A Randomized Comparison of Percutaneous Closure to Manual Compression for Hemostasis of Multiple Venous Access Sites Among Patients Undergoing Catheter Ablation for Atrial Fibrillation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Michael S. Lloyd

A RANDOMIZED COMPARISON OF PERCUTANEOUS CLOSURE TO MANUAL 
COMPRESSION FOR HEMOSTASIS OF MULTIPLE VENOUS ACCESS SITES AMONG 
PATIENTS UNDERGOING CATHETER ABLATION FOR ATRIAL FIBRILLATION 
NCT04180540 
Date: December 12, 2019 
IRB00115958 

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Full Study Title: A randomized comparison of percutaneous closure to manual compression for 
hemostasis of multiple venous access sites among patients undergoing catheter ablation for atrial 
fibrillation.
Short Study Title: PerClose Proglide
Emory University Investigator: 
Michael Lloyd, MD, Associate Professor of Medicine-Cardiology, Emory School of Medicine

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Introduction/Backround:
Radiofrequency ablation for treatment of atrial fibrillation (AF) using percutaneous venous 
access at the groin is one of the most common procedures performed by cardiac 
electrophysiologists1.  However, compared to other catheter-based interventions, patients 
undergoing AF ablation pose a unique set of challenges.  First, AF ablation requires multiple 
points of transfemoral venous access with large diameter sheaths, ranging in size from 8F to 14F 
for cryoablation procedures.  Second, operators are forced to balance the competing risk of 
thrombosis and bleeding in these patients.  In order to minimize the risk of intraprocedural 
thrombosis, anticoagulation with heparin with a goal anticoagulation time (ACT) >300-350 
seconds is necessary2.  However, operators typically require ACTs to normalize prior to removal 
of sheaths and manual compression, which significantly delays hemostasis and ambulation.  
While reversal agents are an option, there is currently clinical equipoise on their role and safety 
in this setting3 and they require additional time to exert their full effect.  Lastly, patients require 
at least 1-2 months of therapeutic oral anticoagulation after the procedure to mitigate ongoing 
stroke risk1.  These factors culminate in longer times to hemostasis and ambulation and raise 
concerns for post-procedure access related complications for patients undergoing AF ablation.  
PerClose ProglideTM has recently gained FDA approval for closure of percutaneous venous 
access sites for catheter-based interventions and remains the only commercially available 
solution for access sites >14F inner diameter.  Percutaneous closure of venotomy sites may 
facilitate rapid hemostasis without the need for reversal of anticoagulation, potentially 
attenuating bleeding risk.  Additionally, typical bedrest times after percutaneous closure are 
based on data derived from arterial closure.  Prior limited data4, as well as frequent anectodical 
reports, have suggested that earlier ambulation may be feasible.  Because the venous circulation 
is a lower pressure system, it is possible that earlier than standard ambulation times after 
PerClose is both safe and feasible.  However, a rigorous prospective investigation of the 
PerClose ProglideTM device in the context of AF ablation has not been performed. 
Objectives/Hypotheses: 
We hypothesize that, among patients undergoing ablation for AF, percutaneous closure of access 
sites with PerClose ProglideTM will lead to shorter times to hemostasis as compared to manual 
compression.  Our secondary hypothesis is that patients undergoing PerClose after AF ablation, 
will be able to safely ambulate at one hour, as opposed to two hours, after hemostasis.  We will 
also evaluate several other secondary endpoints comparing those undergoing PerClose to those 
undergoing manual hemostasis including: frequency of access site related complications, pain 
and need for post-procedure narcotics, patient satisfaction, as well as cost and overall resource 
utilization.  
Research Design:
The study will occur in patients undergoing routine ablation for atrial fibrillation as standard of 
care.  This is a prospective randomized trial.  Patients will be randomized (see Randomization) in 
a 1:1 ratio to either manual compression or use of the PerClose for hemostasis at the end of the 
ablation procedure.  Based on our clinical experience, we estimate the PerClose procedure for 3 
access sites will require ~3 minutes of additional procedure time.  In our experience, hemostasis 
is typically immediate (<1 minute to lock all three sutures) and this corroborated in the available 
literature5.  Prior published data for manual compression with figure-of-eight sutures are reported 
as 7.9 minutes6.  We also intend to have a secondary treatment arm in which post-hemostasis 

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ambulation time will be one hour (currently, the standard is two hours after vascular closure). 
The length of follow-up will be up to 30 days at routine clinical follow-up after the procedure.  
Patient Selection:
Study patients will be recruited among all patients older than 18 years old undergoing elective 
atrial fibrillation ablation at Emory University Hospital, Emory University Hospital Midtown, or 
Emory St. Joseph’s Hospital.  Exclusion criteria are: 1) women who are pregnant (based on 
standard pre-procedure pregnancy test); 2) patients who are not able to ambulate pre-procedure; 
or 3) patients who are unable to provide informed consent.   
Pilot Cohort:
In order to demonstrate feasibility, we propose an initial pilot cohort of 50 patients (25 patients 
in each group).  The purpose of this cohort is to demonstrate feasibility of patient enrollment, 
data collection, and produce initial pilot data.  This cohort is not anticipated to be sufficiently 
powered to evaluate the primary endpoint definitively.  However, it is likely than any trends in 
data would become apparent with a cohort of this size. 
Full Study Cohort:
Based on these estimates, we preliminarily calculated a sample size of 100 patients (50 in each 
arm, including the pilot cohort) to achieve an alpha-level of 0.05 with a beta-level of 0.2 (power 
of 80%).   We would argue for a goal of approximately 65 patients in each arm to account for 
loss to follow up at the 30-day period, for a goal total of 130 patients enrolled.   
Data to be collected:
Baseline Clinical Information:
Routine baseline clinical characteristics including preprocedural oral anticoagulation regimen, 
antiplatelet regimen, and INR for those on warfarin therapy as are routinely collected as part of 
standard care. 
Procedural data will include:

Time to hemostasis

Case length (routinely collected)

Anticoagulation time (ACT) at the completion of the case prior to sheath pull (routinely
collected)

Success rate of PerCloseTM deployment and number of PerCloseTM devices used.

Success rate of hemostasis with manual compression or “figure-of-eight” suture.
Post procedural data collected will include:

Time to ambulation after ablation

Major and minor* access related complications prior to discharge, at 48 hours, and at 30
day follow up appointment:
o
Superficial bruising
o
Hematoma
o
Retroperitoneal bleeding
o
Hemorrhage of any kind
o
Need for transfusion of blood products

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o
Pain (see below).
o
Presence of post-procedure venous thromboembolism
*A major complication would be defined as the following: management, at the discretion
of the treating physician, requiring direct procedural or medical intervention (other than 
observation) for any complication noted above. 

Groin access site pain as measured by:
o
A 10-point visual analog scale (0 = none; 10 = worst imaginable) on discharge, as
validated in the PEVAR trial7, and is already routinely used at our institution.
o
By short form inguinal pain questionnaire on 30-day follow up8.
o
Opiate medication requirement prior to discharge (total dosage to be standardized
to milligrams of morphine).
o
Opiate medication prescription on discharge (binary).

Economic and cost data related to:
o
The cost of the PerClose devices used.
o
Ancillary resource utilization (i.e. devices used for hemostasis, sutures for “figure
of eight”, cost of protamine for heparin reversal if used)
o
Length of stay
o
Post-procedure area time
o
Access site complication related cost including imaging required for workup and
any interventions for management including medications administered or
procedure charges.

Nursing utilization (number of nursing encounters while in the post procedure area
[routinely collected]).
Randomization:
Patients will be randomized in two one of two groups: those undergoing percutaneous closure 
with PerCloseTM and those with manual compression (manual hemostasis with, or without 
“figure of eight” suture6 for hemostasis at the discretion of the treating physician).  Patients will 
be randomized in a 1:1 ratio to groups and stratified on sex to ensure equal proportions of males 
and females in both groups.  Block randomization with block sizes of 6 will be used.  Blocks will 
be generated as needed using a computer model.  In the PerClose arm, patients will be 
randomized secondarily in 1:1 fashion as either standard ambulation (2 hours bed rest) or early 
ambulation (1-hour bedrest) after hemostasis.  
Informed Consent:
Following education on the study protocol, patients will be offered the option to enroll. Informed 
consent will be obtained by approved research personnel in a private area. If the patient agrees to 
participate, consent will be documented. Consent will occur the day of the scheduled ablation 
procedure.  
Compensation for time and effort:
There is no compensation for participation in this study as there are no additional expenses and 
time requirement beyond standard of care.
Risks/Benefits:

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The most common risks and discomforts expected in this study are rare but possible: 
development of a blood clot in the leg (less than 1%), bleeding (less than 1%) or a large bruise 
called a hematoma at the IV site (less than 1%). 
Possible benefits, although unproven, may include less time in the post-procedure area and the 
ability to walk sooner after the ablation procedure.  This study is designed to learn more about 
the use of percutaneous closure with the PerClose ProglideTM after atrial fibrillation ablation. The 
study results may be used to help others in the future.
Data Analysis:
The primary endpoint of the study will be time to hemostasis (starting from sheath pull) in 
minutes for the PC and MC groups.   The secondary endpoints will include: 1) time to 
ambulation in minutes, 2) a composite of all major access site complications and venous 
thromboembolism, 3) each individual outcome comprising the composite outcome, 4) minor 
complications, 5) quality of life metrics (as measured by the inguinal pain questionnaire), 6) 
procedure length in minutes, 7) patient satisfaction , 8) pain medication requirement after 
hemostasis until discharge from the post-procedure area, 9) overall cost comparison related to 
hemostasis and complications over 30 days, 10) number of nursing encounters while in the post-
procedure area.  We will also compare all secondary endpoints between the primary and 
secondary treatment arms. Access related complications include: hematoma, hemorrhage, 
retroperitoneal bleeding, pseudoaneurysm, arteriovenous fistula, or access site infection.  
Thromboembolism will include any arterial or venous thromboembolism that are clinically overt.  
Major complications will be defined as any of the above pre-specified complications that require 
direct procedural intervention (surgical or percutaneous repair), placement of an external 
compression hemostatic device (i.e. pneumatic compression dressing or femoral compression 
device), or medical therapy (including, but not limited to transfusion, reversal of anticoagulation, 
or initiation of other new medical therapy).  Minor complications will include any complication 
that does not require any intervention beyond observation. 
Normality of distribution of continuous variables will be tested using the Shapiro-Wilk test.  
Comparisons of continuous baseline variables across groups will be performed using Student’s t 
and Mann-Whitney U tests for normally and non-normally distributed data, respectively.  
Comparison of categorical variables will be performed using Chi-squared and Fisher’s Exact 
tests for binary categorical variables where appropriate, and Mann-Whitney U test for ranked 
ordinal level variables.  Complication-free survival will be evaluated using Kaplan-Meier 
analysis, with separate strata for patients in each group.  Patients will be censored at the time of 
their last confirmed encounter or at the completion of the follow up time of the study.  All 
analyses will be performed using IBM SPSS ver. 25 (2017; IBM SPSS Statistics for Macintosh, 
Version 25.0. Armonk, NY: IBM Corp).
Safety analysis:
Safety assessments will consist of monitoring and recording all adverse events and serious 
adverse events. While they are not anticipated, adverse events will be summarized using the 
frequency of subjects for each level.
Data and Safety Monitoring and Reporting:

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Oversight of the progress and safety of the trial will be provided by the PI. Adverse events are 
not anticipated, but any occurring will be reported to Emory IRB policies and procedures.
Confidentiality: 
Patients will be assigned an identifier number. Data will be stored on a secure drive supported by 
Emory healthcare. Only pertinent members of Emory Healthcare/ SOM who have undergone 
HIPAA training will have access to the spreadsheet. PHI information including the informed 
consent forms will be stored in a locked space in the PI’s office. 
REFERENCES:
1.
Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE
expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart
Rhythm. 2017;14(10):e275-e444.
2.
Winkle RA, Mead RH, Engel G, Patrawala RA. Safety of Lower Activated Clotting
Times During Atrial Fibrillation Ablation Using Open Irrigated Tip Catheters and a
Single Transseptal Puncture. American Journal of Cardiology. 2011;107(5):704-708.
3.
Use of Protamine for Heparin Reversal After Catheter Ablation of Atrial Fibrillation.
4.
Sekhar A, Sutton BS, Raheja P, et al. Femoral arterial closure using ProGlide(R) is more
efficacious and cost-effective when ambulating early following cardiac catheterization.
Int J Cardiol Heart Vasc. 2016;13:6-13.
5.
Mahadevan VS, Jimeno S, Benson LN, McLaughlin PR, Horlick EM. Pre-closure of
femoral venous access sites used for large-sized sheath insertion with the Perclose device
in adults undergoing cardiac intervention. Heart. 2008;94(5):571-572.
6.
Payne J, Bickel T, Gautam S. Figure-of-eight sutures for hemostasis result in shorter lab
recovery time after ablation for atrial fibrillation. Pacing Clin Electrophysiol. 2018.
7.
Nelson PR, Kracjer Z, Kansal N, et al. A multicenter, randomized, controlled trial of
totally percutaneous access versus open femoral exposure for endovascular aortic
aneurysm repair (the PEVAR trial). J Vasc Surg. 2014;59(5):1181-1193.
8.
Olsson A, Sandblom G, Franneby U, Sonden A, Gunnarsson U, Dahlstrand U. The Short-
Form Inguinal Pain Questionnaire (sf-IPQ): An Instrument for Rating Groin Pain After
Inguinal Hernia Surgery in Daily Clinical Practice. World J Surg. 2019;43(3):806-811.