A Multicenter, Prospective, Randomized, Controlled, Open Label Trial to Evaluate the Safety and Efficacy of Mynx Control Venous Vascular Closure Device 6F-12F vs Manual Compression in Patients Who Have Undergone Endovascular Procedures Utilizing up to 12F Procedural Sheaths
Phase: NA
Conditions: Venous Vascular Closure
Sponsor: Cordis US Corp.

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The information in this document is the property of Cordis and is CONFIDENTIAL and PROPRIETARY. 
Neither the document nor the information contained therein may be reproduced or disclosed outside Cordis 
without the written consent of the company. 
 
 CONFIDENTIAL 
 
 
 
 
 
 
 
 
 Version 3.0 
Clinical Study Protocol 
A MULTICENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED, OPEN LABEL TRIAL TO EVALUATE THE SAFETY AND 
EFFICACY OF MYNX 
 VENOUS VASCULAR CLOSURE DEVICE 6F-12F VS. MANUAL COMPRESSION IN 
PATIENTS WHO HAVE UNDERGONE ENDOVASCULAR PROCEDURES UTILIZING UP TO 12F PROCEDURAL SHEATHS  
ReliaSeal 
 
Protocol Number: 
Cordis Document Control Number: 
P22-8301 
100606833 
Protocol Version/Date: 
3.0 / 31Jan2023 
Product: 
MYNX CONTROL
 Venous Vascular Closure Device 6F-12F  
Model/Specification: 
MX61260  
 
Cordis US Corp. 
14201 NW 60th Ave 
Miami Lakes, FL 33014 
 
 
National Principal Investigator 
Name/Address: 
Javier Sanchez, MD 
Medical City Dallas Heart Hospital 
11970 North Central Expressway 
Dallas, TX  75243 
Registration Number(s): 
NCT005554471 
Author Name: 
Jenny Jimenez, Sr Clinical Project Manager 
 
 
 
Version History 
 
Version Number
Version Date
Summary of Revisions
1.0 
25May2022 
N/A (original version) 
1.1 
27May2022 
Administrative Changes. 
2.0 
13Nov2022 
Changes to address FDA  study design 
considerations and clarifications for 
Investigational sites   
3.0 
31Jan2023 
 from the 
19Jan2023 letter 
 
 
 

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                                                                                                            Version 3.0 
 
 
A MULTICENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED, OPEN LABEL TRIAL TO EVALUATE THE 
SAFETY AND EFFICACY OF 
 VENOUS VASCULAR CLOSURE DEVICE 6F-
12F VS. MANUAL COMPRESSION IN PATIENTS WHO HAVE UNDERGONE ENDOVASCULAR 
PROCEDURES UTILIZING UP TO 12F PROCEDURAL SHEATHS 
ReliaSeal 
Protocol Number: P22-8301 
Version: 3.0 
Version Date: 31Jan2023 
 
Approval Signatures 
 
I AM THE PRIMARY AUTHOR OF THIS STUDY PROTOCOL AND CONFIRM TO THE BEST 
OF MY KNOWLEDGE IT IS COMPLETE AND ACCURATE. 
Name 
Role 
Signature 
Date 
Jenny Jimenez 
Clinical Project Manager 
 
 
 
I HAVE REVIEWED THE STUDY PROTOCOL AND CONFIRM TO THE BEST OF MY 
KNOWLEDGE IT IS COMPLETE AND ACCURATE. 
Name 
Role 
Signature 
Date 
Dr. Nusrath Sultana 
Medical Monitor 
 
 
 
Steve Ullery 
Statistician 
 
 
 
Crystal Placona 
Regulatory Affairs 
 
 
 
Dr Nusrath Sultana 
Clinical Management 
 
 
 
 
 
 
 

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A MULTICENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED, OPEN LABEL TRIAL TO EVALUATE THE 
SAFETY AND EFFICACY OF 
 VENOUS VASCULAR CLOSURE DEVICE 6F-12F 
VS. MANUAL COMPRESSION IN PATIENTS WHO HAVE UNDERGONE ENDOVASCULAR 
PROCEDURES UTILIZING UP TO 12F PROCEDURAL SHEATHS  
ReliaSeal 
Protocol Number: P22-8301 
 
Version: 3.0 
Version Date: 31Jan2023 
Investigator Protocol Signature Page 
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will 
conduct the study in accordance with the design and specific provisions outlined herein. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who 
assist in the conduct of this study. I will discuss this material with them to ensure they are fully informed 
regarding the investigational product and the conduct of the study. 
I will use the informed consent form approved by Sponsor and the IRB and will fulfill all responsibilities for 
submitting pertinent information to the IRB responsible for this study. 
I also agree to report all information or data in accordance with the protocol and I agree to report any serious 
adverse events (SAE), and unanticipated adverse device effect (UADE) as defined in the protocol. 
I further agree that Sponsor and/or designee have access to any original source documents from which 
case report form (CRF) information may have been generated. 
I also agree to have control over all clinical supplies (including investigational product) provided by Sponsor 
and/or designees and collect and handle all clinical specimens in accordance with the protocol. 
The below signed confirm herewith to have read and understood this study protocol and/or amendment and 
appendices; furthermore, to accomplish this study in accordance with the protocol, ICH/GCP guidelines, 
applicable international standards and all applicable country, local and federal regulations; and to accept 
respective revisions conducted by authorized personnel of Sponsor and by regulatory authorities. 
 
 
 
 
 
 
 
Principal Investigator 
(print) 
 
 
 
 
 
 
 
 
 
Principal Investigator 
(signature) 
 
Date 
 
 
 
 
 
 
 
Institution Name/Location 
 
 
 
 
 

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Table of Contents 
Approval Signatures ................................................................................................................ 2 
Investigator Protocol Signature Page..................................................................................... 3 
Table of Contents ..................................................................................................................... 4 
Protocol Synopsis ................................................................................................................... 8 
1 
Study Management Team ...........................................................................................14 
2 
Introduction .................................................................................................................15 
2.1 
Product characteristics ................................................................................................................... 15 
2.2 
Structural composition, operation principle and mechanism of action ........................................... 16 
3 
Study Objectives .........................................................................................................16 
4 
Indication .....................................................................................................................17 
5 
Contraindications ........................................................................................................17 
6 
Precautions ..................................................................................................................17 
7 
Warnings ......................................................................................................................17 
8 
Benefits/Risks ..............................................................................................................18 
8.1 
Benefits .......................................................................................................................................... 18 
8.2 
Risks............................................................................................................................................... 18 
9 
Study Design ...............................................................................................................19 
9.1 
Overview ........................................................................................................................................ 19 
9.2 
Duplex Ultrasound sub-study ......................................................................................................... 19 
10 
Study Population/Selection Criteria ...........................................................................20 
10.1 Inclusion Criteria ............................................................................................................................ 20 
10.2 Exclusion Criteria ........................................................................................................................... 20 
10.2.1 
Pre-procedural Exclusion Criteria .................................................................................. 20 
10.2.2 
Intra-Procedural Exclusion Criteria ................................................................................ 21 
11 
Study Endpoints ..........................................................................................................22 

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11.1 Primary Endpoints .......................................................................................................................... 22 
11.1.1 
Primary Safety Endpoint ................................................................................................ 22 
11.1.2 
Primary Effectiveness Endpoint ..................................................................................... 22 
11.2 Secondary Endpoints ..................................................................................................................... 22 
11.2.1 
Secondary Safety Endpoint............................................................................................ 22 
11.2.2 
Secondary Effectiveness Endpoints include the following: ............................................ 23 
11.3 Other/Additional Endpoints ............................................................................................................ 23 
12 
Informed Consent ........................................................................................................23 
13 
Screening and Enrollment ..........................................................................................25 
13.1 Screening Period ............................................................................................................................ 25 
13.1.1 
Screening Assessments ................................................................................................. 25 
13.1.2 
Screen Failures and Pre-screen Failures ...................................................................... 25 
13.2 Enrollment ...................................................................................................................................... 26 
14 
Treatment Plan ............................................................................................................26 
14.1 Index Procedure ............................................................................................................................. 26 
14.2 Post-Procedure Care/Discharge .................................................................................................... 27 
14.3 Recommended Medication Regimen ............................................................................................. 28 
14.4 Follow-up Visits/Assessments ....................................................................................................... 28 
14.5 Lost to Follow-up ............................................................................................................................ 29 
14.6 Unscheduled Visits ......................................................................................................................... 29 
14.7 Subject Early Discontinuation ........................................................................................................ 30 
14.8 Subject Study Completion .............................................................................................................. 30 
15 
Adverse Event Reporting ............................................................................................30 
15.1 Adverse Event ................................................................................................................................ 30 
15.2 Serious Adverse Events ................................................................................................................. 31 
15.3 Unanticipated Adverse Device Effects ........................................................................................... 32 
15.4 Sponsor Progress Reports ............................................................................................................. 32 
16 
Statistics/Data Analyses .............................................................................................32 
16.1 Randomization ............................................................................................................................... 32 

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16.2 Device Failures and Malfunctions .................................................................................................. 33 
16.3 Analysis Population ........................................................................................................................ 33 
16.4 Statistical Hypotheses for Endpoints ............................................................................................. 34 
16.5 Primary Safety Endpoint ................................................................................................................ 34 
16.6 Secondary Safety Endpoint ........................................................................................................... 35 
16.7 Secondary Effectiveness Endpoints .............................................................................................. 36 
16.8 Sample Size Determination ........................................................................................................... 36 
16.9 Statistical Analysis Methods .......................................................................................................... 38 
16.9.1 
Primary Analysis ............................................................................................................ 39 
16.9.2 
Secondary Safety Analysis ............................................................................................ 40 
16.9.3 
Secondary Efficacy Analyses ......................................................................................... 40 
16.9.4 
Additional analysis ......................................................................................................... 41 
16.9.5 
Analysis of Roll-in Subjects ............................................................................................ 41 
16.9.6 
Study site poolability ...................................................................................................... 41 
16.9.7 
Interim Analysis .............................................................................................................. 41 
16.10 Sub-Group Analysis ....................................................................................................................... 42 
16.11 Missing Data .................................................................................................................................. 43 
16.12 Reporting ........................................................................................................................................ 43 
17 
Quality Control and Quality Assurance .....................................................................43 
17.1 Regulatory and Ethical Compliance ............................................................................................... 43 
17.2 Data Quality Assurance ................................................................................................................. 44 
17.3 Clinical Data ................................................................................................................................... 44 
17.4 Monitoring ...................................................................................................................................... 45 
17.5 Protocol Modifications .................................................................................................................... 46 
17.5.1 
Protocol Amendments .................................................................................................... 46 
17.5.2 
Protocol Deviations/Noncompliance .............................................................................. 46 
17.5.3 
Emergency Deviations ................................................................................................... 46 
17.6 Audits ............................................................................................................................................. 46 
17.7 Subject Confidentiality.................................................................................................................... 47 
17.8 Institutional Review Board (IRB) .................................................................................................... 47 

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18 
Record Keeping/Publication Policy ...........................................................................48 
18.1 Record Retention ........................................................................................................................... 48 
18.2 Use of Information and Publications .............................................................................................. 48 
19 
Investigational Product Accountability ......................................................................49 
19.1 Study Investigational Product Accountability ................................................................................. 49 
19.2 Instructions for Return of Investigational Product .......................................................................... 50 
20 
Committees ..................................................................................................................50 
20.1 Clinical Events Committee ............................................................................................................. 50 
20.2 Data and Safety Monitoring Board ................................................................................................. 50 
21 
Early Termination or Suspension ...............................................................................51 
Appendix A. 
Definitions ......................................................................................................53 
Appendix B. 
Acronyms and Abbreviation .........................................................................55 
Appendix C. 
References .....................................................................................................58 
 
 
 

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A MULTICENTER, PROSPECTIVE, RANDOMIZED, CONTROLLED, OPEN LABEL TRIAL TO EVALUATE THE 
SAFETY AND EFFICACY OF MYNX CONTROL
 VASCULAR CLOSURE DEVICE 6F-
12F VS. MANUAL COMPRESSION IN PATIENTS WHO HAVE UNDERGONE ENDOVASCULAR 
PROCEDURES UTILIZING UP TO 12F PROCEDURAL SHEATHS 
ReliaSeal 
Protocol Number: P22-8301 
Version: 3.0 
Version Date: 31Jan2023 
Protocol Synopsis 
Primary Objective  
To demonstrate safety and efficacy of the 
 Venous 
Vascular Closure Device 6F-12F vs. manual compression in sealing 
femoral venous access sites in patients who have undergone 
endovascular procedures utilizing up to 12F, with single or multiple 
access sites in one or both limbs. 
Device Name  
MYNX CONTROL
 Venous Vascular Closure Device 6F-12F  
Device Model Number  
MX61260CL  
Device Category  
Class III medical device  
Indication for Use  
Current indication:  
Vascular Closure Device is indicated for use to 
seal femoral arterial access sites while reducing times to hemostasis 
and ambulation in patients who have undergone diagnostic or 
interventional endovascular procedures utilizing a 5F, 6F, or 7F 
procedural sheath.  
 
Proposed expanded indication sought:  
The MYNX CONTROL
 Venous VCD 6F-12F is indicated for use to 
seal femoral venous access sites while reducing times to hemostasis 
and ambulation in patients who have undergone diagnostic or 
interventional endovascular procedures utilizing 6F to 12F procedural 
sheaths, with single or multiple access sites in one or both limbs.  
Hypothesis  
Time to ambulation will be significantly less for patients treated with the 
MYNX CONTROL 
 than those 
using manual compression. 
 
Time to hemostasis will be at least 5 minutes less for patients treated 
with the MYNX CONTROL 
 than 
those using manual compression. 
 
Rate of combined major venous access site closure-related 
complications through 30 days post procedure for patients treated with 
the MYNX CONTROL 
 will be non-
inferior to the rate for patients using manual compression. 
Study Design  
A multicenter, prospective, randomized, controlled, open label clinical 
trial designed to evaluate safety and efficacy of use of MYNX 
 Venous Vascular Closure Device 6F-12F vs. 
manual compression to seal femoral access sites in patients who have 
undergone endovascular procedures utilizing up to 
12F procedural sheaths in one or both limbs.  
Number of Patients  
 204 patients (2:1 randomized - 136 VCD:68 manual compression) 
Reference/Control Treatment
Manual Compression 

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Study Purpose
To demonstrate safety and eff
Venous Vascular Closure Device 6F-12F vs. manual compression in 
sealing femoral venous access sites in patients who have undergone 
endovascular procedures utilizing one or more procedural sheaths up 
to 12F with single or multiple access sites in one or both limbs. 
Study Centers
Approximately 15 study sites will participate in United States, with a 
minimum of 5 sites enrolling in the trial. 
Duplex Ultrasound sub study
At select sites, a subset of 72 subjects (48 from the device group and 
24 from the control group) will have an ultrasound examination of the 
access sites performed during the index procedure, at the time of 
discharge and at the 30 day (± 7 days) office visit (only for those 
subjects that have documented evidence of complications at the 
discharge ultrasound). 
Eligibility Criteria
Inclusion Criteria: 
 
ALL patients must meet the following criteria prior to enrollment: 
 
1.) Age 18 
2.) Able and willing to provide informed consent and to complete a 
follow-up visit at 30 ± 7 days  
3.) Planned catheter-based procedures via the common femoral 
vein(s) using up 6F to 12F introducer sheaths which meet 
indications for elective, nonemergent interventions of disease 
state, without contraindications for emergent vascular surgery or 
manual compression of the venous access sites 
 
Exclusion Criteria: 
 
Patients will be excluded if ANY of the following exclusion criteria 
apply: 
 
1.) 
Any use of systemic steroids (IV or oral) within 30 days of 
procedure 
2.) 
History of deep vein thrombosis, pulmonary embolism, or 
thrombophlebitis within 6 months of procedure 
3.) 
Presence of thrombocytopenia (platelet count < 100,000 
cells/mm3) or anemia (hemoglobin < 10 g/dL, hematocrit < 
30%)  
4.) 
History of bleeding disorders such as hemophilia or von 
 
5.) 
Currently involved in any other investigational clinical trial  
6.) 
Documented history of uncontrolled hypertension (i.e., systolic 
blood pressure > 180 mm Hg), or critical illness requiring 
intravenous vasopressors for blood pressure stabilization  
7.) 
Femoral arteriotomy or venotomy in either limb within 10 days 
pre procedure 
8.) 
Use of VCD in either limb within 30 days of procedure 
9.) 
Any planned procedure involving femoral arterial or venous 
access in either limb within 30 days of procedure or prior to 
study exit  
10.) Renal insufficiency (i.e., serum creatinine > 2.5 mg/dL) 
11.) Patients who are pregnant, planning to become pregnant during 
the study period, or lactating  
12.) Body-mass index (BMI) > 45 kg/m2 or <20 kg/m2 
13.) Unable to routinely walk at least 20 feet without assistance  

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14.) Known allergy/adverse reaction to polyethylene glycol or 
contrast medium  
15.) Planned procedures (including staged) or concomitant 
extend ambulation attempts beyond 2-3 hours, and/or require 
extended hospitalization or re-hospitalization  
16.) Previous vascular surgery or repair in the vicinity of the target 
access site within the previous 90 days of the procedure  
17.) Active systemic infection, or cutaneous infection or 
inflammation in the vicinity of the target access site 
18.) Current COVID-19 infection (with or without symptoms), 
positive test for COVID- 19 within 14 days, or recent exposure 
to a person with COVID-19 infection 
19.) Patients who refuse blood transfusion if it were to be needed  
20.) Patients with expected life of less than 30 days 
 
Patients who meet ANY of the following criteria during the index 
procedure will be excluded:  
 
1.) 
Any attempt at femoral arterial access or inadvertent arterial 
puncture with hematoma during the procedure  
2.) 
Any procedural complications that may interfere with routine 
recovery, ambulation, or discharge eligibility times  
3.) 
Physician deems that a different hemostasis approach for 
venous access sites is necessary  
4.) 
Physician deems that the subject should not attempt protocol-
required ambulation (reference ambulation protocol per section 
14.2)  
5.) 
Venous access site location is noted to be above the inguinal 
ligament (cephalad to lower half of the femoral head or the 
inferior epigastric vein origin from the external iliac vein) 
6.) 
Intra-procedural bleeding around sheath, or suspected 
intraluminal thrombus, hematoma, pseudoaneurysm, or AV 
fistula 
7.) 
Difficult insertion of procedural sheath or needle stick problems 
at the onset of the procedure (e.g., multiple stick attempts, 
 
8.) 
A < 6F or > 12F procedural sheath is present at any time during 
the procedure or at closure  
  
Primary Endpoint(s) 
Primary Effectiveness Endpoint 
 
 
Time to Ambulation (TTA): Defined as time (in hours) 
between removal of the MYNX CONTROL
 Venous 
Vascular Closure Device 6F-12F device (device group) or of 
the final sheath (control group) and when subject stands and 
walks 20 feet without evidence of rebleeding from any 
femoral venous access site. 
 
 
Time to Hemostasis (TTH): Defined as time (in minutes) 
between removal of each MYNX CONTROL
Vascular Closure Device 6F-12F device (device group) or of 
each sheath (control group) and first observed and confirmed 
venous hemostasis (per access site analysis) 

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Primary Safety Endpoint: 
 
Rate of CEC adjudicated combined major venous access site 
closure- related complications through 30 days post procedure, 
attributed directly to VCD or manual compression without other likely 
cause.   
 
Access site-related bleeding requiring transfusion, surgical 
intervention, or rehospitalization 
 
Vascular injury requiring surgical repair 
 
Access site-related infection confirmed by culture and 
sensitivity, requiring intravenous antibiotics and/or extended 
hospitalization 
 
New onset, permanent (i.e., persisting at 30-day follow-up) 
access site-related nerve injury 
 
New onset access site-related nerve injury requiring surgical 
repair  
 
Pulmonary embolism requiring surgical or endovascular 
intervention and/or resulting in death, to be confirmed by CT 
pulmonary angiography, lung ventilation/perfusion scan (VQ 
scan), or autopsy 
 
Pulmonary embolism not requiring surgical or endovascular 
intervention and/or not resulting in death, to be confirmed by 
CT pulmonary angiography or lung ventilation/perfusion scan 
(VQ scan) 
Secondary Endpoint(s) 
Secondary Safety Endpoint: 
 
Rate of CEC adjudicated combined minor venous access site 
closure related complications within 30 days post-procedure, 
attributed directly to VCD or manual compression without other 
likely cause.  
 
Pseudoaneurysm  Treated with thrombin injection, fibrin 
adhesive injection, or ultrasound guided compression and 
documented by ultrasound 
 
Pseudoaneurysm  Not requiring treatment 
 
AV Fistula requiring treatment, documented by ultrasound 
 
AV Fistula not requiring treatment, documented by ultrasound
 
Access site related hematoma > 6 cm documented by 
ultrasound 
 
Access site-related bleeding requiring > 30 min to achieve 
hemostasis 
 
Late access site-related bleeding (following hospital 
discharge eligibility) 
 
Transient loss of ipsilateral lower extremity pulse 
 
Ipsilateral deep vein thrombosis documented by ultrasound 
 
Transient access site-related nerve injury 
 
Access site-related vessel laceration 
 
Access site wound dehiscence 
 
Local access site infection confirmed by culture and 
sensitivity, treated with intramuscular or oral antibiotics  
minor 
 
Local access site inflammatory reaction  Minor 
 
Allergic reaction 
 
Ecchymosis 

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Secondary Effectiveness Endpoints: 
 
Time to Discharge Eligibility- defined as elapsed time (in 
hours) between removal of the final MYNX CONTROL
 
Venous VCD (device group) or removal of the final sheath 
(control group) and when subject is eligible for discharge from 
the institution based on the assessment of the attending 
physician.  
 
 
Procedural Success: attainment of final hemostasis at all 
venous access sites without major venous access site 
closure-related complications through 30 days  
 
 
Device Success (for device group): ability to successfully 
deploy the MYNX CONTROL
Venous VCD delivery 
system, deliver the polyethylene glycol hydrogel sealant, and 
achieve hemostasis (device group only)  
Additional Endpoints
Pain score at time of discharge eligibility. 
Sample Size
Total enrollment of 204 patients (2:1 randomized  136 VCD: 68 
manual compressions) 
Duration of Subject
Participation 
ALL patients will be followed through 30 days post procedure. Once 
all enrolled patients have completed follow-up, the study will be 
considered complete.  
Statistics/Testing Methods
Data analysis will follow the intention-to-treat principle and will be 
conducted at the per access site or per patient level as indicated 
below, with a non-inferiority analysis for primary safety endpoint and 
superiority analyses for primary and powered secondary 
effectiveness endpoint. 
 

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Table 1. Time and Event Schedule (Please refer to Section 14 for details) 
 
 
Screening
(-30 to day
0) 
At time of 
Index 
Procedure 
(day 0) 
Post-
Procedure/  
 
Pre-
discharge 
1-Month 
(30 ± 7 days) 
Informed consent (within 60 days of 
index procedure) 
X 
 
 
 
 
Pre-op Inclusion / Exclusion Criteria 
Assessment 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Physical exam/Medical History 
X 
 
 
 
X 
Laboratory Tests (PLT, WBC, HGB, 
HCT, creatinine, PT or INR)  
X1 
 
 
 
X 
Intra-procedural Exclusion Criteria 
Assessment 
 
X* 
 
 
 
Randomization  
 
X 
 
 
 
Study Endpoint Data Collection: 
 
 
 
 
 
TTH determination 
 
X 
 
 
 
TTA determination 
 
 
X 
 
 
TTDE determination 
 
 
X 
 
 
Device Success 
 
X 
 
 
 
Procedure Success 
 
 
 
 
X 
Concomitant Medications (e.g., anti-
platelet, anti-coagulant, anti-thrombotic 
agents, etc.) 
X 
X 
X 
 
X 
Post Op Pain assessment 
 
 
X 
 
 
Adverse Events 
 
X 
X 
 
X 
Ultrasound Exam (DUS sub-
study only) 
 
 
 
X ** 
X *** 
1 Laboratory tests should be done within -7 to 0 days of index procedure 
* Intra-op inclusion/exclusion criteria will be evaluated once operator is able to visualize and assess sheath 
placement and the anatomy of all venous access sites 
** Ultrasound is required for subjects in the DUS sub-study only 
*** Ultrasound may be required at 30 days if complication is observed on discharge DUS for subjects in DUS sub-
study 
 
 

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1 
Study Management Team 
 
Table 2: Study Management Team
Sponsor 
Cordis US Corp 
Medical Monitor  
Nusrath Sultana, MD 
National Principal Investigator 
Javier Sanchez, MD 
Monitoring 
NAMSA 
Data Management 
Medrio 
Safety Management 
NAMSA 
Statistics 
NAMSA 
Medical Writing 
NAMSA 
Duplex Ultrasound Core Lab 
NAMSA 
 
 
 
 

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2 
Introduction 
Techniques for closure of an arteriotomy or venotomy site have evolved from direct suture-based 
surgical closure to the use of VCDs. VCDs were developed in the 1990s with the aim of achieving 
hemostasis efficiently in a way that is satisfactory to the patient with limited complications.9, 10 
Ideally, VCDs should safely attain complete hemostasis, close the access site regardless of the 
size, and this should be achievable even with the use of anticoagulants.9 
The target patient population indicated for VCDs are patients undergoing diagnostic and/or 
interventional procedures involving access to the coronary or peripheral vascular system and 
patients with contraindications to undergo surgery due to operative risk and comorbidities. 
Following percutaneous vascular access, VCDs are used to achieve hemostasis after 
interventional or diagnostic endovascular procedures. VCDs, such as the MYNX VCD Product 
Family and EXOSEAL VCD Product Family provide a method of achieving hemostasis at the 
femoral access sites in patients who have undergone endovascular procedures utilizing a 5F, 6F, 
or 7F procedural sheath. These procedures are generally performed by physicians from a broad 
range of medical specialties to include interventional radiology, vascular surgery, and cardiology, 
as well as smaller subspecialists trained in the application of endovascular techniques. For this 
study, we have expanded the indication of the MYNX CONTROL VCD to include up to 12F 
procedural sheath for femoral venous access. Procedures treated using this larger bore sheath 
include, but are not limited to, cardiac ablations, structural heart procedures, and cardiac 
interventions. 
The traditional and most used alternative to VCDs is manual compression (MC). MC is considered 
the standard of care and is relied upon either primarily or when VCDs fail. MC is labor-intensive 
and results in considerable discomfort for the patient. Meta-analyses comparing MC to VCDs 
showed that with MC there was an increase in time-to-hemostasis (TTH), time-to-ambulation 
(TTA). 15, 16 An increased risk of hematoma formation was associated with MC. 15 The rate of 
complications was comparable between VCDs and MC (12% for VCDs and 13% for MC), 
however, major complications were lower in the VCD group.16 VCDs were associated with a low 
risk of infection and thrombosis (0.6% for infection; 0.3% for thrombosis).16 
The 
 is indicated for use to seal 
femoral arterial access sites while reducing times to hemostasis and ambulation in patients who 
have undergone diagnostic or interventional endovascular procedures utilizing a 5F, 6F or 7F 
procedural sheath. 
2.1 
Product characteristics 
The MYNX CONTROL
 Venous Vascular Closure Device (VCD) is designed to achieve femoral 
-
soluble synthetic hydrogel, using a balloon catheter in conjunction with a standard procedural 
sheath
which expands upon contact with blood and subcutaneous fluids. Refer to Figure 1 (below). 

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2.2
Structural composition, operation principle and mechanism of action
The MYNX VCD product family are designed to achieve hemostasis of femoral access sites 
following diagnostic or interventional endovascular procedures. Hemostasis is accomplished via 
delivery of an extravascular polyethylene glycol (PEG) sealant using a balloon catheter (delivery 
system) in conjunction with a standard procedural sheath. Upon contact with blood and 
subcutaneous fluids, the sealant expands and adheres to the arteriotomy or venotomy to 
achieve hemostasis. The sealant is resorbed by the body within 30 days.
The design of the MYNX CONTROL
Venous VCD is based on the design of the current MYNX 
CONTROL
VCD (arterial). The only difference in design is the Sheath Catch. The Sheath Catch 
facilitates the withdrawal of the 6F/7F Catheter Sheath Introducer (CSI) from the tissue tract 
during the withdrawal of the MYNX CONTROL
VCD (current). This is achieved by a distal hook 
which latches onto the sideport on the CSI. The proposed sheath catch design on the MYNX
CONTROL
Venous VCD will be based on the current design but will allow larger CSIs (up to 
12F) to fit into the Sheath Catch. Like the current Sheath Catch design, connection to the CSI will 
be achieved with a distal hook and be universally compatible with the leading CSI brands on the 
market.
Venous Vascular Closure Device 6F-12F
3
Study Objectives
To demonstrate safety and efficacy of the MYNX CONTROL
Venous Vascular Closure Device 
6F-12F vs. manual compression in sealing femoral venous access sites in patients who have 
undergone endovascular procedures utilizing one or more procedural sheaths up to 12F.

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4 
Indication 
Proposed Indications for Use:  
The MYNX CONTROL
 Venous VCD 6F-12F is indicated for use to seal femoral venous access 
sites while reducing times to hemostasis and ambulation in patients who have undergone 
diagnostic or interventional endovascular procedures utilizing  6F to 12F procedural sheaths, with 
single or multiple access sites in one or both limbs. 
5 
Contraindications 
There are no known contraindications for the 
Device 6F-12F. 
6 
Precautions 
The MYNX CONTROL
 Venous VCD should only be used by a trained licensed physician or 
healthcare professional. The MYNX CONTROL
 Venous VCD should not be used in patients 
with a known allergy to PEG. The MYNX CONTROL
 Venous VCD should not be used with 
sheaths longer than 12 cm effective length or incompatible sheaths listed in Table 3. Exposure to 
temperatures above 25°C (77°F) may damage the components. 
 
Table 3 
 
7 
Warnings 
Do not use if components or packaging appear to be damaged or defective or if any portion of the 
packaging has been previously opened. DO NOT REUSE OR RESTERILIZE. The MYNX 
CONTROL
 Venous VCD 6F-12F is for single use only. The catheter is loaded with a single 
Hydrogel sealant. Reuse of the device would result in no delivery of Hydrogel sealant. Reuse of 
this product, including after reprocessing and/or re-sterilization, may cause a loss of structural 
integrity which could lead to a failure of the device to perform as intended and may lead to a loss 
of critical labeling/use information all of which present a potential risk to patient safety. Do not use 
the MYNX CONTROL
 Venous VCD 6F-12F if the puncture site is located above the inguinal 
ligament based upon bony landmarks, since such a puncture site may result in a 
hematoma/bleed.  Perform a femoral venogram (as applicable) to verify the location of the 
puncture site. Do not use the MYNX CONTROL
 Venous VCD 6F-12F if the puncture is through 
the posterior wall as such punctures may result in a retroperitoneal hematoma/bleed. 
 

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8 
Benefits/Risks 
8.1 
Benefits 
There are several resource and time saving benefits associated with the use of VCDs. Time-to-
hemostasis (TTH), time-to-ambulation (TTA) and time-to-discharge eligibility(TTDE) have all been 
reported to be reduced with the use of VCDs.70 Meta-analyses of RCTs showed that that TTH was 
significantly shorter with VCDs compared to MC.12, 15, 16, 71, 72 TTH was reduced by approximately 
11-17 minutes using VCDs compared to MC.15, 71 TTA has also been shown to be significantly 
reduced by using VCDs compared to MC.15, 16, 71 In a meta-analysis of RCTs, TTA was reduced 
by 4.5 hours using VCDs compared to MC.71 One study showed that clip-based VCDs were 
associated with a shorter TTH and TTA compared to suture based-devices.72 TTD was also shown 
to be shorter when VCDs were used compared to MC. However, it was noted that TTD has 
generally reduced since 2005 due to the emphasis on same day discharge.71 The use of VCDs 
also has a cost-benefit, due to the reduction in labor incurred by MC, the decreased length of 
hospital stay and utilization of hospital resources.70 Cost-effectiveness analysis shows that 
diagnostic or interventional procedures where VCDs were used were less expensive.61 Other 
benefits of VCDs include improved patient satisfaction and comfort levels, due to the reduced 
TTA and earlier TTD.61 
As per clinical study data available for CORDIS VCDs, the devices provide an acceptable 
risk/benefit profile. Based on the clinical study data accumulated to evaluate the safety and 
effectiveness of these devices, the results for clinical studies show excellent rates of technical 
success and reduced time to hemostasis, ambulation, and discharge for the CORDIS VCDs. This 
indicates that with the use of these devices, patients have the potential to experience significant 
clinical improvements. 
The potential benefits of the MYNX CONTROL
 Venous VCD for 6-12F over manual 
compression alone to achieve venous hemostasis have not yet been proven and outcomes will 
be evaluated because of this trial.  
8.2 
Risks 
The most serious recognized risks associated with femoral vessel closure procedures occur rarely 
and include, but are not limited to, the following: 
 
 
Vascular injury requiring repair 
 
New onset, permanent (i.e., persisting at 30-day follow-up) access site-related nerve 
injury  
 
Bleeding or hematoma at any venous access site requiring 
transfusion, surgical intervention, or re-hospitalization  
 
New ipsilateral lower extremity ischemia requiring invasive/non-invasive intervention 
 
Generalized access site related infection requiring intravenous antibiotics and/or 
extended hospitalization  
 
Retroperitoneal bleed 

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Vessel Occlusion 
 
Pulmonary embolism  
 
Death 
Other less serious potential risks (can be managed clinically or pharmaceutically) are included, 
but are not limited to, the following: 
 
 
Pseudoaneurysm  Treated with thrombin injection 
 
Pseudoaneurysm  Not requiring treatment 
 
AV Fistula 
 
Hematoma > 6 cm 
 
Access site-related bleeding requiring > 30 min to achieve hemostasis 
 
Late access site-related bleeding (following hospital discharge) 
 
Ipsilateral lower extremity arterial emboli 
 
Transient loss of ipsilateral lower extremity pulse 
 
Ipsilateral deep vein thrombosis 
 
Transient access site-related nerve injury 
 
Access site-related vessel laceration 
 
Local access site infection  Minor 
 
Local access site inflammatory reaction  Minor 
 
Allergic reaction 
 
Ecchymosis 
9 
Study Design 
9.1 
Overview 
This study is a multicenter, prospective, randomized, controlled, open label clinical study to enroll 
204 patients with an additional group of patients to be part of the initial roll-in phase. The 204 
patients will be randomized to either a device arm or a manual compression arm using a 2:1 
randomization scheme (136 MYNX CONTROL
 patients and 68 manual compression patients).  
Two (2) roll-in patients per physician will be allowed. All patients who sign the informed consent 
and randomized to either treatment group will be followed through 30 days post procedure. There 
will be up to 15 participating study sites, with a minimum of five (5) sites, all located in the United 
States. Details of the randomization and roll-in process can be found in section 16.1.  Each study 
site will be limited to enrolling a maximum of 45 subjects. 
9.2 
Duplex Ultrasound sub-study 
A sub-study of this pivotal U.S. clinical trial will be performed utilizing independent analysis of 
non-invasive duplex ultrasound (DUS) imaging in 48 device subjects and 24 MC subjects pre-
discharge and potentially again at the 30-day follow-up if an observation of a complication 
occurred on the pre-discharge ultrasound. Specific investigational sites will be designated as 
ultrasound sites. These sites will include subjects in the ultrasound subset imaging until a total of 
72 patients have been evaluated in both groups. Informed consent will be obtained from all 

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subjects participating in this sub-study. All sub-study sites will be instructed to perform duplex 
ultrasonography of the femoral vascular structures.  Images will be uploaded and interpreted by 
an independent core lab. NAMSA is the core lab for this sub study.  
 
NAMSA 
4 World Trade Center 
150 Greenwich Street, 49th FL 
New York, NY  10007 
10 
Study Population/Selection Criteria 
The following outline the specific inclusion and exclusion criteria for the study. Before the study 
randomization, a patient must meet all the inclusion and no exclusion criteria.  
Prior to any study-specific activities, all patients must sign and date the most current IRB-
approved Informed Consent Form (ICF). 
10.1 
Inclusion Criteria 
Patients must meet ALL the following inclusion criteria to be enrolled in the study:  
 
1. Age >18 
2. Able and willing to provide informed consent and to complete a follow-up visit at 30 days  
3. Planned catheter-based procedures via the common femoral vein(s) using up 6F to 12F 
introducer sheaths which meet indications for elective, nonemergent interventions of 
disease state, without contraindications for emergent vascular surgery or manual 
compression of the venous access sites 
10.2 
Exclusion Criteria  
Patients will be excluded if they meet ANY of the following exclusion criteria: 
10.2.1 
Pre-procedural Exclusion Criteria 
Patients who meet any of the following criteria before the index procedure will be excluded:  
 
1. Any use of systemic steroids (IV or oral) within 30 days of procedure 
2. History of deep vein thrombosis, pulmonary embolism, or thrombophlebitis within 6 
months of procedure 
3. Presence of thrombocytopenia (platelet count < 100,000 cells/mm3) or anemia 
(hemoglobin < 10 g/dL, hematocrit < 30%)   
4. History of bleeding disorders such hemophilia or 
 
5. Currently involved in any other investigational clinical trial  
6. Documented history of uncontrolled hypertension (i.e., systolic blood pressure > 180 mm 
Hg), or critical illness requiring intravenous vasopressors for blood pressure stabilization  
7. Femoral arteriotomy or venotomy in either limb within 10 days pre procedure  

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8. Use of VCD in either limb within 30 days of procedure 
9. Any planned procedure involving femoral arterial or venous access in either limb within 
30 days or prior to study exit  
10. Renal insufficiency (i.e., serum creatinine > 2.5 mg/dL)  
11. Patients who are pregnant, planning to become pregnant during the study period, or 
lactating  
12. Body-mass index (BMI) > 45 kg/m2 or <20 kg/m2 
13. Unable to routinely walk at least 20 feet without assistance  
14. Known allergy/adverse reaction to polyethylene glycol or contrast medium  
15. Planned procedures (including staged) or concomitant conditions/comorbidities that per 
-3 hours, and/or 
require extended hospitalization or re-hospitalization  
16. Previous vascular surgery or repair in the vicinity of the target access site within the 
previous 90 days of the procedure 
17. Active systemic infection, or cutaneous infection or inflammation in the vicinity of the 
target access site 
18. Current COVID-19 infection (with or without symptoms), positive test for COVID- 19 
within 14 days, or recent exposure to a person with COVID-19 infection 
19. Patients who refuse blood transfusion if it were to be needed  
20. Patients with expected life of less than 30 days 
10.2.2 
Intra-Procedural Exclusion Criteria 
Patients who meet any of the following criteria during the index procedure will be excluded:  
 
1. Any attempt at femoral arterial access or inadvertent arterial puncture with hematoma 
during the procedure  
2. Any procedural complications that may interfere with routine recovery, ambulation, or 
discharge eligibility times  
3. Physician deems that a different hemostasis approach for venous access sites 
is necessary  
4. Physician deems that the subject should not attempt protocol required ambulation 
(reference ambulation protocol per section 14.2) 
5. Venous access site location is noted to be above the inguinal ligament (cephalad to 
lower half of the femoral head or the inferior epigastric vein origin from the external iliac 
vein)  
6. Intra-procedural bleeding around sheath, or suspected intraluminal thrombus, 
hematoma, pseudoaneurysm, or AV fistula  
7. Difficult insertion of procedural sheath or needle stick problems at the onset of the 
procedure (e.g., multiple stick attempts, accidental arterial stick with 
  
8. A < 6F or > 12F procedural sheath is present at any time during the procedure or at 
closure  

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11 
Study Endpoints 
11.1 
Primary Endpoints 
11.1.1 
Primary Safety Endpoint 
Rate of CEC adjudicated combined major venous access site closure-related complications 
through 30 days post procedure, attributed directly to VCD or manual compression without other 
likely cause. 
 
 
Access site-related bleeding requiring transfusion, surgical intervention, or 
rehospitalization 
 
Vascular injury requiring surgical repair 
 
Access site-related infection confirmed by culture and sensitivity, requiring intravenous 
antibiotics and/or extended hospitalization 
 
New onset, permanent (i.e., persisting at 30-day follow-up) access site-related nerve 
injury 
 
New onset access site-related nerve injury requiring surgical repair  
 
Pulmonary embolism requiring surgical or endovascular intervention and/or resulting in 
death, to be confirmed by CT pulmonary angiography, lung ventilation/perfusion scan 
(VQ scan), or autopsy 
 
Pulmonary embolism not requiring surgical or endovascular intervention and/or not 
resulting in death, to be confirmed by CT pulmonary angiography or lung 
ventilation/perfusion scan (VQ scan) 
11.1.2 
 Primary Effectiveness Endpoint  
Time to Ambulation (TTA): Defined as elapsed time (in hours) between removal of the MYNX 
CONTROL
 Venous Vascular Closure Device 6F-12F device (device group) or of the final 
sheath (control group) and when subject stands and walks 20 feet without evidence 
of rebleeding from any femoral venous access site.  
Time to Hemostasis (TTH): Defined as elapsed time (in minutes) between removal of each MYNX 
CONTROL
 Venous Vascular Closure Device 6F-12F device (device group) or of each sheath 
(control group) and first observed and confirmed venous hemostasis (per access site analysis). 
11.2 
Secondary Endpoints  
11.2.1 
Secondary Safety Endpoint 
Rate 
of 
CEC 
adjudicated 
combined 
minor 
venous 
access 
site 
closure related complications within 30 days post-procedure, attributed directly to VCD or manual 
compression without other likely cause. Types of minor complications include: 

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Pseudoaneurysm  Treated with thrombin injection, fibrin adhesive injection, or 
ultrasound guided compression and documented by ultrasound 
 
Pseudoaneurysm  Not requiring treatment 
 
Arteriovenous fistula requiring treatment, documented by ultrasound 
 
Arteriovenous fistula not requiring treatment, documented by ultrasound 
 
Access site-related Hematoma > 6 cm documented by ultrasound 
 
Access site-related bleeding requiring > 30 min to achieve hemostasis 
 
Late access site-related bleeding (following hospital discharge eligibility) 
 
Transient loss of ipsilateral lower extremity pulse 
 
Ipsilateral deep vein thrombosis documented by ultrasound 
 
Transient access site-related nerve injury 
 
Access site-related vessel laceration 
 
Access site wound dehiscence 
 
Localized access site infection confirmed by culture and sensitivity, treated with 
intramuscular or oral antibiotics  Minor,  
 
Local access site inflammatory reaction  Minor 
 
Allergic reaction 
 
Ecchymosis 
11.2.2 
Secondary Effectiveness Endpoints include the following: 
Time to Discharge Eligibility: defined as elapsed time (in hours) between removal of the final 
MYNX CONTROL
 Venous Vascular Closure Device 6F-12F device (device group) or removal 
of the final sheath (control group) and when subject is eligible for discharge from the institution 
based on the assessment of the attending physician.  
Procedural Success: attainment of final hemostasis at all venous access sites without major 
venous access site closure-related complications through 30 days.  
Device Success (for device group): ability to successfully deploy the MYNX CONTROL
Venous 
VCD delivery system, deliver the polyethylene glycol hydrogel sealant, and achieve hemostasis 
(device group only).  
11.3 
Other/Additional Endpoints  
 
Venous access site related pain at time of discharge eligibility measured by 
pain scores 
12 
Informed Consent 
Written Informed Consent must be obtained for all patients who are potential study candidates. 
Patients who meet pre-op inclusion/exclusion entry criteria will be invited to participate, and asked 
to sign the study-specific, Institutional Review Board (IRB)-approved Informed Consent form 

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before any study-specific tests or procedures are performed which are not standard-of-care. The 
study team shall follow all steps below when obtaining Informed Consent: 
1. Provide each prospective subject/legal representative with a full explanation of the study 
(including all potential benefits and risks) and the informed consent form (ICF). 
 
a. The informed consent form (ICF) should enable the subject or legal 
representative to understand:  
 
the nature, objectives, benefits, implications, risks, and 
inconveniences of the clinical investigation 
 
the subject's rights and guarantees regarding his/her 
protection, his/her right to refuse to participate in and the right to 
withdraw from the clinical investigation at any time without any 
resulting detriment and without having to provide any justification  
 
the conditions under which the clinical investigation is to be 
conducted, including the expected duration of the subject's 
participation in the clinical investigation; and the possible treatment 
alternatives, including the follow-up measures if the participation of 
the subject in the clinical investigation is discontinued.  
 
b. The ICF shall:  
 
Be comprehensive, concise, clear, relevant, and understandable to 
the subject or legal representative  
 
Be provided in a prior interview with a member of the clinical 
investigation team who is appropriately qualified under national 
law and delegated to this responsibility; gives special attention to the 
information needs of specific patient populations and individual 
patients as well as to the methods used to provide the information; 
verifies the subject has understood the 
  
 
Include information about an applicable damage compensation 
system; and  
 
Include the unique, study identification number and information about 
the availability of clinical study results to the subject, to the extent 
possible, via a clinical study report and summary presented in terms 
understandable to the intended user, irrespective of the outcome of 
the clinical study.   
2. Allow the prospective subject/legal representative to read the most current IRB approved 
informed consent form (ICF) and address any/all their questions.  
3. Obtain written consent (signature and date on the ICF) from the prospective subject/legal 
representative after the Investigator and/or designee is assured they understand all 
implications of participating in the study. 

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A copy of the ICF signed by the subject/legal representative and the Investigator and/or designee 
obtaining consent will be provided to the subject. In addition to the most current, IRB-approved 
ICF, the subject/legal representative must provide a signed HIPAA authorization and any other 
locally required documents, as applicable. 
The Investigator and/or designee must clearly document the process for obtaining informed 
 It is the 
ss is performed in 
accordance with ICH-GCP applicable international standards and all applicable local and federal 
regulations. 
Documented informed consent must be obtained within 60 days prior to the index procedure.  
Exceptions to obtaining documented informed consent prior to the initiation of study-specific 
procedures would be in cases where necessary to eliminate an immediate apparent 
hazard and protect the life or physical well-being of a study subject. 
13 
Screening and Enrollment 
13.1 
Screening Period 
13.1.1 
Screening Assessments 
In addition to obtaining written consent, the following assessments must be performed, and the 
subject verified to meet all pre-procedural inclusion criteria and none of the exclusion criteria prior 
to the procedure. 
 
1) Demographic Data: Including but not limited to age, sex, weight, height, and race. 
2) Medical/Surgical History: (30 days prior to the procedure) Review and 
documentation of 
, allergy assessment and risk factors. 
3) Physical Examination: Assessment per sites Standard of Care and to include 
collection of concomitant med and Laboratory Evaluations as below, height, weight, 
and BMI 
4) Concomitant Medications: Peri-procedural medications that are taken within 24 
hours of the procedure that may affect bleeding (e.g., anti-platelet, anti-coagulant, anti-
thrombotic agents, etc.) will be documented   
5) Laboratory Evaluations: (within one week prior to index procedure):  
 
blood routine examination (PLT, WBC, HCT, HGB, and creatinine), 
 
coagulation function (prothrombin time (PT) or INR),  
 
pregnancy testing for women with fertility. 
13.1.2 
Screen Failures and Pre-screen Failures 
Any consented patient who is confirmed to not qualify for study participation according to the 
eligibility criteria will be considered a screen failure and will neither be treated with the 

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investigational device nor be followed per protocol. Signed informed consent forms and all 
applicable documentation including source records indicating rationale for screen failure 
classification and screening logs will be reviewed during monitoring visits for all screen failure 
patients. 
Pre-screen 
failures are 
defined 
as 
patients 
who are 
confirmed 
to not qualify 
for 
study participation according 
to the eligibility criteria 
after 
review 
of 
their 
medical 
records (i.e. prior 
to providing informed consent). 
Such 
patients will neither 
be 
treated 
with the study devices nor followed per protocol.  
13.2 
Enrollment 
The subject will be enrolled into the study at the end of the index procedure and once all 
procedural sheaths are in place under imaging guidance. It is at this time that the anatomy of all 
venous access sites is evaluated, and intra-procedural eligibility criteria can be verified. Each 
venous access site must meet all intra-procedural access site-specific criteria for the subject to 
be eligible. Once it has been determined that the subject does not meet any of the general intra-
operative exclusion criteria, and that none of the venous access sites meet the specific access 
site exclusion criteria, then the subject is eligible for randomization. 
14 
Treatment Plan 
14.1 
Index Procedure 
The Instructions for Use (IFU) provides detailed information on the product, safety, storage, 
design, deliverability, and sizing specifications. All information within the IFU should be referenced 
prior to each procedure and implantation of the study device.  
If a subject is randomized to receive manual compression, it should be performed according to 
  If protamine is administered, the Investigator should 
follow institutional practice guidelines for re-checking ACT levels and/or waiting a specified time 
or for a target ACT value prior to removal of sheaths and application of manual compression. 
If a subject is on Warfarin, any pre-procedure standard of care requirements should be followed. 
 
The following will be collected at the time of the procedure:  
 
A0: Time of first index procedure sheath insertion  
 
A1 Time: time of removal of final index procedure device 
 
Sheath sizes used during procedure 
 
For each access site, the following should be recorded: 
o Access site location (left/right leg and location with respect to 2nd access 
site, if applicable) 
o HX.1 Time: time of removal of 
Venous device 
(device group) or removal of sheath (control group) 

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o HX.2 Time: time venous hemostasis is achieved. 
o Confirm venous hemostasis is maintained at 5 min after recorded 
hemostasis time (HX.2) 
o Use of adjunctive compression (e.g., light manual compression, 
sandbags, or mechanical compression devices) 
14.2 
Post-Procedure Care/Discharge 
Following the index procedure, the site will notify the Sponsor of the subject enrollment status 
within the study database 
 
The following will be documented after the procedure: 
 
1. A2 Time: Date and time the subject was able to ambulate 20 feet without venous re-
bleeding from the access site(s). 
2. A3 Time: Date and time the subject is eligible for discharge based on the assessment 
of the attending physician or delegate. 
3. A4 Time: Date and time the subject was discharged. 
4.  Concomitant Medications: Peri-procedural medications that are taken within 24 hours 
of the procedure that may affect bleeding (e.g., anti-platelet, anti-coagulant, anti-
thrombotic agents, etc.) will be documented   
5.  Adverse event monitoring, including labs as per standard of care to assess any 
adverse event 
6. Time to Ambulation- Defined as time (in hours) between removal of the final VCD 
(device group) or of the final sheath (control group) and when subject stands and 
walks 20 feet without evidence of rebleeding from any femoral venous access site.  
NOTE: Since TTA is a primary effectiveness endpoint, the following ambulation 
guidelines apply to both groups. 
 
 
For the device group, ambulation must be attempted within 2-2.5 hours from 
time of final VCD removal. The groin should be checked every 15 minutes to 
verify status.  Any ambulation delay beyond 2.5 hours will be considered a 
protocol deviation unless it is medically justified and documented.   
 
 
For the control group, institutional guidelines should be followed for 
ambulation. The groin should be checked every 15 minutes to verify status.  
Reasons for any ambulation delays 
practice should be documented. 
7.  Time to Discharge Eligibility- defined as elapsed time between removal 
of the final MYNX CONTROL
 Venous VCD (device group) or removal 

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of the final sheath (control arm) and when subject is eligible for 
discharge from the institution based on the assessment of the attending 
physician or delegate. (Per-patient analysis) 
8.  Pain scale assessment 
9.  Duplex Ultrasound (pre-discharge) for those patients enrolled in DUS sub-study 
NOTE 1:  If there is any sign of active bleeding at the access site(s) after 
ambulation, measures should be taken to re-achieve hemostasis and then the 
subject re-ambulated when the Investigator determines that it is appropriate to do 
so. In these cases, TTA and TTDE will be repeated and documented when 
successful, and the re-bleeding will be documented as an adverse event. 
NOTE 2:  TTDE is not intended to impact the actual discharge time of the 
subjects from the hospital.  Any delay of this discharge eligibility 
determination (i.e. >30 minutes following successful ambulation) unrelated 
to access site(s) assessment will be documented as a protocol deviation. 
14.3 
Recommended Medication Regimen  
Discharge medication should be administered per institutions standard of care and at the 
discretion of the Investigator. Details of this regimen must be recorded in the appropriate Case 
Report Form. 
14.4 
Follow-up Visits/Assessments 
All subjects will be required to complete a 30±7-day follow-up. The follow-up will include the 
following assessments: 
 
1) Concomitant Medications: Peri-procedural medications that are taken within 24 
hours of the procedure that may affect bleeding (e.g., anti-platelet, anti-coagulant, anti-
thrombotic agents, etc.) will be documented   
2) Laboratory Evaluations:  
 blood routine examination (PLT, WBC, HCT, HGB and creatinine), 
 coagulation function (prothrombin time (PT) or INR)  
3) Adverse event monitoring 
4) Duplex Ultrasound: for those subjects included in the DUS sub-study where a 
documented access site complication has been observed on the Discharge 
Ultrasound. Subjects should have their ultrasound appointments scheduled to ensure 
compliance. 
NOTE: Every effort should be made to complete the required 30-day follow-up 
assessments on-site. If the subject is unable to complete an on-site 30-day follow-
up, visit may be conducted by phone. If visit is conducted via phone, concomitant 
medications and safety information should be collected from subject or from 
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attempt should be made to acquire all study assessments (including lab 
evaluations).  
For DUS subset study  this must be obtained on-site. If visit is out of window to 
obtain DUS, document this as protocol deviation. 
A Protocol Deviation will need to be completed for all study subjects who do not 
complete all 30-day follow-up visit assessments. If the missed visit is COVID-
related, it will be categorized as such in the protocol deviation.  
14.5 
 Lost to Follow-up 
For all active subjects, the site must first make three (3) contact attempts to reach the subject. If 
unsuccessful, the Investigator must then send a certified letter to the subject. All contact attempts 
must be adequately 
cuments. When possible, the subject
primary care physician should also be asked for assistance with contacting the subject.  
The subject will be considered lost to-follow-up only under the following circumstances: 
 
The site learns that all methods of contacting the subject are no longer viable (e.g., 
telephone number not in service, no forwarding address provided, no current/correct 
contact information available from the subject
primary care physician).   
 
Failure to reach/hear from the subject for the final protocol-required follow-up visit after all 
required contact attempts have been made. 
14.6 
Unscheduled Visits 
Unscheduled follow-up visits may be required to evaluate a subject from time to time to ensure 
the safety of study subjects. All complications and adverse events will be evaluated by the 
Investigator and reported according to Sponsor and IRB regulations. 
If an unscheduled follow-up visit is required, the site study team will assess if the subject has 
undergone any interventional treatment or experienced any adverse events since the last protocol 
specified visit and will record such information on the appropriate CRF pages. All relevant 
information required to assess the event should be maintained in the 
records 
and all relevant documentation required for event adjudication should be provided as requested 
by the Sponsor. 
The following assessments may need to be completed at an unscheduled visit: 
 
 
Concomitant medications  
 
Physical examination  
 
Duplex Ultrasound (for subjects in the DUS sub-study with complications at 
discharge DUS) 
 
Adverse event monitoring 
 
Laboratory evaluations (see follow-up visit assessments in section 14.4) 

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14.7 
Subject Early Discontinuation  
Every subject should be encouraged to remain in the study until they have completed the final, 
protocol-required follow-up visit at 30 days +/- 7 days post-discharge. If subject participation is 
prematurely discontinued, the reason for such must be documented 
documents and the CRF. Possible reasons for 
early exit from the study may include, 
but are not limited to, the following: 
 
 
Withdrawal of consent  Subject decides to withdraw from the study. This 
(i.e., made by the subject) and documented in 
the 
source records and the CRF. The reason for withdrawal of consent 
should also be inquired from the subject and documented if provided. 
 
Physician discretion  The Investigator may choose to withdraw a subject from 
the study for reasons which include, but are not limited to, safety concerns. 
 
Death 
 
Lost to follow-up  all methods of contacting the subject are no longer viable or 
the subject is unable to be reached to complete the 30-day follow-up visit. 
Subjects who discontinue from the study early will not be replaced. Subjects who withdraw 
voluntarily or are withdrawn from the study per Investigator discretion cannot re-enter the study. 
The investigator(s)/institution(s) should arrange for any continued safety monitoring, treatment 
and/or follow-up of subjects who withdraw/are withdrawn from the study or determined as lost to 
follow-up as per standard-of-care/best clinical judgement. The Investigator can use existing data 
and may ask for the subject
permission to collect follow-up data about status and/or condition, 
including information related to the device performance, effectiveness, or safety. If permission is 
granted, the relevant data will be included in the clinical study report. 
14.8 
Subject Study Completion 
The clinical study will be considered complete when the last enrolled subject has completed 
the 30-day follow-up visit or protocol-required assessment. The sponsor will provide end-of-study 
notification to all participating sites for submission to their IRBs.  
15 
Adverse Event Reporting  
Any person who identifies an event or information that could impact subjects
obligation to inform the Investigator and the sponsor of their concerns.  
15.1 
Adverse Event  
An Adverse Event (AE) is any untoward medical occurrence in a subject, whether anticipated or 
unanticipated. All AEs are reported from the subject
start time of enrollment until their exit from 
the study (i.e., point of study completion or premature discontinuation). AEs will be recorded and 
followed until resolution or stabilization of the event or until the subject has exited the study.  

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Anyone should be encouraged to report AEs immediately upon awareness and may volunteer 
information at any time. At each evaluation, the Investigator will assess if an adverse event has 
occurred and will obtain all information required to complete the appropriate AE CRF(s). If an 
event occurs at an outside institution, the Investigator should obtain all or as much of the required 
AE information as possible. 
For each AE, the Investigator should report at a minimum, the term/description, start/end dates, 
severity, serious/non-serious classification, treatment, and outcome of the AE and determine its 
causality/association to the investigational product or procedures involved in the clinical study. 
All sites will be trained on severity and causality of AEs and completing the AE Case Report Form 
15.2 
Serious Adverse Events 
A Serious Adverse Event (SAE) is a type of AE and defined as any untoward medical 
occurrence that: 
a) Led to a death 
b)  Led to a serious deterioration in the health of the subject that 
 
Results in a life-threatening illness or injury 
 
Results in a permanent or significant impairment of a body structure or a body 
function 
 
Requires hospitalization or prolongation of existing hospitalization 
 
Results in an important medical event which jeopardizes the subject and may 
require medical or surgical intervention to prevent permanent impairment to a 
body structure or one of the above outcomes  
c)  Led to fetal distress, fetal death or a congenital abnormality or birth defect 
The Investigator must report all SAEs to the Sponsor and/or designee by any applicable method 
within 24 hours or one working day of first awareness of the event by the study team at the 
institution and provide any additional information as required by the Sponsor/designee. The 
Electronic Data Capture (EDC) system should be the principal system used in reporting these 
events, if possible. In the case of death, all available information, e.g., autopsy or other post-
mortem findings, including causality/association to the investigational product, should be 
provided. The medical monitor of this study will decide if more follow-up information is needed in 
case the event is not resolved at the time of subject exit from the study. 
The Investigator shall notify their IRB of SAEs which occurred at their site in accordance with their 
institutional requirements.  
SAEs will be recorded and followed until resolution or stabilization of the event or until the subject 
has exited the study.  

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In the case of death, all available information, e.g., autopsy or other post-mortem findings, 
including causality/association to the investigational product, should be provided.  
15.3 
Unanticipated Adverse Device Effects  
An unanticipated adverse device effect (UADE) is defined as any serious adverse effect on health 
or safety or any life-threatening problem or death caused by or associated with an investigational 
product, if that effect, problem or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with an investigational 
product that relates to the rights, safety, or welfare of patients. 
Potential UADEs occurring during the study must be reported by the Investigator to the Sponsor 
[through the EDC system or by other available means within 24 hours or one working day of first 
awareness of the event by the study team at the institution.  
 
If the Sponsor confirms the reported event qualifies as a UADE and presents as an 
unreasonable risk(s) to study subjects, they will terminate the entire study, or parts of the 
study presenting that risk, within 5 working days of that determination and within 15 
working days of first receipt of UADE notification as well as notify the applicable regulatory 
authorities.  
 
If the Sponsor confirms the reported event qualifies as a UADE, sponsor will notify the 
applicable regulatory authority(ies), all participating Investigators and reviewing IRBs/ECs 
within 10 working days of first receipt of UADE notification. Investigators are responsible 
for reviewing information received about UADEs.  
UADEs will be recorded and followed until resolution or stabilization of the event or until the 
subject has exited the study. 
15.4 
Sponsor Progress Reports 
The Sponsor will submit progress reports with safety updates to the FDA, all participating 
Investigators, and all participating IRBs on at least an annual basis, as per federal regulations. 
These updates will be individualized for each institution and will include a summary of the study 
status, enrollment figures, any safety concerns, any outcomes, or recommendations from the 
Data Safety Monitoring Board (DSMB) as well as a listing of all adverse events reported. 
16 
Statistics/Data Analyses 
16.1 
Randomization  
This is a randomized, controlled, open label study. Before the first subject is enrolled in the study, 
a randomization schedule will be generated by the study statistician and uploaded into an 
electronic database that can be accessed via computer. The schedule will be generated using a 

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permuted block approach. Randomization will be performed at the conclusion of the index 
procedure, while the patient is on the table and the operator is able to visualize all access sites to 
verify eligibility. Since one of the primary endpoints of this study is time to ambulation, 
randomization will be done at the patient level to avoid the possibility of a patient receiving both 
MYNX 
 Randomization will be stratified by 
study center with a 2:1 randomization ratio for MYNX CONTROL
 Venous VCD vs. manual 
compression for access site closure. Roll-in patients will not be randomized. All roll-in patients will 
receive the MYNX CONTROL
 
O
Delegation of Authority log needs to have two (2) 
roll-in patients prior to randomizing any subject.  
16.2 
Device Failures and Malfunctions 
A device malfunction is considered a failure of a device to meet any of its performance 
specifications or otherwise perform as intended. Performance specifications include all claims 
made in the IFU/Clinical Protocol. 
If a product malfunction occurs, the site must notify within 24 hours or one working day the 
Sponsor and/or enter details of the complication and its management in the respective CRF. If 
applicable, the malfunctioned product and any other materials used during the index procedure 
should be returned according to the Spo
 
If a product malfunction occurs, detailed information on the product, circumstances of the 
malfunction as well as any complications and their management will be collected and reported.  
Any patients randomized to the device arm who do not receive the MYNX CONTROL
 Venous 
VCD due to device malfunction would be treated with (converted to) manual compression, or 
much less likely  surgery  to close the access site. All device failure patients should be followed 
to 30 days and have a visual assessment of the access site(s) at that time. Such visual 
assessments are particularly important since patients experiencing device failures are more likely 
to have access site-related complications, and a complete and accurate evaluation of these 
patients is important to help ensure a rigorous IDE study. 
16.3 
Analysis Population 
Analyses for the safety and efficacy endpoints will be performed using the intent-to-treat (ITT) 
population. The ITT population will consist of all patients randomized in the study and will be 
analyzed in the group to which they were randomized regardless of the treatment actually 
received. 
Supportive analyses for the safety and efficacy endpoints will be performed on the as-treated (AT) 
population and the per-protocol (PP) population. The AT population will consist of all randomized 
subjects, but they will be analyzed according to what device/treatment they actually received. The 

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PP population is a subset of the ITT population consisting of subjects that do not have any major 
protocol deviation that might affect the measurement of the primary endpoints. 
16.4 
Statistical Hypotheses for Endpoints 
Primary Effectiveness Endpoint- Primary efficacy will be measured using co-primary endpoints 
consisting of Time to Ambulation (TTA) and Time to Hemostasis (TTH) as defined below: 
 
 
Time to Ambulation (TTA)-Defined as elapsed time (in hours) between removal of the 
final VCD (device group) or of the final sheath (control group) and when subject stands 
and walks 20 feet without evidence of rebleeding from any femoral venous access site. 
The null and alternative hypotheses of the primary effectiveness comparison for TTA are 
given below 
 
 
 
 
 
 
 
Where 
 is the average time to ambulation for the specified group 
 
Time to Hemostasis (TTH)- Defined as elapsed time (in minutes) between removal of 
each VCD (device group) or of each sheath (control group) and first observed and 
confirmed venous hemostasis (per access site analysis)  
The null and alternative hypotheses of the primary effectiveness comparison for TTH are given 
below: 
 
 
Where 
is the mean time to hemostasis for the indicated group and 5 
minutes is the superiority margin. 
16.5 
Primary Safety Endpoint  
The primary safety endpoint is defined as the rate of combined major venous access site 
closure- related complications through 30 days post procedure, attributed directly to VCD or 
manual compression without other likely cause. 
 
 
Access site-related bleeding requiring transfusion, surgical intervention, or 
rehospitalization 
 
Vascular injury requiring surgical repair 
 
Access site-related infection confirmed by culture and sensitivity, requiring intravenous 
antibiotics and/or extended hospitalization 

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New onset, permanent (i.e., persisting at 30-day follow-up) access site-related nerve 
injury 
 
New onset access site-related nerve injury requiring surgical repair  
 
Pulmonary embolism requiring surgical or endovascular intervention and/or resulting in 
death, to be confirmed by CT pulmonary angiography, lung ventilation/perfusion scan 
(VQ scan), or autopsy 
 
Pulmonary embolism not requiring surgical or endovascular intervention and/or not 
resulting in death, to be confirmed by CT pulmonary angiography or lung 
ventilation/perfusion scan (VQ scan) 
The null and alternative hypotheses of the primary safety comparison are given below: 
 
 
where PX is the proportion limbs experiencing a major venous access site 
closure- related complications through 30 days post procedure 
non-inferiority window. 
16.6 
Secondary Safety Endpoint 
Rate of CEC adjudicated combined minor venous access site closure related complications within 
30 days post- procedure, attributed directly to VCD or manual compression without other likely 
cause. 
 
Pseudoaneurysm  Treated with thrombin injection, fibrin adhesive injection, or 
ultrasound guided compression and documented by ultrasound 
 
Pseudoaneurysm  Not requiring treatment 
 
AV Fistula requiring treatment, documented by ultrasound 
 
Arteriovenous fistula not requiring treatment, documented by ultrasound 
 
Access site related Hematoma > 6 cm documented by ultrasound 
 
Access site-related bleeding requiring > 30 min to achieve hemostasis 
 
Late access site-related bleeding (following hospital discharge eligibility) 
 
Transient loss of ipsilateral lower extremity pulse 
 
Ipsilateral deep vein thrombosis documented by ultrasound 
 
Transient access site-related nerve injury  
 
Access site-related vessel laceration 
 
Access site wound dehiscence 
 
Local access site infection confirmed by culture and sensitivity, treated with 
intramuscular or oral antibiotics  Minor 
 
Local access site inflammatory reaction  Minor 
 
Allergic reaction 
 
Ecchymosis 

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16.7 
Secondary Effectiveness Endpoints 
 
Time to Discharge Eligibility- defined as elapsed time (in hours) between removal of the 
final MYNX CONTROL
Venous VCD (device group) or removal of the final sheath 
(control group) and when the subject is eligible for discharge from the institution based 
on the assessment of the attending physician.  
 
Procedural Success: attainment of final hemostasis at all venous access sites without 
major venous access site closure-related complications through 30 days.  
 
Device Success: ability to successfully deploy the MYNX CONTROL
Venous VCD 
delivery system, deliver the polyethylene glycol hydrogel sealant, and achieve 
hemostasis (device group only).  
16.8 
Sample Size Determination 
In determining sample size for this study, it is necessary to take both TTA and TTH into account 
since the study is using both as co-primary endpoints. The total sample size for the study is 
determined to be 204 patients and is based on the following assumptions: 
TTA Assumptions 
Power 
90% 
Alpha 
1-sided 0.025 
Allocation 
2:1 VCD:MC 
VCD mean 
3 hours78 
MC mean 
6 hours 
Standard Deviation 
 6 hours 
Attrition correction 
5% 
Power 
SD 
MC SS 
VCD SS 
Total SS 
90 
6 
68 
136 
204 
TTH Sample size justification: For the endpoint of time to hemostasis, a generalized linear 
mixed model will be used to compare the 
 Venous VCD device with manual 
compression (control). Initial estimates of the average time to hemostasis were taken from 
historical MYNX family devices and compared to manual compression. Previous MYNX family 
studies only studied one access site per subject within the femoral artery. The observed average 
time to hemostasis as well as the standard deviations of those measurements helped inform the 
design of this trial where the standard deviation would be used as an estimate of subject-to-
subject variation. For the current study, it is assumed that each subject will have up to 4 access 

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sites in the femoral vein. These access sites will be closed with either the 
 
Venous VCD device or manual compression. Only one method of closure will be used per subject. 
Time to hemostasis will be measured for each access site separately. 
It is assumed that hemostasis times are log-normally distributed. Using previous study data, 
obtained and used in the calculation of 
sample size for this endpoint.  
A generalized linear mixed model is used with the subject as a random effect. To adjust for the 
correlation in hemostasis time between the access sites within subject, it is assumed that the 
correlation structure is compound symmetric. The Type I error rate was set to a one-sided 0.025 
(or equivalently, a two-sided 0.05 level) for the purposes of sample size calculation. A sample 
size of 150 patients (100 
Venous VCD and 50 manual compression) will 
provide approximately 95% power to detect a difference in hemostasis times of seven (7) minutes 
between 
 Venous VCD and manual compression. Note that these 
calculations were made in the log transformed space to assess power. Also, the variation between 
access sites within patients was estimated as approximately half of the variation observed 
between patients. 
The specific model used is: 
 
where  is the treatment effect and 
 is the random effect of subject within treatment. 
 is the 
unexplained variation in the model. Further, it is assumed that: 
 
) 
and 
 
TTH Assumptions 
Power 
~95% 
Alpha 
1-sided 0.025 
Allocation 
2:1 VCD:MC 
VCD mean 
6 
MC mean 
13 
Standard Deviation 
Determined in the log transformed space 
Attrition correction 
5% 

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Total Sample Size 
150 patients 
 
Sample Size for Primary Safety Endpoint: The primary safety endpoint of major venous access 
site closure-related complications through 30 days post-procedure, attributed directly to VCD or 
manual compression without other likely causes will be analyzed using a non-inferiority approach 
based on a generalized estimating equation (GEE) approach for logistic regression, using a 
working compound-symmetric covariance structure. This method would account for potential 
within subject correlation. We will perform the test at the one-sided 0.025 alpha level. For the 
purposes of sample size calculation, both groups are assumed to have a 1.5% major complication 
rate. The non-inferiority window has been established at 5 percentage points.  
Within-subject correlation can affect the power of the study depending on the degree of 
correlation. However, the degree of correlation within-subject due to potentially multiple limbs is 
unknown and there is no robust and relevant data on which to base any associated assumption. 
Since this is unknown, sample size is conservatively calculated assuming only one limb per 
subject, or in other words, the number of subjects in the study assuming independence between 
subjects. Calculations for a two-sample test of binomial proportions for a Z test under a normal 
approximation show a sample size of 204 subjects should provide approximately 80% power for 
this endpoint. To the extent that some subjects will contribute multiple limbs to the actual analysis, 
the power would be higher than that from calculations based only on the number of independent 
subjects. Though missing data for the primary safety endpoint is unlikely, the additional data 
contributed by multiple limbs will help offset any power loss due to missing data.  
Sample Size for Secondary Endpoint: Initial estimates for the secondary endpoint of time to 
discharge eligibility were obtained from the VASCADE MVP Venous Vascular Closure System 
(Cardiva Medical Inc.) Summary of Safety and Effectiveness Data.  The average time to discharge 
eligibility for VASCADE was 3.1 ± 1.3 hours and for manual compression it was 6.5 ± 1.9 hours.  
For sample size calculation, the Type 1 error rate was set to 0.025.  A sample size of 23 total 
subjects provides more than 95% power to demonstrate that the average time to discharge 
eligibility is significantly less for the MYNX CONTROL
 Venous group relative to manual 
compression. 
The sample size for adequate power on the primary safety endpoint was the largest and will be 
used as the sample size for this trial. 
16.9 
Statistical Analysis Methods 
Except where otherwise specified, the following general principles apply to the planned statistical 
analyses. All descriptive statistical analyses will be performed using SAS version 9.4 or higher, 
unless otherwise noted (SAS Institute Inc., Cary, NC) or other widely accepted statistical or 
graphical software as required. Derived variables will be independently verified by an independent 
programmer / statistician. The program review will also include whether analyses conform to 
specifications of the Statistical Analysis Plan.  

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For categorical variables, the numerator, denominator, rate (%) and exact 95% CI will be 
calculated. For continuous variables, the median, mean, standard deviation, interquartile 
range, number of observations, minimum and maximum values, and 95% CI, as appropriate, will 
be presented.  
For each parameter, the baseline value will be defined as the last non-missing value collected at 
the time closest to but before treatment with the investigational device.  
All statistical tests will be performed at the two-sided 0.05 significance level, unless otherwise 
noted. Listings of patient data will be created for all study parameters.  
16.9.1 
Primary Analysis 
Efficacy  
The primary efficacy endpoints will be analyzed separately. 
The average time to ambulation in each treatment group will be compared using a standard T-
test.  
The average time to hemostasis will be compared to the treatment groups using a generalized 
linear mixed model where subject is considered a random effect with multiple access sites. The 
times to hemostasis in the manual compression group will be reduced by 5 minutes to account 
for the hypothesis that the time to hemostasis for the MYNX 
 is at least 
5 minutes less than manual compression. The analysis will consist of testing the coefficient on 
the fixed effect for treatment group. If that coefficient is found to be significantly different from 
zero, then the direction will be evaluated to assure that the hemostasis time is reduced on average 
when using MYNX CONTROL 
 VCD. 
 
Safety  
The safety analysis will be completed on a per-limb basis.  
This endpoint will be analyzed using a GEE approach for a logistic regression model with a 
compound symmetric working covariance structure where occurrence of an AE is the binary 
response variable and treatment group is the only explanatory variable.  Least square means for 
each treatment group and the risk difference between groups will be calculated along with the 
two-sided 95% confidence interval.  The one-sided 97.5% confidence bound (equivalent to the 
appropriate bound from the two-sided 95% interval) will be compared to the non-inferiority 
window.  If the upper bound is less than the non-inferiority window, then the two treatment 
groups will be considered non-inferior relative to the proportion of limbs experiencing a major 
venous access site closure-related complication. 
As a supplementary analysis, a generalized linear mixed model will be used where subject will be 
entered into the model as a random effect and a compound symmetric correlation structure 
applied to those subjects contributing two limbs. 

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Trial Success 
This trial will be considered a success if both primary efficacy endpoints and the primary safety 
endpoint are achieved. 
16.9.2 
Secondary Safety Analysis 
The secondary safety analysis of combined minor venous access site closure related 
complications within 30 days post-procedure, attributed directly to VCD or manual compression 
without other likely cause will be summarized on a per-limb basis. The proportion of limbs 
experiencing a minor closure related complication will be calculated for each treatment group 
along with 95% confidence intervals. The difference between the proportions will then be 
estimated along with a 95% confidence interval. 
16.9.3 
Secondary Efficacy Analyses 
Time to Discharge Eligibility, defined as the elapsed time between removal of the final MYNX 
CONTROL
Venous VCD (device group) or removal of the final sheath (control group), and when 
the subject is eligible for discharge from the institution (in hours) will be summarized on a per-
patient basis. 
Time to discharge eligibility is a powered secondary endpoint.  The average time to discharge 
eligibility will be compared between the device and control groups at the 0.025 level of 
significance.  The specific hypotheses being tested are: 
 
 
where 
 is the average time to discharge eligibility for the specified group.  A p-value for this 
one-sided test less than 0.025 will indicate that the time to discharge eligibility for the subjects 
using the 
 was significantly less 
than for those where manual compression was used.  The standard two group T-test will be 
used to make this comparison. 
The difference between treatment groups in average time to discharge will also be estimated with 
95% confidence intervals calculated using the T-distribution. 
The following secondary endpoints are considered ad hoc analyses and are not powered. 
Procedural Success defined as the attainment of final hemostasis at all venous access sites 
without major venous access site closure-related complications through 30 days will be 
summarized on a per access site basis and on a per-limb basis. Procedural success will be 
estimated for each treatment group separately with 95% confidence intervals followed by an 

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estimate of the difference in procedural success between the treatment groups and a 95% 
confidence interval on the difference. 
Device Success defined as the ability to deploy the VCD delivery system, deliver the polyethylene 
glycol hydrogel sealant, and achieve hemostasis will be summarized on a per access site basis 
for the device group only. The proportion of device successes will be estimated along with a 95% 
confidence interval. 
16.9.4 
Additional analysis 
The type of major complication will also be compared on a per-limb basis. Frequency distributions 
for the type of complication will be constructed for each treatment group and the frequency 
distributions will be examined informally. This analysis is for information purposes only. 
16.9.5 
Analysis of Roll-in Subjects 
The roll-in subjects will be summarized descriptively. No formal analysis will be done. Roll-in 
subjects will not be part of the main analysis population. Details can be found in the statistical 
analysis plan. 
16.9.6 
Study site poolability 
Study site poolability for the primary endpoint of time to ambulation will be analyzed using a two-
way analysis of variance (ANOVA) model.  The first factor in this model will be treatment group 
and the second factor will be study site.  The treatment group by study site interaction will also 
be added to the model.  If the interaction term is not significant at the 0.15 level, then the study 
sites will be pooled for the analysis of this endpoint. 
Study site poolability for the primary endpoint of time to hemostasis will be analyzed using the 
general linear mixed model outlined in section 16.8.  To that model fixed effects for study site 
and treatment group by study site interaction will be added.  If the interaction term is not 
significant at the 0.15 level, then the study sites will be pooled for the analysis of this endpoint. 
Study site poolability for the safety endpoint will be analyzed on a per limb basis.  A GEE logistic 
regression model with main effects of treatment group and study site along with an interaction 
term between those main effects will be fit to the data.  If the interaction term is not significant at 
the 0.15 level, then the study sites will be pooled for the analysis of this endpoint. 
16.9.7 
Interim Analysis 
An interim analysis in support of a CE Mark submission will be conducted to analyze initial 
subjects randomized to the device group only with respect to efficacy and safety. This interim 
analysis is not intended to support a decision to continue or to discontinue the trial, or to implement 
any modifications to trial procedures. To alleviate potential statistical and operational bias that 
may be introduced, the execution of the interim analysis shall be a completely confidential process 
to the study team. All sponsor staff, staff contracted by the sponsor, and investigator staff directly 

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involved in the conduct of the ongoing IDE trial will remain blind to the process and results of the 
analyses, with the exception of contracted resources involved in the execution of the interim 
analysis and submission of the results on behalf of the sponsor. Endpoints to be evaluated using 
descriptive statistics are as follows:  
 
. 
 
arge Eligibility, Procedure success, and  
 Device Success. 
 
 
 
 
This is a single-arm analysis, therefore subjects randomized to control arm will be excluded from 
the interim analysis. A sample size of 68 sequential subjects randomized to treatment arm will be 
collected for the interim analysis. A final clinical report will be prepared at the conclusion of the 
interim analysis by an agent of the sponsor who is independent from the conduct of the study. 
 
16.10 Sub-Group Analysis  
A sub-group analysis will be completed for the primary safety and primary efficacy endpoints. This 
analysis is not powered and is strictly for information purposes. The sub-groups for this analysis 
are those subjects that contributed only 1 limb and those subjects that contributed 2 limbs. The 
same analysis outlined above for the primary safety and efficacy endpoints will be completed 
within each sub-group separately. Additional analyses to demonstrate the homogeneity of the 
treatment effect and homogeneity of the major complication rates are detailed in the SAP. 
Major and minor complications will also be analyzed based on the number of access sites and 
sheath size, major and minor complications will be stratified by number of access sites per leg (1, 
2, 3, or 4 sites), total number of access sites per patient (1, 2, 3, or 4 sites), and sheath size (small 
size vs. large size).  Details are provided in the SAP. 
A sub-group analysis will also be performed utilizing independent analysis of non-invasive duplex 
ultrasound (DUS) imaging in 72 subjects from both arms (48 device and 24 control) at the time of 
the procedure, pre-discharge and potentially again at the 30-day follow-up (only for those subjects 
that have documented evidence of access site complications at the discharge ultrasound). 
Specific investigational sites will be designated as ultrasound sites. These sites will include 
subjects in the ultrasound subset imaging until a total of 72 patients have been evaluated in both 
treatment arms. Ultrasound will be performed at the follow-up office visit only if a complication 
was detected at discharge. All sub-study sites will be instructed in performance of duplex 
ultrasonography of the femoral vascular structures. Images will be interpreted by:  
 
 
 
NAMSA 
 
4 World Trade Center 

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150 Greenwich Street, 49th FL  
 
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At the time of the procedure, and at discharge, the proportion of subjects exhibiting a complication 
on DUS imaging will be calculated along with 95% confidence intervals constructed using the 
Clopper-Pearson method. For those subjects that required a DUS at the 30 day follow-up, the 
proportion of subjects still exhibiting a complication will be calculated along with a 95% confidence 
interval constructed using the Clopper-Pearson method. 
16.11 Missing Data 
While all reasonable efforts will be made to obtain the data required to evaluate this endpoint, it 
is expected that some patients may not be able to provide data due to several reasons (loss to 
follow-up, study withdrawal, death). For all primary and secondary analyses, no imputation of 
missing data is planned. Patients who have ascertainment of status at a later out-of-window date 
(for example, patients who are known to be free of events past discharge eligibility but missed 
the discharge visit) are not considered missing as their status is known and their data will be used 
as noted previously. The primary endpoint rate will be calculated as the number of patients who 
had 
an 
event 
prior 
to 
the 
milestone 
visit divided 
by 
patients
e.g., at least discharge visit) plus any patients who had an 
event prior to the milestone visit. In other words, the denominator will be adjusted for missing 
follow up data.  
A sensitivity analysis will be done to assess the impact of missing data on the conclusion of the 
primary analyses.  Details of the analysis are provided in the SAP. 
16.12 Reporting 
A final clinical summary will be developed for this study upon completion of all subject follow-up 
visits/database lock for the last required follow-up visit in the study.  
This will be provided to the applicable regulatory authorities as well as all participating 
Investigators and Institutional Review Boards. Interim reports will also be developed 
and provided only as required.  
17 
Quality Control and Quality Assurance 
17.1 
Regulatory and Ethical Compliance 
The Sponsor maintains a quality management system with written Standard Operating 
Procedures (SOP) to ensure that clinical studies are conducted, and data are generated, 
documented, and reported in compliance with the study protocol and the requirements of ICH E6 
Good Clinical Practice, and the requirements of all applicable regulatory authorities. The staff at 
Cordis is trained regularly to ensure adherence to these SOPs. 

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17.2 
Data Quality Assurance 
Study procedures to ensure the quality of all data collected and analyzed within this study include, 
but are not limited to, the following:  
 
Qualified Investigators, study sites and monitors will be selected. 
 
The investigational device was provided to Investigators/sites after being tested and 
released according to appropriate standards. 
 
Training will be provided to and documented for all Investigators and study personnel, 
which includes, but is not limited to, a review of the protocol, investigational product, CRFs, 
EDC system, GCP guidelines and study expectations. Training of Investigators will occur 
at the site initiation visit (prior to the start of any study-related activities), at any Investigator 
meetings and as necessary (e.g., when there are changes to the study team)  
 
Training 
will 
be 
provided 
to 
all 
study 
monitors 
on 
the 
study 
protocol, 
background/therapeutic area and GCP-conforming monitoring activities. Monitors will 
receive project-specific monitoring conventions and all forms needed to document the 
monitoring activity (e.g., forms for monitoring reports, investigational product 
accountability). 
 
The Sponsor and/or designee will conduct source document verification, as specified in 
plan by comparing original source documentation against the 
CRFs. Any discrepancies identified will be resolved with the Investigator, or designee, as 
appropriate.  
 
Appropriate edit checks incorporated within the EDC system and regular/periodic reviews 
of the data by Data Management will verify the completeness and accuracy of the data. 
Like the study monitor, Data Management will post queries to data points in need of further 
clarification and/or correction from sites (like the study monitor) and will keep the Sponsor 
informed of the status of queries and completeness of the study database. 
17.3 
Clinical Data 
The case report form (CRF) for each subject is a record of their eligibility to enter the study, 
medical 
history, 
pre-procedure/baseline 
assessments, 
concomitant 
medications, 
all 
investigational product used during the index procedure, all procedural complications, and 
adverse events as well as data from discharge, all follow-up, and any unscheduled visits. It is the 
obligation of each Investigator (or designee) to ensure that all source documents (e.g., medical 
files, clinic charts, diagnostic films, nursing files), are available to support all data points collected 
within the CRF for every screened and/or enrolled subject. All information obtained during and 
between all protocol-
source documentation and CRF. 
Qualified site staff trained to the protocol, CRFs and EDC system will perform primary data 
collection and data entry into the CRFs in a timely manner following subject enrollment and/the 
completion of study-required assessments/follow-up visits. Data will be collected from patients' 
hospital charts, imaging films, and/or other medical records, which the Investigator is responsible 
to ensure are adequate to support all CRF entries. Corrections to CRFs will be performed by the 

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Investigator or other authorized study site personnel.  A record of study site personnel authorized 
to perform CRF data entry and/or corrections will be maintained by the site and provided to the 
Sponsor.  
The Investigator must sign and date the specified section(s) within the CRF to confirm that s/he 
has reviewed the data and that the data are complete and accurate. 
17.4 
Monitoring 
The Sponsor (and/or designee) will oversee the conduct and progress of the study at each 
investigational site. In addition to regular communications with the site, the Sponsor (and/or 
designee) will conduct interim monitoring visits (IMV) at periodic intervals to verify the following: 
 
The rights and well-being of the patients are protected 
 
The study is conducted according to International Council for Harmonization (ICH) and 
Good Clinical Practices (GCP) (ICH E6), the Declaration of Helsinki (1964) and all 
national, state, and local laws of the pertinent regulatory authorities 
 
The study is conducted in compliance with all requirements identified within the approved 
protocol/ amendment(s)  
 
The data reported in the CRFs/EDC system are accurate, complete, and verifiable from 
source documentation. 
The study monitor will complete verification of the above primarily from review and assessment 
of regulatory documents, signed informed consent forms, accountability records and storage of 
investigational product and CRF/EDC system entries against all source documents. The monitor 
will also post and address queries within the EDC system and discuss the conduct of the study 
with the Investigator and study team. CRFs would need to be completed in a timely manner, within 
five (5) working days or one (1) week, to ensure availability for IMVs. Complete details regarding 
the monitoring procedures followed for the study are described in the study monitoring plan.  
The Investigator must agree to provide study monitors with direct access to the 
office/clinic/facilities, medical records/source data/source documents for all enrolled patients, 
regulatory documents, and any/all other applicable study-related documents to enable the proper 
completion of IMVs.  
Interim monitoring visits (IMVs) will be conducted throughout the course of this study according 
 Monitoring visit frequency at sites will be based on factors 
including, but not limited to, the rate and volume of enrollment, timing of completing follow-up 
visits and overall compliance. 

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17.5 
Protocol Modifications 
17.5.1 
Protocol Amendments 
Changes to the research covered by this protocol must be implemented through a formal protocol 
amendment. Change(s) to only logistical or administrative aspects of the study will be reflected in 
the study protocol if/when it is next amended to address any changes to the research. Protocol 
amendments may be initiated by the Sponsor or at the request of the Investigator. In either case, 
however, all protocol amendments must be approved by the Sponsor, signed, and dated by the 
Investigator and approved by the IRB prior to implementation.  
17.5.2 
Protocol Deviations/Noncompliance 
A protocol deviation is defined as a divergence from a specific element of the study protocol (e.g., 
missed assessment, visit out of window, violation of inclusion/exclusion criteria). Sites must 
comply with all requirements of the study protocol to control the number of protocol deviations to 
the extent possible. This does not include circumstances where necessary to eliminate an 
immediate hazard to study subjects (see section below) or that involve only logistical or 
administrative aspects of the study. 
Protocol deviations for inability to perform office visits, exams or procedures due to 
COVID-19 pandemi
-
each deviation. 
The study monitor will verify the conduct of the study follows the currently approved protocol at 
each site and will identify any deviations from the protocol. The study monitor will also determine 
if there are any other issues of noncompliance (e.g., with IRB requirements, regulations from 
applicable regulatory authorities). If any protocol deviations or other areas of noncompliance are 
noted, the Investigator, site staff and/or study monitor will ensure corrective actions are 
implemented and evaluate the effectiveness of those corrective actions. Recurrence of 
noncompliance may require development of a formal corrective action plan that includes a 
suspension in enrollment and/or other actions. All protocol deviations and other issues of 
noncompliance at a site will be monitored closely by the Sponsor and/or designee(s) and will be 
reported to the applicable regulatory authorities and/or the IRB, as required.  
17.5.3 
Emergency Deviations 
Emergency deviations are allowed only in cases where the change is necessary to eliminate an 
immediate apparent hazard and protect the life or physical well-being of a study subject. Such 
cases must be reported to the Sponsor/Medical Monitor and the IRB in writing within five (5) 
working days of the occurrence and will still be entered as protocol deviations in the CRF. 
17.6 
Audits 
The Sponsor and/or designee and the FDA may contact the participating institution to inform the 
Investigator of an upcoming audit and/or inspection, which may be routine or 
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event the Investigator receives notification from FDA of an audit/inspection for this study, the 
Investigator should immediately notify the Sponsor. The Investigator must agree to provide direct 
access to the office/clinic/facilities, medical records/source documents for all enrolled patients, 
regulatory documents, and any/all other applicable study-related documents to all representatives 
of the Sponsor and/or designee and all regulatory authorities to enable proper completion of the 
audit/inspection. 
17.7 
Subject Confidentiality 
Subject confidentiality will be maintained throughout the clinical study. A unique subject 
identification number will be assigned to every consented study subject, which will identify all data 
reported for that subject and ensure the data can be traced back to their source records. Subject 
identification will be created using a five-digit numeric value beginning with site number (XX) 
followed by subject numbers (YYY) such as 01-001. 
Data relating to the study may be made available to all representatives of the Sponsor and/or 
designee and third parties (e.g., in the case of an audit performed by regulatory authorities) 
provided the data are treated confidentially and that the patien
 
17.8 
Institutional Review Board (IRB) 
Prior to study initiation, the protocol, informed consent form and all other applicable study-related 
documents, including any written materials to be provided to patients, and any advertisement for 
patient recruitment (if applicable), must be submitted for review by a certified IRB. The IRB must 
be registered with the U.S. Department of Health and Human Services (HHS). Written approval 
or favorable opinion of these documents must be obtained and submitted to the Sponsor prior to 
screening and enrolling any patients and initiating any study-related activities.  
The Investigator will prepare the draft informed consent form (ICF) and provide to the Sponsor 
and/or designee for approval prior to submission to the IRB. If the Sponsor requires any changes, 
a revised draft of the ICF incorporating these changes must be approved by the Sponsor prior to 
IRB submission. If the IRB requires additional changes, these must be reviewed and approved 
by the Sponsor prior to resubmission to the IRB. Copies of the final, IRB-approved ICF and all 
other IRB-approved study documents must be submitted to Sponsor or designee. 
The Investigator or authorized designee will promptly report all changes in research activity and 
all unanticipated events/issues involving risks to human patients to the IRB. All Sponsor-approved 
amendments to the study protocol, ICF, etc. must be approved by the IRB prior to implementation. 
All other changes to research activities must be approved by the Sponsor and IRB prior to 
implementing, except when necessary to eliminate an immediate apparent hazard to the patient.   
At least annually, or more frequently if required by IRB policy, the Investigator or authorized 
designee must submit a study progress report to their IRB to obtain continuing review approval 
for the study prior to the expiration of the most recent approval. Additionally, the Investigator must 
provide notification to their IRB, within three (3) months following the completion, termination, or 

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discontinuation of the study at the specific site and provide the acknowledgement letter from the 
IRB to the Sponsor.  
For U.S. sites, IRBs must retain all study-related records for at least three (3) years following 
completion of the study, per the requirements of applicable regulatory authorities, or longer if 
required by local laws. 
18 
Record Keeping/Publication Policy 
All required subject data must be recorded on CRFs provided by the Sponsor and/or designee for 
verification against subject source documents by the study monitor(s). A printout of the CRFs 
cannot be used as source documentation.  
18.1 
Record Retention 
All study records (e.g., correspondence, regulatory documents, CRFs and all source documents 
(informed consent forms, laboratory reports, progress notes, medical histories, physical and 
diagnostic findings, diagnoses, procedure/assessment dates and investigational product 
disposition records etc.) that support the CRFs) must be retained in the files of the responsible 
Investigator for a minimum of two (2) years from the latter of these two (2) dates, as communicated 
by the Sponsor, unless a longer retention period is required by the IRB or applicable local laws: 
 
the date on which the entire investigation is terminated or completed, or  
 
the date the records are no longer required to support a premarket approval (PMA) 
application  
If the Investigator plans to archive or relocate/transfer the study records, (s)he must notify the 
Sponsor, in writing, of the transfer location, duration, and the procedure for accessing the study 
documentation. The Sponsor must approve of the planned archival or relocation/transfer, in 
writing, prior to its occurrence. All study records must be accessible upon request by the 
applicable regulatory authorities, the Sponsor and/or designee until destruction is possible.   
If the Investigator retires, relocates, or for other reasons, withdraws from assuming primary 
responsibility for keeping the study records, written notice (transfer of obligation) must be 
submitted to the Sponsor and IRB indicating the name and address of the new custodian 
accepting primary responsibility.  
For U.S. sites, IRBs must retain all study-related records for at least three (3) years following 
completion of the study, per the requirements of applicable regulatory authorities, or longer if 
required by local laws. 
18.2 
Use of Information and Publications 
This study will be registered in Clinicaltrials.gov, a publicly accessible database, through which 
the results of this study will also be reported. All information concerning the Sponsor (Cordis), 
MYNX CONTROL
Venous Vascular Closure Device, patent application, manufacturing 

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processes, and scientific data supplied by the Sponsor to the Investigator and not previously 
published, is considered confidential and remains the sole property of the Sponsor. The 
Investigator understands the information developed in the clinical study will be used by the 
Sponsor in connection with a PMA application and thus may be disclosed as required to other 
Investigators or government regulatory authorities.  
At the conclusion of the study, a manuscript may be prepared for publication of results across 
multiple study centers in a reputable scientific journal. The publication of the principal results from 
any single study center is not allowed until the preparation and publication of the multi-center 
results. Exceptions to this rule require prior approval of the Sponsor. The analysis of pre-specified 
and non-pre-specified endpoints will be performed by (the Sponsor/designated entity for data 
management/statistics). Secondary analyses as well as other proposed investigations will require 
the approval of the Sponsor. For purposes of timely abstract presentation and publication, 
secondary publications will be delegated to the appropriate principal authors. 
19 
Investigational Product Accountability  
19.1 
Study Investigational Product Accountability 
The investigational product must be kept in a secure location with restricted access to authorized 
members of the study team and stored according to the conditions outlined in the Instructions for 
Use (IFU)/ Investigator Brochure (IB). The investigational product is intended solely for use by the 
Investigator or Sub-Investigator(s) and can only be used in clinical study patients. Investigational 
product-related study documentation to be maintained includes, but is not limited to, the following: 
 
 
Packing slips provided with each investigational product shipment (signed and dated)  
 
An up-to-date, complete, and accurate investigational product accountability log showing 
receipt, usage or implant and return or final disposition of all investigational product 
shipped to the site 
 
All other device accountability records including source documents and/or package 
labels of investigational product used in implanted patients, shipping labels, delivery 
confirmations, etc. 
 
Copies of investigational product malfunction and return forms (for sterile and 
opened/malfunctioned product) 
All product on site 
CAUTION Investigational device: Limited by Federal (or United 
States) law to investigational use. , regardless of whether used or opened and/or unused, will be 
inventoried and accounted for throughout the study. The Investigator and/or authorized designee 
will maintain adequate records of the receipt, use, and disposition of the investigational product 
as required by protocol and applicable country, local and federal regulations  
Product on site will be inventoried and accounted for in the CRFs. At a minimum, the lot number, 
size (length and diameter) and use by date (UBD) of all products will be captured. All AEs, 
investigational product malfunctions and other product issues must also be recorded in the CRFs. 

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19.2 
Instructions for Return of Investigational Product 
The Sponsor will provide instructions and ensure training to all sites on the re-package and return 
of investigational product, the appropriate form(s) that must be completed and the address(es) to 
which the product must be returned based on whether it is opened/unopened and unused, 
expired, damaged, mislabeled, a product complaint or malfunction has occurred, or study 
enrollment has been completed.  
20 
Committees 
20.1 
Clinical Events Committee 
The Clinical Events Committee (CEC) is responsible for the review and final adjudication of 
adverse events using source documents provided by sites to categorize clinical events and clinical 
endpoints in the study. The CEC will establish study-related guidelines for the requisite source 
data and the algorithm followed to classify a clinical event (according to the study definition). The 
Sponsor will review the definitions prior to the start of the adjudication process. 
The CEC will consist of qualified physicians with the appropriate expertise for the type of 
investigational product or condition under study. The CEC is an independent body, functioning 
separately from the Sponsor, the investigational sites or anyone otherwise involved in the conduct 
of the study or the clinical care of study patients. Members will not have any scientific, financial, 
or other conflict of interest related to the Sponsor or the study Investigators. As appropriate, 
members of the CEC will be blinded to the primary results of the trial. 
The CEC will be responsible for providing adjudication results and minutes of their meetings to 
the Sponsor for internal review.  
The structure and function of the CEC will be documented in the CEC Charter. 
20.2 
Data and Safety Monitoring Board 
The Data and Safety Monitoring Board (DSMB) is a body of professionals (primarily comprised of 
physicians, a biostatistician, and/or a medical ethicist) which reviews overall study data at 
intervals pre-determined before the start of the study and/or based on subject enrollment accrual 
and/or event accrual to assess progress and identify any safety concerns or other issues. The 
DSMB is independent of the Sponsor, the investigational sites or anyone otherwise involved in 
the conduct of the study. Members will not have any scientific, financial, or other conflict of interest 
related to the Sponsor or the study Investigators.  
All serious adverse events, device-related complications/malfunctions and events related to the 
primary safety endpoint will be included in safety reports provided to the DSMB.  

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The DSMB will be responsible for providing to the Sponsor, minutes of their meetings and any 
recommendations regarding early termination, suspension, or modifications to the study, if the 
safety and well-being of the patients is in jeopardy.   
The structure and function of the DSMB will be documented in the DSMB Charter. 
21 
Early Termination or Suspension 
The Sponsor, DSMB, IRBs, regulatory authorities or the Investigator may choose to temporarily 
suspend or prematurely terminate the study if the safety and well-being of the patients is in 
jeopardy.  
The Sponsor reserves the right to temporarily suspend or prematurely terminate this study either 
at a single site, multiple sites or across all sites at any time for reasons including, but not limited 
to: 
 
 
Safety or ethical issues  e.g., if in the opinion of the responsible investigator, the 
incidence and/or severity of adverse events in the study indicates a potential health 
hazard caused by treatment with the investigational product 
 
Inaccurate or incomplete reporting of data 
 
Non-compliance 
 
Unsatisfactory enrollment with respect to quality or quantity 
 
Technical reasons (e.g., change in personnel) 
If the Sponsor prematurely terminates or suspends the study, they will promptly notify the 
applicable Investigator(s)/institution(s) and the regulatory authority(ies) of the termination or 
suspension and the reason(s) for such, in accordance with applicable regulatory requirement(s). 
The applicable IRB(s)/EC(s) should also be informed and provided with the reason(s) for 
termination or suspension by the Sponsor or by the Investigator(s)/institution(s), in accordance 
with applicable regulatory requirement(s). Additionally, in the case of premature termination, the 
Sponsor will provide direction on the return of all unused investigational product and other study 
materials. In the case of a temporary suspension at a single site, multiple sites, or across all sites, 
the Sponsor will ensure all the necessary activities are performed before resuming the study, if 
approved to continue (e.g., benefit-risk reviewed and remain acceptable or revised). 
If the Investigator terminates or suspends the study without prior agreement with the Sponsor, 
he/she will promptly provide all details to the institution, the Sponsor, and the IRB.  
If the IRB terminates or suspends the study, the Investigator will promptly inform the Sponsor with 
written explanation. 
In any case, the investigator(s)/institution(s) must arrange for any continued safety monitoring, 
treatment and/or follow-up of patients, unless it has been determined by the Investigator that the 
continued follow-up may jeopardize the rights, safety, and/or welfare of the subject. 

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Subject enrollment may be paused or terminated early if the Sponsor or DSMB determines that 
the potential benefits of the investigational product/procedure are unlikely to outweigh the risks. 
For example, if the probability of achieving the target primary endpoint falls below a certain 
threshold, the trial will be stopped or paused for re-evaluation. 
 
 

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Appendix A. 
Definitions  
 
 
 
Allergic reaction: The hypersensitive response of the immune system of an allergic individual 
to a substance. 
Asymptomatic: Without symptoms. For example, an asymptomatic infection is an infection with 
no symptoms. 
Blood clot: Blood that has been converted from a liquid to a solid state. Also called a thrombus. 
Complication: In medicine, an additional problem that arises following a procedure, treatment 
or illness and is secondary to it.  
Device related complication - complication attributed to the device (e.g., graft migration, graft 
infection, etc.). 
 
Procedure-related complications - complication not attributed to device but arises following 
the procedure (e.g., cardiac issue, renal insufficiency, etc.). 
Death: All-cause mortality. 
Device deficiency: Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. Includes malfunctions, use errors, and inadequate 
labelling. 
Device malfunction: The failure of a device to meet any of its performance specifications or 
otherwise perform as intended. Performance specifications include all claims made in the 
IFU/IB. 
Dilation: The process of enlargement, stretching, or expansion. The word "dilatation" means the 
same thing. Both come from the Latin "dilatare" meaning "to enlarge or expand." 
Inflammation: A basic way in which the body reacts to infection, irritation or other injury, the key 
feature being redness, warmth, swelling and pain. Inflammation is now recognized as a type of 
nonspecific immune response.  
Occlusion: A complete absence of flow within a blood vessel. 
Peripheral: Situated away from the center, as opposed to centrally located. 
Rupture: A break or tear in any organ or soft tissue  
Scan: The data or image obtained from the examination of organs or regions of the body by 
gathering information with a sensing device. 
Stroke: Any acute, new, persistent, documented neurological deficit ending in death or lasting 
greater than 24 hours and classified by a physician as a stroke. 

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Thrombosis  Formation of thrombus within a blood vessel leading to significant limitation of 
blood flow, requiring secondary intervention to restore blood flow (e.g., thrombolysis, 
thrombectomy, PTA) 
Ultrasound: High-frequency sound waves used to bounce off tissues using special devices. 
The echoes are then converted into a picture called a sonogram.  
 
 
 

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Appendix B. 
Acronyms and Abbreviation 
Acronym / 
Abbreviation 
Term 
ACT  
AE  
AP 
ARF w/ Dialysis 
ARF w/o Dialysis 
atm  
AV 
BID  
BMI 
BP 
BUN  
CAD 
CAD 
CBC  
cc 
CEC  
CFA 
CFR  
CHF  
CI 
CK  
CK-MB  
cm  
COPD 
CPK  
CRF 
CRO  
CSR 
CT 
CVA  
DIC 
dl 
DM 
DSMB  
DUS 
EC  
eCRF  
EDC 
Fr 
GCP  
GGE 
GI  
gm  
HCT  
HGB  
HHS  
HIPAA  
Activated clotting time 
Adverse event 
Anterior/Posterior 
Acute Renal Failure with Dialysis 
Acute Renal Failure without Dialysis 
Atmospheric pressure 
Arterial Venous 
Twice Daily 
Body Mass Index 
Blood Pressure 
Blood urea nitrogen 
Coronary Artery Disease 
Carotid Artery Disease 
Complete blood count 
cubic centimeter 
Clinical Events Committee 
Common Femoral Artery 
Code of Federal Regulations 
Coronary Heart Failure  
Confidence Interval 
Creatine kinase 
Creatine kinase myocardial-band isoenzyme 
Centimeter 
Chronic Obstructive Pulmonary Disease 
Creatine Phosphokinase 
Case Report Form 
Contract Research Organization 
Clinical Study Report 
Computerized Axial Tomography Scan 
Cerebrovascular accident 
Disseminated Intravascular Coagulation 
deciliter  
Data Management 
Data and Safety Monitoring Board 
Duplex Ultrasound 
Ethics Committee 
Electronic Case Report Form 
Electronic Data Capture 
French (sizing unit for devices) 
Good Clinical Practice  
Generalized Estimating Equation  
Gastrointestinal 
Gram 
Hematocrit 
Hemoglobin 
Health and Human Services (Department of) 
Health Insurance Portability and Accountability Act 

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Acronym / 
Abbreviation 
Term 
HR 
IB 
ICF 
ICH  
ICU 
IDE 
IFU  
IMA 
in  
IRB  
ITT  
IV 
IVRS  
IVUS  
LPO 
L/l  
m/Mon 
MC 
MedDRA  
mg 
MI  
mm 
mmHg 
MHLW 
NSTEMI 
NYHA  
OR 
PE 
PLT  
PMA 
PMS  
PRN  
RPO 
PRO 
PT 
PTA  
PTT 
PVD  
QD  
RBC  
RCT  
RVD  
SAE  
SD  
SMA 
SVS 
TAA  
TIA 
TLR  
Heart Rate 
Investigator Brochure 
Informed Consent Form 
International Council for Harmonization 
Intensive Care Unit 
Investigational Device Exemption 
Instructions for Use 
Inferior Mesenteric Artery 
Inch 
Institutional Review Board 
Intent-to-treat 
Intravenous 
Interactive Voice Response System 
Intravascular ultrasound 
Left Posterior Oblique 
Liter 
Month 
Manual Compression 
Medical Dictionary for Regulatory Activities 
milligram 
Myocardial infarction 
Millimeter  
Millimeters of mercury (unit of pressure) 
Ministry of Health, Labor and Welfare 
Non-ST segment Elevation Myocardial Infarction 
New York Heart Association 
Operation Room 
Physical Examination 
Platelet 
Premarket Approval 
Post Marketing Surveillance study 
As Required 
Right Posterior Oblique 
Patient-Reported Outcomes 
Prothrombin Time 
Percutaneous transluminal angioplasty 
Partial Thromboplastin Time 
Peripheral Vascular Disease 
Once Daily 
Red blood cell 
Randomized Controlled Trial 
Reference vessel diameter 
Serious adverse event 
Standard deviation 
Superior Mesenteric Artery 
Society for Vascular Surgery 
Thoracic Aortic Aneurysm  
Transient Ischemic Attack 
Target lesion(s) revascularization 

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Acronym / 
Abbreviation 
Term 
TTA 
TTDE 
TTH 
UADE  
UBD 
ULN  
US/USA 
USFDA  
VCD 
VO  
WBC  
WHO  
WNL 
Time to Ambulation 
Time to Discharge Eligibility 
Time to Hemostasis 
Unanticipated Adverse Device Effect 
Use by date 
Upper Limit of Normal  
United States/United States of America 
United States Food and Drug Administration 
Vascular Closure Device 
Volume obstruction 
White blood cell 
World Health Organization 
Within Normal Limit 
 
 
 

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Appendix C. 
References 
1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews 
and meta-analyses: the PRISMA statement. PLoS medicine. 2009;6(7):e1000097. 
10.1371/journal.pmed.1000097 
 
2. Baker NC, Escarcega RO, Lipinski MJ, Magalhaes MA, Koifman E, Kiramijyan S, et al. Active 
Versus Passive Anchoring Vascular Closure Devices Following Percutaneous Coronary 
Intervention: A Safety and Efficacy Comparative Analysis. Journal of interventional cardiology. 
2016;29(1):108-12.10.1111/joic.12264 
 
3. Fargen KM, Hoh BL, Mocco J. A prospective randomized single-blind trial of patient comfort 
following vessel closure: extravascular synthetic sealant closure provides less pain than a self-
tightening suture vascular compression device. Journal of neurointerventional surgery. 
2011;3(3):219-23.10.1136/jnis.2010.003988 
 
4. Hutchings D, Hayat A, Karunakaran A, Malik N. Success, Safety, and Efficacy of the Mynx 
Femoral Closure Device in a Real-World Cohort: Single-Center Experience. The Journal of 
invasive cardiology.2016;28(3):104-8. 
 
5. Noor S, Meyers S, Curl R. Successful reduction of surgeries secondary to arterial access site 
complications: a retrospective review at a single center with an extravascular closure device. 
Vascular and endovascular surgery. 2010;44(5):345-9. 10.1177/1538574410366760 
 
6. Pruski MJ, Jr., Blachut AM, Konkolewska M, Janas A, Hrycek E, Buszman PP, et al. 
MynxGrip for Closure of Antegrade Puncture After Peripheral Interventions With Same-Day 
Discharge. Vascular and endovascular surgery. 2017;51(2):67-71. 10.1177/1538574416689424 
 
7. Scheinert D, Sievert H, Turco MA, Schmidt A, Hauptmann KE, Mueller R, et al. The safety 
and efficacy of an extravascular, water-soluble sealant for vascular closure: initial clinical results 
for Mynx. Catheterization and cardiovascular interventions : official journal of the Society for 
Cardiac Angiography & Interventions. 2007;70(5):627-33. 10.1002/ccd.21353 
 
8. Wong SC, Bachinsky W, Cambier P, Stoler R, Aji J, Rogers JH, et al. A randomized 
comparison of a novel bioabsorbable vascular closure device versus manual compression in the 
achievement of hemostasis after percutaneous femoral procedures: the ECLIPSE (Ensure's 
Vascular Closure Device Speeds Hemostasis Trial). JACC Cardiovascular interventions. 
2009;2(8):785-93. 10.1016/j.jcin.2009.06.006 
. 
9. Sheth RA, Walker TG, Saad WE, Dariushnia SR, Ganguli S, Hogan MJ, et al. Quality 
improvement guidelines for vascular access and closure device use. Journal of vascular and 
interventional radiology: JVIR. 2014;25(1):73-84. 10.1016/j.jvir.2013.08.011 
 
10. Rao SV, Stone GW. Arterial access and arteriotomy site closure devices. Nature reviews 
Cardiology. 2016;13(11):641-50. 10.1038/nrcardio.2016.133 
 
11. Patel MR, Jneid H, Derdeyn CP, Klein LW, Levine GN, Lookstein RA, et al. Arteriotomy 
closure devices for cardiovascular procedures: a scientific statement from the American Heart 
Association. Circulation. 2010;122(18):1882-93. 10.1161/CIR.0b013e3181f9b345 
 
12. Iannaccone M, Saint-Hilary G, Menardi D, Vadala P, Bernardi A, Bianco M, et al. Network 
metaanalysis of studies comparing closure devices for femoral access after percutaneous 

ReliaSeal / P22-8301 
 
 
 
 
 
 
 
 
                                       
Version: 3.0 / 31Jan2023                                                               
 
         
 
 
 
 
 
Page 59 of 66 
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coronary intervention. Journal of cardiovascular medicine (Hagerstown, Md). 
2018.10.2459/jcm.0000000000000697 
 
13. Kennedy SA, Rajan DK, Bassett P, Tan KT, Jaberi A, Mafeld S. Complication rates 
associated with antegrade use of vascular closure devices: a systematic review and pooled 
analysis. Journal of vascular surgery. 2020. 10.1016/j.jvs.2020.08.133 
 
14. Schwartz BG, Burstein S, Economides C, Kloner RA, Shavelle DM, Mayeda GS. Review of 
vascular closure devices. The Journal of invasive cardiology. 2010;22(12):599-607. 
 
15. Dahal K, Rijal J, Shahukhal R, Sharma S, Watti H, Azrin M, et al. Comparison of manual 
compression and vascular hemostasis devices after coronary angiography or percutaneous 
coronary intervention through femoral artery access: A meta-analysis of randomized controlled 
trials. Cardiovascular revascularization medicine : including molecular interventions. 
2018;19(2):151-62.10.1016/j.carrev.2017.08.009 
 
16. Noori VJ, Eldrup-Jørgensen J. A systematic review of vascular closure devices for femoral 
artery puncture sites. Journal of vascular surgery. 2018;68(3):887-99. 10.1016/j.jvs.2018.05.019 
 
17. Vierhout BP, Pol RA, El Moumni M, Zeebregts CJ. Editor's Choice - Arteriotomy Closure 
Devices in EVAR, TEVAR, and TAVR: A Systematic Review and Meta-analysis of Randomised 
Clinical Trials and Cohort Studies. European journal of vascular and endovascular surgery : the 
official journal of the European Society for Vascular Surgery. 2017;54(1):104-15. 
10.1016/j.ejvs.2017.03.015 
 
18. Rigattieri S, Sciahbasi A, Brilakis ES, Burzotta F, Rathore S, Pugliese FR, et al. Meta-
Analysis of Radial Versus Femoral Artery Approach for Coronary Procedures in Patients With 
Previous Coronary Artery Bypass Grafting. The American journal of cardiology. 
2016;117(8):1248-55.10.1016/j.amjcard.2016.01.016 
 
19. Rigattieri S, Sciahbasi A, Ratib K, Alonzo A, Cox N, Chodor P, et al. Comparison Between 
Radial Approach and Femoral Approach With Vascular Closure Devices on the Occurrence of 
Access-Site Complications and Periprocedural Bleeding After Percutaneous Coronary 
Procedures: A Systematic Review and Meta-Analysis. The Journal of invasive cardiology. 
2016;28(12):473-9. 
 
20. Kiesz RS, Wiernek BK, Wiernek SL, Merritt C, Ybarra T, Iwanski A, et al. Cardiva Catalyst II 
vascular access management device in percutaneous diagnostic and interventional procedures 
with same-day discharge (Catalyst II trial). Journal of endovascular therapy : an official journal 
of the International Society of Endovascular Specialists. 2011;18(1):46-53. 10.1583/10-3237.1 
 
21. Aksoy M, Becquemin JP, Desgranges P, Allaire E, Kobeiter H. The safety and efficacy of 
angioseal in therapeutic endovascular interventions. European journal of vascular and 
endovascular surgery : the official journal of the European Society for Vascular Surgery. 
2006;32(1):90-3. 10.1016/j.ejvs.2005.12.014 
 
22. Albert B, Davaine JM, Chaillet MP, Grimandi G, Guyomarch B, Azema L, et al. Clinical and 
economic evaluation of ambulatory endovascular treatment of peripheral arterial occlusive 
lesions. Annals of vascular surgery. 2014;28(1):137-43. 10.1016/j.avsg.2013.06.008 
 
 
 

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Version: 3.0 / 31Jan2023                                                               
 
         
 
 
 
 
 
Page 60 of 66 
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23. Alshehri AM, Elsharawy M. Comparison of Angioseal and Manual Compression in Patients 
Undergoing Transfemoral Coronary and Peripheral Vascular Interventional Procedures. The 
International journal of angiology : official publication of the International College of Angiology, 
Inc. 2015;24(2):133-6.10.1055/s-0035-1547449 
 
24. Andrade PB, Mattos LA, Rinaldi FS, Bienert IC, Barbosa RA, Labrunie A, et al. Comparison 
of a vascular closure device versus the radial approach to reduce access site complications in 
non-ST-segment elevation acute coronary syndrome patients: The angio-seal versus the radial 
approach in acute coronary syndrome trial. Catheterization and cardiovascular interventions : 
official journal of the Society for Cardiac Angiography & Interventions. 2017;89(6):976-82. 
10.1002/ccd.26689 
 
25. Applegate RJ, Turi Z, Sachdev N, Ahmed A, Szyniszewski A, Foster M, et al. The Angio-
Seal Evolution registry: outcomes of a novel automated Angio-Seal vascular closure device. 
The Journal of invasive cardiology. 2010;22(9):420-6. 
 
26. Behan MW, Large JK, Patel NR, Lloyd GW, Sulke AN. A randomised controlled trial 
comparing the routine use of an Angio-Seal STS device strategy with conventional femoral 
haemostasis methods in a district general hospital. International journal of clinical practice. 
2007;61(3):367-72. 10.1111/j.1742-1241.2006.01229.x 
 
27. Brancheau D, Sarsam S, Assaad M, Zughaib M. Accelerated ambulation after vascular 
access closure device. Therapeutic advances in cardiovascular disease. 2018;12(5):141-4. 
10.1177/1753944718756604 
 
28. Burke MN, Hermiller J, Jaff MR. StarClose vascular closure system (VCS) is safe and 
effective in patients who ambulate early following successful femoral artery access closure--
results from the RISE clinical trial. Catheterization and cardiovascular interventions : official 
journal of the Society for Cardiac Angiography & Interventions. 2012;80(1):45-52. 
10.1002/ccd.23176 
 
29. Chen CP, Huang HK, Hsia CH, Chang YM, Lin LS, Lee CL. Short-Term Safety and Efficacy 
of Femoral Vascular Closure after Percutaneous Coronary Intervention with Combination of the 
Boomerang(TM) Device and Intravenous Protamine Sulfate. Acta Cardiologica Sinica. 
2013;29(6):531-8. 
 
30. Chodor P, Kurek T, Kowalczuk A, Swierad M, Was T, Honisz G, et al. Radial vs femoral 
approach with StarClose clip placement for primary percutaneous coronary intervention in 
patients with STelevation myocardial infarction. RADIAMI II: a prospective, randomised, single 
centre trial. Kardiologia polska. 2011;69(8):763-71. 
31. De Poli F, Leddet P, Couppie P, Daessle JM, Uhry S, Hanssen M. FemoSeal Evaluation 
Registry (FER). Prospective study of femoral arterial closure with a mechanical system on 100 
patients who underwent angioplasty procedures. Annales de cardiologie et d'angeiologie. 
2014;63(5):339-44.10.1016/j.ancard.2014.08.009 
 
32. Deuling JH, Vermeulen RP, Anthonio RA, van den Heuvel AF, Jaarsma T, Jessurun G, et al. 
Closure of the femoral artery after cardiac catheterization: a comparison of Angio-Seal, 
StarClose, and manual compression. Catheterization and cardiovascular interventions : official 
journal of the Society for Cardiac Angiography & Interventions. 2008;71(4):518-23. 
10.1002/ccd.21429 
 

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33. Fargen KM, Velat GJ, Lawson MF, Ritchie CA, Firment C, Hoh BL, et al. Occurrence of 
angiographic femoral artery complications after vascular closure with Mynx and AngioSeal. 
Journal of neurointerventional surgery. 2013;5(2):161-4. 10.1136/neurintsurg-2011-010217 
 
34. Fastner C, Behnes M, Unsal M, El-Battrawy I, Ansari U, Mashayekhi K, et al. Clinical 
outcomes of femoral closure compared to radial compression devices following percutaneous 
coronary intervention: the FERARI study. Heart and vessels. 2017;32(5):520-30. 
10.1007/s00380-016-0901-3 
 
35. Fujihara M, Haramitsu Y, Ohshimo K, Yazu Y, Izumi E, Higashimori A, et al. Appropriate 
hemostasis by routine use of ultrasound echo-guided transfemoral access and vascular closure 
devices after lower extremity percutaneous revascularization. Cardiovascular intervention and 
therapeutics. 2017;32(3):233-40. 10.1007/s12928-016-0409-x 
 
36. Goswami NJ, Smalling RG, Sinha S, Gammon RS, Ramaiah VG. Comparison of the 
boomerang wire vascular access management system versus manual compression alone 
during percutaneous diagnostic and interventional cardiovascular procedures: The boomerang 
wire vascular access management trial II. Catheterization and cardiovascular interventions : 
official journal of the Society for Cardiac Angiography & Interventions. 2016;87(1):75-81. 
10.1002/ccd.25842 
 
37. Heo YJ, Jeong HW, Baek JW, Lee SJ, Choo HJ, Jung HS, et al. Ultrasound Evaluation of 
Puncture Sites After Deployment of Two Different Types of Vascular Closure Devices: A 
Prospective Comparative Study. Cardiovascular and interventional radiology. 2018;41(11):1654-
63. 10.1007/s00270-018-2056-3 
 
38. Hermanides RS, Ottervanger JP, Dambrink JH, de Boer MJ, Hoorntje JC, Gosselink AT, et 
al. Closure device or manual compression in patients undergoing percutaneous coronary 
intervention: a randomized comparison. The Journal of invasive cardiology. 2010;22(12):562-6. 
 
39. Hermiller JB, Leimbach W, Gammon R, Karas SP, Whitbourn RJ, Wong SC, et al. A 
prospective, randomized, pivotal trial of a novel extravascular collagen-based closure device 
compared to manual compression in diagnostic and interventional patients. The Journal of 
invasive cardiology. 2015;27(3):129-36. 
 
40. Holm NR, Sindberg B, Schou M, Maeng M, Kaltoft A, Bottcher M, et al. Randomised 
comparison of manual compression and FemoSeal vascular closure device for closure after 
femoral artery access coronary angiography: the CLOSure dEvices Used in everyday Practice 
(CLOSE-UP) study. EuroIntervention: journal of EuroPCR in collaboration with the Working 
Group on Interventional Cardiology of the European Society of Cardiology. 2014;10(2):183-90. 
10.4244/eijv10i2a31 
 
41. Imam A, Carter RM, Phillips-Hughes J, Boardman P, Uberoi R. StarClose vascular closure 
device: prospective study on 222 deployments in an interventional radiology practice. 
Cardiovascular and interventional radiology. 2007;30(4):738-42. 10.1007/s00270-007-9079-5 
 
42. Jensen J, Saleh N, Jensen U, Svane B, Jonsson A, Tornvall P. The inflammatory response 
to femoral arterial closure devices: a randomized comparison among FemoStop, AngioSeal, 
and Perclose. Cardiovascular and interventional radiology. 2008;31(4):751-5. 10.1007/s00270-
008-9323-7 
 

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43. Jones LE, Yang KH, Feldtman RW, Uceda PV, Ferrara CA, Caruso JM, et al. Safety and 
Efficacy of Arterial Closure Devices in an Office-Based Angiosuite. Annals of vascular surgery. 
2018;51:10-7.10.1016/j.avsg.2018.02.011 
 
44. Kalsch HI, Eggebrecht H, Mayringer S, Konorza T, Sievers B, Sack S, et al. Randomized 
comparison of effects of suture-based and collagen-based vascular closure devices on post-
procedural leg perfusion. Clinical research in cardiology : official journal of the German Cardiac 
Society. 2008;97(1):43-8. 10.1007/s00392-007-0575-z 
 
45. Kara K, Kahlert P, Mahabadi AA, Plicht B, Lind AY, Longwitz D, et al. Comparison of 
collagen-based vascular closure devices in patients with vs. without severe peripheral artery 
disease. Journal of endovascular therapy : an official journal of the International Society of 
Endovascular Specialists. 2014;21(1):79-84. 10.1583/13-4401mr.1 
 
46. Kara K, Mahabadi AA, Berg MH, Kahlert P, Longwitz D, Erbel R, et al. Utilization of 
collagen-based vascular closure devices in patients with severe peripheral artery disease. The 
Journal of invasive cardiology. 2013;25(1):19-22. 
 
47. Ketterle J, Rittger H, Helmig I, Klinghammer L, Zimmermann S, Hohenforst-Schmidt W, et 
al. Comparison of Exo-Seal((R)) and Angio-Seal ((R)) for arterial puncture site closure: A 
randomized, multicenter, single-blind trial. Herz. 2015;40(5):809-16. 10.1007/s00059-015-4306-
3 
 
48. Klein-Wiele O, Baliota M, Kara K, Kaunicke M, Schafer H, Garbrecht M, et al. Safety and 
efficacy of clip-based vs. suture mediated vascular closure for femoral access hemostasis: A 
prospective randomized single center study comparing the StarClose and the ProGlide device. 
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac 
Angiography & Interventions. 2018;91(3):402-7.10.1002/ccd.27116 
 
local haemostasis with the AngioSeal® vascular closure device in peripheral endovascular 
interventions via 6-9F femoral artery access. 
Kardiologii Interwencyjnej. 2012;8(1):1-7. 10.5114/pwki.2012.27918 
 
50. Manolis AS, Georgiopoulos G, Stalikas D, Koulouris S. Simplified swift and safe vascular 
closure device deployment without a local arteriogram: Single center experience in 2074 
consecutive patients. Indian heart journal. 2016;68(4):529-38. 10.1016/j.ihj.2015.11.036 
 
51. Martin JL, Pratsos A, Magargee E, Mayhew K, Pensyl C, Nunn M, et al. A randomized trial 
comparing compression, Perclose Proglide and Angio-Seal VIP for arterial closure following 
percutaneous coronary intervention: the CAP trial. Catheterization and cardiovascular 
interventions: official journal of the Society for Cardiac Angiography & Interventions. 
2008;71(1):1-5. 10.1002/ccd.21333 
 
52. Minko P, Katoh M, Graber S, Buecker A. Obesity: an independent risk factor for insufficient 
hemostasis using the AngioSeal vascular closure device after antegrade puncture. 
Cardiovascular and interventional radiology. 2012;35(4):775-8. 10.1007/s00270-011-0230-y 
 
53. Rajan JE, Kannath SK, Sarma S, Kapilamoorthy TR. Prospective Evaluation of Factors 
Affecting the Safety and Efficacy of Perclose Proglide Vascular Closure Device in 
Neurovascular Interventions. Neurology India. 2019;67(5):1305-9. 10.4103/0028-3886.271252 
 

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Version: 3.0 / 31Jan2023                                                               
 
         
 
 
 
 
 
Page 63 of 66 
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54. Rashid MN, Ahmed B, Straight F, Bradley JT, Gilbert K, Gogo PB, et al. Extravascular 
closure for patients with high-risk femoral anatomy. The Journal of invasive cardiology. 
2008;20(7):328-32. 
 
55. Rastan A, Sixt S, Schwarzwalder U, Schwarz T, Frank U, Burgelin K, et al. VIPER-2: a 
prospective, randomized single-center comparison of 2 different closure devices with a 
hemostatic wound dressing forclosure of femoral artery access sites. Journal of endovascular 
therapy : an official journal of the International Society of Endovascular Specialists. 
2008;15(1):83-90. 10.1583/07-2253.1 
 
56. Ratnam LA, Raja J, Munneke GJ, Morgan RA, Belli AM. Prospective nonrandomized trial of 
manual compression and Angio-Seal and Starclose arterial closure devices in common femoral 
punctures. Cardiovascular and interventional radiology. 2007;30(2):182-8. 10.1007/s00270-006-
0226-1 
 
57. Rittger H, Schmidt M, Breithardt OA, Mahnkopf C, Brachmann J, Sinha AM. Cardio-
respiratory exercise testing early after the use of the Angio-Seal system for arterial puncture site 
closure after coronary angioplasty. EuroIntervention : journal of EuroPCR in collaboration with 
the Working Group on Interventional Cardiology of the European Society of Cardiology. 
2011;7(2):242-7. 10.4244/eijv7i2a39 
 
58. Sacherer M, Kolesnik E, von Lewinski F, Verheyen N, Brandner K, Wallner M, et al. Thermic 
sealing in femoral catheterization: First experience with the Secure Device. Cardiology journal. 
2019;26(3):233-40. 10.5603/CJ.a2018.0035 
59. Sato M, Matsumaru Y, Sakai N, Imamura H, Hirohata M, Takeuchi Y, et al. Usefulness of an 
accesssite hemostasis device in neuroendovascular treatment. Acta neurochirurgica. 
2017;159(12):2331-5. 10.1007/s00701-017-3299-5 
 
60. Sciahbasi A, Fischetti D, Picciolo A, Patrizi R, Sperduti I, Colonna G, et al. Transradial 
access compared with femoral puncture closure devices in percutaneous coronary procedures. 
International journal of cardiology. 2009;137(3):199-205. 10.1016/j.ijcard.2008.06.045 
 
61. Sekhar A, Sutton BS, Raheja P, Mohsen A, Anggelis E, Anggelis CN, et al. Femoral arterial 
closure using ProGlide(R) is more efficacious and cost-effective when ambulating early 
following cardiac catheterization. International journal of cardiology Heart & vasculature. 
2016;13:6-13. 10.1016/j.ijcha.2016.09.002 
 
62. Spiliopoulos S, Kitrou P, Christeas N, Karnabatidis D. Starclose SE(R) hemostasis after 6F 
direct antegrade superficial femoral artery access distal to the femoral head for peripheral 
endovascular procedures in obese patients. Diagnostic and interventional radiology (Ankara, 
Turkey). 2016;22(6):542-7. 10.5152/dir.2016.15614 
 
63. Tavris DR, Wang Y, Jacobs S, Gallauresi B, Curtis J, Messenger J, et al. Bleeding and 
vascular complications at the femoral access site following percutaneous coronary intervention 
(PCI): an evaluation of hemostasis strategies. The Journal of invasive cardiology. 
2012;24(7):328-34. 
 
64. Tay EL, Co M, Tai BC, Lee YP, Low A, Lim YT, et al. Clinical experience of StarClose 
vascular closure device in patients with first and recurrent femoral punctures. Journal of 
interventional cardiology. 2008;21(1):67-73. 10.1111/j.1540-8183.2007.00291.x 
 
 

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Page 64 of 66 
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Version 3.0 
 
 
65. Teblick A, Vanderbruggen W, Vandendriessche T, Bosmans J, Haine SEF, Miljoen H, et al. 
Comparison of radial access versus femoral access with the use of a vascular closure device for 
the prevention of vascular complications and mortality after percutaneous coronary intervention. 
Acta cardiologica. 2018;73(3):241-7. 10.1080/00015385.2017.1363947 
 
66. Veasey RA, Large JK, Silberbauer J, Paul G, Taggu W, Ellery S, et al. A randomised 
controlled trial comparing StarClose and AngioSeal vascular closure devices in a district general 
hospital--the SCOAST study. International journal of clinical practice. 2008;62(6):912-8.  
10.1111/j.1742-1241.2008.01761.x 
 
67. Wong HF, Lee CW, Chen YL, Wu YM, Weng HH, Wang YH, et al. Prospective comparison 
of angioseal versus manual compression for hemostasis after neurointerventional procedures 
under systemic heparinization. AJNR American journal of neuroradiology. 2013;34(2):397-401. 
10.3174/ajnr.A3226 
 
68. Wu PJ, Dai YT, Kao HL, Chang CH, Lou MF. Access site complications following 
transfemoral coronary procedures: comparison between traditional compression and angioseal 
vascular closure devices for haemostasis. BMC cardiovascular disorders. 2015;15:34. 
10.1186/s12872-015-0022-4 
 
69. Yeni H, Axel M, Ornek A, Butz T, Maagh P, Plehn G. Clinical and Subclinical Femoral 
Vascular Complications after Deployment of two Different Vascular Closure Devices or Manual 
Compression in the Setting of Coronary Intervention. International journal of medical sciences. 
2016;13(4):255-9. 10.7150/ijms.14476 
 
70. Tonolini M, Ierardi AM, Carrafiello G, Laganà D. Multidetector CT of iatrogenic and self-
inflicted vascular lesions and infections at the groin. Insights into imaging. 2018;9(4):631-42. 
10.1007/s13244-018-0613-6 
 
71. Cox T, Blair L, Huntington C, Lincourt A, Sing R, Heniford BT. Systematic Review of 
Randomized Controlled Trials Comparing Manual Compression to Vascular Closure Devices for 
Diagnostic and Therapeutic Arterial Procedures. Surgical technology international. 2015;27:32-
44. 
 
72. Robertson L, Andras A, Colgan F, Jackson R. Vascular closure devices for femoral arterial 
puncture site haemostasis. The Cochrane database of systematic reviews. 2016;3:Cd009541. 
10.1002/14651858.CD009541.pub2 
 
73. Jiang J, Zou J, Ma H, Jiao Y, Yang H, Zhang X, et al. Network Meta-analysis of Randomized 
Trials on the Safety of Vascular Closure Devices for Femoral Arterial Puncture Site 
Haemostasis. Scientific reports. 2015;5:13761. 10.1038/srep13761 
 
74. Resnic FS, Arora N, Matheny M, Reynolds MR. A cost-minimization analysis of the angio-
seal vascular closure device following percutaneous coronary intervention. The American 
journal of cardiology. 2007;99(6):766-70. 10.1016/j.amjcard.2006.10.032 
 
75. Ben-Dor I, Craig P, Torguson R, Rogers T, Buchanan KD, Pokharel S, et al. MynxGrip(R) 
vascular closure device versus manual compression for hemostasis of percutaneous 
transfemoral venous access closure: Results from a prospective multicenter randomized study. 
Cardiovascular revascularization medicine : including molecular interventions. 2018;19(4):418-
22. 10.1016/j.carrev.2018.03.007 
 

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76. Mallow P, Belk K, Carver C, Almedhychy A, editors. Use of Vascular Closure Devices in the 
Hospital Setting for Percutaneous Coronary Procedures and Gender Differences of the Mynx® 
Vascular Closure Device: Results from a Hospital Claims Analysis. International Society for 
Pharmacoeconomics and Outcomes Research (ISPOR) 23rd Annual International Meeting; 
2018; Baltimoare, MD, USA: Value in Health. 
 
77. Boschewitz JM, Andersson M, Naehle CP, Schild HH, Wilhelm K, Meyer C. Retrospective 
evaluation of safety and effectiveness of the EXOSEAL vascular closure device for single 
vascular closure and closure after repeat puncture in diagnostic and interventional radiology: 
single-center experience. Journal of vascular and interventional radiology : JVIR. 
2013;24(5):698-702. 10.1016/j.jvir.2013.02.014 
 
78. Boschewitz JM, Pieper CC, Andersson M, Nadal J, Schild HH, Meyer C. Efficacy and time-
to hemostasis of antegrade femoral access closure using the ExoSeal vascular closure device: 
a retrospective single-center study. European journal of vascular and endovascular surgery : the 
official journal of the European Society for Vascular Surgery. 2014;48(5):585-91. 
10.1016/j.ejvs.2014.08.006 
 
79. Grandhi R, Kanaan H, Shah A, Harrison G, Bonfield C, Jovin T, et al. Safety and efficacy of 
percutaneous femoral artery access followed by Mynx closure in cerebral neurovascular 
procedures: a single center analysis. Journal of neurointerventional surgery. 2014;6(6):445-50. 
10.1136/neurintsurg-2013-010749 
 
80. Grandhi R, Zhang X, Panczykowski D, Choi P, Hunnicutt CT, Jadhav AP, et al. Incidence of 
delayed angiographic femoral artery complications using the EXOSEAL vascular closure device. 
Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures 
and related neurosciences. 2015;21(3):401-6. 10.1177/1591019915581776 
 
81. Hackl G, Gary T, Belaj K, Hafner F, Rief P, Deutschmann H, et al. Exoseal for puncture site 
closure after antegrade procedures in peripheral arterial disease patients. Diagnostic and 
interventional radiology (Ankara, Turkey). 2014;20(5):426-31. 10.5152/dir.2014.14002 
 
82. Kara K, Mahabadi AA, Rothe H, Muller P, Kruger J, Neubauer H, et al. Safety and 
effectiveness of a novel vascular closure device: a prospective study of the ExoSeal compared 
to the Angio-Seal and ProGlide. Journal of endovascular therapy : an official journal of the 
International Society of Endovascular Specialists. 2014;21(6):822-8. 10.1583/14-4744mr.1 
 
83. Maxien D, Behrends B, Eberhardt KM, Saam T, Thieme SF, Reiser MF, et al. Evaluation of 
the 6-F ExoSeal vascular closure device in antegrade femoral artery punctures. Journal of 
endovascular therapy : an official journal of the International Society of Endovascular 
Specialists. 2012;19(6):836-43. 10.1583/jevt-12-3922r.1 
 
84. Pieper CC, Thomas D, Nadal J, Willinek WA, Schild HH, Meyer C. Patient Satisfaction After 
Femoral Arterial Access Site Closure Using the ExoSeal((R)) Vascular Closure Device 
Compared to Manual Compression: A Prospective Intra-individual Comparative Study. 
Cardiovascular and interventional radiology. 2016;39(1):21-7. 10.1007/s00270-015-1204-2 
 
85. Rimon U, Khaitovich B, Yakubovich D, Bensaid P, Golan G, Silverberg D. The Use of 
ExoSeal Vascular Closure Device for Direct Antegrade Superficial Femoral Artery Puncture Site 
Hemostasis. Cardiovascular and interventional radiology. 2015;38(3):560-4. 10.1007/s00270-
014-0984-0 
 

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86. Schelp V, Freitag-Wolf S, Hinzmann D, Bramlage P, Frey N, Frank D. Large-scale 
experience with an anchorless vascular closure device in a real-life clinical setting. Clinical 
research in cardiology : official journal of the German Cardiac Society. 2015;104(2):145-53. 
10.1007/s00392-014-0766-3 
 
87. Schmelter C, Liebl A, Poullos N, Ruppert V, Vorwerk D. Suitability of Exoseal vascular 
closure device for antegrade femoral artery puncture site closure. Cardiovascular and 
interventional radiology. 2013;36(3):659-68. 10.1007/s00270-012-0501-2 
88. Moher D, Pham B, Lawson ML, Klassen TP. The inclusion of reports of randomised trials 
published in languages other than English in systematic reviews. Health technology assessment 
(Winchester, England). 2003;7(41):1-90. 10.3310/hta7410