Randomized Trial Comparing Dual Perclose Vs Single Angioseal And Perclose in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement
Phase: NA
Conditions: Transcatheter Aortic Valve Replacement, Closure Technique
Sponsor: Baylor Research Institute

 
 
 
 
 
STUDY TITLE: 
RANDOMIZED TRIAL COMPARING DUAL PERCLOSE VS SINGLE 
ANGIOSEAL AND PERCLOSE IN PATIENTS UNDERGOING TRANSFEMORAL 
TAVR 
“TAVI-CLOSE” 
 
 
Protocol IRB #: 024-458 
 
PROTOCOL HISTORY 
 
Date: 
 
12/13/24 
 
 
Version: 
1.3 
 
Principal Investigator: 
 
Imran Baig, MD 
 
 
Sub-Investigator(s):                                      
 
 
Karim Al-Azizi, MD 
 
 
Statistician: 
 
Tsung-Wei Ma, PhD 
 
 
 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
2 
 
PROTOCOL SIGNATURE PAGE 
Study Title:   
Randomized trial comparing dual Perclose vs single Angioseal and Perclose in patients 
undergoing transfemoral TAVR  
TAVI-CLOSE 
 
Protocol Number:  N/A 
 
IRB Number: 024-458 
 
I have read this protocol and agree to adhere to the requirements outlined within. I will provide 
copies of this protocol and all pertinent information to the study personnel under my supervision. 
I will review and discuss this material with them and ensure they are fully informed regarding the 
requirements of this protocol. I will also ensure that this study is conducted in compliance with 
this protocol, Good Clinical Practice (GCP), and all applicable regulatory agencies and their 
requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator (Printed Name) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator (Signature) 
 
 
 
 
 
Date 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
3 
 
 
STUDY TEAM CONTACT INFORMATION 
 
Name 
Contact Information 
Role on Study 
Imran Baig, MD
Imran.Baig@BSWHealth.org
Primary Investigator
Karim Al Azizi, MD
Karim.AlAzizi@BSWHealth.org
Sub-Investigator
Tsung-Wei Ma, PhD
TsungWei.Ma@BSWHealth.org
Statistician
Sarah Hale 
Sarah.Hale@BSWHealth.org 
Research Manager 
Cody Dorton, DO
Cody.Dorton@BSWHealth.org
Research Fellow
Kyle McCullough, MD
Kyle.McCullough@BSWHealth.org
Research Fellow
Madhura Shah 
MadhuraKapil.Shah@BSWHealth.org 
Regulatory/ Other 
Research Associate
Bonnie Ostergren 
Bonnie.ostergren@BSWHealth.org 
Research Project 
Coordinator
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
4 
 
Table of Contents 
1 
TABLE OF CONTENTS ................................................................................................................ 4 
2 
LIST OF ABBREVIATIONS .......................................................................................................... 5 
3 
SYNOPSIS .................................................................................................................................... 6 
4 
INTRODUCTION ........................................................................................................................... 8 
4.1 
BACKGROUND .................................................................................................................................. 8 
5 
STUDY OBJECTIVES .................................................................................................................. 8 
6 
STUDY DESIGN ........................................................................................................................... 8 
7 
STUDY POPULATION .................................................................................................................. 9 
7.1 
ELIGIBILITY CRITERIA ...................................................................................................................... 9 
7.1.1 
Inclusion Criteria ............................................................................................................................. 9 
7.1.2 
Exclusion Criteria ...........................................................................................................................10 
8 
STUDY VISITS AND ACTIVITIES .............................................................................................. 10 
8.1 
SCREENING AND BASELINE ............................................................................................................. 10 
8.2 
ENROLLMENT ................................................................................................................................. 11 
8.3 
PROCEDURE/STUDY VISITS ............................................................................................................. 11 
8.4 
FOLLOW-UP .................................................................................................................................... 12 
8.5 
WITHDRAWAL FROM STUDY ........................................................................................................... 12 
9 
COMPENSATION ....................................................................................................................... 12 
10 
COSTS ........................................................................................................................................ 12 
11 
RISK AND BENEFIT TO PARTICIPANTS ................................................................................. 12 
11.1 
POTENTIAL BENEFITS ...................................................................................................................... 12 
11.2 
POTENTIAL RISKS ........................................................................................................................... 13 
11.2.1 
Physical Risks ................................................................................................................................13 
11.2.2 
Psychosocial and Privacy Risks .....................................................................................................13 
11.2.3 
Adverse Event Reporting ...............................................................................................................13 
12 
RISK/BENEFIT ASSESSMENT.................................................................................................. 14 
13 
STATISTICAL METHODS .......................................................................................................... 14 
13.1 
ANALYSIS OF PRIMARY OUTCOME .................................................................................................. 15 
13.2 
ANALYSIS OF SECONDARY OUTCOMES ............................................................................................ 15 
13.3 
EXPLORATORY OBJECTIVES ............................................................................................................ 15 
13.4 
SAMPLE SIZE ................................................................................................................................... 15 
13.5 
LOSS TO FOLLOW UP ....................................................................................................................... 15 
14 
PROCEDURES AND INSTRUCTIONS ...................................................................................... 15 
14.1 
PROTOCOL DEVIATIONS ................................................................................................................. 15 
14.2 
PROTOCOL AMENDMENTS ............................................................................................................... 15 
14.3 
RECORDING OF DATA, DOCUMENTATION, AND RETENTION OF DOCUMENTS ................................. 15 
14.4 
PUBLICATION OF RESULTS .............................................................................................................. 15 
14.5 
DISCLOSURE AND CONFIDENTIALITY.............................................................................................. 16  
15 
ETHICS AND GOOD CLINICAL PRACTICE ............................................................................. 16 
15.1 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE ............................................... 16 
15.2 
INFORMED CONSENT ....................................................................................................................... 16 
16 
REFERENCES ............................................................................................................................ 16 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
5 
 
ABBREVIATIONS 
Abbreviation 
Term 
 
 
 
 
TAVR 
Transcatheter Aortic Valve Replacement 
Perclose ProGlide 
PP 
AngioSeal 
AS 
Common Femoral Artery 
CFA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
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SYNOPSIS 
Summary/Rationale:  
This prospective, randomized, parallel controlled, single 
center, open-label, non-inferiority study will evaluate the 
safety and potential complications of dual ProGlide vs single 
ProGlide and Angioseal for common femoral arteriotomy 
closure following TAVR. 
Study Objectives: 
The primary objective of this study is to evaluate the safety 
and potential complications of dual ProGlide versus single 
ProGlide and Angioseal for common femoral arteriotomy 
closure in TAVR. 
Study Design: 
Single-center, randomized, parallel controlled, open-label, 
single center, non-inferiority study 
AoStudy 
Intervention(s): 
Randomization of subjects undergoing femoral arteriotomy to 
dual ProGlide suture closure devices versus closure with 
combination of single ProGlide and Angioseal device. 
Number of Subjects:  
90 
Inclusion Criteria: 
A patient will be eligible for inclusion in this study if he or 
she meets all of the following criteria:  
1.  Age ≥ 18 years old 
2.  Planned to undergo TAVR via femoral access 
     3.  Able to provide written informed consent  
Exclusion Criteria: 
A patient will be ineligible for inclusion in this study if he or 
she meets any of the following criteria:  
1. Nonfemoral access 
2. Previous repair or intervention of the common 
femoral artery 
3. Previous pseudoaneurysm of the common femoral 
artery 
4. Children below 18 years, prisoners, and patients 
who are unable to provide consent are excluded.
Sponsor: 
Baylor Scott and White Research Institute 
Principal Investigator: 
Imran Baig, MD 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
7 
 
Primary Study 
Site/Data Center: 
The Heart Hospital Baylor Plano  
1100 Allied Drive | 5th Floor Research Dept. 
Plano, Texas 75093 
Duration of Study: 
18-months 
 
 
 
 
 
 
 
 
4. 
 
INTRODUCTION 
4.1 
Background 
 Transcatheter aortic valve replacement (TAVR) is an established treatment option for patients 
with severe symptomatic aortic stenosis and is routinely performed through the transfemoral 
access route. Percutaneous access site closure is usually achieved using two pre-deployed 6F 
Perclose ProGlide (PP) sutures. Recent studies have supported the use of single PP plus 
AngioSeal (AS) as a safe and effective method for TAVR access closure [1,2,3,4]. Bazarbashi et 
al, from the Cleveland clinic performed a retrospective review evaluating the utilization of single 
PP versus double PP devices for transfemoral aortic valve replacement access closure [1]. They 
reported successful arteriotomy closure with the single PP plus AS in nearly 75% of cases. For 
the remaining 25%, only a single PP was necessary for closure. A recent randomized study by 
Rheude et al. In Germany showed decreased risk of bleeding events when using a single PP plus 
AS, randomized comparative studies are scarce, and there is a need for validating studies to 
confirm results from these small series within different populations, including in the United 
States (1,2,4,54). 
 
 
5.  
 
STUDY OBJECTIVES  
This study will examine the safety and efficacy of the single Perclose Proglide (PP) plus 
AngioSeal (AS) versus double PP for large bore access during TAVR. VARC-3 criteria will be 
utilized for vascular complications. The need for an additional closure device will be assessed. 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
8 
 
6.  
 
STUDY DESIGN 
This is a prospective, randomized, parallel controlled, open-label, single-center, non-inferiority 
clinical trial.   
Approximately 90 patients undergoing TAVR with femoral access will be randomized in a 1:1 
fashion to receive femoral access closure using either dual PP or single PP and AS for closure.  
The primary end point of this study is the composite endpoint of main access-related bleeding 
≥Type 2 and main access related major vascular complication. Secondary end points include 
periprocedural complications (such as acute vessel closure, leg embolization and perforation), 
procedural characteristics (total duration, fluoroscopy time, contrast volume, Length of hospital 
stay), and cost of hospitalization. A routine follow-up visit assessment will be performed at 30 
days in the valve clinic (± 15-day window) and the assessment will include: any clinical change, 
re-interventions, and peripheral pulse evaluation.  
 
7.  
 
STUDY POPULATION 
The study population will consist of approximately 90 patients undergoing TAVR with femoral 
access. 
7.1 
Eligibility Criteria 
7.1.1 Inclusion Criteria 
A patient will be eligible for inclusion in this study if he or she meets all of the following 
criteria:  
1.  Age ≥ 18 years old 
2.  Planned to undergo TAVR via femoral access 
3.  Able to provide written informed consent prior to study participation 
 
7.1.2  Exclusion Criteria  
A patient will be ineligible for inclusion in this study if he or she meets any of the following 
criteria:  
1. Non-femoral access 
2. Previous repair or intervention of the common femoral artery 
3. Previous pseudoaneurysm of the common femoral artery 
4. Children below 18 years, prisoners, and patients who are unable to provide consent are 
excluded. 
5. In another research study that has not granted permission to dual-enroll. 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
9 
 
8.  
 
STUDY VISITS AND ACTIVITIES 
8.1 
Screening and Baseline 
Consenting for study enrollment will follow standard procedures set by Baylor Scott & White 
Research Institute (BSWRI) IRB. The study team may perform consent procedures over the phone 
after a subject is mailed or emailed the consent form. Informed consent will include, but not be 
limited to, full understanding by the patient of study goals, procedures, risks, and endpoint. 
Subjects must meet the inclusion criteria and have none of the exclusion criteria in order to be 
eligible for participation in this study. 
Screening assessments will be collected through review of medical records and by interview 
after informed consent is signed. These screening evaluations may include: 
 Complete Medical History (including history of previous vascular or endovascular 
procedures) 
 Demographics 
 Physical exam 
 Vital signs 
 Relevant lab values already in the medical record (including CBC, BMP, PT/INR, 
clotting time, etc.) 
 Any and all relevant preoperative imaging studies (including echocardiogram, left or 
right heart catheterizations, angiograms, CT scans, MRI’s, PFT’s, ABI/PVR’s, ultrasound 
images, etc.) 
A subject is considered a screen-fail if they do not meet inclusion/exclusion criteria and/or 
withdraw before being randomized.  
 
8.2 
Enrollment 
Patients will be seen and evaluated in valve clinic. Once need for TAVR has been established, 
subjects will be consented for this study. Subjects will be randomized using the REDCap 
database. Due to need for procedural intervention, clinicians will not be able to be blinded. A 
patient is considered enrolled when consent is obtained and they have been randomized into a 
cohort. If a subject does not undergo a TAVR, the subject is withdrawn for the study. Subject 
enrollment will continue until 90 subjects are randomized and undergo a TAVR. If more than 90 
subjects are enrolled to meet this goal, a revision will be submitted to the IRB to increase 
enrollment. 
 
 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
10 
 
8.3  
Procedure/Study Visits 
Pre-Procedure Visit 
 
Patients requiring TAVR will be seen routinely in the THH Plano TAVR Clinic. At this time, a 
complete medical history is obtained including relevant medical conditions, demographics, exam 
findings, vitals, and relevant lab values as described above. Of note, the decision to undergo a 
TAVR will be made clinically prior to enrollment in this study. Data for the study will be 
collected for study purposes from the Electronic Health Record (EHR) only after informed 
consent is signed. Data collected from the EHR should be selected based on the most recent data 
prior to the TAVR and collected with 60 days of the procedure 
 
Randomization 
A subject will be randomized via a REDCap database prior to the routine TAVR. The study staff 
will communicate the randomization to the physicians on the case that will also need to be sub-
investigators on the study. The randomization and communication will be documented in the 
research chart. 
 
Procedure 
Patients will undergo the planned TAVR procedure. The procedure will be conducted in the 
manner deemed most appropriate by the clinician. Upon completion of valve replacement, 
closure will proceed based on the study protocol. One cohort will be closed using two PP 
devices, and the other closed using one PP and AS. A routine post-closure angiogram will be 
obtained to ensure adequate hemostasis. Operative reports and postoperative notes will be 
obtained and reviewed to obtain and measure the primary and secondary endpoints of the study. 
Primary endpoint collected will be composite endpoint of main access-related bleeding ≥Type 2 
and main access related major vascular complication (VARC 3 Criteria). Secondary endpoints 
will be periprocedural complications, acute vessel closure, embolization, and vessel perforation, 
procedural characteristics (duration, fluoroscopy time, contrast volume), length of hospital stay, 
and cost of hospitalization.  
 
In the event of inadequate hemostasis on the post-closure angiogram, operators will proceed as is 
clinically indicated. Options for subsequent closure could include prolonged pressure, balloon 
tamponade, covered stent application, or cutdown. If any intervention beyond the prescribed 
closure devices is required, this will be recorded as an additional endpoint. 
 
8.4 
 Follow-up 
Subject management post-procedure will proceed via standard institutional protocol. Subjects 
will have a follow-up visit 30-days post-procedure in the valve clinic (± 10-day window).  
Follow-up data documented at 30-days for research purposes will include: 
1. Any clinical change 
2. Any unplanned or planned re-interventions 
3. Peripheral pulse evaluation 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
11 
 
8.5  
 
Withdrawal from Study 
Subjects may voluntarily discontinue participation in the study at any time, for any reason. The 
Investigator also has the right to discontinue subjects from the study if he/she feels it is in the 
best interest of the subject. 
 
Schedule of Events 
Task/Procedure 
Routine 
or 
Research
Pre-
procedure
In-hospital 
procedure 
(Day 0) 
Discharge 
(+/-5 days)
Day 30 
(+/-15 
days) 
Pre-op procedures 
including imaging 
and blood draw 
Routine 
Data 
collection 
 
 
 
Pregnancy test (if 
applicable) 
Routine 
Data 
collection 
 
 
 
TAVR 
Routine 
 
Data 
collection 
 
 
Randomization to 
Single PP plus AS or 
Double PP 
Research 
 
X 
 
 
Single PP plus AS 
and Double PP 
Routine 
 
Data 
collection 
 
 
Angiogram 
Routine 
 
Data 
collection 
 
 
Clinic Visit 
Routine 
 
 
 
Data 
collection
Chart Review/ 
Data Collection 
Research 
X 
X 
X 
X 
KEY 
+ = plus 
- = minus 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
12 
 
9. 
 
COMPENSATION 
Participants will not receive any compensation for participating in this study. 
 
10. 
 
COSTS 
Participants will not incur any additional research-related costs due to study participation. 
Subject or their insurance company will be required to pay for all expenses related to regular care 
including procedure and other hospital care.  
 
11. 
 
RISK AND BENEFITS TO PARTICIPANTS 
11.1.  
Potential Benefits 
There is no guarantee of direct benefit to the subjects who participate in this study. There is a 
possibility that closure with a single PP and AS device will decrease the cost of procedure. 
Future patients may benefit from the knowledge gained. 
 
11.2 
 
Potential Risks 
11.2.1 Physical Risks 
 Possible risks a potentially increased risk of bleeding events based on treatment group, however 
the data to suggest an increased risk based on closure type is minimal and unconfirmed. Other 
risks include those common to patients undergoing a TAVR without being included in the study. 
These risks include femoral artery dissection, pseudoaneurysm, thrombosis, stricture, access site 
seroma, hematoma, infection, abscess, embolization of endovascular devices. 
 
11.2.2  
Psychosocial & Privacy Risks 
Any time information is collected there is a potential for loss of confidentiality. Every effort will 
be made to keep participant’s information confidential, however this cannot be guaranteed. 
Participation in research study may make participants feel uncomfortable. Participants will be 
informed that they may refuse to participate or stop their participation at any time without effect 
on future medical treatment or relationship with the treating physician. 
 
11.2.3  
Reproductive Risks  
Women that are pregnant or think they may be pregnant, cannot take part in this study as the 
radiation involved may endanger the fetus. For women of child-bearing potential, a pregnancy 
test will be performed. All subjects of childbearing potential will need to have a blood serum 
pregnancy test which includes collecting 1-2 mL of blood. A urine pregnancy test is not as 
sensitive as a blood pregnancy test and a negative urine test does not completely rule out an early 
pregnancy in progress. 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
13 
 
11.2.4 Adverse Event Reporting 
An Adverse Event (AE) is any untoward sign, symptom or medical condition occurring at any 
time after the subject receives his/her procedure, even if the event is not considered to be related 
to the study. Since this study is collecting information on routine procedures, we are seeking a 
waiver from the IRB to only collect Adverse Events related to the primary and secondary 
endpoints listed in section 13.1 and 13.2. These vascular events would include: 
 Aortic dissection or aortic rupture 
 Vascular (arterial or venous) injury (perforation, rupture, dissection, stenosis, ischaemia, 
arterial or venous thrombosis including pulmonary embolism, arteriovenous fistula, 
pseudoaneurysm, haematoma, retroperitoneal haematoma, infection) or compartment 
syndrome resulting in death, VARC type ≥2 bleeding, limb or visceral ischaemia, or 
irreversible neurologic impairment 
 Distal embolization (non-cerebral) from a vascular source resulting in death, amputation, 
limb or visceral ischaemia, or irreversible end-organ damage 
 Unplanned endovascular or surgical intervention resulting in death, VARC type ≥2 
bleeding, limb or visceral ischaemia, or irreversible neurologic impairment 
 Closure device failure resulting in death, VARC type ≥2 bleeding, limb or visceral 
ischaemia, or irreversible neurologic impairment 
 Vascular (arterial or venous) injury (perforation, rupture, dissection, stenosis, ischaemia, 
arterial or venous thrombosis including pulmonary embolism, arteriovenous fistula, 
pseudoaneurysm, haematoma, retroperitoneal haematoma, infection) not resulting in 
death, VARC type ≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic 
impairment 
 Distal embolization treated with embolectomy and/or thrombectomy, not resulting in 
death, amputation, limb or visceral ischaemia, or irreversible end-organ damage 
 Any unplanned endovascular or surgical intervention, ultra-sound guided compression, or 
thrombin injection, not resulting in death, VARC type ≥2 bleeding, limb or visceral 
ischaemia, or irreversible neurologic impairment 
 Closure device failure not resulting in death, VARC type ≥2 bleeding, limb or visceral 
ischaemia, or irreversible neurologic impairment 
 
Adverse events will be monitored and reported from the start of the study procedure until 30-
days after the index procedure. Investigator or Sub-Investigator will assess all AEs/SAEs for 
severity and relatedness to study intervention. 
A Serious Adverse Event (SAE) is an undesirable sign, symptom or medical condition which: 
 is fatal  
 is life threatening 
 requires or prolongs hospitalization 
 results in persistent or significant disability/incapacity  
 constitutes a congenital anomaly or a birth defect 
 is medically significant, in that it may jeopardize the subject and may require medical or 
surgical intervention to prevent 1 of the outcomes listed above 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
14 
 
 Hospitalizations not necessarily considered to be SAEs are hospitalizations for:  
o treatment, which was elective or preplanned, for a pre-existing condition that did 
not worsen 
o treatment on an emergency, outpatient basis for an event not fulfilling any of the 
definitions of serious given above and not resulting in hospital admission  
Only SAEs in the above listed AE categories will be collected and submitted. A death and its 
cause will always be collected and reported.  All applicable SAEs will be followed up until 
resolution or permanent outcome of the event.  
All AEs will be reported to IRB at the yearly continuing review of study.   
SAEs and AEs will be entered on an AE log in the patient binder. 
 
12. 
RISK/BENFIT ASSESSMENT 
Large bore access for TAVR procedures requires percutaneous closure devices. Common 
practice is use of dual PP devices prior to upsizing the catheter (preclosure). Emerging data 
shows that use of a single PP device to decrease the size of the arteriotomy and subsequent 
placement of an AS collagen plug device has no difference in complication rate, and some have 
reported decreased rate of femoral artery stenosis. Reported risk of bleeding in second generation 
TAVR valve is 7.5%6, access site infection is 2%7, and risk of device failure is 4.4%-8.7%8. 
 
13.  
 
STATISTICAL METHODS 
13. Statistical Methods 
Kolmogorov–Smirnov tests and Q-Q plot will be used to test normality of continuous variables. 
For descriptive statistics, continuous variables with normal distribution will be presented as 
mean with standard deviation, continuous variables without normal distribution will be presented 
as median with first and third quartile, and categorical variables will be presented as frequencies 
with counts. To compare patient demographics factors, procedural characteristics, and secondary 
outcomes between study groups, two-sample t-test will be applied to continuous variables with 
normal distribution, Wilcoxon rank-sum test will be applied to continuous variables without 
normal distribution, and chi-square test or Fisher’s exact test will be applied to categorical 
variables. A significant level of 5% will be utilized throughout the study unless otherwise. 
Unpooled Z test will be used to evaluate if success (free of primary end point) rate of one PP 
plus one AS is non-inferior to dual PP devices. Non-inferiority test is a one-sided test; thus 2.5% 
significance level will be used. 
 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
15 
 
13.1 Analysis of Primary Outcome 
Primary outcome of this study is a composite endpoint of main access-related bleeding and main 
access related major vascular complication. We will define vascular complication according to 
the VARC-3 criteria. This includes the following: 
 
 Major- One of the following: 
o Aortic dissection or aortic rupture 
o Vascular (arterial or venous) injury (perforation, rupture, dissection, stenosis, 
ischaemia, arterial or venous thrombosis including pulmonary embolism, 
arteriovenous fistula, pseudoaneurysm, haematoma, retroperitoneal haematoma, 
infection) or compartment syndrome resulting in death, VARC type ≥2 bleeding, 
limb or visceral ischaemia, or irreversible neurologic impairment 
o Distal embolization (non-cerebral) from a vascular source resulting in death, 
amputation, limb or visceral ischaemia, or irreversible end-organ damage 
o Unplanned endovascular or surgical intervention resulting in death, VARC type 
≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic impairment 
o Closure device failure resulting in death, VARC type ≥2 bleeding, limb or 
visceral ischaemia, or irreversible neurologic impairment 
 Minor- One of the following: 
o Vascular (arterial or venous) injury (perforation, rupture, dissection, stenosis, 
ischaemia, arterial or venous thrombosis including pulmonary embolism, 
arteriovenous fistula, pseudoaneurysm, haematoma, retroperitoneal haematoma, 
infection) not resulting in death, VARC type ≥2 bleeding, limb or visceral 
ischaemia, or irreversible neurologic impairment 
o Distal embolization treated with embolectomy and/or thrombectomy, not resulting 
in death, amputation, limb or visceral ischaemia, or irreversible end-organ 
damage 
o Any unplanned endovascular or surgical intervention, ultra-sound guided 
compression, or thrombin injection, not resulting in death, VARC type ≥2 
bleeding, limb or visceral ischaemia, or irreversible neurologic impairment 
 Closure device failure not resulting in death, VARC type ≥2 bleeding, limb or visceral 
ischaemia, or irreversible neurologic impairment 
o  
 
13.2 Analysis of Secondary Outcomes 
The following secondary outcome measures will be monitored 
 Need for secondary closure device 
 Periprocedural complications: 
o Acute vessel closure 
o Leg embolization 
o Vessel perforation/dissection 
 Procedural characteristics 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
16 
 
o Total duration 
o Fluoroscopy time 
o Contrast volume 
 Length of hospital stay 
 Cost of hospitalization 
These will be obtained primarily by chart review. Interview with patient will be used as 
necessary to obtain further information. 
 
13.3 Sample Size 
Un-pooled Z test is utilized to test if success (free of primary end point) rate of one Perclose 
ProGlide (PP) plus one AngioSeal (AS) is non-inferior to dual PP devices. Based on a study by 
Gmeiner et al. [4], success (free of primary end point) rate is 0.73 and 0.46 with one PP plus one 
AngioSeal (AS) and dual PP devices, respectively. 
To achieve 85% statistical power and keep one-sided type I error as 2.5%, and an equivalence 
margin of 5%, a sample size of n= 40 per group is required to detect if one PP plus one AS is 
non-inferior to dual PP devices. After adjusting for 10% dropout rate, a sample size of n=45 per 
group is required. The total sample size should be 90 if patients are randomized 1:1 to both 
groups. 
 
13.4 Loss to Follow-up 
Subjects lost to follow-up will be excluded from the analyses. Demographics and baseline 
characteristics will be compared between included and lost-to-follow-up subjects. 
 
13.5 Interim Analysis 
Once half of the patients have been enrolled and completed the study, an interim analysis will be 
conducted with the goal of monitoring safety and presence of adverse events. 
 
14. 
 
PROCEDURES AND INSTRUCTIONS 
14.1 Protocol Deviations 
Deviations from this protocol will be reported to the IRB in the following manner: 
 Unplanned deviations that do not increase the potential risk of the subject will be reported 
to the IRB at the Continuing Review 
 Unplanned deviations that do have the potential of increasinig the risk of the subject will 
be reported to the IRB within 10 days of the deviation or becoming aware of the 
ocurrence. 
 Emergency planned deviations (under the control of the research team), the study team 
will email the IRB within 24 hours of implementation and then the study team will send a 
report to the IRB within 10 days of implementation. 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
17 
 
 Non-emergency planned deviations (under the control of the research team), the study 
team will report it to the IRB before implementation. 
Study staff will keep a study specific protocol deviation log for tracking of all protocol 
deviations throughout the trial. 
 
14.2 
  
Protocol Amendments  
Any substantive changes will be made as formal amendments to the protocol and will be 
submitted for appropriate review by the institutional review board (IRB). 
These requirements for approval should in no way prevent any immediate action from being 
taken by the Investigator to ensure the safety of all subjects included in the study. 
 
14.3   
Recording of Data, Documentation, and Retention of Documents 
Data will be stored and evaluated in such a way as to guarantee subject confidentiality in 
accordance with the legal stipulations applying to confidentiality of data. All study records must 
be available for inspection by the Sponsor (BSWRI), its authorized representatives, the FDA and 
other regulatory authorities. 
Data on subjects collected for research purposes will be done securely and electronically on the 
BSWH REDCap system. A patient ID will be assigned and only approved research staff will 
have access to the study database. 
The Investigator must maintain source documents for each subject in the study including a copy 
of the signed ICF.  
 
14.4   
Publication of Results  
An integrated clinical and statistical report will be prepared at the completion of the treatment 
period. It is intended that the results of the study will be included on http://clinicaltrials.gov (if it 
is an applicable study) and published and/or presented at scientific meetings.  
 
14.5   
Disclosure and Confidentiality 
The Investigator must assure that subjects’ anonymity will be maintained and that their identities 
are protected from unauthorized parties. The Investigator will keep a subject enrollment log 
relating codes to the names of subjects. The Investigator should maintain documents not for 
submission to the Sponsor (Baylor Scott & White Research Institute), e.g., subjects’ signed 
consent forms, in strict confidence. 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
18 
 
14.6   
Monitoring Plan 
A member of the QA team will review the study at the following timepoints: 
1. Within 30 business days of the 1st patient enrollment 
2. After 50% enrollment 
3. After 100% enrollment or nearing study closure 
 
15.  
 
ETHICS AND GOOD CLINICAL PRACTICE 
15.1  Institutional Review Board/Independent Ethics Committee 
Before implementing this study, the protocol, the proposed informed consent form and other 
information to subjects will be reviewed by the BSWRI IRB. The Investigators will not begin 
any study subject activities until approval from the IRB has been documented and provided as a 
letter to the Investigator. Before implementation, the Investigators will submit to and receive 
documented approval from the IRB of any modifications made to the protocol or any 
accompanying material to be provided to the subject after initial IRB approval, with the 
exception of those necessary to reduce immediate risk to study subjects. 
 
15.2  Informed Consent 
Each subject will be informed that participation in the study is voluntary, that he/she may 
withdraw from the study at any time, and that withdrawal of consent will not affect his/her 
subsequent medical treatment or relationship with the treating physician. 
This informed consent should be given by means of a standard written statement, written in 
nontechnical language. The study team may perform consent procedures over the phone after a 
subject is mailed or emailed the consent form.  The subject should read and consider the 
statement before signing and dating it (wet ink or DocuSign), and should be given a copy of the 
signed document. No subject can enter the study before his/her informed consent has been 
obtained. 
 
 
 
 
 
 
 
 

PI: Dr. Baig 
[12/13/24, version no. 1.3] 
IRB#  
024-458 
 
 
19 
 
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