Lab 
 Modified First Pass Effect (mTICI ≥ 2b), as determined by Core 
Lab 
 Time to recanalization (Time from arterial puncture to complete 
recanalization mTICI ≥ 2b), as determined by Core Lab 
 Modified Rankin Scale 0-2 at 90 Days 
Secondary Safety 
Endpoints 
 Devices related serious adverse events within 90 days  
 sICH at 24h post procedure specified according to the 
Heidelberg Bleeding Classification (HBC) 
 NIHSS at 24h post procedure 
 90 Day All-Cause Mortality 
Health Economic 
Endpoints 
 Hospitalization length of stay for index procedure and 
unscheduled re-hospitalizations  
 Healthcare resource utilization for index procedure, post-
procedure and re-hospitalizations for unscheduled events  
Inclusion Criteria 
1. Subject ≥ 18 years old. 
2. Subject experiencing acute ischemic stroke with angiographic 
confirmation of Large Vessel Occlusion (LVO) of the distal 
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intracranial internal carotid artery, middle cerebral artery (M1 
or M2) or anterior cerebral artery (A1 or A2).  
3. A clinical decision has been made to use the EMBOVAC™ 
aspiration catheter prior to enrollment in the research. 
4. EMBOVAC™ Aspiration Catheter is attempted to be used for 
the first 3 clot removal passes for the target intracranial 
occlusion (if 3 passes are needed) using A Direct Aspiration, 
First Pass Technique (ADAPT).  
Exception: it is not considered rescue therapy if use of another 
device is needed to remove distal occlusion in a vessel smaller 
than 2 mm after the first pass. 
5. Pre-stroke mRS ≤ 1 
6. NIHSS ≤ 30  
7. Informed Consent has been provided by the subject or the 
subject's legally authorized representative. 
Exclusion Criteria 
1. Potential study candidate has already undergone standard of 
care assessments or treatment that deviate from the clinical 
research protocol requirements (e.g., 24 hour imaging 
conducted outside the protocol specified window). 
2. All patients with severe hypertension on presentation (SBP > 
220 mmHg and/or DBP > 120 mm Hg). All patients, in whom 
intravenous therapy with blood pressure medications is 
indicated, with hypertension that remains severe and sustained 
despite intravenous antihypertensive therapy (SBP >185 mmHg 
and/ or DBP >110 mmHg). 
3. Known cerebral vasculitis. 
4. Known cancer with life expectancy less than 12 months. 
5. Stenosis, or any occlusion, in a vessel proximal to the target 
occlusion that requires treatment or prevents access to the site 
of occlusion. 
6. Computed tomography (CT) or Magnetic Resonance Imaging 
(MRI) evidence of recent/ fresh hemorrhage on presentation. 
7. Baseline computed tomography (CT) or MRI showing mass 
effect or intracranial tumor (except small meningioma). 
8. Evidence of dissection in the extra or intracranial cerebral 
arteries. 
9. Occlusions in multiple vessels.  
10. Confirmation of positive pregnancy test according to site 
specific standard of care (e.g. test, verbal communication). 
11. Currently participating in an investigational (drug, device, etc.) 
clinical trial that may confound study endpoints. Patients in 
observational, natural history, and/or epidemiological studies 
not involving intervention are eligible.  
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Sample Size Justification 
There is no statistical power calculation and no hypothesis testing 
for this post-market study. 100 subjects are deemed sufficient to 
characterize the performance of EMBOVACTM Aspiration 
Catheter. 
 
Approximately 100 subjects will be enrolled. With an enrolled 
sample size of 100 and an attrition rate of no more than 5%, the 
precision (margin of error) for the primary endpoint is anticipated 
to be around 8.0% based on 2-sided 95% confidence intervals, 
where the primary endpoint rate is estimated to be 80%. 
𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝑜𝑜𝑜𝑜 𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒≈1.96 × 𝑆𝑆𝑆𝑆= 1.96 × ඨ 𝑝𝑝(1 −𝑝𝑝)
𝑛𝑛 
 = 
= 1.96 × ඨ 0.8 × (1 −0.8)
95 
= 8.0% 
 
where SE denotes the standard error and p denotes the proportion of 
subjects who achieve the primary endpoint. 
Statistical Analysis  
Demographics, 
baseline 
subject 
characteristics, 
procedure 
characteristics and the primary and secondary endpoints will be 
presented for each analysis population.  
 
Descriptive summary statistics will be presented for all endpoints. 
The number and percentage of subjects will be summarized for 
categorical variables. Descriptive statistics for continuous variables 
will include the number of subjects, mean, standard deviation, 
median, minimum and maximum. 
Interim Analysis 
Interim analyses will be conducted for regional (outside Europe, as 
well as for European MDR) regulatory submission purposes. Only 
descriptive statistics will be reported. Results of the interim 
analyses will not be used as a basis for stopping the trial early.  
Laboratories  
Imaging Core Lab 
 
 
 
Clot analysis lab 
 
 
 
 
 
 
 
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SCHEDULE OF ASSESSMENTS 
Table 1 Schedule of Assessments 
 
Enrollment 
Follow-up 
Assessments 
Baseline 
Procedure 
24hrs  
post-
procedure  
(+/- 12 hrs) 
7 days/ 
discharge (- 
1/+7 days) 
(whichever 
comes first) 
 
90 Day  
Follow-up 
(+/- 14 days) 
Unscheduled  
(6) 
Eligibility Screening 
X 
X 
X 
X 
 
 
Informed Consent 
Patient consent may be obtained up to 45 days post 
procedure 
 
Demographics and 
Medical History 
X 
 
 
 
 
 
IV t-PA administration 
O 
 
 
 
 
 
Imaging (1) 
X 
 
X 
 
 
O 
NIH Stroke Scale 
(NIHSS) 
X (4) 
 
X (4) 
O 
O 
O 
Modified Rankin Scale 
(mRS) 
X (5) 
 
 
O 
X(7) 
O 
Angiography (2) 
 
X 
 
 
 
 
Review of Reportable 
AEs(8) 
 
X 
X 
X 
X 
X 
Clot Collection (3) 
 
X 
 
 
 
 
Health Economics Data 
Collection 
 
X 
X 
X 
X 
X 
 
(1) Imaging will be sent to independent Imaging Core Lab for review 
(2) Procedural angiography will be sent to Imaging Core Lab for review 
(3) Per pass clot collection to be sent to Clot Analysis Lab for processing 
(4) If more than one NIHSS was performed during this time period, select the worst (highest) value 
(5) To be administered pre-procedure by a qualified evaluator; pre-stroke mRS should reflect the subject’s condition just prior to 
the stroke onset.  For example, if the subject was hospitalized during stroke onset, the subject’s reason for hospitalization should 
be taken into account when evaluating the subject’s pre-stroke mRS 
(6) Assessments should be completed for unscheduled visits from the time of Discharge up to (but not including) the 90-day Follow-
up, where imaging, NIHSS or mRS is performed as part of stroke management care for the subject   
(7) The 90 day mRS must be performed by a qualified independent evaluator. This may be performed by phone per the site’s SOC. 
(8)  AEs will be reported and recorded (via eCRF) if any of the following apply: (a) The event is neurological in nature (b) The 
event is a serious adverse event (SAE) (c) AE where causality is related to the device or procedure. 
 
 
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SCHEMATIC OF STUDY DESIGN 
A subject can be enrolled in this study from the angiographic confirmation of an LVO  up to 45 
days post-procedure. Assessments and imaging performed for this study are part of standard of 
care (SOC) for stroke treatment and screening can occur without obtaining consent. Informed 
consent is mandatory and must be obtained before any data is captured in the electronic Case 
Report Form (eCRF). 
 
 
 
Figure 1 Schematic of Study Design 
 
 
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1. 
Background Information and Scientific Rationale 
1.1. 
Background Information 
According to the World Health Organization, 15 million people suffer from a stroke per 
year, leaving 5 million dead and 5 million severely disabled[1]. Approximately 90% of all 
strokes are Acute Ischemic Strokes (AIS), occurring when blood flow to the brain is 
blocked by a clot / thrombus [2]. The most severe AIS are due to Large Vessel Occlusions 
(LVO) and are associated with significant disability and mortality due to obstruction of the 
major vessels in the brain which include – Internal Carotid Artery (ICA), Middle Cerebral 
Artery (MCA), Vertebral Artery (VA), and the Basilar Artery (BA). Numerous studies 
have shown that removing the blood clot or occlusion can limit disability and drastically 
improve the patient’s chances of having a good functional outcome.  
 
1.2. 
Current Treatment Options  
Intravenous Tissues Plasminogen Activator (IV t-PA) is routinely used to treat patients 
experiencing AIS in the United States, Europe and other regions. However, many patients 
do not meet the therapy’s eligibility criteria. In the US, the FDA has approved IV t-PA in 
patients presenting up to 3 hours after symptom onset, while in the EU per ECASS 
(European Cooperative Acute Stroke Study) criteria, patients are eligible for IV t-PA up to 
4.5 hours after symptom onset [3]. In addition to the time constraints, IV t-PA has shown 
to be less effective in recanalizing proximal LVOs [4].  Due to the limitations of IV t-PA, 
mechanical thrombectomy surfaced as a valuable alternative to effectively treat patients, 
regardless of IV t-PA eligibility[5].   
 
Recent randomized controlled trials (SWIFT PRIME, ESCAPE, EXTEND IA, 
MRCLEAN, THERAPY) were successful in demonstrating the safety and effectiveness of 
thrombectomy with stent retrievers compared to IV-t-PA alone in treating AIS in patients 
with LVOs [6-10]. As a result, treatment guidelines have changed to include mechanical 
thrombectomy as part of standard of care (SOC) [11].  
 
Advancement of catheter design and development has led to “A Direct Aspiration First 
Pass Technique” (ADAPT) that permits intracranial delivery of large-caliber aspiration 
catheters to the thrombus interface allowing for direct clot extraction. It was reported that 
ADAPT therapy is associated with similar reperfusion rates, clinical outcomes and 
complication rates compared with thrombectomy with stent retrievers [12]. 
 
A literature review involving 17 ADAPT studies and 5 Randomized Controlled Trials 
(ESCAPE, EXTEND, MRCLEAN, REVASCAT, and SWIFT PRIME) were successful in 
demonstrating higher rates of complete revascularization and reduced time from groin 
puncture to recanalization compared to standard methods – IV tPA and mechanical 
thrombectomy with stent retrievers[13].  
 
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Further, three randomized control trials compared endovascular approaches of aspiration 
vs stent retriever – ASTER, Penumbra Separator 3D and COMPASS. ASTER and 
Penumbra Separator 3D showed successful revascularization rates were similar between 
both techniques[14, 15].  COMPASS showed aspiration as first pass as non-inferior to stent 
retriever first line, on an intent to treat basis and showed a faster recanalization time [16]. 
These studies support the use of direct aspiration as an alternative to stent retriever as first 
line therapy for stroke thrombectomy[17].  
 
1.3. 
Previous Experience with EMBOVACTM Aspiration Catheter 
No prior clinical investigations have been performed for the EMBOVACTM Aspiration 
Catheter. Table 1 below provides an overview of the pre-clinical design verification and 
validation testing conducted on EMBOVACTM Aspiration Catheter to demonstrate its 
safety and performance. 
Table 2 Pre-clinical Design Verification and Validation Testing 
Title 
Description of Section 
Design Verification Testing 
Design Verification testing of the EMBOVACTM 
Aspiration Catheter confirmed that the design outputs 
meet the design inputs. 
Design Validation 
Design Validation testing of the EMBOVACTM 
Aspiration Catheter confirmed that the design outputs 
meet the customer requirements. 
In-Vivo Animal Testing 
Fourteen Yorkshire pigs underwent a single 
interventional procedure on Day 0 in which selected 
arteries were treated with the Cerenovus 
EMBOVACTM Aspiration Catheter and control device 
(SOFIA Plus) (16 devices each tested with clot, 12 
each without clot). A minimum of 3 passes were 
performed in all vessels. Acute performance 
characteristics of the catheters were evaluated, 
including assessment of the preparation, compatibility 
between components, trackability, pushability, 
positioning, radiopacity and withdrawal. On Days 3 
and Day 30, histologic evaluation was used to assess 
local tissue response and downstream organ/tissue 
effects.  
 
This study demonstrated that the Cerenovus 
EMBOVACTM Aspiration Catheter performed 
comparably to the control device (SOFIA Plus) with 
respect to handling, positioning, and pushability; and 
better with respect to RHV/microcatheter 
compatibility, and trackability. Clot was retrieved in 
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100% of the Cerenovus Aspiration Catheter arteries 
and TICI 3 was achieved in 81% of those arteries after 
the third pass, comparably to SOFIA Plus. There were 
no dissections or perforations in the treated vessels. 
Vasospasm was a persistent observation which is 
typical in the swine model and not specific to the either 
the test or control devices. There were no health or 
clinical problems associated with the treatments and all 
animals survived to their scheduled end point. 
Biocompatibility 
The results of biocompatibility testing of the 
EMBOVACTM Aspiration Catheter have demonstrated 
biocompatibility in compliance with applicable 
sections of EN ISO 10993.  
Sterilization 
Sterilization/microbiology validation testing of the 
EMBOVACTM Aspiration Catheter was completed to 
demonstrate sterilization to a 10-6 Sterility Assurance 
Level (SAL).  
Packaging 
Packaging and labeling, conforms to defined customer 
requirements and patient needs.  
 
1.3.1. Rationale  
This study aims to assess the performance of the EMBOVACTM Aspiration Catheter when 
used by multiple interventionalists and centers in a real-world clinical setting, as well as to 
explore the benefit of a ‘system approach’ using the Cerenovus products which have been 
designed for use together in the treatment of acute ischemic stroke (e.g., distal access 
catheter, balloon guide catheter). This study will also look at association between clot 
composition and reperfusion in order to gain better insight into the etiology of the disease 
and means for effective clot removal.  
1.4. 
Commercial Product 
The EMBOVACTM Aspiration Catheter is commercially available in the EU since 2019.  
Please refer to the Instructions for Use (IFU) for instructions on use of the device. 
 
1.5. 
Potential Risks and Benefits 
1.5.1. Known Potential Risks 
Risks that may be associated with the use of the EMBOVACTM Aspiration Catheter can be 
found in the commercially available IFUs found with the device.  
 
 
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1.5.2. Minimization of Risk 
EMBOVACTM Aspiration Catheter must only be used by investigators who have received 
appropriate training in interventional neuroradiology and the treatment of ischemic stroke. 
Efforts will be made to minimize the potential risks of the study through the following: 
1. 
Investigators who participate in the study will be experienced with EMBOVACTM 
Aspiration Catheter and will have performed a minimum of 2 cases with the device 
using ADAPT prior to study enrollment. 
2. 
The site will have adequate resources to conduct the clinical study.    
3. 
The study has been designed to ensure treatment and follow-up of subjects are 
consistent with current SOC. 
4. 
The investigator and study personnel will be trained on the study protocol.   
5. 
Each investigator will ensure oversight and approval of the study by the EC prior to 
activation of the study at the investigation site. Subject status will be monitored by 
the investigator or designee throughout the follow-up period as defined in the study 
protocol.     
6. 
A CEC will review and adjudicate safety endpoints, as defined in CEC charter, 
throughout the course of the study. 
 
1.5.3. Known Potential Benefits 
Although there may be no direct benefits of study participation, subject participants 
records will undergo an enhanced level of clinical scrutiny compared to routine SOC, 
which may provide some indirect health benefits. The potential benefits in this study of 
the commercially approved device outweigh any anticipated risks. 
The results of the study may be beneficial to the research and medical community. The 
information learnt from this study may improve treatment to patients who require 
treatment for acute ischemic stroke in the future. 
 
2. 
Objectives and Purpose  
2.1. 
Objectives 
The primary objective of this post-market clinical follow-up (PMCF) study is to characterize 
the performance of the EMBOVACTM Aspiration Catheter in the treatment of acute ischemic 
stroke in a real-world clinical setting, as well as to confirm the benefits of a “system 
approach” using the Cerenovus products which have been designed for the use together in 
the treatment of acute ischemic stroke (e.g., distal access catheter, balloon guide catheter). 
 
 
 
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3. 
Study Design and Endpoints 
3.1. 
Description of the Study Design 
This is a prospective, multi-center, single-arm, post-market clinical follow-up study that 
will enroll approximately 100 subjects at approximately 10 sites primarily in Europe, with 
clot collection for follow-on histopathological analysis. Subjects will be included in the 
study for a period of 3 months after the procedure, including follow up visits at 24 hours, 
7 days (or discharge) and 90 days after the procedure.   
3.2. 
Study Endpoints 
3.2.1. Primary Endpoint   
Successful Revascularization (final mTICI ≥ 2b) – Proportion of subjects with 
substantial angiographic reperfusion assessed using the modified Thrombolysis in 
Cerebrovascular Infarction (mTICI) scale at the end of the procedure. Successful 
achievement of the endpoint is defined as achieving a final mTICI score of 2b or 
greater in the target vessel as determined by the independent Imaging Core Lab.  
3.2.2. Secondary Effectiveness Endpoints 
1. Successful Revascularization (final mTICI ≥ 2b) without rescue therapy, as 
determined by Core Lab – Successful achievement of the endpoint is defined as 
achieving a final mTICI score of 2b or greater in the target vessel as determined by 
the independent Imaging Core Lab without use of rescue therapy.  
2. Complete Revascularization (final mTICI ≥ 2c), as determined by Core Lab - 
Successful achievement of the endpoint is defined as achieving a final mTICI score 
of 2c or greater in the target vessel as determined by the independent Imaging Core 
Lab. 
3. First Pass Effect (mTICI ≥ 2c without rescue), as determined by Core Lab – 
Subjects with complete angiographic reperfusion defined as mTICI of 2c or greater 
after the first pass with the EMBOVACTM Aspiration Catheter as determined by the 
independent Imaging Core Lab without use of recue therapy.  
4. Modified First Pass Effect (mTICI ≥ 2b), as determined by Core Lab – Subjects 
with complete angiographic reperfusion defined as mTICI of 2b or greater after the 
first pass with the EMBOVACTM Aspiration Catheter as determined by the 
independent Imaging Core Lab.  
 
 
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5. Time to recanalization (Time from arterial puncture to complete recanalization   
mTICI ≥ 2b), as determined by Core Lab – as the time from arterial puncture to 
achievement of the first mTICI score of 2b or greater, or visualization of final 
angiographic result if an mTICI score of 2b or greater is not achieved, as determined by 
the independent Imaging Core Lab. 
6. Modified Rankin Scale (mRS) of 0 - 2 at 90 days - Must be performed by a qualified 
independent evaluator. Whenever possible, mRS should be recorded at the follow-up 
clinic visit. If not possible, then a telephone assessment may be used.  
 
3.2.3. Safety Endpoints 
1. Device related serious adverse events within 90 days –where the EMBOVACTM 
Aspiration Catheter caused, or cannot be ruled out as having caused, an event that has 
resulted in any of the consequences characteristic of an SAE. Device relatedness will 
be adjudicated by an independent CEC. 
2. Symptomatic Intracerebral Hemorrhage (sICH) at 24 hours specified according 
to the Heidelberg Bleeding Classification – adjudicated by an independent CEC - 
defined as a new intracranial hemorrhage as detected by brain imaging, measured 24 
hours after intervention [18], associated with any of the following: 
 
• ≥4 points total NIHSS at the time of diagnosis compared to immediately before 
worsening. Note that a 4 points change is not compared with the baseline admission 
NIHSS score but instead to the immediate pre-deterioration neurological status 
 
• ≥2 point in one NIHSS category. The rationale for this is to capture new 
hemorrhages that produce new neurological symptoms, making them clearly 
symptomatic but not causing worsening in the original stroke territory. For 
example, a new remote hemorrhage in the contralateral occipital lobe may cause 
new hemianopia that is clearly symptomatic, but the subject will not have 
worsening of ≥4 points on the NIHSS score 
 
• Leading to intubation/hemicraniectomy/EVD placement or other major 
medical/surgical intervention 
 
• Absence of alternative explanation for deterioration 
 
3. NIHSS at 24 hours post procedure – NIHSS will be measured at 24 hours and 
compared to the baseline score.  
4. 90 Day All-Cause Mortality – All mortality regardless of cause at 90 days post-
procedure.  
 
 
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3.2.4. Health Economic Endpoints 
Medical Resource Utilization and Health Economics related data including: 
 
1. Hospitalization length of stay for index procedure and unscheduled re-
hospitalizations 
2. Healthcare resource utilization for index procedure, post procedure and 
rehospitalizations for unscheduled events 
3.3. 
Rescue Therapy 
In order to provide an evaluation of the device, rescue therapy should not be used prior to 
completion of the first three passes with the EMBOVACTM Aspiration Catheter.  
 
Rescue therapy is defined as: 
• Any change in frontline device therapy to remove the target occlusion in a vessel at 
least 2mm in size.  
• Use of intra cranial stenting during the procedure 
• Use of an intra-arterial thrombolytic agent during the procedure (e.g., tissue 
plasminogen activator, urokinase, prourokinase) 
 
Progression in therapy to address thrombus/occlusion that is no longer appropriate for 
treatment with EMBOVACTM (e.g., use of another device to remove distal occlusion in a 
vessel smaller than 2mm) will be considered an appropriate evolution in the standard of 
care and NOT considered rescue therapy. 
 
4. 
Study Population 
4.1. 
Participant Inclusion Criteria 
Investigators will assess potential subjects who are candidates for the study. Candidates 
who meet the protocol inclusion / exclusion criteria may be enrolled.  The subject selection 
criteria are in place for protection of participants and to address factors that may 
compromise the outcome of the investigation or interpretation of the results. 
Candidates for this study must meet ALL of the following criteria: 
1. Subject ≥ 18 years old. 
2. Subject experiencing acute ischemic stroke with angiographic confirmation of Large 
Vessel Occlusion (LVO) of the distal intracranial internal carotid artery, middle 
cerebral artery (M1 or M2) or anterior cerebral artery (A1 or A2). 
3. A clinical decision has been made to use the EMBOVAC™ aspiration catheter prior 
to enrollment in the research.  
4. EMBOVAC™ Aspiration Catheter is attempted to be used for the first 3 clot 
removal passes for the target intracranial occlusion (if 3 passes are needed) using A 
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Direct Aspiration First Pass Technique (ADAPT). Exception: it is not considered 
rescue therapy if use of another device is needed to remove distal occlusion in a 
vessel smaller than 2mm after the first pass. 
5. Pre-stroke mRS ≤ 1 
6. NIHSS ≤ 30  
7. Informed consent has been provided by the subject or the subject's legally 
authorized representative. 
4.2. 
Exclusion Criteria 
Candidates will be excluded from participation if ANY of the following apply: 
1. Potential study candidate has already undergone standard of care assessments or 
treatment that deviate from the clinical research protocol requirements (e.g., 24 hour 
imaging conducted outside the protocol specified window). 
2. All patients with severe hypertension on presentation (SBP > 220 mmHg and/or DBP 
> 120 mm Hg). All patients, in whom intravenous therapy with blood pressure 
medications is indicated, with hypertension that remains severe and sustained despite 
intravenous antihypertensive therapy (SBP >185 mmHg and/ or DBP >110 mmHg). 
3. Known cerebral vasculitis. 
4. Known cancer with life expectancy less than 12 months. 
5. Stenosis, or any occlusion, in a vessel proximal to the target occlusion that requires 
treatment or prevents access to the site of occlusion. 
6. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of 
recent/ fresh hemorrhage on presentation. 
7. Baseline computed tomography (CT) or MRI showing mass effect or intracranial tumor 
(except small meningioma). 
8. Evidence of dissection in the extra or intracranial cerebral arteries. 
9. Occlusions in multiple vessels  
10. Confirmation of positive pregnancy test according to site specific standard of care (e.g. 
test, verbal communication). 
11. Currently participating in an investigational (drug, device, etc.) clinical trial that may 
confound study endpoints. Patients in observational, natural history, and/or 
epidemiological studies not involving intervention are eligible. 
 
 
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4.3. 
Strategies for Recruitment and Retention 
The study will enroll approximately 100 subjects across approximately 10 clinical sites in 
Europe. Once enrolled, each subject will participate in the study for up to 90 days post-
procedure per the hospital’s Standard of Care and the protocol schedule of assessments. 
 
Principal investigators and clinical sites will be evaluated based upon the following factors: 
 
• Previous experience with thrombectomy using large bore aspiration catheters: 
Each treating investigator must have performed at least 20 thrombectomy 
procedures using ADAPT, of which at least 2 cases are with the EMBOVACTM 
device. 
• Experience in conducting clinical studies. 
• Currently treating subjects who meet the inclusion / exclusion criteria. 
• Ability to enroll an adequate number of subjects. 
• Ability to perform required clinical testing, including: angiography, CT, and/or 
MRI. 
• Ability and willingness to provide the sponsor’s representatives and local 
regulatory authorities access to the hospital records, study files, and subject files 
as they pertain to the study. 
• Willingness to participate, including compliance with all aspects of the study. 
 
 
Adequate staffing to conduct the study includes: 
• Principal Investigator (PI): Responsible for overall clinical management of 
subjects enrolled at his/her institution. Assumes overall responsibility and 
accountability for the clinical team and for data obtained from each subject 
participating in the study. Ensures compliance with the protocol, applicable 
laws, and applicable regulations; ensures informed consents are signed, and 
reviews and signs electronic case report forms eCRFs indicating documents are 
accurate and complete. 
• Sub-Investigator (Sub-I): Any individual member of the clinical trial team 
designated and supervised by the investigator to perform clinical trial-related 
procedures and/or make important trial-related decisions. A site is not required to 
have a Sub-I. 
• Study Coordinator: Assists PI with study activities as delegated by the PI, 
including tracking subjects involved in the study, scheduling testing and follow-
up visits, maintaining study records, completing eCRFs to the sponsor in a timely 
manner. A site is not required to have a Study Coordinator but must have an 
individual other than the PI dedicated to support the study. 
 
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To best capture real-world experience with the EMBOVACTM Aspiration Catheter, the 
Sponsor will attempt to include a diversified group of investigational sites by engaging 
with a variety of institutions. To ensure generalizability of results, sites will be 
geographically distributed throughout Europe so that multiple countries are represented. 
Influence from any one site will be minimized by limiting maximum enrollment per site to 
20 percent of overall study enrollment or approximately 20 subjects. 
 
4.4 Participant Withdrawal or Termination   
4.4.1 Reasons for Withdrawal or Termination 
Subjects are free to withdraw from participation in the study at any time upon request.  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.   
4.4.2 Handling of Participant Withdrawals or Termination 
Subjects that withdraw consent after treatment are not required to undergo 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 and any remaining clot sample from 
that subject will be discarded by the Clot analysis lab if no longer needed for study purposes 
(i.e., will not be stored for future research purposes). All data collected prior to withdrawal 
will be included in for data analysis, as permitted per country regulations. 
 
5. 
Study Device  
5.1 Study Device Description 
5.1.1 Device Acquisition 
The EMBOVACTM Aspiration Catheter is CE Marked. As a result, shipments will not be 
tracked for this study, devices will be fully traceable though the company’s 21 CFR 820 
and ISO 13485 compliant quality system.      
 
 
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5.1.2 Device Returns 
Any suspected device malfunction with the EMBOVACTM Aspiration Catheter should be 
properly documented on the Electronic Case Report Forms (eCRFs). In the event of a 
suspected malfunction, the device should be returned to Cerenovus for analysis.  Site will 
retain tracking information. All study devices should be returned to:  
 
 
6. 
Study Procedures and Evaluations 
The medical devices used and all treatment related activities (i.e. the tests and procedures) 
carried out during this study are in line with Good Clinical Practice and are conducted per 
standard operating policies at the treating hospital (study site). The conduct of this study 
does not affect the hospitals standard operating policies and does not impact the patient’s 
standard of care. 
Study-related activities exclusively consists of the structured collection and evaluation of 
data; this includes the patient angiographic imaging and analysis of blood clots retrieved 
from the patient during the procedure. This data (as outlined in the informed consent form) 
will only be shared with the Sponsor if a signed informed consent is obtained from the 
study subject or their legal authorized representative. 
6.1. 
Study Specific Procedures  
The procedures completed as part of this study are in line with SOC and include relevant 
medical history, relevant medication history, NIHSS, mRS, imaging (CT/MRI), procedural 
angiography and review of any reportable AEs. Patients presenting with acute ischemic 
stroke 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. 
Clot samples will be collected on a per pass basis and shipped by the site to the Clot analysis 
lab for follow on analysis.  
 
6.1.1. Imaging  
In this study, revascularization will be measured by an independent adjudicating Imaging 
Core Lab and reported using the eTICI (inclusive of the 2C rating) scale [19]. For 
purposes of data comparisons, a minimum threshold of mTICI 2b is equal to eTICI 2b50. 
 
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Table 3 eTICI Scale 
0 
No reperfusion; 0% filling of the downstream territory,  
1 
Thrombus reduction without any reperfusion of distal arteries 
2 
• 2a     Reperfusion in less than half (1-49%) of the territory 
• 2b50 Reperfusion in (50-66%) of downstream territory  
• 2b67 Reperfusion in (67-89%) of downstream territory 
• 2c     Reperfusion in (90-99%) of downstream territory 
3 
Complete or 100% reperfusion 
 
All imaging should be in line with SOC. This includes CT or MR at baseline and 24 hours 
post procedure to assess any presence of hemorrhage, recanalization of the occluded artery, 
reperfusion, and infarct growth. Angiographic images obtained during the study should 
consist of (1) Baseline angiogram - prior to device advancement to assess clot location, (2) 
Post device angiogram - after each reperfusion attempt/pass of the device (a pass being 
defined as use of aspiration followed by evaluation of revascularization with 
angiography), (3) Final Angiogram – after all treatment has been completed.  Any other 
imaging of the head or neck performed per SOC (for example as a result of clinical 
deterioration) must also be provided.  
 
6.1.2. Independent Imaging Core Lab for Image Evaluation 
All imaging collected will be SOC, no additional imaging will be requested for this 
study. An independent Imaging Core Lab will be utilized to provide an unbiased and 
standardized assessment of all collected imaging. All subject PHI will be removed before 
an image is uploaded and evaluated by the Imaging Core Lab.   
 The objective of the Imaging Core Lab will be to:  
• Review all angiograms obtained 
• Provide an unbiased assessment of the rate of revascularization defined by 
mTICI score based on angiographic imaging from the study sites 
• Evaluate CT/MRI examinations to detect and assess hemorrhages.  
This study will be collecting the following imaging data to be assessed by Imaging Core 
Lab: 
 
 
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Baseline - CT/ MR imaging 
• 
ASPECTS (Alberta Stroke program early CT score) 
• 
Infarct volume  
• 
Clot location 
• 
Clot length  
• 
Clot density 
• 
Clot enhancement 
 
Procedural Angiography   
• 
eTICI score for every pass  
• 
Emboli to new territories 
• 
Collateral score 
 
Post Procedure - CT/ MR imaging  
• 
Infarct volume 
• 
Intracranial Hemorrhage 
 
Hemorrhages will be classified according to the following categories [18]: 
• HI 1 – Scattered small petechiae, no mass effect  
• HI 2 – Confluent petechiae, no mass effect 
• PH1 – Hematoma within infarcted tissue, occupying <30%, no substantive 
mass effect 
• PH2 – Hematoma occupying 30% or more of the infarcted tissue, with obvious 
mass effect 
• RIH – Parenchymal hematoma remote from infarcted brain tissue 
• IVH – Intraventricular Hemorrhage 
• SAH – Subarachnoid Hemorrhage 
• SDH – Sub Dural Hemorrhage 
 
The Imaging Core Lab assessor will be blinded to subjects’ chart/clinical records. Each 
angiogram will be read independently by an experienced Imaging Core Lab Neurology 
reviewer.  
6.1.3. Procedural Angiogram Shipment 
A copy of the angiograms collected during the study will be submitted to the independent 
Imaging Core Lab electronically via batch upload through the Imaging Core Lab website 
or through shipping pseudonymized imaging discs. All personally identifying information 
(e.g., name, date of birth, etc.) will be removed from images.  
 
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6.1.4. Clot Collection and Processing  
Normally, following thrombectomy, the retrieved clot may be discarded, sent to internal 
departments, or retained for other purposes. However, for subjects in this study, clot 
samples will be collected for follow-on analysis.  
 
Sites collecting clot for analysis will place the clot collected for each pass in a container of 
neutral buffered formalin solution for preservation. If more than one clot fragment is 
retrieved during a retrieval attempt/pass with the device, these fragments will be placed 
together in one container. Each container will have a unique subject identifier noting the 
retrieval attempt/pass number on the label. This unique identifier will be entered in the 
eCRF by the site along with other relevant data and linked to subject ID. Samples will 
subsequently be shipped by the site to the Central Lab for follow on analysis (Section 
6.1.5).  
 
All materials for collecting, processing and shipping samples to the Central Labs will be 
provided by the Sponsor or the Sponsor’s selected vendor. For additional details on sample 
processing refer to Clot Collection and Processing Manual provided by Cerenovus.  
 
6.1.5. Independent Central Lab for Clot Evaluation 
Clot materials collected for this study will be processed by an independent Clot analysis 
lab.  Standardized procedures and techniques have been established by the Core Lab for 
the analysis of AIS clots.  These techniques comprise of morphological, histological and 
immunohistochemistry testing, which will help in defining clot features and in clot 
compositional analysis for this study.  
 
These samples will be securely stored by the independent core lab in a study specific 
storage cabinet at the lab. 
Samples will be sent to the core lab by the hospital in a vial with a generated “vial accession 
number”. This number will be generated by the site and will contain no patient information. 
The clots will be stored in containers containing this number for identification for research 
purposes.  
The purpose of collecting and analyzing these clots is to determine the composition of 
different clot types to better understand the etiology of stroke and clot types successfully 
removed by direct aspiration. 
The following parameters of the clot will be measured/analyzed: 
• Histology of the retrieved clot (including the red blood cell and fibrin content) will 
be measured using MSB (Martius Scarlett Blue) stain and H&E (Hematoxylin and 
Eosin) stain 
• Immunohistochemistry to determine Platelets and Von Willebrand Factor 
• Geometry of clot by measuring total weight and clot area 
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Additionally, samples may be tested for the presence of novel biomarkers that are 
associated with difficult clot retrieval by mechanical thrombectomy. Any remaining clot 
material will be retained and may be used in further scientific testing associated with the 
PERFECT study.  
The Clot analysis lab will not have access to the subjects’ chart/clinical records.  
6.1.6. Neurological Evaluations 
The following neurological evaluations will be used in this study and are part of SOC:  
 
NIHSS Score - The National Institutes of Health Stroke Scale, or NIH Stroke Scale 
(NIHSS) is a tool used by healthcare providers to objectively quantify the impairment 
caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific 
ability between a 0 and 4. For each item, a score of 0 typically indicates normal function 
in that specific ability, while a higher score is indicative of some level of impairment. The 
individual scores from each item are summed in order to calculate a subject's total NIHSS 
score. The maximum possible score is 42, with the minimum score being a 0. 
 
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 event and is conducted by a qualified evaluator. It is a scale with seven 
categories ranging from no symptoms to severe disability and death. Qualifications of 
evaluator training will be documented for this study.   
 
7. 
Study Schedule 
7.1. 
Pre-Screening / Screening 
Subjects presenting with AIS to enrolling medical treatment facilities will be evaluated and 
treated by the physician according to the institutional practice prior to enrollment in the 
study. All assessment and imaging performed for this study are part of SOC for stroke 
treatment. Informed consent is mandatory and must be obtained before any data is captured 
in the eCRF. 
A subject can be consented to participate in this study from the point of imaging confirming 
a large vessel occlusion up to 45 days post-procedure. During the eligibility screening, the 
investigator or designee will perform an initial evaluation of potential study subjects 
according to the inclusion/exclusion criteria. Post-procedure, the eligibility criterion to be 
confirmed will be the requirement for the EMBOVACTM aspiration catheter and ADAPT 
to be attempted to be used in the first 3 passes, if required, unless evolution of care is 
required to remove a clot in a distal vessel of <2mm in diameter, and confirmation that all 
assessments were in alignment with the schedule of assessments (See Table 1 Schedule of 
Assessments). 
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For subjects in whom consent in sought, the investigator, or designee, will explain the 
research study to the subject and answer any questions that may arise. The possible risks 
and possible benefits of participation will be discussed. The subject will be asked to read, 
review and sign the EC approved informed consent form. The informed consent process is 
detailed further in Section 11.3.  
All subjects screened will be documented on the Screening/Enrolment log, including the 
reason for non-participation for subjects who do not enroll. 
If for any reason the subject does not meet the eligibility criteria when assessed by the 
investigator for inclusion in the study, the subject will not be considered enrolled in this 
study or be followed per this clinical protocol.  
All subjects who provide informed consent will be entered into eCRF regardless of whether 
or not they participate in the study. 
7.2. 
Baseline  
The following baseline data will be collected and entered into the eCRF by the site:  
• 
Demographics will be collected from a review of the subject’s medical records to 
include age, gender, ethnicity etc. unless prohibited by local regulations (e.g., 
France) 
• 
Relevant medical history will be collected from a subject interview and a review 
of the subject’s medical records to include blood pressure, height, weight, BMI, 
History of smoking and diabetes etc.   
• 
Relevant medication history will be collected from a subject interview and a 
review of the subject’s medical records if necessary.  Specifically, a thrombolytic 
agent (e.g., tissue plasminogen activator, urokinase, prourokinase) delivered prior 
to and during the procedure will be the only medication collected. 
• 
CT / MR Imaging 
• 
NIHSS  
• 
Pre-stroke mRS Modified Rankin Scale – must be performed by a qualified 
evaluator 
7.3. 
Procedure  
The clinical decision to use the EMBOVACTM Aspiration Catheter, as well as the 
revascularization procedure are independent (regardless) of the research.  Physicians 
should follow the most current EMBOVACTM Aspiration Catheter Instructions for Use 
(IFU) at all times with regards to the device compatibility, preparation and the 
recommended retrieval procedure. The research procedures are limited to the collection of 
data.  Data will be collected before, during, and after use of the EMBOVACTM Aspiration 
Catheter. 
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 During the procedure, the following data will be collected: 
• 
Total number of passes: A pass is defined as use of aspiration followed by 
evaluation of revascularization with angiography. 
• 
Procedural angiography – The following will be recorded by the clinical site: 
 mTICI score per each attempted pass  
 Procedure Time defined as time from arterial puncture to complete 
recanalization (first mTICI ≥ 2b)  
• 
Thrombectomy techniques and devices utilized per pass 
• 
Additional interventions performed (if applicable) 
• 
Record any reportable AEs per this protocol which occur during the procedure 
and up to the time of the 24hour examination. 
• 
Clot collection per pass: this study aims to collect the clot from all subjects 
enrolled.  However, in consideration of the urgent nature of stroke treatment, if 
the clot cannot be collected in a study procedure, it will not be considered a 
protocol deviation. 
 
Once subject eligibility has been confirmed, the subject can be enrolled in the study.  
A subject is considered enrolled in this study once the physician confirms the subject 
meets all eligibility criteria and the subject or their legal representative has provided 
informed consent.  
A subject will not meet inclusion criteria and must not be enrolled if the EMBOVACTM 
Aspiration Catheter is not used for the first 3 clot removal passes for the target intracranial 
occlusion (unless use of another device is needed to remove clot in a distal vessel <2mm 
in diameter). 
 
7.4. 
 24 Hours Post Procedure (±12hours)  
The 24-hour follow-up visit includes 
• 
NIHSS examination 
• 
CT or MRI imaging 
• 
Record any reportable AEs and device related SAEs which occur after the procedure 
and up to the time of the 24hour examination. 
 
 
 
 
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7.5. 
Discharge or 7 days (whichever occurs first) (-1/+7 days) 
• 
NIHSS examination (optional) 
• 
mRS evaluation (optional) 
• 
Record any reportable AEs per this protocol which occurred after the 24hour time 
examination and up to the time of the discharge or 7-day examination. 
 
7.6. 
90 Day (±14 Days) Follow-up 
• NIHSS (optional - to be collected only if performed per SOC) 
• An mRS assessment must be conducted. This mRS assessment must be performed 
by a qualified evaluator who is independent of the interventional treating team 
and the subject’s direct clinical care (e.g., neurologist, CRNC).  
• Record any reportable AEs per this protocol which occurred after 7 day / 
discharge time point and up to the time of the 90-day examination. 
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 rescheduled. The 
90-day assessments may be done via telephone (reportable AEs, mRS).   
 
7.7. 
Unscheduled Visit 
Subjects returning for an unscheduled visit to the study center that is related to the stroke 
treatment recorded in the study or indicating new or unresolved signs and/or symptoms 
will be documented as an unscheduled follow-up. Assessments should be completed from 
the time of discharge up to (but not including) the 90-day follow-up, where imaging or 
NIHSS or mRS may be performed as part of stroke management care for the subject. 
Corresponding data to be collected includes those listed below.  Any imaging performed 
as SOC for unscheduled visit will be documented and sent to the Core Lab. 
• NIHSS examination 
• mRS 
• Any imaging (CT, MRI, DSA, etc) 
• Review of SAEs 
 
7.8. 
Early Termination  
During the study, it is possible that subjects will be withdrawn from the study. Factors 
leading to subject early termination may include, but are not limited to the following: 
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• Subject withdraws consent prior to study completion of all study follow up 
requirements 
• The Investigator decides to discontinue subject’s or site’s participation in the study   
• The subject is lost to follow-up 
• Death  
• The study is terminated at a site or as a whole 
 
The study can be discontinued at the discretion of the investigator or study Sponsor for 
reasons including, but not limited to, the following: 
• 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 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), the Sponsor shall inform the clinical 
investigator/investigational center of the termination or suspension in enrollment and the 
reason for this. 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 90-day follow-up visit and then be exited from the study. The Sponsor’s 
communication to the investigator/investigational center will also include instructions for 
the investigator to promptly inform the EC regarding the change in study status, along with 
the reason for termination or suspension by the Sponsor.   
If the entire study is discontinued or suspended prematurely, the Sponsor shall promptly 
inform all clinical investigators/investigational centers of the termination or suspension in 
enrollment and the reason for this.  
 
7.9. 
Lost to Follow-up 
If a subject fails to return for the follow-up visit at 90 days, the subject will be contacted at 
their last known telephone number. When all reasonable attempts to locate the subject have 
been exhausted including contacting the subject’s general practitioner, the subject will be 
considered lost to follow-up and their data will be excluded from the data analysis from 
the time of last contact onward. A subject will not be considered lost to follow-up prior to 
the 90 day visit. All data collected prior to last contact will be included in for data analysis, 
as permitted per country regulations. 
To prevent and/or reduce loss to follow-up the following measures will be implemented 
for this study:  
• The Informed Consent will provide a clear explanation of the expected duration of 
the subject’s participation in the study and a description of the study follow-up 
requirements to ensure subjects understand and agree to the study requirements.    
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• 
At the time each subject is enrolled in the study, sites will obtain contact 
information for the subject.  
• 
Site personnel will be encouraged to question the subject about any difficulties with 
adhering to the study schedule. If underlying conditions are identified, the site will 
make reasonable efforts to address these conditions on a case by case basis and this 
may require site arrangements or schedule adjustments to allow the subject to 
continue study participation.  
• 
For each missed or overdue follow-up visit, site personnel will document the reason 
for the missed or overdue follow-up visit in the subject’s medical record or office 
chart.   
• 
Site personnel re-training will be conducted by Cerenovus or their representatives, 
when needed, to reinforce the follow-up visit requirements and the necessity of 
adhering to the protocol’s follow-up schedule. 
 
7.10. Study Design  
A subject can be enrolled in this study from angiographic confirmation of an LVO up to 45 days 
post procedure. Assessments and imaging performed for this study are part of standard of care 
(SOC) for stroke treatment.  Informed consent is mandatory and must be obtained before any data 
is captured in the electronic Case Report Form (eCRF).  
 
A schematic of the study design may be found in Figure 1 Schematic of Study Design and Table 1 
Schedule of Assessments. 
 
8. 
Assessment of Safety 
For purposes of obtaining long-term safety surveillance in this study, AEs will be reported 
and recorded (via eCRF) if any of the following apply: 
• 
The event is neurological in nature 
• 
The event is a serious adverse event (SAE) 
• 
Causality is related to: 
o The device 
o The procedure  
 
 
 
 
 
 
 
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8.1. 
Specific Safety Parameters 
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 
use of investigational medical devices or comparators. 
 
Any medical condition that is present at the time the participant is screened or prior to the 
start of the study procedure will be considered as baseline. 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 
any of the following: 
• Death 
• 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 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 
• Fetal distress, fetal death or 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. 
 
 
 
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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 
• Note 3: This includes ‘comparator’ if the comparator is a 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. Device Deficiency, Device Malfunction, and Use Error 
All study device deficiencies shall be documented in the eCRF throughout the clinical 
investigation and appropriately managed by the Sponsor.  
A device deficiency is defined as inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, usability, safety or performance (ISO 14155:2020). 
• Note 1: Device deficiencies include malfunctions, use errors, and inadequacy in the 
information supplied by the manufacturer including labelling.  
• Note 2: This definition includes device deficiencies related to the investigational 
medical device or the comparator. 
If a study device deficiency is detected or suspected that could have led to a SADE, it must 
be documented on the appropriate eCRF, and the device failure must be reported to the 
Sponsor within 72 hours upon study site staff awareness. All non-study device 
malfunctions should be reported via the manufacturer’s complaints handling process. 
 
Device deficiencies that did not lead to an adverse event but could have led to a serious 
adverse device effect: 
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• 
if either suitable action had not been taken, 
• 
if intervention had not been made, or 
• 
if circumstances had been less fortunate, 
shall be reported as specified in Section 8.2.5. Where applicable, the analysis of used or 
explanted investigational devices shall be included as supportive information. 
 
Device malfunction is defined as a failure of an investigational medical device to perform 
in accordance with its intended purpose when used in accordance with the instructions for 
use or clinical investigation plan (ISO 14155:2020).   
Use error is defined as user action or lack of user action while using the medical device 
that leads to a different result than that intended by the manufacturer or expected by the 
user.   
• 
Note 1: Use error includes the inability of the user to complete a task 
• 
Note 2: Use errors can result from a mismatch between the characteristics of the 
user, user interface, task or use environment 
• 
Note 3: Users might be aware or unaware that a use error has occurred 
• 
Note 4: An unexpected physiological response of the patient is not by itself 
considered a use error 
• 
Note 5: A malfunction of a medical device that causes an unexpected result is not 
considered a use error (ISO 14155:2020) 
 
8.2. 
Classification of an Adverse Event 
8.2.1. Severity of Event 
The intensity or severity of each AE must be assessed according to the following 
classifications: 
 
 
 
 
 
 
 
 
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Table 4 Intensity or Severity Definitions 
Mild 
Awareness of signs, symptoms, or events that are otherwise easily 
tolerated that may result in minimal transient impairment of a body 
function or damage to a body structure, but do not require intervention 
other than monitoring. 
Moderate 
Any event that results in moderate transient impairment of a body 
function or damage to a body structure that causes interference with 
usual activities, or that warrants possible intervention, such as the 
administration of medication, to prevent permanent impairment of a 
body function or damage to a body structure. 
Severe 
Any event that is incapacitating (an inability to do usual activities) or is 
life-threatening and results in permanent impairment of a body function 
or damage to a body structure, or requires intervention, such as major 
surgery, to prevent permanent impairment of a body function or damage 
to a body structure. 
 
8.2.2. Relationship to Study Device  
The clinician who examines and evaluates the participant will determine the AE’s causality 
based on temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below.   
Table 5 Adverse Event Causality Classifications 
Caused By Relation 
Definition of Relation 
Device 
Causal 
relationship 
The event is associated with the investigational device 
beyond reasonable doubt  
Probable 
The relationship with the use of the investigational device 
seems relevant and/or the event cannot reasonably be 
explained by another cause, but additional information 
may be obtained  
Possible 
The relationship with the use of the investigational device 
is weak but cannot be ruled out completely  
Not related  
Relationship to the investigational device can be excluded  
Study 
Procedure 
Causal 
relationship 
The event is associated with the study procedure beyond 
reasonable doubt  
Probable 
The relationship with the study procedure seems relevant 
and/or the event cannot reasonably be explained by another 
cause, but additional information may be obtained  
Possible 
The relationship with the study procedure is weak but 
cannot be ruled out completely  
Not related  
Relationship to the study procedure can be excluded  
 
 
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8.2.3. Outcome  
The outcome of each AE must be assessed according to the following classifications: 
Table 6 Adverse Event Outcome Classifications 
Classification 
Definition 
Recovered/Resolved 
Subject fully recovered with no observable 
residual effects 
Recovering/Resolving 
Subject’s condition is improving, but residual 
effects remain 
Recovered/Resolved with sequelae 
Subject recovered with observable residual 
effects 
Not Recovered/Not Resolved 
AE is ongoing without improvement in the overall 
condition 
Fatal 
Subject died as a result of the AE (whether or not 
the AE is related to the device or procedure) 
Unknown 
AE outcome is unknown (e.g., subject is lost to 
follow-up) 
8.2.4. Time Period and Frequency for Adverse Event Assessment and Follow-up 
Adverse events shall be assessed and documented for enrolled subjects starting at the 
point of procedure and at all study follow-up visits.  
A subject is considered enrolled, once the physician confirms the subject meets all 
eligibility criteria and the subject signs the ICF.Adverse events that occur during this 
study should be treated by established standards of care which will protect the life and 
safety of the subject. Each investigator shall provide source documentation as requested 
by the Sponsor to facilitate reporting and adjudication of these events. 
 
8.2.5. Adverse Event and Device Deficiency Documentation and Reporting Requirements 
Reportable adverse events and device deficiencies will be recorded and reported on the 
eCRFs throughout the study and provided to the Sponsor.  In the event EDC is unavailable, 
adverse events can be notified via email to the EMBOVAC study mailbox: 
  
If an adverse event occurs, all sections of the Adverse Event eCRF must be completed. 
In the case of serious device effects and device deficiencies that could have led to serious 
adverse device effects, the Sponsor will determine whether the risk analysis needs to be 
updated and whether corrective or preventative action is required. 
Copies of all relevant source documentation (i.e. procedure reports, physician/nursing 
notes, discharge summary, etc.) should be compiled and provided to the Sponsor for the 
adjudication process for all AEs recorded in the study.   
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Timing for reporting the different types of adverse events and device deficiencies is 
described in Table below.  
If sites become aware of an AE prior to the subject providing informed consent, the 
awareness data will be considered the date of consent. 
Table 7 Adverse Event Reporting Requirements 
Type of Adverse Event 
Reporting Requirements 
• SAE  
• Any study device deficiency or 
malfunctions that could have 
led to a SADE* 
 
Report to Sponsor immediately upon study 
site staff awareness of event but no later 
than 72 hours 
• All other AEs reportable in this 
study  
• All other study device 
deficiencies* 
Report to Sponsor immediately upon study 
site staff awareness but no later than 14 
calendar days     
* Non-study device deficiencies should be reported via the manufacturer’s complaints handling process.  
 
There are specifics for safety reporting that would be applied for each country, reporting 
timelines will comply with country regulations. The investigator is responsible for 
informing the EC of adverse events as required by local reporting requirements. The 
Sponsor will submit on regular basis (unless otherwise indicated by the EC or 
recommended by the Sponsor’s medical safety officer) to all participating investigators an 
update of reported events and device deficiencies occurred at the participating study site. 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities per country specific regulations. 
 
A licensed medical doctor employed by the Sponsor will review all reported adverse events 
on an ongoing basis. The site reported event term will be reviewed to assess if the event 
should remain as reported or be re-classified using a term based on the applicable event 
definition. Recorded AEs will be evaluated by the Sponsor for significance and relevance 
with respect to trends that may represent a previously unknown or unanticipated risk that 
may relate to the study device or treatment. 
 
9. 
Clinical Monitoring  
The study will be conducted in accordance with GCP, ISO 14155 requirements, local 
regulations, the signed clinical study contract with the Sponsor, the protocol outlined 
herein, as well as with the principals of the Declaration of Helsinki. 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 is in compliance 
with the country regulations, and the currently approved protocol. Each site will undergo 
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periodic monitoring visits, and subject medical records shall be made available during the 
visits.   
Monitoring visits may include but are not limited to the following: 
• 
Protocol adherence 
• 
Source documentation verification and accuracy of the eCRFs as specified in the 
monitoring plan 
• 
Verification that informed consent are being obtained for all subjects participating 
in the study in accordance with requirements described in the study protocol 
• 
Verification of completeness of the Regulatory Binder 
• 
Verification of accuracy of all study logs such as the Delegation of Responsibility 
Log, etc.  
• 
Compliance with applicable regulations 
• 
Identification and action to resolve any issues or problems 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. Cerenovus 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. 
 
10. Statistical Methods 
10.1. 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. 
 
10.2. Analysis Sets 
For the analysis of study endpoints, the analysis populations defined in the following will 
be used: 
• Modified Intent-To-Treat (mITT) Population: The mITT population will consist of 
enrolled subjects who have received treatment (at least one pass) with the study 
device.  The mITT population will be used to analyze the effectiveness endpoints. 
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• Safety Population (SP): The SP will consist of all enrolled subjects in whom the 
treatment was attempted, defined by the advancement of the EMBOVACTM 
Aspiration Catheter inside of the patient. The SP will be used to analyze safety 
endpoints.  
10.3. Levels of Significance 
There are no formal hypothesis tests for this study. 95% confidence intervals may be 
constructed around the mean percentages if not otherwise specified. 
 
10.4. Sample Size Justification  
There is no statistical power calculation and no hypothesis tests for this post-market study. 
100 subjects are deemed sufficient to characterize the performance of EMBOVACTM 
Aspiration Catheter. 
 
Approximately 100 subjects will be enrolled. With an enrolled sample size of 100 and an 
attrition rate of no more than 5%, the precision (margin of error) for the primary endpoint 
is anticipated to be around 8.0% based on 2-sided 95% confidence intervals, where the 
primary endpoint rate is estimated to be 80%. 
𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝑜𝑜𝑜𝑜 𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒≈1.96 × 𝑆𝑆𝑆𝑆= 1.96 × ඨ 𝑝𝑝(1 −𝑝𝑝)
𝑛𝑛 
 =  1.96 × ඨ 0.8 × (1 −0.8)
95 
= 8.0% 
 
where SE denotes the standard error and p denotes the proportion of subjects who achieve 
the primary endpoint.  
 
10.5. Analyses to be Conducted 
10.5.1. General Conventions 
Standard descriptive summaries for continuous data include the number of subjects and 
events with non-missing outcome, mean, standard deviation, median, minimum, and 
maximum values. For categorical data, the count and percentage will be provided. 
Percentages will be based on the number of subjects without missing data.  
10.5.2. Disposition of Study Subjects 
Subject disposition (e.g. completed, lost-to-follow-up, early termination/withdrawal) as 
well as analysis populations will be summarized for all enrolled subjects. 
10.5.3. Demographic, Baseline and Procedural Characteristics 
All demographic, baseline characteristics and procedural data will be summarized.    
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10.5.4. Primary and Secondary Endpoint Analyses 
10.5.4.1. Primary Endpoint Analysis 
The analysis of the performance endpoints will be conducted in the mITT population. 
•    Successful revascularization (final mTICI ≥ 2b)  
The number and percentage of subjects achieving a final mTICI score ≥ 2b, as determined 
by Imaging Core Lab, will be summarized. Two-sided 95% confidence intervals using the 
normal approximation method will be constructed around the percentage. 
10.5.4.2. Secondary Endpoint Analyses 
 
All secondary effectiveness endpoints will be analyzed in the mITT population; and 
 
secondary safety endpoints will be analyzed in the safety population.  
10.5.4.2.1. Secondary Effectiveness Endpoints 
• Successful Revascularization (final mTICI ≥ 2b) without rescue therapy, as determined 
by Core Lab   
The number and percentage of subjects achieving a final mTICI score ≥ 2b as determined by 
Imaging Core Lab without use of rescue therapy, will be summarized. Two-sided exact 95% 
confidence intervals will be constructed around the percentage. 
• Complete revascularization (final mTICI ≥ 2c), as determined by Core Lab 
The number and percentage of subjects achieving a final mTICI score ≥ 2c, as determined 
by Imaging Core Lab, will be summarized. Two-sided exact 95% confidence intervals will 
be constructed around the percentage. 
 
• First Pass Effect (mTICI ≥ 2c without rescue), as determined by Core Lab 
The number and percentage of subjects with complete angiographic reperfusion defined as 
mTICI score of ≥ 2c after first pass with the EMBOVACTM Aspiration Catheter as 
determined by Imaging Core Lab without use of rescue therapy, will be summarized. Two-
sided exact 95% confidence intervals will be constructed around the percentage. 
• Modified First Pass Effect (mTICI ≥ 2b), as determined by Core Lab 
The number and percentage of subjects with complete angiographic reperfusion defined as 
mTICI score of ≥ 2b after first pass with the EMBOVACTM Aspiration Catheter as 
determined by Imaging Core Lab, will be summarized. Two-sided exact 95% confidence 
intervals will be constructed around the percentage. 
 
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• Time to recanalization (Time from arterial puncture to complete recanalization mTICI 
≥ 2b), as determined by Core Lab 
The procedure time from arterial puncture to complete recanalization (achievement of the 
first mTICI score of at least 2b or greater), as determined by Imaging Core Lab, will be 
summarized. If a subject was not able to achieve an mTICI score of 2b or greater, the time 
from arterial puncture to visualization of the final angiogram will be summarized. 
• Modified Rankin Scale (mRS) 0-2 at 90 days  
The number and percentage of subjects achieving mRS 0-2 at 90 days will be summarized. 
Subjects with missing mRS scores due to all-cause mortality are considered to have an 
mRS score of 6 in the analysis, all other data will be summarized using observed data.  
Two-sided exact 95% confidence intervals will be constructed around the percentage. 
10.5.4.2.2. Secondary Safety Endpoints 
•   Devices related serious adverse events within 90 days of follow up 
The number and percentage of subjects with device related SAEs will be summarized. The 
number of events will also be summarized. Device relatedness will be adjudicated by an 
independent CEC. 
• sICH at 24h post procedure specified according to the Heidelberg Bleeding 
Classification (HBC) 
sICH at 24 hours post procedure as specified by HBC will be assessed by an independent 
CEC. The number and percentage as well as the two-sided 95% confidence intervals around 
the percentage will be summarized. 
• NIHSS at 24h post procedure 
The observed NIHSS total score at 24 hours post-procedure and changes from the baseline 
score will be summarized. 
 
• 90 Day All-Cause Mortality  
All-cause mortality at 90 days post-procedure will be summarized. Two-sided exact 95% 
confidence intervals will be constructed around the percentage. 
 
10.5.5. Health Economic Endpoints 
Hospitalization data will be analyzed using the mITT population: 
• Hospitalization length of stay for index procedure and unscheduled re-hospitalizations 
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The mean, median, minimum and maximum duration of hospitalization length of stay will 
be summarized for subjects who have been treated with study device during index procedure. 
The number and percentage of subjects with hospitalization length of stay in the 0-1 day, 1-
2 days and >2 days categories will be summarized for the index procedure.  
• Healthcare resource utilization for index procedure, post-procedure and re-
hospitalizations for unscheduled events 
The number and proportion of subjects with re-hospitalizations post index procedure, and 
the number of re-hospitalizations after the index procedure will be summarized for subjects 
who have been treated with study device. 
10.5.6. Clot Analysis 
Clot data assessed by the independent Clot analysis lab will be summarized using the mITT 
population. 
 
Composition of clot components to be evaluated includes: Red Blood Cells (RBC), White 
Blood Cells (WBC), platelets, fibrin and other fibrous proteins. Clot composition along 
with weight and area data will be summarized per pass and overall.   
 
10.5.7. Plans for Interim Analyses 
Interim analyses will be conducted for regional (outside Europe, as well as for European 
MDR) regulatory submission purposes. Only descriptive statistics will be reported. Results 
of the interim analyses will not be used as a basis for stopping the trial early. 
10.5.8. Handling of Missing Data 
All data will be summarized as observed, no missing data will be imputed in the study 
unless specified elsewhere.  
 
10.6. Measures to Minimize Bias 
Cerenovus will be diligent in controlling for bias by utilizing proper study design and 
implementation of the approved study protocol.  EC approval will be obtained at all clinical 
sites prior to study initiation.  Study agreements/contracts will be made with the 
hospitals/universities and all compensation for conduct of the study will be paid to the 
hospitals/universities and not to the investigators. Inclusion and exclusion criteria will be 
implemented to avoid selection bias.  
 
An independent Clinical Events Committee (CEC) will review and adjudicate the safety 
endpoints, as specified in the CEC charter. CEC members will provide an impartial review 
and will not hold a financial interest in Cerenovus.  An independent core laboratory will 
perform the angiographic assessments for the primary and secondary effectiveness 
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endpoints. These evaluations will be performed by an independent reader who does not 
hold a financial interest in Cerenovus. 
 
Clinical outcomes will be measured in a standardized manner using the National Institutes 
of Health Stroke Scale, a standardized, objective, clinical assessment tool used to quantify 
and document the neurological status of patients and to act as a predictor for clinical 
outcomes. It is used to determine stroke and the severity of stroke.  
 
Clinical outcomes will be measured in a standardized manner using the Modified Rankin 
Scale, a commonly utilized seven-point scale measuring functional outcome and disability 
in patients with stroke. The mRS measures independence and dependence related to 
activities of daily living and can be used over time to determine recovery or regression. In 
this study, 90 day mRS evaluations will be conducted by an independent evaluator who is 
not part of the interventional treating team,the patient’s direct clinical care or involved in 
data entry (e.g., neurologist CRNC).   
An independent CEC will review and adjudicate safety endpoints to determine whether 
they meet protocol-specified criteria.  CEC members will provide an impartial and 
standardized review of these safety events.  
 
An independent Imaging Core Lab will perform the angiographic assessments for the 
primary effectiveness endpoint, as well as the secondary effectiveness endpoints that are 
based on imaging. The Imaging Core Lab will provide an impartial and standardized 
review of imaging outcomes. 
 
Study monitors will have clinical research experience and be proficient at study 
monitoring.  Study data will be source data verified (SDV) as specified in the monitoring 
plan using the subject’s medical records, study source worksheets, clinic notes, and 
radiographic reports as applicable as source documentation. 
 
In order to minimize potential bias, subject screening logs will be maintained at the sites. 
These will document all first-line aspiration mechanical thrombectomies performed at the 
site. All cases of EMBOVACTM being used in stroke treatment, will be taken into account 
for total screening numbers, noting why the potential subject was not enrolled.  
 
11. Ethics and Protection of Human Subjects 
11.1. Ethical Standard 
As the Sponsor of this study, Cerenovus has the overall responsibility for the conduct of 
the study and, is conducted in accordance with GCP, ISO 14155 requirements, local 
regulations, the signed clinical study contract with Sponsor, the protocol outlined herein, 
as well as with the principals of the Declaration of Helsinki.   
 
 
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• General Responsibilities   
Sponsor’s general duties consist of assuring that sites have received EC approvals, 
selecting investigators, ensuring proper clinical site monitoring and ensuring subject 
informed consent is obtained.  Any additional requirements imposed by an EC or 
regulatory authority shall be followed, if appropriate. 
• Data Quality and Reporting 
Sponsor is responsible for providing quality data that satisfy applicable regulations and 
informing proper authorities of unanticipated adverse effects and deviations from the 
protocol as applicable.   
• 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 investigators to obtain 
EC re-approval.  A justification for each amendment will be documented.   
• Maintaining Records  
Sponsor will maintain copies of correspondence, device and procedure related Serious 
Adverse Events and other records related to the study. Sponsor will maintain records 
related to the signed Investigator Agreements. 
 
11.2. Ethics Committee (EC)  
The protocol, informed consent form, recruitment materials, and all participant materials 
will be submitted to the EC for review and approval.  EC approval of both the protocol and 
the consent form must be obtained before any participant is consented.   
Any amendment to the protocol will require review and approval by the EC before the 
changes are implemented to the study.  Cerenovus and the 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 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 EC. 
 
 
 
 
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11.3. Informed Consent and Data Release Form Process 
11.3.1. Consent and Other Informational Documents Provided to Participants 
Subject’s informed consent must be obtained and documented according to the principles 
of informed consent. Due to the emergent nature of AIS, consent may be obtained up to 45 
days post-procedure, as permitted by the local regulations and EC. 
The 45-day window of consent is a mid-point in the patient’s follow-up and will prevent 
study bias for the following reasons: 
• Due to the nature of AIS and its treatment, subjects may require several weeks to regain 
the capacity to provide their consent to be part of the study or to physically sign the 
informed consent form 
• Due to precautionary restrictions at hospitals to prevent the spread of infectious disease, 
it is not always possible for the treating physician to request the subject’s LAR/relative 
to provide informed consent on the subject’s behalf. The 45 day consenting window 
gives the physicians more chances to connect with subject’s relatives 
In the event that a subject is not capable of giving their informed consent, all reasonable 
efforts will be made to obtain informed consent from the subject’s LAR (for example, 
relative or caregiver). This includes cases where the subject dies during the intervention or 
shortly thereafter, before they can provide their informed consent, or when the severity of 
the subject’s condition prohibits them from providing informed consent. This will vary 
from case to case, depending on the status / mental state of the patient or if the patient is in 
life threating condition at the time of screening. In this case, the investigators should follow 
their standard practice to determine if a patient is able to provide their own consent or 
whether consent should be obtained from a patient’s LAR. 
The EC must review and approve an informed consent form (ICF) specific to this study.  
Cerenovus will provide each study center with an example ICF or data release form.  The 
clinical center, to meet specific EC requirements, may modify this example ICF.   The 
original, subject’s ICF must be retained by the investigational site for monitoring, and a 
copy provided to the subject. 
If applicable per local regional requirements, a data release form must be obtained prior to 
releasing subject information. The EC must review and approve the data release form 
specific to this study and the written data release form must be signed and dated by the 
subject prior to participation in this study. The original, signed and dated data release form 
must be retained by the investigational site for monitoring, and a copy provided to the 
subject. 
 
 
 
 
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11.3.2. Consent and Data Release Form 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 discussed with the patient and their families 
as requested prior to enrollment in the study and being considered a subject. The 
investigator, or designee, will explain the research study to the potential subject 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 informed consent form and to ask 
questions prior to providing their consent. The patients must be allowed additional time as 
desired to consider the study prior to agreeing to participate. Prior to participation in the 
study, the Patient Informed Consent Form will be signed and personally dated by the 
patient or his/her legal representative. Local regulations may allow for alternative 
approaches to the written informed consent form, such as witnessed phone consent. The 
site’s alternative approach to obtaining informed consent must be approved by the sponsor 
and the site’s EC/regulatory authority (if applicable) prior to implementation. Approval 
must be documented in the Investigator Site File. 
 
The subject may withdraw consent at any time throughout the course of the study. The 
rights 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. The completed Patient Informed Consent Form 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 
protected health information, in accordance with 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 that the subject’s privacy is guaranteed. 
As applicable per local regional requirements, a data release form may also be required and 
must be obtained prior to releasing patient information, if required. Similar to consenting 
procedures, the consent discussion must be conducted in non-technical wording 
understandable for the patient and the patient must have ample time and opportunity to 
inquire about further details.  Once a patient decides to participate in the study, the written 
data release form must be signed and dated by both the investigator and the patient. The 
original, signed and dated data release form must be retained by the investigational site for 
monitoring, and a copy provided to the subject. 
 
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11.4. Participant and Data Confidentiality 
During this clinical investigation, all representatives of the Sponsor will comply with all 
in-country privacy laws 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, Central Clot Lab, Clinical Research Associate 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 used in the analysis and reporting of this evaluation will exclude 
identifiable reference to the subject. 
 
11.4.1. Research Use of Stored Human Samples, Specimens and data 
Clot samples and related data collected under this protocol may be used to further study 
the etiology of AIS. Any remaining clot material will be retained and may be used in further 
scientific testing associated with the study. Access to stored samples and data will be 
limited to study related personnel, to include Cerenovus appointed vendors and not for 
other researchers or research groups. Samples will not be used as part of genetic research, 
and will be used for study related research.  This material will not be used outside of the 
study. Samples and data will be stored using de-identified codes assigned to subjects. 
Results of the testing will remain the property of Cerenovus.  
 
11.5. Future Use of Stored Specimens  
With the subject’s consent and as approved by local EC, de-identified biological samples 
will be stored at the Clot analysis lab for future analysis associated with the PERFECT 
study. These samples could be used for research into the causes of AIS and will be used 
until the Research and Development testing is complete or the sample is completely used. 
Samples not completely used will be stored for future use in stroke related research for 
approximately 15 years.  
The samples will only be available for researchers working for or delegated by Cerenovus 
and not for other researchers or research groups. There will be no transfer of the biological 
samples to third parties not delegated by Cerenovus. 
 
 
 
 
 
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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 
compliance with the protocol, ISO 14155, GCP, and the applicable regulatory 
requirements. If noncompliance is identified, Sponsor will 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 by the Sponsor, 
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. 
Data protection will abide by regulation (EU) 2016/679 of the European Parliament and of 
the Council of 27 April 2016 on the protection of natural persons with regard to the 
processing of personal data and on the free movement of such data. Data transfer outside 
the EU and to the US will be performed under adequate levels of protection and inspired 
by data transfer modalities at least as protective as the data protection laws within Europe. 
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. 
 
 
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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. 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, certified electronic record 
copies will have to be printed and added to the subject’s paper file. A print-out of a 
completed 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 device and procedure related Serious Adverse Events, 
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 
• Shipping records and traceability for clots sent for histopathological analysis 
• Notes of phone calls and/or correspondences 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, and 
local government authorities, will have access to these confidential files. 
 
 
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13.1.4. Health Economic Data 
Subject hospitalization information will be collected in the eCRF by the investigator and 
study-site personnel for all subjects throughout the study. Subject admission and discharge 
date will be collected for the index procedure. Re-hospitalization data for unscheduled 
events will include admission and discharge date.   
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. 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 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. 
13.1.8. Study Record Retention and Archiving 
The sponsor and principal investigator shall maintain the clinical investigation documents 
as required by the applicable regulatory requirement(s). It is the principal investigator 
responsibility to retain study essential documents and source documentation that support 
the data collected on the study subjects for at least two years after the final report. They 
shall take measures to prevent accidental or premature destruction of these documents. The 
principal investigator or sponsor may transfer custody of records to another person/party 
and document the transfer at the investigation site or at the sponsor's facility. These 
documents may be retained for a longer period if required by local laws and/or an 
agreement with Cerenovus. Prior to disposal of any records, the Investigator should notify 
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Cerenovus.  The investigator will take measures to ensure that these essential documents 
are not accidentally damaged or destroyed. If for any reason the investigator withdraws 
responsibility for maintaining these essential documents, custody must be transferred to an 
individual who will assume responsibility. Cerenovus must receive written notification of 
this custodial change.  
Each site must maintain a file of all documents and records relating to the conduct of this 
study that will include but will not be limited to the following documents: 
• 
A copy of the Protocol and each Amendment (if applicable) 
• 
EC Approval(s) for the Protocol, Protocol Amendment(s) and study ICF(s) 
• 
EC approved ICF(s) template,  
• 
EC and Sponsor Correspondence, including Reports 
• 
Clinical Study Contract, fully executed 
• 
Principal Investigator, Sub-investigator(s), site personal Curriculum Vitae 
• 
Protocol Signature Page (s) 
• 
Site Training Records  
• 
Study Personnel Authorization Form (Site Delegation Log) 
• 
Screening and Enrolment Log 
• 
Subject Identification Log (not to be removed from site) 
• 
IFU 
• 
ICFs for each subject enrolled 
 
Only authorized Cerenovus personnel or representatives, authorized site personnel, and 
local government authorities, will have access to these confidential files. 
 
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 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.  
Any standard of care assessments performed outside of the protocol requirements prior to 
consent/enrollment will be considered an eligibility deviation. Deviations will be reviewed 
and assessed by the Sponsor.   
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It is the responsibility of the site to use vigilance to identify and report deviations to the 
Sponsor and EC per 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 from the protocol to protect the rights, safety and 
well-being of human subjects may proceed without prior approval of the sponsor and the 
ethics committee. Such deviations shall be documented and reported to the sponsor and 
ethics committee 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 including, 
but not limited to www.ClinicalTrials.gov. 
 
16.2. Steering Committee 
A Steering Committee of experts with experience in the areas of neurosurgery, neurology 
or interventional neuroradiology will be 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 provide oversight of the study 
• Review of clinical data and statistical analyses, assist in data interpretation and writing 
• Provide oversight of the study 
 
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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. 
 
 
 
 
 
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