A Multicenter Observational Study to Evaluate Outcomes of EmboCube Gelatin Embolization to Control Bleeding or Hemorrhaging
Conditions: Hemorrhage, Bleeding Hemorrhage
Sponsor: Merit Medical Systems, Inc.

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CONFIDENTIAL 
 
 
 
 
 
A Multicenter Observational Study to Evaluate Outcomes of 
EmboCube Gelatin Embolization to Control Bleeding or 
Hemorrhaging 
 
 
Protocol Number: EGE-P4-21-01 
Version: 3.0 
Date: 27 June 2022 
(inclusive of administrative update 30 June 2022) 
 
 
 
Sponsor: 
Merit Medical Systems, Inc. 
1600 West Merit Parkway 
South Jordan, Utah 84095 
U.S.A.  
Telephone:  +1 801-253-1600 
 
 
 
 
 
 
 
CONFIDENTIAL - DO NOT COPY 
This Protocol contains confidential information for use by the principal investigators and their 
designated representatives participating in this study. It should be held confidential and maintained in a 
secure location. It should not be copied or made available for review by any unauthorized person or firm. 
 
 

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CONFIDENTIAL 
 
INVESTIGATOR’S SIGNATURE PAGE 
 
Study Title: 
A Multicenter Observational Study to Evaluate Outcomes of 
EmboCube Gelatin Embolization to Control Bleeding or 
Hemorrhage 
Protocol Number & Issue: 
3.0 
Study Center: 
(Print name of study center) 
 
I, the undersigned, have read and understand the protocol specified above and agree with its content. 
I agree to perform and conduct the Study as described in the protocol, and according to Good Clinical 
Practice, any local and National Regulations and any requirements specified by the reviewing IRB/EC. 
In addition, when applicable, I agree to enlist sub-investigators who also agree to perform and conduct 
the Study as described in the protocol. I will provide copies of this Protocol and all pertinent information 
to the Study personnel under my supervision and my hospital Institutional Review Board/Ethics 
Committee. I will discuss this material with them and ensure they are fully informed regarding the 
conduct of the Study according to applicable Good Clinical Practice (GCP), Declaration of Helsinki, and 
any local or National regulations. 
 
 
 
 
Principal Investigator – Print Name 
 
Signature 
 
 
DATE 
 
 

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CONTENTS 
 
Investigator’s Signature Page ............................................................................................................. 2 
Contents ................................................................................................................................................ 3 
Version History ..................................................................................................................................... 5 
Abbreviations ........................................................................................................................................ 5 
Protocol Summary ................................................................................................................................ 6 
1 
Introduction And Background ................................................................................................. 8 
1.1 
Introduction ............................................................................................................................. 8 
1.2 
Literature Summary ................................................................................................................ 8 
1.3 
Alternative Treatments / Interventions .................................................................................... 8 
1.4 
Device Description .................................................................................................................. 8 
1.5 
Study Purpose ........................................................................................................................ 8 
2 
Study Device ............................................................................................................................. 9 
2.1 
Intended Use .......................................................................................................................... 9 
2.2 
Device Regulatory Status ....................................................................................................... 9 
2.3 
Device Preparation and Use ................................................................................................... 9 
3 
Study Plan ................................................................................................................................. 9 
3.1 
Study Objective....................................................................................................................... 9 
3.2 
Design ..................................................................................................................................... 9 
3.3 
Enrollment ............................................................................................................................... 9 
3.4 
Study Population..................................................................................................................... 9 
3.5 
Study Duration and Follow-Up ................................................................................................ 9 
4 
Endpoints And Subject Population ...................................................................................... 10 
4.1 
Primary Outcome Measures ................................................................................................. 10 
4.2 
Secondary Endpoints ........................................................................................................... 10 
4.3 
Eligibility Criteria ................................................................................................................... 10 
5 
Screening And Enrollment .................................................................................................... 11 
5.1 
Screening .............................................................................................................................. 11 
5.2 
Informed Consent ................................................................................................................. 11 
5.3 
Enrollment ............................................................................................................................. 11 
5.4 
Withdrawal ............................................................................................................................ 11 
6 
Data Collection Procedures ................................................................................................... 12 
6.1 
Visit Schedule ....................................................................................................................... 12 
6.2 
Baseline ................................................................................................................................ 13 
6.3 
Procedural Information ......................................................................................................... 13 
6.4 
Follow-Up .............................................................................................................................. 13 
7 
Adverse Events ....................................................................................................................... 13 
7.1 
Adverse Event definitions ..................................................................................................... 14 
7.2 
Reportable Adverse Events .................................................................................................. 15 
7.3 
Events Not Considered Adverse Events .............................................................................. 15 
7.4 
Adverse Event Reporting Requirements .............................................................................. 15 
8 
Risk/Benefit Assessment ....................................................................................................... 16 
8.1 
Risks ..................................................................................................................................... 16 
8.2 
Risk Minimization .................................................................................................................. 16 
8.3 
Potential Benefits .................................................................................................................. 16 
8.4 
Overall Assessment of Risk-Benefits ................................................................................... 17 
9 
Statistical Analysis ................................................................................................................. 17 

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9.1 
Population Demographics .................................................................................................... 17 
9.2 
Primary Endpoint Analysis .................................................................................................... 17 
9.3 
Secondary Endpoint Analysis ............................................................................................... 17 
9.4 
Sample Size .......................................................................................................................... 17 
9.5 
Handling of Missing Data ...................................................................................................... 18 
9.6 
Interim Analysis .................................................................................................................... 18 
10 
Ethical, Quality Assurance And Administrative Aspects ................................................... 18 
10.1 
Good Clinical Practices ........................................................................................................ 18 
10.2 
Sponsor Responsibilities ...................................................................................................... 18 
10.3 
Investigator Responsibilities ................................................................................................. 18 
10.4 
Selection of Clinical Sites & Investigators ............................................................................ 19 
10.5 
Investigator Training ............................................................................................................. 19 
10.6 
EC/IRB Approvals ................................................................................................................. 19 
10.7 
Required Documentation ...................................................................................................... 20 
10.8 
Clinical Data Collection ......................................................................................................... 20 
10.9 
Device Accountability ........................................................................................................... 20 
10.10 
Subject Compensation ......................................................................................................... 21 
10.11 
Confidentiality ....................................................................................................................... 21 
10.12 
Monitoring ............................................................................................................................. 21 
10.13 
Audits and Inspections ......................................................................................................... 21 
10.14 
Amendments to the Protocol ................................................................................................ 21 
10.15 
Protocol Compliance/ Deviations .......................................................................................... 21 
10.16 
Investigational Site or Study Termination ............................................................................. 22 
10.17 
Independent Physician Adjudicator ...................................................................................... 22 
10.18 
Measures to Minimize bias ................................................................................................... 23 
11 
Records, Reports And Publication ....................................................................................... 23 
11.1 
Record Retention .................................................................................................................. 23 
11.2 
Reporting Timelines .............................................................................................................. 23 
11.3 
Study Reports ....................................................................................................................... 24 
11.4 
Publication Policies ............................................................................................................... 24 
12 
Study Definitions .................................................................................................................... 24 
13 
References .............................................................................................................................. 26 
14 
Appendix A – Study Contacts ............................................................................................... 27 
14.1 
Sponsor ................................................................................................................................ 27 
14.2 
Investigators ......................................................................................................................... 27 
14.3 
Third Parties ......................................................................................................................... 27 
 
 
 
 

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VERSION HISTORY 
Version and date 
Summary of Changes 
1.0, 25 JAN 2022 
Not applicable – first version 
2.0, 09 JUN 2022 
Study definitions updated to include Device Failure and Device 
Malfunction.   
Estimated Study Duration dates and Study PI were updated.  
3.0, 27JUN 2022 
Addition of one inclusion and one exclusion criteria applicable to 
sites in France only. 
 
ABBREVIATIONS 
ADE:  
Adverse Device Effect 
AE:  
Adverse Event  
(e)CRF 
Case Report Form/ Electronic Case Report Form 
EC:  
Ethics Committee  
GCP 
Good Clinical Practice  
IFU:  
Instructions for Use  
IPA 
Independent Physician Adjudicator 
IRB:  
Institutional Review Board  
ITT:  
Intent to Treat  
mITT:  
Modified Intent to Treat 
PI 
Principal Investigator 
SADE:  
Serious Adverse Device Effect 
SAE:  
Serious Adverse Events 
UADE:  
Unanticipated Adverse Device Event 
 
 
 

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PROTOCOL SUMMARY 
Study Title: 
A Multicenter Observational Study to Evaluate Outcomes of 
EmboCube Gelatin Embolization to Control Bleeding or Hemorrhage 
Study Objective: 
To collect clinical safety and performance outcome data associated 
with the use of EmboCube Embolization Gelatin to control bleeding 
or hemorrhage. 
Study Device:  
EmboCube Embolization Gelatin 
Study Design: 
Multicenter observational post-market clinical follow-up study in 
subjects treated with EmboCube 
Device Regulatory 
Status: 
CE mark approved March 2019 (CE 667862).  
Sample size: 
A minimum of 100 subjects will be included. This sample size is based 
on a one-sample non-inferiority analysis of Clinical Success based on 
the parameters listed below and a 15% loss-to-follow-up:  
• 
Reference Clinical Success rate (p0): 92%   
• 
Treatment rate (p): 90%  
• 
Non-inferiority margin: 10%  
• 
α: 0.05  
• 
Power: 80% 
The reference Clinical Success rate is based on historical clinical 
literature data for benchmark gelatin embolic devices.   
Subject Population: 
Subjects who are treated with EmboCube to control bleeding or 
hemorrhage in accordance with the current approved CE Mark 
indication for use as stated in the Instructions for Use (IFU). 
Clinical Sites: 
Up to 7 centers may be included to allow enrollment of required 
subjects.   
Study Follow-Up: 
Data will be collected to 28 days post procedure.   
Estimated Study 
Duration: 
First patient enrolled: July 2022 
Last patient enrolled:  July 2023 
Last patient, last visit: August 2023 
Primary Endpoints: 
The primary performance endpoint will be clinical success defined as 
cessation of bleeding post-embolization and absence of rebleeding 
at the treated site requiring reintervention (repeat embolization or 
additional surgery) within 24 hours.  
 
The primary safety endpoint will be absence of unanticipated serious 
adverse device effects within 24 hours. 
Secondary Endpoints: 
1. Incidence of adverse events (serious and device and/or 
procedure-related) to 24 hours post-operative. 
2. Incidence of adverse events (serious and device- and/or 
procedure-related) between 24 hours and 28 days post-
operative. 
3. Technical success defined as successful occlusion of the target 
area as seen on post-embolization angiography. 
4. Incidence of device observations relating to EmboCube. 
Inclusion Criteria: 
1. Age ≥18 years  
2. Subject requires embolization and is suitable for treatment with 
EmboCube in accordance with device Instructions For Use for the 
treatment of bleeding or hemorrhage. 

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3. Subject provides written informed consent to study data collection. 
4. The subject has Social Security (applicable only in France) 
Exclusion Criteria: 
1. Bleeding site in the neck, head, or brain. 
2. Subject has co-morbidity with survival prognosis of less than 
30 days, in the opinion of the treating physician. 
3. In the investigator’s opinion, participation in the study may not 
be in the subject’s best interest. 
4. Pregnant woman, person under guardianship or curatorship, 
persons under judicial protection, and persons who do not 
write or speak French (applicable in France only). 
Refer to the EmboCube Embolization Gelatin IFU for a complete list 
of device contraindications.  

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1 
INTRODUCTION AND BACKGROUND 
1.1 
Introduction 
This is a multicenter, observational study of the use of EmboCube Embolization Gelatin to control 
hemorrhaging and bleeding. The study is designed to enable the collection, analysis and reporting of 
data from “real-world” use of EmboCube used in accordance with the Instructions for Use (IFU) 
associated with the product’s CE Mark approval. 
Data collection will include that relating to safety and effectiveness and the period of observation during 
which data will be collected will extend from the index procedure through 28 days post procedure.  Data 
collection will be according to the standard follow-up practice of the enrolling institution. 
1.2 
Literature Summary 
Gelatin based embolics are among the earliest materials utilized for therapeutic arterial embolization. 
Due to absorbability, this material is the preferred device when shorter occlusion time is the objective, 
a permanent implantable is not desired, or distal super selective targeting is not the goal. A principal 
use of resorbable embolic material is the management of hemorrhage from spontaneous conditions, 
instrumentation, or trauma. In each of these uses the goal typically is to achieve an immediate plugging 
of the source of blood loss without causing permanent ischemia. A large number of publications of case 
studies and cohort evaluations of comparable gelatin embolics demonstrate clinical success rates of 
80-100% (depending on condition) in the control of acute bleeding and massive hemorrhage.  
The indication of control of hemorrhaging and bleeding and pre-operative embolization covers a wide 
range of causes (trauma, postpartum, instrumentation, idiopathic, etc.) in a variety of anatomical 
locations (limbs, uterus/reproductive tract, viscera, etc.), and in populations ranging from healthy to 
those with multiple comorbidities or polytrauma. Frequently the bleeding occurs in an emergency 
situation, requiring rapid medical response and treatment. Although comparable resorbable gelatin 
embolics have been used to stop bleeding and hemorrhaging and for pre-operative embolization for 
decades, EmboCube is a more recent product. 
1.3 
Alternative Treatments / Interventions 
There are a number of different hemostatic agent classes and respective methods utilized to mitigate 
bleeding or hemorrhage. The class and agent(s) a physician chooses are influenced by multiple factors, 
including how rapidly the bleeding can be controlled, location and type of wound, preference of the 
medical professional treating the patient, etc.  
On a more systemic scale, mechanical agents used to control bleeding and hemorrhage include 
clamps, tourniquets, sutures, etc. However, for control of acute bleeding and hemorrhage (including 
intravascular use) temporary mechanical hemostatic agents, like EmboCube Embolization Gelatin are 
frequently selected. These agents work to obstruct the bleeding site and function temporarily as a 
scaffold to accelerate the formation of a blood clot and return to homeostasis. Gelatin, collagen, and 
oxidized regenerated cellulose are three materials that constitute the majority of mechanical agents. 
(Chiara 2018) 
1.4 
Device Description 
EmboCube Embolization Gelatin consists of biocompatible, hydrophilic, and dry pre-cut cubes of 
resorbable porcine gelatin packaged in a 10-mL syringe with a standard luer lock tip. Where approved, 
EmboCube Embolization Gelatin is sold in two sizes (2.5 mm and 5.0 mm) and three weight 
configurations.  Each sterile syringe is intended for single patient use only. 
A full description of the device can be found in the Instructions for Use (IFU). 
1.5 
Study Purpose 
The study is designed to enable the collection, analysis, reporting and presentation of data from use of 
EmboCube in accordance with the Instructions for Use associated with the product’s CE Mark approval. 

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The intent of this study is to increase the understanding of the performance of EmboCube in ‘real world’ 
patient population, encompassing a broad spectrum of causes of bleeding, treated areas, and patient 
profiles, to confirm the product’s performance and safety in general clinical practice. The intended use 
of EmboCube includes high-risk anatomical sites and conditions, and so the data collected will be used 
to amplify knowledge about known or estimated risks, clinical and technical performance, and to identify 
and evaluate any potential unanticipated adverse device effects, and to integrate that information into 
product risk analysis and update the clinical evaluation report and labeling, if appropriate. 
2 
STUDY DEVICE 
2.1 
Intended Use 
EmboCube Embolization Gelatin will be used in accordance with the current approved CE Mark 
indication for use as stated in the Instructions for Use (IFU): 
EmboCube Embolization Gelatin is indicated for use in embolization of blood vessels to occlude blood 
flow to control bleeding/hemorrhaging in the peripheral vasculature. 
2.2 
Device Regulatory Status 
CE Mark was approved March 13, 2019, by BSI (CE 667862). 
2.3 
Device Preparation and Use 
EmboCube Embolization Gelatin will be prepared and used as described in the IFU that accompanies 
each device. 
Procedures for patient treatment and follow-up, including medication, will be according to hospital / 
institutional standard of care and physician medical judgement. 
3 
STUDY PLAN 
3.1 
Study Objective 
To collect clinical safety and performance outcome data associated with the use of EmboCube 
Embolization Gelatin to control bleeding or hemorrhage.  
3.2 
Design 
Multicenter, observational, post-market clinical follow-up study in subjects treated with EmboCube.  
This study does not involve submitting subjects to any procedures additional to those performed under 
normal conditions of use of the device.  
3.3 
Enrollment 
A minimum of 100 subjects undergoing embolization with EmboCube for the treatment of bleeding or 
hemorrhage will be enrolled in the study. The study will be conducted at up to 7 centers globally. 
3.4 
Study Population 
Subjects undergoing embolization with EmboCube for the treatment of bleeding or hemorrhage who meet 
the inclusion and exclusion criteria are intended to participate in this study. The eligibility criteria are 
kept to a minimum to better represent the subject profile treated in actual clinical practice without 
selecting sub-groups of particular low/high risk or excluding certain diseases or anatomies. 
3.5 
Study Duration and Follow-Up 
It is anticipated that enrollment will commence in July 2022 and is expected to continue until July 2023. 
The last subject visit is expected in August 2023. 
Subject follow up visits will be in accordance with standard of care. Data will be collected from available 

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medical records for baseline (medical history), index hospitalization, up to 24 hours post procedure, 
and until 28 days post-procedure.  If there is no routine clinic visit or follow-up between 4- and 6-weeks 
post procedure (28 days +14 days), subjects will be contacted by telephone during this time to collect 
safety follow-up to 28 days. 
Start of study is defined as the date of initiation (authorization to start enrollment) of the first site. 
Completion of the study is defined as the completion of the last follow-up visit/contact for the last 
subject. 
4 
ENDPOINTS AND SUBJECT POPULATION 
4.1 
Primary Outcome Measures 
4.1.1 
Primary effectiveness endpoint 
The primary performance endpoint will be clinical success defined as cessation of bleeding post-
embolization and absence of rebleeding at the treated site requiring reintervention (repeat embolization 
or additional surgery), within 24 hours.     
4.1.2 
Primary safety endpoint  
The primary safety endpoint will be absence of unanticipated serious adverse device effects within 24 
hours. 
4.2 
Secondary Endpoints  
1. Incidence of adverse events (serious and device- and/or procedure-related) to 24 hours post-
operative. 
2. Incidence of adverse events (serious and device- and/or procedure-related) between 24 hours 
and 28 days post-operative. 
3. Technical success defined as successful occlusion of the treated site as seen on post-
embolization angiography. 
4. Incidence of device observations relating to EmboCube. 
4.3 
Eligibility Criteria 
Subjects are required to meet ALL the following criteria in order to be included in this study: 
4.3.1 
Inclusion Criteria 
1. Age ≥18 years  
2. Subject requires embolization and is suitable for treatment with EmboCube in accordance with 
device Instructions For Use for the treatment of bleeding or hemorrhage. 
3. Subject provides written informed consent to study data collection.   
4. The subject has Social Security (applicable only in France) 
4.3.2 
Exclusion Criteria 
1. Bleeding site in the neck, head, or brain. 
2. Subject has co-morbidity with survival prognosis of less than 30 days, in the opinion of the 
treating physician 
3. In the investigator’s opinion, participation in the study may not be in the subject’s best interest. 
4. Pregnant woman, person under guardianship or curatorship, persons under judicial protection, 
and persons who do not write or speak French (applicable in France only). 
 

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Refer to the EmboCube Embolization Gelatin IFU for a complete list of device contraindications.  
 
5 
SCREENING AND ENROLLMENT 
5.1 
Screening 
All consecutive patients who meet the eligibility criteria should be considered for enrollment in the study. 
Sites should maintain a cumulative log of all screened and enrolled subjects. The Investigator or 
designee should determine potential eligibility according to Section 4.3.  Patients who meet all criteria 
should be provided with further information on the study in accordance with the procedures in Section 
5.2. 
5.2 
Informed Consent 
As bleeding or hemorrhaging requiring embolization occurs in unplanned and/or emergency 
circumstances, it is anticipated that, in many cases, it will not be possible to obtain written informed 
consent prior to procedure.  This is an observational study and study consent is required for collection 
and use of patient data, including telephone contact for safety review if required.  There are no 
additional procedures or tests required in addition to routine standard of care.  Written informed consent 
(or non-opposition consent, if applicable), to collect and use data will be collected with the Ethics 
Committee (EC)/Institutional Review Board (IRB) approved consent form prior to procedure, if feasible.  
If written consent cannot be collected before the procedure, it should be collected as soon as possible 
after procedure but no later than time of subject discharge or 7 days post-procedure, whichever occurs 
first.  No data collection can occur until subject has provided written informed consent.  
The subject shall be given adequate time to read the Informed Consent form and have the data 
collection and data transmission procedures explained prior to signing the Informed Consent form. All 
subjects providing informed consent for data collection are to receive copies of their signed informed 
consent documentation.  
The Sponsor will inform the investigators whenever information becomes available that may be relevant 
to the subject’s confirmed participation in the study. The investigator or designee should inform the 
subject in a timely manner. 
The Sponsor will revise the Informed Consent form whenever new information becomes available that 
may be relevant to the subject’s confirmed participation in the study. The revised information will be 
sent to the investigator for approval by the EC/IRB. After approval by the EC/IRB, a copy of this 
information must be provided to the participating subjects, and the informed consent process as 
described above needs to be repeated. 
5.3 
Enrollment 
All subjects who provide written informed consent for the study, meet all eligibility criteria, and are treated 
with EmboCube Embolization Gelatin will be considered enrolled in the study.  
Subjects who are consented prior to procedure but subsequently do not receive EmboCube 
Embolization Gelatin will be considered screen failures. These subjects will be entered on the screening 
log, but no data will be collected on screen failures. 
Subjects who are enrolled and treated, but who are later are discovered to not meet all the eligibility 
criteria will remain in the study for follow-up and a Protocol Deviation form will be completed. 
Point of enrollment is the time of informed consent. 
5.4 
Withdrawal 
Subjects may withdraw at any time from the study without prejudice; participation is entirely voluntary. 
If a subject prematurely terminates from the study, the reason for termination will be recorded in the 
eCRF. 

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The Investigator should follow all unresolved serious adverse events until the events are resolved, the 
subject is lost to follow-up, the subject has withdrawn consent, the subject completes the study follow- 
up, or the adverse event is otherwise explained. 
All reasonable efforts will be made to obtain complete data for all subjects; however, missing 
observations will occur due to loss to follow-up, withdrawal, or variation in site standard of care 
assessments.  
Sites shall make all reasonable efforts to contact subjects who do not attend for a routine clinic visit 
between 4 to 6 weeks by telephone to confirm status. In the event subject does not respond to a final 
contact attempt via certified letter, subject will be documented as lost to follow-up on the Study Exit 
form. Subjects who withdraw consent after treatment will have their data evaluated until the time of 
their withdrawal (unless consent for data retention is removed in accordance with local or national 
regulations). Subjects who withdraw or are lost to follow-up will not be replaced.  
6 
DATA COLLECTION PROCEDURES 
6.1 
Visit Schedule 
Study participation will last for a total of 28 days (+14 days). Follow-up will be by clinic visit or telephone 
according to site standard of care.  Data will be collected from available medical records for baseline, 
index hospitalization, and standard of care follow-up until 28 days post-procedure.  If there is no routine 
clinic visit or follow-up between 4 and 6-weeks post procedure (28 days +14 days) subjects will be 
contacted by telephone during this time to collect safety follow-up to 28 days. 
A summary schedule of the data collection for tests and evaluations is in Table 1. Data will only be 
collected if tests and evaluations are completed per standard of care. 
Table 1 Data Collection Schedule 
Data 
Pre-operative/ 
baseline 
Procedure to 24 
hours 
28-day follow-up2 
(28 to 42 days) 
Informed consent1 
X 
 
 
Demographics 
X 
 
 
Diagnosis, i.e., cause and location 
of bleeding or hemorrhage  
X 
X 
 
Procedural information  
 
X 
 
Clinical Success 
 
X 
 
Technical success 
 
X 
 
EmboCube use (size, type, and 
amount) 
 
X 
 
No/type other adjuvant embolics 
employed  
 
X 
 
Device and/or procedure related 
serious adverse events 
 
X 
X 
Occurrence of re-intervention to 
control bleeding at the treated site 
 
X 
X 
Concomitant antiplatelet and 
anticoagulant medications 
X 
X 
X 
 
1 Subject will be asked to provide written informed consent for data collection either preoperatively or prior to 
hospital discharge.  
2 If subject is not seen by site between 4-6 weeks (28 to 42 days) for clinical visit, subject will be telephoned to 
collect information on potential device related adverse events and reinterventions. 

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6.2 
Baseline 
The following baseline data will be collected: 
• 
Demographic information (age at time of treatment/enrollment, sex, and ethnicity [if 
permitted by local regulations]) 
• 
Relevant medical history 
• 
Diagnosis, i.e., cause and location of bleeding or hemorrhage. 
• 
Height and weight/BMI 
• 
Concomitant anticoagulants and antiplatelet medications 
6.3 
Procedural Information 
All procedures should be conducted in accordance with site standard of care and patient needs, there 
are no prohibited concomitant treatments. EmboCube Embolization Gelatin shall be used in 
accordance with the IFU. 
Data collected will include the following: 
• 
Procedure type  
• 
Treated vessel and treated area 
• 
Occlusion of the target area as seen on post-embolization angiography 
• 
Time to hemostasis (TTH) post-EmboCube embolization  
• 
EmboCube Embolization Gelatin size, type and number of units used 
• 
Additional embolic agents used in procedure (e.g., coils, glue, microspheres) - number and 
type and whether used pre- or post EmboCube 
• 
Transfusion/ use of blood products  
• 
Coagulation status (PT, PTT, INR) 
• 
Repeat embolization or additional surgery to address bleeding within 24 hours 
o 
Rebleeding due to treated vessel 
• 
Serious and device and/or procedure related adverse events  
• 
Device observations – any observations relating to handling and delivery of EmboCube 
• 
Concomitant anticoagulants and antiplatelet medications 
6.4 
Follow-Up 
The following data will be collected by review of all medical records available for the period between 
index procedure and 28 days. In the event the subject is not seen for routine clinic visit or follow-up 
between 4- and 6-weeks post procedure (28 days +14 days), subjects will be contacted by telephone 
during this time to confirm their current status and collect safety information. 
• 
Date of discharge post-index procedure    
• 
Concomitant anticoagulants and antiplatelet medications 
• 
Number, type, and timing of additional interventions to treat bleeding 
o 
Rebleeding due to treated vessel 
• 
Serious and device and/or index procedure related adverse events 
Subjects will continue to be treated according to standard routine practice after completion of study. 
7 
ADVERSE EVENTS 
For the purpose of this Study, all serious and potentially device-related and/or index procedure-related 
adverse events will be documented to 28 days post-index procedure and reported to Sponsor via the 
eCRF. 

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All deaths will be reported to 28 days, regardless of investigator assessment of causality. 
The Sponsor shall review all reported adverse events for their relationship to the study device and/or 
procedures and comparative anticipated safety event rates. The Sponsor will conduct evaluations of 
any device-related event per standard operating procedures. 
An independent Physician Adjudicator will be responsible for review and adjudication of events defined 
in Section 10.17. 
7.1 
Adverse Event definitions 
Adverse events will be classified according to ISO 14155:2020 definitions.  Where the definition 
indicates “investigational medical device”, it refers to the EmboCube Embolization Gelatin used in the 
index procedure. 
Adverse Event (AE): (ISO14155:2020, 3.2) 
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. 
Note 1 to entry: This definition includes events related to the investigational medical device or 
the comparator. 
Note 2 to entry: This definition includes events related to the procedures involved. 
Note 3 to entry: For users or other persons, this definition is restricted to events related to the use 
of investigational medical devices or comparators. 
Adverse Device Effect (ADE): (ISO14155:2020, 3.1) 
Adverse event related to the use of an investigational medical device. 
Note 1 to entry: 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 to entry: This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
Note 3 to entry: This includes ‘comparator’ if the comparator is a medical device. 
Serious Adverse Event (SAE): (ISO 14155:2020 3.45) 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users, or other persons as defined by 
one or more of the following: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function including chronic 
diseases, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function, 
c) foetal distress, foetal death, a congenital abnormality, or birth defect including physical or 
mental impairment 
Note 1 to entry: Planned hospitalization for a pre-existing condition, or a procedure required by 
the CIP, without serious deterioration in health, is not considered a serious 
adverse event. 
Serious Adverse Device Effect (SADE): (ISO 14155:2020 3.44) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event.  
 
In addition to the ISO14155:2020 definitions, the following study specific definitions apply: 

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Procedure-Related Adverse Event: an adverse event is considered to be procedure-related 
when, in the judgment of the Investigator, it is reasonable to believe that the event is associated 
with the assigned study procedure and is not solely to the device. Other products, surgical 
techniques, or medications required specifically for the procedure are likely to have contributed to 
the occurrence of the event.  
7.2 
Reportable Adverse Events 
For the purpose of this study, events which meet the definition of both serious adverse events and that are 
potentially device-related and/or procedure-related will be reported.   
All deaths will be reported as SAE regardless of Investigator assessment of causality. 
7.3 
Events Not Considered Adverse Events 
For purposes of this study, there are no specific events which are not considered adverse events.  All 
events which meet the definition of both serious adverse events and that are potentially device-related 
and/or procedure-related, and all deaths will be reported. 
7.4 
Adverse Event Reporting Requirements 
7.4.1 
General Reporting Requirements 
Reportable adverse events should be recorded on the eCRF through 28 days post index-procedure. 
The report should include: the description of event, severity, duration, action taken, treatment outcome 
and relationship of the adverse experience to the study device and/or procedure (refer to section 12 
for definitions for causality and severity). 
All reportable events should be followed until resolution, or study exit. 
7.4.2 
Reporting Requirements for Serious Adverse Events 
All serious and potentially device and/or procedure-related adverse events, and all deaths must be 
reported to the Sponsor within 24 hours of knowledge of the event or by the end of the next working 
day. This may be done via eCRF or by phone, fax, or email using the contact details provided separately 
to sites. 
The Sponsor will review all reported events for potential reporting in accordance the requirements of 
Regulation (EU)2017/745 of the European Parliament and of the Council of 5 April 2017 on Medical 
Devices (MDR), and any applicable guidance(s).   Sponsor may request medical record documentation 
(e.g., procedure notes, operative notes, discharge summary, relevant progress notes, imaging, or lab 
studies) to facilitate this review. 
The Sponsor will determine whether all of the local Investigators need to be informed immediately of an 
SAE, or whether this can be postponed until the next regularly scheduled study update. 
The Sponsor will ensure reporting of applicable events to Regulatory Authorities as clinical study safety 
reports, if required by Local/national regulations.  
The Investigator is responsible for reporting applicable serious adverse events to their EC/IRB as 
required by EC/IRB procedures and local/national regulations. A copy of each EC/IRB safety report will 
be provided to Sponsor. 
Local, specific safety reporting will be specified in a separate safety plan. 
7.4.3 
Device Failures and Malfunctions 
All device observations / performance issues, malfunctions, or failures, whether or not associated with 
an adverse event must be reported to the Sponsor within 24 hours of knowledge of the event or by the 
end of the next working day. This may be done via eCRF or by phone, fax, or email using the contact 

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details provided separately to sites. 
The Sponsor will review all reported events for potential reporting in accordance with the requirements 
of Regulation (EU)2017/745 of the European Parliament and of the Council of 5 April 2017 on Medical 
Devices (MDR), and any applicable guidance(s). The Sponsor may request medical record 
documentation (e.g., procedure notes, operative notes, discharge summary, relevant progress notes, 
imaging, or lab studies) to facilitate this review. 
 
8 
RISK/BENEFIT ASSESSMENT 
8.1 
Risks 
EmboCube Embolization Gelatin is being used in accordance with the approved CE Mark indication 
and Instructions for Use.  
Vascular embolization is a high-risk procedure. Complications may occur at any time during or after 
the procedure, and may include, but are not limited to, the following as listed in the device IFU: 
• 
Stroke or cerebral infarction 
• 
Occlusion of vessels in healthy territories 
• 
Vascular rupture 
• 
Neurological deficits 
• 
Infection or hematoma at the injection site 
• 
Allergic reaction, cutaneous irritations 
• 
Transient pain and fever 
• 
Vasospasm 
• 
Death 
• 
Ischemia at an undesirable location, including ischemic stroke, ischemic infarction 
(including myocardial infarction), and tissue necrosis 
• 
Blindness, hearing loss, loss of smell, and/or paralysis 
There are no interactions with concomitant medical treatments identified in the device IFU. 
8.2 
Risk Minimization 
As with any surgical procedure, appropriate safety precautions will be followed. In addition, this Protocol 
provides additional steps to minimize risk to study subjects. These include the following: 
• 
Investigator Selection & Training: All investigators are required to be appropriately 
qualified by education, training, and expertise in vascular embolization. Embolization with 
EmboCube Embolization Gelatin should only be performed by physicians who have 
received appropriate interventional embolization training in the region to be treated. 
• 
Subject Screening: Subject selection will be in accordance with the Protocol and the IFU. 
Subjects with known contraindications to use of embolics should not be enrolled in the 
study. 
8.3 
Potential Benefits 
There are no specific benefits to the subject from participating in the study and subject treatment is not 
determined by the protocol. 

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8.4 
Overall Assessment of Risk-Benefits 
This is an observational registry using commercially available devices and there are no new risks or 
benefits to the individual subject associated with study participation.    
The additional information obtained on the safety and effectiveness profile of the device may benefit 
physician understanding of the use of embolics and may support the development of new devices in 
general.  Therefore, Sponsor’s assessment is that the potential benefits justify the study.   
9 
STATISTICAL ANALYSIS 
The analysis of the data from this study will be primarily descriptive. Continuous endpoints will be 
summarized by N, mean, standard deviation, median, minimum, and maximum. Categorical or binary 
endpoints will be summarized by N and percentage with confidence intervals as appropriate. Kaplan 
Meier plots will be used to display and summarize time to event data. 
The planned sample size for analysis is at least 100 subjects which is believed to be adequate to provide 
an accurate characterization of EmboCube in a “real-world” clinical setting.   
Analysis Population 
• 
Intention-to-Treat (ITT) Analysis Set: includes all enrolled subjects. 
• 
Per-Protocol (PP) Analysis Set: includes all enrolled subjects who met all inclusion/exclusion 
criteria with no major protocol deviations. This is a secondary analysis set for the primary safety 
and effectiveness endpoints, as well as secondary endpoints. 
While ITT is intended as the primary analysis set for all safety and effectiveness endpoints, the primary 
safety and effectiveness endpoints will additionally be evaluated in the PP analysis sets as supportive 
information. All subjects excluded from ITT analysis set will be described. 
9.1 
Population Demographics 
The demographics and medical history will be presented in tabular form for all subjects enrolled in this 
study (ITT analysis set). Means, standard deviations, and sample size will be used to summarize 
continuous characteristics such as age. Frequencies and percentages will be used to summarize 
categorical characteristics such as gender. Demographic and medical history data will be additionally 
tabulated for the ITT and PP analysis sets. 
9.2 
Primary Endpoint Analysis 
Endpoints will be analyzed using the intention-to-treat analysis set. An additional supportive analysis 
will be conducted in the PP analysis sets for the primary safety and effectiveness endpoints. All 
available data will be used for each endpoint and no imputations will be done. 
The primary endpoint of clinical success will be presented as frequency and percentage. 
The primary safety endpoint of absence of SADE within 24 hours, will be presented as frequency and 
percentage. 
9.3 
Secondary Endpoint Analysis 
All secondary endpoints will be tabulated. Means, standard deviations and sample size will be used to 
summarize continuous characteristics. Distributions of continuous data will be examined and if non- 
normality is exhibited, medians and interquartile ranges will be presented. Frequencies and 
percentages will be used to summarize categorical characteristics. All available data will be used for 
each endpoint and no imputations will be done.  
9.4 
Sample Size 
The sample size of 100 subjects is based on a one-sample non-inferiority analysis of Clinical Success 
based on the parameters listed below and a 15% loss-to-follow-up:  
• 
Reference Clinical Success rate (p0): 92%   

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• 
Treatment rate (p): 90%  
• 
Non-inferiority margin: 10%  
• 
α: 0.05  
• 
Power: 80% 
The reference Clinical Success rate is based on historical clinical literature data for benchmark gelatin 
embolic devices. 
9.5 
Handling of Missing Data 
No imputation of missing data is planned.  
9.6 
Interim Analysis 
Interim analyses will be performed to support regulatory submission(s) and may be performed as 
needed to support conferences, presentations, or publications. No pre-stated study stopping rules are 
planned.   
10 ETHICAL, QUALITY ASSURANCE AND ADMINISTRATIVE ASPECTS 
10.1 Good Clinical Practices 
This study will be conducted in accordance with ethical principles that have their origins in the 
Declaration of Helsinki. This study shall be conducted in accordance with ISO14155:2020 and all local 
or national regulations applicable to this study.   
The following ISO14155:2020 requirements do not apply to this study, any additional exceptions from 
the standard will be justified in the study files: 
• 
Device accountability procedures where commercial products are used. 
• 
Device labelling specific for clinical investigations. 
• 
No Investigator Brochure will be written as sufficient information is available in the commercial 
IFU and this protocol. 
• 
Reporting to regulatory authorities will be completed only if required by regulations. 
• 
Informed consent will be collected for collection of study data. 
10.2 Sponsor Responsibilities 
The Sponsor is responsible for the overall conduct and quality of the study, including the assurance that 
the study complies with Declaration of Helsinki, applicable Good Clinical Practices, relevant Data 
Protection regulations and all relevant international standards and regulations applicable to medical 
device observational studies.  
The Sponsor will ensure that all applicable national regulatory and Data Protection approvals are in 
place, and that EC/IRB approval is in place prior to commencement of the study at each site.  
The Sponsor will obtain and maintain appropriate insurance in accordance with national and local 
requirements and will provide a copy of the insurance policy to the Investigators, EC/IRB, other national 
regulatory agencies (as applicable). 
The Sponsor will implement systems to select and train investigators, collect data, oversee the quality 
of the study and monitor investigator compliance with their responsibilities as detailed in this Protocol.   
10.3 Investigator Responsibilities 
The Investigators are responsible for ensuring that this study is conducted according to this Protocol, 
Declaration of Helsinki, applicable Good Clinical Practices, relevant Data Protection regulations, and 
any other applicable local or national regulations and any requirements imposed by the EC/IRB or 
regulatory authorities . 

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It is also the Investigator’s responsibility to ensure that all sub-investigators and staff assisting with this 
study have the appropriate qualifications and that they complete training on the Protocol procedures, 
and that subject confidentiality is respected. Other Investigator responsibilities are detailed throughout 
Section 10. 
10.4 Selection of Clinical Sites & Investigators 
The Sponsor is responsible for selection of sites for study participation based upon review of the 
following criteria: 
• 
Investigator(s) are appropriately qualified by education, training, and expertise in vascular 
embolization. Embolization with EmboCube Embolization Gelatin should only be 
performed by physicians who have received appropriate interventional embolization 
training in the region to be treated. 
• 
Investigator(s) are willing to conduct the study in accordance with this Protocol and all 
applicable local and national regulatory requirements, including Informed Consent 
requirements. 
• 
Adequate staff to comply with study data collection and reporting standards. 
• 
Appropriate facilities, resources, and equipment to conduct the study including ability to 
support EDC requirements. 
• 
Willing to allow access to representatives of the Sponsor and/or regulatory authorities for 
data monitoring/audit. 
10.5 Investigator Training 
The Sponsor will ensure that Investigators and site staff are trained in the Study Protocol, including 
consent requirements and data collection procedures. Training may be completed by on-site visit, 
WebEx and/or web-based training modules. No additional device training or case support is required for 
study participation. 
10.6 EC/IRB Approvals 
The Investigator at each site is responsible for obtaining EC/IRB approval for the Protocol and the 
Informed Consent documents prior to enrollment of the first study subject at site. The Sponsor must 
also review and approve the final Informed Consent documents prior to their use. The Sponsor must 
receive a copy of EC/IRB final approval letter and the final approved Informed Consent. 
The Investigator is responsible for ensuring that all applicable local, national, and Declaration of Helsinki 
requirements are met when completing the informed consent process. Written, Informed Consent is to 
be obtained for all subjects prior to any data collection. 
The Investigator or clinical site staff will not make amendments to this Protocol or the Informed Consent 
form without PRIOR written approval from the Sponsor. All approved amendments must then be 
submitted to the local EC/IRB, as appropriate for approval. 
If the Investigator’s IRB or EC withdraws their approval to conduct this study for any reason, the 
Investigator must notify the Sponsor as soon as possible, but in no event later than five working days 
after the withdrawal of the approval. 
The Investigator must submit and, where necessary, obtain approval from the EC/IRB for all subsequent 
significant Protocol amendments and significant changes to the Informed Consent form. The 
Investigator should notify the EC/IRB of deviations from the Protocol and safety reports in accordance 
with local procedures. 
The Investigator will be responsible for obtaining annual EC/IRB approval and renewal, where 
applicable, throughout the duration of the study. Copies of the Investigator’s reports and the EC/IRB 
continuance of approval must be sent to Sponsor. 

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10.7 Required Documentation 
The Investigator will maintain all CRFs, source documents and all study documents and 
correspondence as required by applicable regulatory requirements for the duration of the study. 
The following documents should be provided to the Sponsor before the study starts: 
• 
Copy of EC/IRB approval and membership list and any other relevant local approvals. 
• 
Copy of the EC/IRB approved Informed Consent form and any other approved patient 
information. 
• 
Financial disclosures for the Investigator and sub-Investigator(s). 
• 
Signed and dated Protocol Signature page. 
• 
Current signed and dated curriculum vitae for each Investigator and sub-Investigator. 
• 
Fully executed study agreement, including financial agreement. 
10.8 Clinical Data Collection 
Standardized electronic case report forms (eCRF) will be used to collect complete and accurate records 
of the clinical data. The Investigator and/or staff under his/her direction is responsible for accurately 
recording the clinical data for this study and submitting it to the Sponsor in a timely manner. All data 
from the trial will be entered into eCRF via a secure, web-based system with password protection. All 
data should be entered completely and promptly. Data will be remotely reviewed and queried to identify 
inconsistent or missing data and any adverse events. 
Investigators are required to maintain adequate source documents including laboratory results, 
supporting medical records, and signed Informed Consent forms. These will be used during monitoring 
visits to verify data contained on the completed eCRF. For source documents, corrections should be 
made in a manner that does not obscure or eliminate the original error, by striking through the original 
data with one line, and initialing and dating the change, along with the reason for the change (if not 
obvious). 
The investigator must ensure accuracy, completeness and timeliness of the data reported in the eCRFs 
and in all other required reports. Data reported on the eCRFs which are derived from source documents 
must be consistent with the source documents or the discrepancies need to be justified in a documented 
rationale, signed and dated by the (principal) investigator, to be filed in the subject file. 
Only authorized persons can complete an eCRF. An eCRF shall be signed by investigators as specified 
on the Delegated Tasks List included in the Investigator Site File. 
The Electronic Data Capture (EDC) system maintains an audit trail on entries, changes or corrections 
in eCRFs. If a person only authorized to complete an eCRF makes changes to an already signed eCRF, 
the investigator shall re-sign this eCRF. 
10.9 Device Accountability 
Device size and lot number will be recorded in the eCRF. Where sites use devices supplied according 
to standard hospital/clinic procedures for commercial products, no other device accountability 
procedures will apply. 
The Sponsor may provide devices specifically for use in the study, providing this is in accordance with 
all applicable national laws and regulations.  The provision of devices for study specific purposes shall 
be documented in the clinical study agreement.  In such cases, Investigators will be responsible for 
providing a secure storage location for the devices, separate to any commercial stock, and the disposal 
and/or return of the devices as instructed by the Sponsor. In addition, Investigators will maintain records 
to document the receipt, use and disposition of all devices received by their site intended for this study 
and provide copies to Sponsor. The Sponsor and/or designee will also maintain records of all shipments 
and disposition of devices. Study specific devices should be available to the monitor for review during 
on-site monitoring.  

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10.10 Subject Compensation 
Study subjects will not be reimbursed or compensated for their time in participating in the trial. 
10.11 Confidentiality 
Confidentiality of subjects will be maintained throughout the study. A unique identification code will be 
assigned to each participating subject. Any data that may be published in abstracts, scientific journals, 
or presented at medical meetings will reference a unique study code and will not reveal the subject’s 
identity. The Investigator, Sponsor and their representatives will make every reasonable effort to protect 
subject confidentiality. 
10.12 Monitoring 
The Sponsor will designate appropriately qualified monitors to review compliance with Protocol and 
data collection procedures, to assess the accuracy and completeness of eCRF data and record 
retention. These will primarily be assessed by remote data review. On-site monitoring visits may be 
undertaken based on review of factors including, but not limited to enrollment rate, adverse event 
reporting and Protocol compliance. 
The Investigator will make available all regulatory documents, completed eCRF, Informed Consent 
documents, source documentation and other relevant records for enrolled subjects at the site.   
It is important that the Investigator and other relevant site personnel are available for consultation with 
the monitor during on-site monitoring visits and remote review and that sufficient time is devoted at the 
site to the monitoring process. 
A detailed monitoring plan for the study will be maintained separately. 
10.13 Audits and Inspections 
The Investigator will allow representatives of the Sponsor, EC/IRB and applicable regulatory agencies 
to inspect all trial records, eCRF, and corresponding portions of the subject’s office and/or hospital 
medical records at regular intervals throughout the trial. These inspections are for the purposes of 
verifying adherence to the Protocol, completeness and exactness of the data being transcribed into the 
eCRF, and compliance with regulatory agency regulations. 
The Investigator will inform the Sponsor in advance if they are to be audited or inspected by any 
regulatory agencies. The Sponsor or the Sponsor’s designee will also inform the site if they are made 
aware of a pending audit or inspection by a regulatory agency. 
The Investigator and/or designees must be available to respond to reasonable requests by authorized 
Sponsor, CRO and regulatory agency representatives during the monitoring and inspection process. 
The Investigator must provide the Sponsor with copies of all correspondence that may affect the review 
of the current study (i.e., Inspection Observations) or their qualification as an Investigator in clinical 
studies conducted by the Sponsor. The Sponsor will provide any needed assistance to the clinical site 
for regulatory audits, if any. 
10.14 Amendments to the Protocol 
The Sponsor will submit any significant amendment to the protocol, including a justification for this 
amendment, to the appropriate regulatory authorities and to the investigators to obtain approval from 
their EC/IRB. The investigator will only implement the amendment after approval of the EC/IRB, 
regulatory authority (if applicable) and sponsor.  
Administrative amendments to the protocol will be submitted to the EC/IRB for notification.  
Investigators shall sign any the initial protocol and subsequent approved amendments for agreement.  
10.15 Protocol Compliance/ Deviations 
The Investigators are responsible for ensuring that this study is conducted according to this Protocol. 

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All deviations from the Protocol must be reported to the Sponsor. 
Investigators shall be required to obtain prior approval from the Sponsor before initiating deviations 
from the Protocol, except where necessary to protect the life or physical well- being of a subject in an 
emergency. Such approval shall be documented in writing and maintained in Sponsor and Investigator 
files. 
Investigators will also adhere to procedures for reporting Protocol deviations to their EC/IRB in 
accordance with their specific EC/IRB reporting policies and procedures. 
For reporting purposes, the Sponsor classifies the following as major protocol deviations: Any deviation 
from subject inclusion and exclusion criteria, failure to obtain subject informed consent and failure to 
report serious adverse events.  Other deviations which occur will be reviewed and classified by 
Sponsor. 
The Sponsor shall report deviations from the approved protocol in the study report.  
If the Sponsor and/or their authorized representative become aware that an Investigator is not 
complying with the study protocol, the Investigator Agreement, the Declaration of Helsinki, applicable 
privacy standards, or any condition of the study imposed by the IRB / EC, the Sponsor or their 
authorized representative may immediately secure compliance or suspend or terminate enrollment at 
site. An inability to secure compliance and/or to complete an investigation into the factors that are 
inhibiting compliance may result in the Investigator’s termination from the study by the Sponsor. 
10.16 Investigational Site or Study Termination 
The Sponsor reserves the right to terminate an investigational site from the study for any of the following 
reasons: 
• 
Failure to obtain Informed Consent. 
• 
Failure to comply with safety reporting requirements. 
• 
Repeated Protocol deviations or safety concerns. 
• 
Repeated failure to complete electronic Case Report Forms. 
• 
Failure to enroll an adequate number of subjects. 
The Sponsor reserves the right to terminate the study at any stage but intends to exercise this right 
only for valid scientific or administrative reasons and reasons related to protection of subjects. 
Investigators, associated IRB/ECs, and regulatory authorities, as applicable, will be notified in writing 
in the event of study termination. Detailed information on how enrolled subjects will be managed after 
termination will also be provided. Possible reasons for premature study termination include, but are not 
limited to, the following. 
• 
Occurrence of unanticipated adverse device effects that present a significant or unreasonable 
risk to subjects enrolled in the study. 
• 
An enrollment rate far below expectation that prejudices the conclusion of the study. 
• 
A decision on the part of Sponsor to suspend or discontinue development of the device. 
10.17 Independent Physician Adjudicator  
An independent Physician Adjudicator (IPA) will be responsible for review and adjudication of all 
serious and potentially device-related adverse events, at minimum.  Other events may be reviewed as 
defined in the IPA Charter.  
In order to enhance objectivity and reduce the potential for bias, the IPA shall be independent of the 
Sponsor as well as the investigational sites and investigators. The methodology for performing these 
responsibilities shall be developed and outlined in the IPA Charter. Operational provisions shall be 
established to minimize potential bias. 

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10.18 Measures to Minimize bias  
The following measures will be implemented to minimize the potential for bias in this single arm 
Registry: 
• 
Sites are requested to screen and enroll consecutive subjects, as far as possible, and enrollment 
activities will be documented in a screening/enrollment log. 
• 
Multiple sites will be included to ensure a representative sample of physicians performing the 
procedure and to provide a reasonable enrollment period. 
• 
Site selection will be performed using predefined parameters to ensure Investigators are 
appropriately qualified to conduct registry. 
• 
Only physicians that are trained and experienced in vascular embolization can participate. 
• 
Site training will be performed to assure full understanding and engagement to comply with the 
study design and all protocol requirements. 
• 
A sample of adverse events will be reviewed and assessed by an independent Physician. 
• 
Any known or foreseeable factors that may compromise the outcome of the Registry or the 
interpretation of results are covered by the Inclusion and Exclusion criteria. 
• 
Financial disclosures will be collected from all investigators to document any potential for bias or 
conflict of interest. 
 
11 RECORDS, REPORTS AND PUBLICATION 
11.1 Record Retention 
Sponsor and Investigators will maintain their study records until two (2) years after the final report is 
completed, or longer if required by local, national or international regulatory agencies. The Sponsor will 
notify each site regarding the regulatory requirements for record retention at the time of study close- 
out. 
11.2 Reporting Timelines 
The Investigator will report information and events according to the timelines below: 
Form/Report 
Submission Timeframe 
eCRF 
Completion within 10 working days of visit/follow-up, or chart review. 
All serious and potentially 
device-related events and 
all deaths 
Submit notification to Sponsor within 24 hours of the site becoming 
aware of the event, or by the end of the next working day; submit to 
the local EC/IRB as required according to local and national 
regulations. 
All device observations / 
performance issues, 
malfunctions or failures 
Submit notification to Sponsor within 24 hours of the site becoming 
aware of the event, or by the end of the next working day; submit to 
the local EC/IRB as required according to local and national 
regulations. 
Major deviations 
Submit notification to Sponsor within 24 hours of the site becoming 
aware of the event, or by the end of the next working day; submit to 
the local EC/IRB as required according to local and national 
regulations. 
Progress Reports 
As required by the local EC/IRB 
Final Report to the EC/IRB 
As required by the local EC/IRB 

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11.3 Study Reports 
All information and data generated in association with the study will be held in strict confidence and 
remains the sole property of the Sponsor. The Investigator agrees to use this information for the sole 
purpose of completing the study and for no other purpose without prior approval of the Sponsor. 
The Sponsor will submit all required reports to regulatory authorities throughout the study. 
Upon receipt of the final study data and the final reports from each center, the Sponsor will complete a 
final study report. Copies of the final report will be provided to each Investigator. 
11.4 Publication Policies 
Publications and presentations will be coordinated by Sponsor to allow the use of all available data. The 
following publication policy will have to be adhered to by all participating investigation sites: 
Authorship on any publication(s) will be assigned according to substantial contributions to conception 
and design, acquisition of data, or analysis and interpretation of data, drafting the article or revising it 
critically for important intellectual content and final approval of the version to be published. This is in 
accordance with the International Committee of Medical Journal Editors’ “Recommendations for the 
Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals (ICMJE 
Recommendations)”, December 2019, as agreed upon by the editors of all major medical journals. The 
number of authors will be dependent on the regulations of the concerning journal with a maximum of 
10 authors. Names of all participating investigators will appear in the Acknowledgment of the paper. 
Based on the principle that Sponsor owns the study data, a single investigation site may access and use 
the data provided by itself for scientific publications following prior approval by Sponsor. 
Pooling data from several investigation sites for publication purposes, national projects and international 
projects all require prior approval by Sponsor. 
Sponsor as the owner of the data can use the data and/or any results derived from the data or 
publications based on that data for marketing purposes, further research and development of devices 
or educational use. 
Participating subjects will not be identified by name in any published reports about the study. This study 
will be registered with www.clinicaltrials.gov. including requirements to make results publicly available.  
 
12 STUDY DEFINITIONS 
ADVERSE EVENT CAUSALITY  
The sponsor and the investigators will use the following definitions to assess the relationship of the 
serious adverse event to the study device, or the investigation procedure1. 
1. Not related: Relationship to the device, or procedures can be excluded when: 
• 
the event has no temporal relationship with the use of the study device, or the procedures 
related to application of the study device; 
• 
the serious adverse event does not follow a known response pattern to the medical device (if 
the response pattern is previously known) and is biologically implausible; 
• 
the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible - and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious adverse event; 
 
1 Definitions derived from “MDCG 2020-10/1 Safety reporting in clinical investigations of medical 
devices under the Regulation (EU) 2017/745” May 2020. 

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• 
the event involves a body-site or an organ that cannot be affected by the device or procedure; 
• 
the serious adverse event can be attributed to another cause (e.g., an underlying or concurrent 
illness/ clinical condition, an effect of another device, drug, treatment, or other risk factors); 
In order to establish the non-relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious adverse event. 
2. Possible: The relationship with the use of the study device, or the relationship with procedures, is 
weak but cannot be ruled out completely. Alternative causes are also possible (e.g., an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug, or treatment). Cases 
where relatedness cannot be assessed, or no information has been obtained should also be classified 
as possible. 
3. Probable: The relationship with the use of the study device, or the relationship with procedures, 
seems relevant and/or the event cannot be reasonably explained by another cause. 
4. Definitely related (Causal relationship): the serious adverse event is associated with the study 
device, or with procedures beyond reasonable doubt when: 
• 
the event is a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
• 
the event has a temporal relationship with study device use/application or procedures; 
• 
the event involves a body-site or organ that 
o 
the study device or procedures are applied to; 
o 
the study device or procedures have an effect on; 
• 
the serious adverse event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
• 
the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious adverse event (when clinically feasible); 
• 
other possible causes (e.g., an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug, or treatment) have been adequately ruled out; 
• 
harm to the subject is due to error in use; 
In order to establish the relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious adverse event. 
ADVERSE EVENT SEVERITY  
The following definitions for rating severity of adverse events will be used: 
Mild: 
Awareness of signs or symptoms, but easily tolerated; are of minor irritant type; 
causing no loss of time from normal activities; symptoms would not require 
medication or a medical evaluation; signs or symptoms are transient. 
Moderate:  
Interferes with the subject’s usual activity and/or requires symptomatic treatment. 
Severe:  
Symptom(s) causing severe discomfort and significant impact of the subject’s usual 
activity and requires treatment. 
Device Failure: A device that is used in accordance with the Instructions for Use, but the device does 
not perform according to the Instructions for Use and negatively impacts the treatment. 
Device Malfunction: A malfunction of a device is an unexpected change to the device that is 
contradictory to the Instructions for Use and may or may not affect device performance. 
 
 

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13 REFERENCES 
1. Chiara, O., Cimbanassi, S., Bellanova, G. et al. A systematic review on the use of topical 
hemostats in trauma and emergency surgery. BMC Surg 18, 68 (2018). 

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14 APPENDIX A – STUDY CONTACTS 
14.1 Sponsor 
This study is sponsored and funded by: 
Merit Medical Systems, Inc. 
1600 West Merit Parkway 
South Jordan, Utah 84095 
U.S.A. Telephone:  +1 801-253-1600 
 
Names and addresses of local representatives, if required in any country, will be maintained separately 
and shall be provided on request and documented in the clinical study report. 
Merit is responsible for all aspects of study management, including but not limited to: data 
management, study management, and study monitoring.    
14.2 Investigators  
Study Principal Investigator: Pr. Olivier Pellerin, MD. PhD. FCIRSE 
An up-to-date list of all Investigators and all study sites will be maintained separately and shall be 
provided on request. The definitive list will be documented in the clinical study report. 
14.3 Third Parties 
At the time this protocol was finalized all third parties involved in the clinical study had not been 
identified. A list with addresses of all external organizations involved in the study, including Clinical 
Research Organizations, consultants, and other contractors and the scope and duties to be entrusted, 
will be maintained separately and provided on request.