A Prospective Post Market Study of Patients With Symptomatic Benign Prostatic Hyperplasia Treated by Prostatic Artery Embolization With Embosphere® Microspheres
Conditions: Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms
Sponsor: Merit Medical Systems, Inc.



 
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INVESTIGATOR PROTOCOL SIGNATURE PAGE 
 
STUDY TITLE: 
A Prospective Post Market Study of Patients with Symptomatic 
Benign Prostatic Hyperplasia treated by Prostatic Artery 
Embolization with Embosphere® Microspheres  
 
PROTOCOL # & 
VERSION: 
PAE-P4-17-01 
4.0 
STUDY CENTER 
NAME & SITE 
NUMBER: 
 
_____________________________________________ 
(Print name & number of study center) 
 
I, the undersigned, have read and understand the protocol specified above and agree with its 
content. I agree to perform and conduct the study as described in the protocol. In addition, 
when applicable, I agree to enlist sub-investigators who also agree to perform and conduct 
the study as described in the protocol. I will provide copies of this protocol and all pertinent 
information to the Study personnel under my supervision and my hospital Institutional 
Review Board/Ethics Committee. I will discuss this material with them and ensure they are 
fully informed regarding the Merit Medical Systems investigational device and the conduct of 
the study according to Good Clinical Practice (GCP), Declaration of Helsinki, 21 CFR Parts 
50, 54, and 56, ISO 14155:2020 and any local regulations. 
 
___________________________________________________________________ 
SITE PI – Print Name 
 
___________________________________________________________________ 
SITE PI – Signature 
 
_______________________ 
DATE 
 
 
 
 

 
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Table of Contents 
1 
Introduction ........................................................................................................................ 5 
2 
Study Rationale .................................................................................................................. 6 
3 
Study Objectives ................................................................................................................ 6 
3.1 
Primary Objective: ...................................................................................................... 6 
3.2 
Secondary Objectives: ................................................................................................. 6 
3.3 
Exploratory Objectives:............................................................................................... 6 
4 
Study Design ...................................................................................................................... 7 
5 
Eligibility Criteria .............................................................................................................. 7 
6 
Visit schedule and actions .................................................................................................. 7 
6.1 
Baseline Visit .............................................................................................................. 7 
6.2 
Prostatic Artery Embolization (PAE) Procedure Information .................................... 8 
6.3 
Visit 1:  4 Weeks (±1 week) Follow-Up ..................................................................... 8 
6.4 
Visit 2, 3 &4: 3 Months (±2 weeks), 12 Months (±8 weeks), 24 Months (±8 weeks) 
Follow-Up .............................................................................................................................. 8 
6.5 
Questionnaire Administration ..................................................................................... 9 
6.6 
Additional Evaluations ................................................................................................ 9 
7 
Patient Completion and Discontinuation ......................................................................... 10 
8 
Statistical Considerations ................................................................................................. 11 
8.1 
Endpoint Definitions ................................................................................................. 11 
8.1.1 
Primary Endpoints ............................................................................................. 11 
8.1.2 
Secondary Endpoints ......................................................................................... 11 
8.1.3 
Exploratory Endpoints ....................................................................................... 11 
8.2 
Primary Statistical Objective ..................................................................................... 12 
8.3 
Sample Size ............................................................................................................... 12 
8.4 
Analysis Populations ................................................................................................. 12 
8.4.1 
Full Analysis Set (FAS) ..................................................................................... 12 
8.4.2 
Evaluable Analysis Set (EAS) ........................................................................... 12 
8.5 
Statistical Analyses ................................................................................................... 12 
8.5.1 
General Approach .............................................................................................. 12 
8.5.2 
Analysis of the Primary Endpoint ...................................................................... 14 
8.5.3 
Analysis of the Secondary Endpoints ................................................................ 15 
8.5.4 
Safety Analyses .................................................................................................. 17 
8.5.5 
Baseline Descriptive Statistics ........................................................................... 17 
8.5.6 
Planned Interim Analyses .................................................................................. 17 

 
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8.5.7 
Subgroup Analyses ............................................................................................ 17 
8.6 
Amended Protocol Version Change .......................................................................... 17 
9 
Device or Procedure-Related Adverse Events ................................................................. 18 
9.1 
Severity of an Adverse Event .................................................................................... 18 
9.2 
Relationship of Adverse Event to Device and/or Procedure ..................................... 18 
9.3 
Device or Procedure-Related Serious Adverse Events ............................................. 18 
9.4 
Reporting of Serious Adverse Events ....................................................................... 19 
10 Data Recording and Retention ......................................................................................... 19 
11 Publication Policy ............................................................................................................ 19 
12 Good Clinical Practice (GCP) .......................................................................................... 20 
13 Ethical Considerations ..................................................................................................... 20 
14 Patient Informed Consent ................................................................................................ 20 
15 Subject Enrollment........................................................................................................... 20 
16 Patient Confidentiality ..................................................................................................... 20 
17 Monitoring, Audit and Inspection .................................................................................... 21 
18 Safety Medical Monitor ................................................................................................... 21 
19 References ........................................................................................................................ 22 
 
 
 
 
 

 
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1 Introduction  
Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in men, with more 
than 50% of men in their sixties and as many as 90% in their seventies and eighties having 
some symptoms of BPH. As life expectancy increases, so does the occurrence of BPH. In the 
United States in 2000, there were 4.5 million visits to physicians for BPH with a direct cost 
of $1.1 billion. 1-2 
Medical treatment is usually the first line therapy for lower urinary tract symptoms (LUTS) 
due to BPH. The two main categories of medications for management of BPH are alpha 
blockers and 5α -reductase inhibitors. Alpha blockers (α1-adrenergic receptor antagonists) 
are the most common choice for initial therapy.  Patients who cannot tolerate these drugs or 
are refractory to treatment typically receive surgery or a minimally invasive therapy. In 
general, transurethral resection of the prostate (TURP) is still considered the gold standard of 
prostate interventions for patients who require a procedure. The procedure involves removing 
part of the prostate through the urethra with a resectoscope.3-4 There are also a number of less 
invasive methods for reducing prostate size, including radiofrequency, microwave and laser 
therapies. All of these treatment methods involve introducing energy into the body and 
urethral access and manipulation.  All these technologies have the same objective—to 
remove prostate tissue to relieve constriction of the urethra or bladder outlet obstruction and 
reduce symptoms of LUTS. They produce outcomes similar to TURP, although there is not as 
much data on long term effectiveness as there is for surgery. The challenge for developing 
new methods of treating symptomatic BPH is to reduce hyperplastic tissue and achieve good 
long-term control of LUTS while reducing adverse events and negative impacts on quality of 
life, such as ejaculatory disorders. 
Embolization of prostate arteries has been used for many years to control serious bleeding 
after biopsy or prostatectomy. The first published case in which it was recognized that 
embolization could have a therapeutic effect on benign prostatic hyperplasia (BPH) was by 
DeMeritt and colleagues.5 Prostate artery embolization (PAE) is an emerging therapy for 
LUTS associated with BPH, and has been demonstrated to reduce symptom burden, improve 
urodynamic measures, and decrease prostate size.6-10  On April 16, 2013 Embosphere 
Microspheres received the CE mark for the indication of embolization of the prostate gland 
for relief of symptoms related to benign prostatic hyperplasia, and on June 21, 2017 Merit 
Medical Systems, Inc received 513(f)(2) (de novo) classification from the FDA to expand the 
indication for Embosphere Microspheres to include prostatic artery embolization (PAE) for 
symptomatic benign prostatic hyperplasia (BPH).   
The indication was granted based on the outcomes of published and unpublished data from 
286 patients. The cohort is typical of the patient population treated for symptomatic benign 
prostatic hyperplasia. Mean age at baseline was 67.7 ± 9.7, lower urinary tract symptoms 
were severe as reflected in a mean International Prostate Symptom Score (IPSS)11 of 21.5 ± 
6.8, and mean quality of life (QOL) score from the IPSS questionnaire was 4.8 ± 0.9 ("mostly 
dissatisfied" to "unhappy").  Bilateral prostate embolization was achieved in 254 patients 
(88.9%), despite including 32 patients over the age of 80 and 54 with indwelling catheters at 
baseline for management of acute urinary retention.  Mean symptom scores improved 
significantly compared to pretreatment values at every follow up interval.  Mean IPSS scores 
improved from 21.5 ± 6.8 at baseline to 6.3 ± 5.8 (<0.0001) and 6.2 ± 5.8 (<0.0001) at the 1-

 
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3 month and 9-16-month follow-ups respectively. A reduction of IPSS score by at least 3 
points was achieved at 9-16 months in 97% of patients, and 90% dropped by at least 1 
symptom category. 
The reduction of LUTS reflected in the IPSS changes affected mean quality of life.  Mean 
QOL scores improved significantly from 4.8 ± 0.9 ("mostly dissatisfied" to "unhappy") pre-
embolization to 1.4 ± 1.2 (<0.0001) and 1.4 ± 1.1 (<0.0001; "pleased"/ “mostly satisfied”) at 
the 1-3 month and 9-16-month follow-ups respectively.   
2 Study Rationale 
Prostatic artery embolization with Embosphere Microspheres is a relatively new procedure. 
The goal of this post market study is to evaluate long-term safety and effectiveness in a 'real 
world' setting.  
3 Study Objectives 
3.1 Primary Objective: 
Evaluate the long-term effectiveness of prostatic artery embolization (PAE) with Embosphere 
Microspheres as assessed by the International Prostate Symptom Score (IPSS) for those 
subjects who are eligible to complete a baseline IPSS for comparative purposes. 
3.2 Secondary Objectives:   
• Evaluate IPSS and QoL after discontinuation of indwelling bladder catheter (IBC) 
post PAE 
• Evaluation of device-related adverse events  
• Evaluation of procedure-related adverse events 
• Evaluate frequency of indwelling bladder catheter (IBC) removal post PAE 
• Technical Success 
o Successful embolization of treated prostate gland 
• Evaluation of additional treatments for refractory or recurrent LUTS due to BPH post 
PAE 
• Evaluation of change from baseline in erectile function at 12 months post PAE using 
the Sexual Health Inventory for Men (SHIM). 12-16 
3.3 Exploratory Objectives:  
If sufficient data is available, additional exploratory analyses will also be conducted. These 
may include, but are not limited to: 
• Comparison of safety and effectiveness outcomes from patients treated with 
Embosphere Microspheres 100-300μ vs 300-500μ 
• Comparison of procedure time for patients embolized with radial vs femoral access 
• Comparison of safety and effectiveness outcomes of embolizations that were/were not 
performed using the PErFecTED technique 
• Comparison of effectiveness outcomes of bilateral vs unilateral embolizations 
• Multivariate analyses to determine factors correlated to better effectiveness outcomes 
• Evaluation of change from baseline prostate size at any time point post PAE 

 
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4 Study Design 
This is a prospective, open label post market study to evaluate the long-term safety and 
effectiveness of PAE using Embosphere Microspheres.  Up to 500 patients with LUTS due to 
BPH will be enrolled in this single arm post market study.  All patients at sites who meet 
eligibility criteria will be offered participation.  Long term effectiveness of PAE on LUTS 
will be evaluated by IPSS score at baseline, 3 months, 12 months, and 24 months.  Note:  All 
subjects will be asked to complete the IPSS. However, study subjects who have an indwelling 
bladder catheter will not be required to complete the IPSS; the IPSS questions may not be 
relevant to subjects with an indwelling bladder catheter. Safety will be assessed by evaluating 
device and procedure-related adverse events at the same time points, plus at 4 weeks 
following embolization.  Erectile function will be assessed at baseline and 12 months by 
SHIM score.  Additional treatments for refractory or recurrent LUTS due to BPH post 
prostatic artery embolization will also be recorded. 
5 Eligibility Criteria  
• Inclusion Criteria 
o Patient has signed informed consent 
o Patient age is 18 years or older at time of informed consent 
o Patient will undergo PAE with Embosphere Microspheres for the treatment of 
symptomatic BPH with LUTS 
• Exclusion Criteria 
o Patient is unable or unwilling to provide follow-up information 
o Patient is undergoing PAE for reasons that do not include symptomatic BPH 
with LUTS 
o Any other reason the investigator deems cause for exclusion 
6 Visit schedule and actions 
6.1 Baseline Visit 
The following baseline data will be collected: 
• Date patient signs informed consent 
• Demographics 
• Prior BPH procedures  
• Current Medication for BPH (5α-Reductase inhibitors, α-blockers, ED medications, 
OTC medications, etc.)  
The following baseline data will be collected within 4 weeks of the study PAE procedure: 
• International Prostate Symptom Score (IPSS) 
o Must be self-administered by patient 
• Sexual Health Inventory for Men (SHIM) 
o Must be self-administered by patient 
The following baseline data will be collected within a timeframe consistent with standard of 
care: 

 
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• Prostate Size Assessment 
• Urinary Evaluations (Indwelling urinary catheter use, Maximum urine flow rate 
(Qmax), and Post void residual volume (PVR)), if done 
• Prostate specific antigen (PSA), if done  
The following baseline data will be collected within 12 months of the study PAE procedure:  
• Prostate Biopsy, if done 
6.2 Prostatic Artery Embolization (PAE) Procedure Information  
The following procedural data will be collected: 
• Date of procedure 
• Date and time of discharge 
• Embolization start and end time 
• Access site (Femoral/Radial) 
• Was the PErFecTED technique used? (If yes, prostate lobe(s) used on) 
• Was Foley catheter with contrast used? 
• Lobes embolized (Right/Left/Both) 
• Size of Embosphere Microspheres 
• Total Volume Administered 
• Device or Procedure-related adverse events 
Patients will be given a form on which to record Device or Procedure-related adverse events 
during the first month post procedure.  
6.3 Visit 1:  4 Weeks (±1 week) Follow-Up 
The following information will be collected: 
• Device or Procedure-related adverse events 
• Changes in indwelling urinary catheter use 
• BPH related medications 
• Additional prostate procedures and/or imaging  
• Prostate specific antigen (PSA), if done 
6.4 Visit 2, 3 &4: 3 Months (±2 weeks), 12 Months (±8 weeks), 24 Months 
(±8 weeks) Follow-Up  
Study participation will last for a total of 24 months (± 8 weeks). Traditional visit windows 
are being expanded to allow for potential impacts due to COVID-19.   
The following information will be collected: 
• International Prostate Symptom Score (IPSS) 
o Must be self-administered by patient  
• Device or Procedure-related adverse events 
• Changes in indwelling urinary catheter use 
• BPH related medications 
• Additional prostate procedures and/or imaging 

 
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• Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up 
If a patient receives any non-PAE BPH procedure other than biopsy after his study PAE he 
will be automatically discontinued from the study, and follow-up data will no longer be 
collected.  BPH procedures that will automatically discontinue the patient include but are not 
limited to TURP, Urolift, microwave ablation, aquablation, laser therapy and non-
Embosphere Microspheres PAE.   
Patients requiring multiple PAE procedures: 
• If a patient receives an additional PAE procedure with Embosphere Microspheres 
after the initial treatment, he will remain in the study, and the schedule for the follow-
up evaluations will begin according to the date of the first PAE with Embosphere 
Microspheres procedure until the subject reaches a total of 24 months follow-up.  End 
of study will be calculated based on first PAE procedure for 24 months. 
• If a patient receives more than one PAE procedure to complete the initial treatment, 
he will remain in the study, and the schedule of the follow-up evaluations will begin 
according to the date of the first PAE with Embosphere Microspheres, but not to 
exceed a total of 24 months from initial treatment date. 
8 Statistical Considerations 
8.1 Endpoint Definitions 
8.1.1 Primary Endpoints 
The primary endpoint is the IPSS at 12 months.  
8.1.2 Secondary Endpoints 
The following are the secondary endpoints: 
• 
IPSS measured at 3, 12, and 24 months post-baseline 
• 
Device or Procedure-Related Adverse event rate at post-procedure, 3, 12, and 24 
months 
• 
Technical Success defined as the successful embolization of the treated prostate 
gland 
• 
Frequency of indwelling bladder catheter removal post PAE at 3, 12, and 24 
months  
• 
Number of patients and types of treatment for refractory or recurrent LUTS due 
to BPH post PAE at 3, 12, and 24 months 
• 
Change form baseline in Sexual Health Inventory for Men (SHIM) at 12 months 
post-PAE. 
8.1.3 Exploratory Endpoints 
During unscheduled visits, depending on the site's standard or care, the following 
measurement may be collected during the visit: 
• 
Maximum Urinary Flow Rate (Qmax) 

 
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• 
Pulse Volume Recording  
• 
Prostate-Specific Antigen 
• 
Prostate size assessment 
• 
Prostate biopsy 
8.2 Primary Statistical Objective 
The primary statistical objective is to evaluate the efficacy of the device by estimating the 
change from baseline in the 12 month IPSS within +/- 1 unit. 
8.3 Sample Size 
The sample size is based on the following assumptions 
• Four countries with asymmetrical countrywide enrollments ranging from 15% to 25% 
of the total enrollment (conservative assumption) 
• Standard Deviation = 8.5 
• Difference between the lower and upper 2-sided 95% Confidence interval = 2 
• 10% of patients missing either baseline or 12 month IPSS 
A sample size of up to 500 patients is required to estimate the 12 month change from baseline 
in the IPSS within +/- 1 unit.  Sample size calculations were performed using NCSS PASS 
2020's procedure for one mean in a stratified design. 
8.4 Analysis Populations 
8.4.1 Full Analysis Set (FAS) 
Includes all patients that were enrolled except those that withdrew consent before the 
index procedure. The FAS is the population that will be used in determining endpoints 
except for efficacy endpoints 
8.4.2 Evaluable Analysis Set (EAS) 
Includes FAS patients where there are no significant deviations (e.g. not meeting the 
inclusion/exclusion criteria) from the protocol that did not have an indwelling catheter 
at the end of the procedure.   
8.5 Statistical Analyses 
8.5.1 General Approach 
Except where otherwise specified, the following general principles apply to the 
planned statistical analyses. All statistical analyses will be conducted using {SAS 
version 9.4 or later (SAS Institute Inc., Cary, NC)} or other widely accepted statistical 
or graphical software as required. 
8.5.1.1 
Descriptive Statistics 
Continuous data will be summarized with mean, standard deviation, median, 
minimum, maximum, and number of evaluable observations. Categorical variables 
will be summarized with frequency counts and percentages. Confidence intervals may 

 
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be presented, where appropriate, using the t-distribution for continuous data and exact 
binomial method for categorical variables. 
8.5.1.2 
Timing 
Overall Timing: Day 0 is the date of the procedure. Study Day will be calculated 
relative to the randomization as follows: 
• Study Day = Assessment Date – Procedure Date 
Duration: Duration variables will be calculated as follows: 
• Duration Days = Start Date – End Date 
A day is defined as 24 hours, from 0:00 to 23:59. 24:00 means 0:00 of the next day. 
Each subject duration in the study will be based on the last study contact date, which 
is the latest date of all follow-up visits, assessments, adverse event onset or resolution, 
and study exit, including date of death. 
Visit Windows: Unless otherwise specified, visit assessments will be analyzed for each 
analysis time point according to the study visit entered in the electronic Case Report 
Form (eCRF) to determine if the visit was within compliance. 
8.5.1.3 
Statistical Significance 
Unless otherwise specified, statistical testing will be performed at the two-sided 0.05 
significance level unadjusted for multiple testing. P-values will be rounded to three 
decimal places. If a p-value is less than 0.001, it will be reported as "<0.001". If a p-
value is greater than 0.999, it will be reported as ">0.999". 
8.5.1.4 
Reporting Precision 
Unless otherwise specified, the following conventions will apply for data displayed. 
In general, percentages will be displayed to 1 decimal place. Percentages <0.05% will 
be reported to 2 decimal places. For continuous parameters, means and medians will 
be reported to 1 additional decimal place than the measured value. In contrast, the 
standard deviation will be reported to 2 additional decimal places than the measured 
value. Minimum and maximum values will be reported to the same precision as the 
measured value. 
8.5.1.5 
Missing Data 
All attempts will be made to limit the amount of missing data. For all analyses of the 
primary endpoints, the number of observations available will be reported so the reader 
can assess the impact of missing data. For all clinical endpoints except for the patient-
reported outcome measurements, an adjustment to the denominator will be made 
based on the amount of evaluable data. For each visit (or reporting time point), the 
event rate will be calculated as the number of subjects with certain event terms over 
the number of evaluable subjects. The evaluable subjects at each reporting time point 
include all subjects who are enrolled and 
1) had an event within (on or before) the reporting cutoff days, or 

 
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2) had a follow-up at or after the lower limit of the reporting window, or 
3) the withdrawal consent date/recorded lost-to-follow-up date at or after the 
lower limit of the reporting window. 
8.5.1.6 
Adverse Event Dates 
More generally, in the case of partial adverse event onset date or date of death, the 
unknown portion of the date of the event will be imputed. If the month and year are 
known, the 15th of the month will be used for analysis. If only the year is known, the 
event will be analyzed as if it occurred on June 30th of the known year. In the rare 
case that the date is fully unknown, the date will be imputed as the initial treatment 
date. Imputation of partial dates is subject to the condition that it must occur on or 
after the initial treatment date. In the case where the imputed date is before the initial 
treatment date, the date of the initial treatment will be used. As death cannot occur 
before any documented subject contact, for date of death, the imputed date of death 
must occur on or after the last known contact in the study. 
8.5.1.7 
Analytical Methods 
Time-dependent response variables will be expressed using the Kaplan-Meier curve, 
and the hazard ratio and the 95% confidence limit will be reported. Data for all 
categorical endpoints (e.g., TLF rate at a specific time point, etc.) are shown with the 
number of patients, percentage, and Clopper-Pearson's exact 95% confidence interval. 
Differences between treatment groups are shown using a 95% confidence interval of 
the difference. Analyses of secondary endpoints are conducted with the FAS 
population. 
8.5.2 Analysis of the Primary Endpoint 
The stratified sample mean change from baseline in 12 month IPSS is estimated as 
follows. 
 
where 𝑥𝑥̅ is the stratified sample mean, L is the number of 
strata, Xhi is change from baseline in 12 month IPSS for 
the ith patient in the hth stratum, N is the overall sample 
size and Nh. is the sample size in stratum h 
 
It can be shown in T. Yahane(1967) that the expected value and variance of 𝑥𝑥̅ (V(𝑥𝑥̅ 
)) assuming sampling without replacement are 
 
 

 
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where  
 
The 95% confidence interval (CI(µ))s calculated as follows: 
 
where α is the type I error and 𝑉𝑉෠(𝑥𝑥̅) is the unbiased estimator of V(𝑥𝑥̅) and is 
calculated as follows: 
 
 
. 
8.5.2.1 
Missing Data 
Missing data for the IPSS will be imputed as the age-specific average for that time 
point.  Also, a tipping point analysis will be performed where the analysis will be 
performed, excluding the missing data. The number of missing data points it takes to 
tip the results from one direction to the other will be reported. 
8.5.2.2 
Multivariate Model 
A multivariate linear model will be developed to describe the IPSS changes over time.  
Univariate analysis will be performed analyses for all the baseline characteristics.  
Based on those results combined with clinical judgment, a final set of baseline 
characteristics will be created for use in the multivariate model.  LASSO (least 
absolute shrinkage and selection operator; also Lasso or LASSO) regression analysis 
method will be used to perform variable selection and regularization to minimize the 
unexplained variability and enhance the interpretability of the statistical model it 
produces.1 
8.5.3 Analysis of the Secondary Endpoints 
8.5.3.1 
IPSS changes over time 
The changes over time in the IPSS using the EAS will be modeled using a linear 
mixed model where country and patient will be considered a random effect.  If there is 
evidence of non-linearity, a nonlinear mixed-effects model using a 3rd-degree 
 
1 Tibshirani, Robert (1996). "Regression Shrinkage and Selection via the lasso". Journal of the Royal Statistical 
Society. Series B (methodological). Wiley. 58 (1): 267–88. JSTOR 2346178. 

 
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polynomial will be implemented.  The predicted curve and 95% confidence interval 
will be reported.  Missing data will not be imputed.   
Sensitivity analyses using complete cases and missing values replaced with an age-
specific average will be performed. 
A multivariate linear model will be developed to predict the IPSS changes over time.  
Univariate analysis will be performed analyses for all the baseline characteristics.  
Based on those results combined with clinical judgment, a final set of baseline 
characteristics will be created for use in the multivariate model.  The LASSO 
regression analysis method will be used to perform variable selection and 
regularization. 
8.5.3.2 
Device or Procedure-Related Adverse event rate at post-
procedure, 3, 12, and 24 months 
Treatment-related adverse event rates will be discussed in section 9.3. 
8.5.3.3 
Technical Success  
Technical success will be reported separately as the proportion and the 95% 
confidence interval of patients in FAS that achieve technical success. 
8.5.3.4 
Successful embolization  
For each of the following, the proportion and the 95% confidence interval of patients 
in FAS will be reported: 
• Successful embolization of the right prostate gland during the index procedure 
• Successful embolization of the left prostate gland during the index procedure 
• Successful embolization of both left and right prostate glands during the index 
procedure 
8.5.3.5 
Number of patients and types of treatment for 
refractory or recurrent LUTS due to BPH post-PAE  
The types of treatment and the number of patients that received that treatment for 
refractory or recurrent LUTS due to BPH post-PAE will be reported at 3, 12, and 24 
months, and overall will be reported using the FAS. 
8.5.3.6 
Sexual Health Inventory for Men over time 
The mean and 95% confidence interval of the change from baseline in the Sexual 
Health Inventory for Men (SHIM) will be reported using the EAS at 12 months post-
PAE. 
8.5.3.7 
Removal of In-dwelling catheter 
Using the FAS, for patients who had an indwelling catheter during the procedure, the 
proportion of indwelling bladder catheter (IBC) removal post-PAE will be reported at 
3 and 12 months PAE. 

 
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• 
 
 
 
 
 
 
 
 
 
 
9 Device or Procedure-Related Adverse Events 
A Device or Procedure-related adverse event is defined in this post market study as any event 
that began on or after the date of the PAE procedure and is considered related to the study 
procedure and/or device by the investigator.  All related events must be reported in the case 
report form and followed until resolution. 
9.1 Severity of an Adverse Event 
The Investigator, based on his/her clinical judgment and the following definitions, must rate 
severity of the adverse event: 
• Mild; Awareness of signs or symptoms, but easily tolerated; are of minor irritant type; 
causing no loss of time from normal activities; symptoms would generally not require 
medication or a medical evaluation; signs or symptoms are transient (e.g., headache 
treated with acetaminophen, common cold, etc. would be considered mild). 
• Moderate; Interferes with the subject’s usual activity and/or requires symptomatic 
treatment. 
• Severe; Symptom(s) causing severe discomfort and significant impact of the subject’s 
usual activity and requires treatment. 
9.2 Relationship of Adverse Event to Device and/or Procedure 
The Investigator, based on his/her clinical judgment and the following definitions, must 
determine the relationship of the adverse event to the device and/or procedure: 
• Possible: The AE/SAE follows a reasonable temporal sequence from the time of study 
procedure, and/or follows a known response pattern to the study procedure but could 
have been produced by other factors. 
• Probable: The AE/SAE follows a reasonable temporal sequence from the time of 
study procedure, follows a known response pattern to the study procedure, and cannot 
reasonably have been produced by other factors. 
• Definite: The AE/SAE follows a reasonable temporal sequence from the time of study 
procedure; follows a known response pattern to the study procedure; and cannot have 
been produced by other factors. 
9.3 Device or Procedure-Related Serious Adverse Events  
A device or procedure-related serious adverse event is defined in this post market study as 
any event that began on or after the date of the PAE procedure and is considered related to 
the study procedure and/or device by the investigator.  A device or procedure-related adverse 
event will be considered serious if it meets one of the following criteria:   

 
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12 Good Clinical Practice (GCP) 
The study will be conducted in accordance with the International Conference on 
Harmonization (ICH) E6 for Good Clinical Practice (GCP). The investigators will be 
thoroughly familiar with the appropriate use of the treatment procedure as described in the 
protocol. Essential clinical documents will be maintained to demonstrate the validity of the 
study and the integrity of the data collected. Master files should be established at the 
beginning of the study, maintained for the duration of the trial, and retained according to the 
appropriate regulations.  
13 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the Declaration 
of Helsinki. The IRB/EC will review all appropriate study documentation to safeguard the 
rights, safety and well-being of the patients.  The protocol, informed consent, advertisements 
(if applicable), written information given to the patients, safety updates, annual progress 
reports, and any revisions to these documents will be provided to the IRB/EC by the 
investigator.  
14 Patient Informed Consent 
After the study has been fully explained, written informed consent will be obtained from 
either the patient or his guardian or legal representative prior to any study procedures. The 
method of obtaining and documenting the informed consent and the contents of the consent 
will comply with ICH-GCP and all applicable regulatory requirement(s).  
Patients who wish to provide information for follow-up visits or receive reminders by email 
or text must sign a consent for this to be done over unsecured media. 
15 Subject Enrollment 
All patients requiring an intervention due to reasons detailed in this protocol are potential 
study candidates and shall be screened for eligibility.  Subjects who are consented and meet 
all the study inclusion criteria and none of the study exclusion criteria and are treated or 
attempted to be treated will be considered enrolled into the study. 
16 Patient Confidentiality 
To maintain patient privacy, all CRFs and study reports will identify the patient by the 
assigned patient number. The Investigator will grant monitor(s) and auditor(s) from Merit 
Medical or its designee and regulatory authority(ies), including the FDA, access to the 
patients' original medical records for verification of data gathered on the CRFs and to audit 
the data collection process. The patients' confidentiality will be maintained and will not be 
made publicly available to the extent permitted by the applicable laws and regulations.  

 
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17 Monitoring, Audit and Inspection 
A Merit Medical monitor, or designee, shall monitor each center periodically to monitor the 
progress of the study and review CRFs and original source documents with the study 
personnel, to verify accuracy of data recording and appropriate consents. Periodically 
some/all of the facilities used in the trial (e.g., laboratory) may be reviewed or inspected by 
the IRB/EC and/or regulatory authorities, including the FDA. 
18 Safety Medical Monitor 
An independent safety medical monitor shall be responsible for systemic review and 
adjudication of specified events (e.g., all treatment-related adverse events and all deaths) .  At 
a minimum, assess the reported event with the associated documented risks of device, 
vascular embolization, and PAE treatment. 
Potential risk for Embosphere Microspheres: 
• Immune reaction in patients who are hypersensitive to collagen or gelatin (careful 
consideration should be given prior to using this product in patients who are suspected 
to be allergic to injections containing gelatin stabilizers) 
Potential risk for vascular embolization: 
• Paralysis resulting from untargeted embolization or ischemic injury from adjacent 
tissue edema 
• Undesirable reflux or passage of Embosphere Microspheres into normal arteries 
adjacent to the targeted lesion or through the lesion into other arteries or arterial beds, 
such as the internal carotid artery, pulmonary, or coronary circulations 
• Pulmonary embolism 
• Ischemia at an undesirable location, including ischemic stroke, ischemic infarction 
(including myocardial infarction), and tissue necrosis 
• Capillary bed occlusion and tissue damage 
• Vessel or lesion rupture and hemorrhage 
• Vasospasm 
• Recanalization 
• Foreign body reactions necessitating medical intervention 
• Infection  
• Complications related to catheterization (e.g., hematoma at the site of entry, clot 
formation at the tip of the catheter and subsequent dislodgment, and nerve and/or 
circulatory injuries, which may result in leg injury) 
• Allergic reaction to medications (e.g., analgesics) 
• Allergic reaction o contrast media or embolic material 
• Pain and/or rash, possibly delayed form the time of embolization 
• Death 
• Blindness, hearing loss, loss of smell, and/or paralysis 
PAE specific potential complications: 

 
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• Non-targeted embolization of the rectum, bladder, scrotum, penis, or other areas 
• The most frequent post-procedure complication includes “Post-PAE Syndrome,” 
which includes nausea, vomiting, fever, pelvic pain, burning sensation, dysuria, and 
frequent or urgent urination 
• Skin burn (radiation exposure) form prolonged fluoroscopy time 
• Blood in urine, semen, or stool 
• Bladder spasm 
• Hematoma at the catheter site 
• Urinary tract infection 
• Urinary retention 
• Constipation 
The safety medical monitor will be an independent physician with experience in 
interventional peripheral endovascular procedures for prostate artery embolization. In order 
to enhance objectivity and reduce the potential for bias, the safety medical monitor shall be 
independent of the Sponsor as well as the investigational sites and investigators.  The 
methodology for performing these responsibilities shall be developed and outlined in the 
safety monitoring charter.  Operational provisions shall be established to minimize potential 
bias. 
19 References 
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2012. 
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prostatic hyperplasia. J Urol 2005: 173(4):1256-1261. 
3. Kacker R, Williams SB. Endourologic procedures for benign prostatic hyperplasia. 
Urol J 2011; 8(3):171-176. 
4. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA Guideline on the 
management of benign prostatic hyperplasia. J Urol 2011; 185:1793-1803. 
5. DeMeritt, JS, Elmasri FF, Esposito MP et al. Relief of benign prostatic hyperplasia-
related bladder outlet obstruction after transurethral polyvinyl alcohol prostate 
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6. Pisco J, Bilhim T, Pinheiro LC, et al. Prostate embolization as an alternative to open 
surgery in patients with large prostate and moderate to severe lower urinary tract 
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7. Carnevale FC, Moreira AM, Harward SH, et al. Recurrence of lower urinary tract 
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8. Amouyal G, Thiounn N, Pellerin O, et al. Clinical results after prostatic artery 
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9. Carnevale FC, Iscaife A, Yoshinaga EM, et al. Transurethral resection of the prostate 
(TURP) versus original and PErFecTED prostate artery embolization (PAE) due to 
benign prostatic hyperplasia (BPH): preliminary results of a single center, 

 
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prospective, urodynamic-controlled analysis. Cardiovasc Intervent Radiol 2016; DOI 
10.1007/s00270-015-1202-4.  
10. Isaacson AJ, Raynor MC, Yu H, et al. Prostatic artery embolization using 
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15. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and 
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Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 
Dec;11(6):319-26  
16. Rhoden EL, Telöken C, Sogari PR, Vargas Souto CA. The use of the simplified 
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