Prostatic Artery Embolization vs Medication for Benign Prostatic Hyperplasia: Single Subject Study Design
Phase: NA
Conditions: BPH, Enlarged Prostate (BPH), Prostatic Hyperplasia
Sponsor: University of North Carolina, Chapel Hill

 
 
Prostatic Artery Embolization vs Medication for Benign Prostatic 
Hyperplasia: Single Subject Study Design  
 
 
 
NCT number NCT04398966 
Document Date 03/11/2022 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
 
 
PROTOCOL TITLE  
Prostatic Artery Embolization vs Medication for Benign Prostatic Hyperplasia: Single 
Subject Study Design  
 
Principal Investigator 
Clayton Commander, MD (UNC-Chapel Hill, Radiology) 
(850) 758-1998 (PHONE)  
Email: clayton_commander@med.unc.edu 
 
Co-Investigators  
Hyeon Yu, MD  
Matthew Raynor, MD 
 
Biostatistician  
Thad Benefield, MS (UNC-Chapel Hill, Radiology) 
 
Sponsor:  University of North Carolina  
 
Funding Source: Terumo Interventional Systems 
 
Version Date: March 11, 2022 
 
 
 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
 
PROTOCOL TITLE  
Prostatic Artery Embolization vs Medication for Benign Prostatic Hyperplasia: Single 
Subject Study Design  
 
Principal Investigator 
Clayton Commander, MD (UNC-Chapel Hill, Radiology) 
(850) 758-1998 (PHONE)  
Email: clayton_commander@med.unc.edu 
 
 
 
 
 
Signature Page 
 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable U.S. federal regulations 
and ICH guidelines. 
 
Principal Investigator (PI) Name:_______________________ 
 
PI Signature: ___________________ 
 
Date:____________________ 
 
Date of Protocol: March 11, 2022 
 
 
 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
1 
TABLE OF CONTENTS 
ABBREVIATIONS AND DEFINITION OF TERMS ...................................................3 
1.0 
BACKGROUND AND RATIONALE ..................................................................4 
1.1 
Study Synopsis ......................................................................................................4 
1.2 
Disease Background ..............................................................................................4 
2.0 
STUDY OBJECTIVES ...........................................................................................4 
2.1 
Primary Objective .................................................................................................4 
2.2 
Secondary Objectives ............................................................................................4 
2.3 
Outcome Variable .................................................................................................5 
3.0 
PATIENT ELIGIBILITY ......................................................................................5 
3.1 
Inclusion Criteria ...................................................................................................5 
3.2 
Exclusion Criteria ..................................................................................................5 
4.0 
STUDY PLAN .........................................................................................................6 
4.1 
Study Procedures ...................................................................................................7 
4.2 
Safety and Effectiveness Assessments ................................................................10 
4.3 
Time and Events Table ........................................................................................10 
5.0 
DEVICE .................................................................................................................10 
5.1 
Name of Device ...................................................................................................11 
5.2 
Intended Use of the Device .................................................................................11 
5.3 
Description of the Device ....................................................................................11 
5.4 
Expected Risks ....................................................................................................11 
5.5 
Risk Minimization ...............................................................................................14 
5.6 
Receiving, Storage, Dispensing and Return ........................................................14 
6.0 
UNANTICIPATED CONCERNS (DEVICES) ..................................................15 
6.1 
Unanticipated Adverse Device Effect (UADE) ..................................................15 
6.2 
Unanticipated Problems (UP)..............................................................................15 
6.3 
Reporting .............................................................................................................16 
7.0 
ADVERSE EVENTS (DRUGS- CONTRAST AGENTS) .................................16 
7.1 
Definitions ...........................................................................................................16 
7.2 
Documentation of non-serious AEs or SARs ......................................................18 
7.3 
SAEs or Serious SARs ........................................................................................18 
8.0 
STATISTICAL CONSIDERATIONS ................................................................19 
8.1 
Study Design/Study Endpoints ...........................................................................19 

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Non-Oncology Imaging Protocol Template 
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February 2017 
 
2 
8.2 
Sample Size Rationale .........................................................................................19 
8.3 
Data Analysis Plans .............................................................................................19 
9.0 
STUDY MANAGEMENT ....................................................................................21 
9.1 
Institutional Review Board (IRB) Approval and Consent ..................................21 
9.2 
Registration Procedures.......................................................................................21 
9.3 
Monitoring/Auditing ...........................................................................................21 
9.4 
Data Management ...............................................................................................23 
9.5 
Adherence to the Protocol ...................................................................................25 
9.6 
Amendments to the Protocol ...............................................................................26 
9.7 
Record Retention .................................................................................................26 
9.8 
Obligations of Investigators ................................................................................26 
10.0 PLANS FOR PUBLICATION .............................................................................26 
11.0 REFERENCES ......................................................................................................27 
12.0 APPENDICES .......................................................................................................28 
12.1 
International Prostate Symptom Score (IPSS) ....................................................29 
12.2 
Adverse Event Questionnaires ............................................................................31 
 
 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
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February 2017 
 
3 
ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation 
Definition 
PAE  
prostatic artery embolization  
BPH 
Benign prostatic hyperplasia 
CT  
computed tomography  
MRI  
magnetic resonance imaging  
IPSS  
international prostate symptom score  
LUTS  
lower urinary tract symptoms  
Qmax  
peak urine flow rate  
PVR 
post void residual 
 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
4 
1.0 
BACKGROUND AND RATIONALE 
1.1 
Study Synopsis 
This will be a single arm, uncontrolled, non-blinded study of PAE using 
HydroPearl Beads in a small population of 30 subjects with benign prostate 
hyperplasia (BPH) to investigate the effectiveness of prostatic artery embolization 
(PAE) relative to previous medication alone for reducing urinary symptoms due 
to BPH. Secondary aims will be to assess adverse effects of medication vs adverse 
events secondary to PAE as well as Quality of Life scores on medication vs after 
PAE.   
1.2 
Disease Background  
Over the past 7 years, data has emerged from numerous countries supporting the 
safety and efficacy of prostatic artery embolization (PAE) for the treatment of 
lower urinary tract symptoms (LUTS) in the setting of benign prostatic 
hyperplasia (BPH) (1). In response, the Food and Drug Administration (FDA) 
recently granted a de novo classification to Merit Medical Systems to expand the 
indications for Embosphere Microspheres to include PAE for the treatment of 
BPH. Moreover, it has given 510(k) clearances to both Embozene Microspheres 
and HydroPearl Microspheres. 
 
Medication is the first line therapy for lower urinary tract symptoms (LUTS) 
secondary to BPH. These medications include alpha-adrenergic inhibitors, 5-alpha 
reductase inhibitors and phosphodiesterase inhibitors. While these medications 
are effective in improving urination in many men, there are also troubling side 
effects including retrograde ejaculation, erectile dysfunction, gynecomastia, 
lightheadedness, nasal congestion and loss of libido. Because of these side effects 
many men will discontinue the use of these medications.    
 
It has been shown that PAE is very unlikely to result in a major complication and 
the minor complications tend to resolve without treatment within several weeks of 
the procedure. Therefore, because of its safety, and the untoward effects of BPH 
medications, it may be reasonable to suggest that PAE could be substituted as first 
line treatment for BPH. To further explore this notion, research comparing PAE to 
medication is needed.  
2.0 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary aim of this study is to determine if PAE will result in a reduction of 
urinary symptoms similar to medication in individual patients. 
2.2 
Secondary Objectives  
The secondary aims are to determine if PAE will result in less adverse events 
compared to medication in individual patients and to determine if self assessed 
quality of life is better on medication or after PAE. 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
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2.3 
Outcome Variable 
2.3.1 Primary Study Outcome Variable 
Reduction in IPSS at 6-month follow-up. 
2.3.2 Secondary Study Outcome Variable 
1. Improvement of QoL score at 6 months 
2. Improvement of uroflowmetry (Qmax, PVR) at 6 months 
3. Reduction of prostate volume at 6 months 
4. Percentage of prostate infarcted at 6 months 
5. Incidence of adverse events at 3 months 
 
3.0 
PATIENT ELIGIBILITY 
Study subjects will be men with benign prostatic hyperplasia who have been 
taking an alpha-blocker, a 5-alpha reductase inhibitor or both for at least 6 
months. 
 
Thirty (30) subjects will be enrolled and all are anticipated to complete the study. 
3.1 
Inclusion Criteria 
Subjects must meet all of the inclusion criteria to participate in this study.   
3.1.1 Male 
3.1.2 Age ≥ 40 
3.1.3 Prostate gland measures ≥50 grams measured by MRI, CT, or ultrasound 
3.1.4 Currently taking BPH medications including either alpha blockers, 5-alpha 
reductase inhibitors or the combination of both for no less than 6 months 
3.1.5 Capable of giving informed consent 
3.1.6 Life expectancy greater than 1 year 
   
3.2 
Exclusion Criteria 
All subjects meeting any of the exclusion criteria at baseline will be excluded 
from study participation. 
3.2.1 Severe vascular disease as defined by severe arterial calcification seen on prior 
imaging, history of lower extremity or pelvic bypass grafts or history of lower 
extremity or pelvic arterial stenting.  For patients that do not have prior imaging at 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
6 
UNC, we will rule out suspected severe arterial calcification given their medical 
history. 
3.2.2 Uncontrolled diabetes mellitus which is defined as A1C >8% 
3.2.3 Patients currently taking SGLT2 inhibitors (cana-, dapa-, empa-, and ertu- 
gliflozin) due to their diuretic effects 
3.2.4 A smoking history of 20 pack-year or greater obtained by patient report 
3.2.5 Prior myocardial infarction 
3.2.6 A stroke within the last 6 months 
3.2.7 Unstable angina  
3.2.8 Immunosuppression 
3.2.9 Neurogenic bladder and/or sphincter abnormalities secondary to Parkinson’s 
disease, multiple sclerosis, cerebral vascular accident, diabetes, etc. 
3.2.10 Complete urinary retention 
3.2.11 Impaired kidney function (serum creatinine level > 1.8 mg/dl or a glomerular 
filtration rate < 60 as approximated using serum creatinine levels) unless anuric 
and on dialysis. 
3.2.12 Confirmed or suspected bladder cancer as assessed based on patients’ medical 
history or current hematuria 
3.2.13 Urethral strictures, bladder neck contracture, or other potentially confounding 
bladder pathology 
3.2.14 Ongoing urogenital infection.  For patients with symptoms of a urogenital 
infection (dysuria, fever, etc.), a urinalysis will be obtained. 
3.2.15 Previous pelvic radiation or radical pelvic surgery 
3.2.16 Confirmed malignancy of the prostate or a history of prostate cancer 
3.2.17 Contrast hypersensitivity refractory to standard medications (antihistamines, 
steroids) 
4.0 
STUDY PLAN 

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Non-Oncology Imaging Protocol Template 
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4.1 
Study Procedures 
4.1.1 Study Design 
This will be a single arm, non-blinded study of PAE in a small population with 
BPH to determine if PAE is as effective as medication (non-inferiority) in 
reducing urinary symptoms due to BPH.  After IRB approval of a written 
informed consent and over approximately a 24 month duration, a total of N=30 
subjects will be recruited at 3 sites.  Only subjects ≥ 40 years will be screened for 
study recruitment.  Clinical procedures and evaluations will consist of a 
preoperative screening assessment to determine if the potential study subject 
meets the inclusion and exclusion criteria, enrollment, surgical procedure for 
prostatic artery embolization (PAE), and follow-up visits at 24 hours, 1 week, 3, 
6, & 12 months.  An MRI will be performed after the 6-month visit in those 
patients who underwent embolization to detect a change in prostatic volume and 
perfusion and to exclude complication. 
4.1.2 Study Treatment 
Subjects will be given a dose of antibiotics on the day of the procedure (Bactrim 
400mg/80mg or Cipro 500 mg if the patient has an allergy to sulfa drugs. 
Additionally, non-steroidal anti-inflammatory medication will be administered on 
the day of procedure (500 mg Naproxen). The patients will be given the choice of 
receiving intravenous anxiolytic and analgesic medication during procedure or 
proceeding with local anesthetic only. 
 
Ultrasound-guided access into common femoral artery or radial artery will be 
obtained. An intra-arterial sheath will be placed. Through this sheath a diagnostic 
catheter will be used to perform pelvic angiography. Additionally, a cone beam 
CT angiogram may be performed. Based on these images and CT angiography 
obtained before the procedure, a microcatheter will be fluoroscopically guided 
into the prostatic artery. HydroPearl® microspheres (ranging from 75-400um 
based on the operator’s discretion) will then be injected under fluoroscopic 
guidance to prevent reflux and non-target embolization. Injection will continue 
until there is stasis. The catheter will then be guided into the contralateral 
prostatic artery and repeat embolization will be performed until stasis. If 
necessary, extraprostatic arterial anastomoses will be embolized with a coil to 
protect against non-target embolization. The catheter and sheath will then be 
removed and hemostasis will be achieved with compression or an intra-arterial 
closure device. The subject subsequently will be discharged home the same day or 
the following day. 
 
It is anticipated that less than 4 milliliters of HydroPearl® microspheres will be 
required for bilateral embolization. The size of the bead (75- 400 µm) will be 
dependent on the operator’s determination of what is most appropriate based on 
the size of the prostate and the prostatic vessels.  The range in size of particles 
will allow the operators to discern the safest, most effective size for the vessels 
targeted. Embolic size will be based on the overall size of the prostate, size of the 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
8 
target vessels, and likelihood of non-target embolization.  For example, depending 
on how far the catheter can be advanced, smaller particles can be safely used to 
induce ischemia in the target tissue. This concept is utilized routinely within 
embolization procedures are commonly performed.   
4.1.3 Method for Assigning Subject to Treatment Groups  
All subjects will receive the intervention. 
4.1.4 Prior and Concomitant Therapy 
The subjects will be required to have been on medical therapy for BPH for at least 
six months prior to undergoing PAE. Such medications include alpha blockers, 5-
ARIs or combination therapy.  The medication usage will be stopped by the 3 
month visit in order to allow an adequate washout period for 5-ARI’s prior to the 
6 –month visit. 
4.1.5 Enrollment/Recruitment 
Subjects will be recruited from the urology and vascular & interventional 
radiology (IR) clinics across three (3) sites. 
4.1.6 Screening Visit (Visit 1) 
If a patient qualifies to be a subject in the study based on the inclusion and 
exclusion criteria listed in section 3.1 and 3.2, the study coordinator will be 
notified.  The coordinator will review the study with the patient and obtain written 
informed consent. Once the subject is enrolled in the study, he will be seen by one 
of the co-investigators in either the IR or Urology clinics at one of the study sites. 
The procedure will be again described to the patient and any questions will be 
answered. International Prostate Symptoms Survey (IPSS) with Quality of Life 
(QOL) questionnaires and Qmax and PVR measurements will be obtained if not 
completed in the prior 3 months during the pre-study work-up. Study specific 
questionnaires to assess medication usage will also be completed.  A MRI of the 
pelvis with and without contrast will be ordered and obtained prior to visit 2 for 
baseline evaluation of the prostate unless the patient has one from the prior 6 
months.  If the patient had a contrast enhanced MRI of the pelvis within the past 6 
months, this MRI will be used. 
4.1.7 Visit 2 - PAE Procedure 
PAE procedure will be performed as described in part 4.1.2 above within 8 weeks 
of Visit 1.  Subjects will be given a pager number to reach a physician (24 hours a 
day) to report any adverse symptoms and receive medical advice.  
 
Patients will be asked medication history questionnaire at this visit prior to the 
procedure. 
4.1.8 Visit 3 -1 Day Follow-up 
Subjects will be seen in clinic or contacted by phone or by teleconference, per the 
subject’s preference, the day following PAE procedure (+3 days). As most 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
February 2017 
 
9 
complications of the procedure will be evident within this time, this visit is to 
evaluate for early AEs. If an AE is suspected based on change in pain scores or 
functionality, an appropriate work-up will be performed which may include MRI 
or CT. 
 
4.1.9 Visit 4 -1 Week Follow-up 
Subjects will be seen in clinic or contacted by phone or by teleconference, per the 
subject’s preference, one week following PAE procedure (+5 days). As most 
complications of the procedure will be evident within this time, this visit is to 
evaluate for early AEs. If an AE is suspected based on change in pain scores or 
functionality, an appropriate work-up will be performed which may include MRI 
or CT. 
 
4.1.10 Visit 5 - 3 Month Follow-Up  
Subjects will return 90 +/- 14 days after PAE procedure to complete IPSS, and 
QOL questionnaires; to have Qmax and PVR measured; medication history 
questionnaires will be completed; and subjects will be evaluated for possible 
adverse events. It will be recorded if subjects are unable to hold medications at 
this time due to residual urinary symptoms.  If an AE is suspected based on 
change in pain scores or functionality, an appropriate work-up will be performed. 
 
4.1.11 Visit 6 - 6 Month Follow-Up  
Subjects will return 180 +/- 14 days after PAE procedure to complete IPSS with 
QOL and medication history questionnaires and to have Qmax and PVR 
measured.  The subjects will be evaluated for possible adverse events. If an AE is 
suspected based on change in pain scores or functionality, an appropriate work-up 
will be performed.   
 
An MRI of the prostate will be acquired.   
 
4.1.12 Visit 7– 12 month follow-up for all subjects 
Subjects will return 360 days +/- 14 days after PAE to complete IPSS and QOL 
questionnaires and to have Qmax and PVR measured. 
4.1.13 Subject Compliance Monitoring 
Study coordinators and physicians will inquire of the subjects to determine if they 
have escalated any current or initiated any new conservative therapies during the 
follow-up period. 
4.1.14 Criteria for Removal from Study 
Subjects will be withdrawn from the study if a major complication occurs that 
prevents completion of PAE or the ability to complete the follow up visits. 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
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Patients may also withdraw at any point at their discretion.  Data will be included 
with an intent to treat analysis. Reasons for study withdrawal will be recorded. 
4.1.15 Follow-up for Withdrawn Subjects 
If a subject withdraws from the study, any recorded data will still be included in 
the analysis. Subjects will only be replaced if they withdrew prior to undergoing 
PAE. 
4.2 
Safety and Effectiveness Assessments 
4.2.1 Safety Assessments 
Subjects will be observed for several hours after PAE to monitor for immediate 
complications to include bleeding, infection and acute ischemia of the rectum and 
bladder. Subjects will be contacted by study personnel the day after PAE to 
inquire about delayed onset complications. The subjects will also be given a 
phone number that they can call to reach a nurse if they believe they have 
developed a complication of the procedure. 
4.2.2 Effectiveness Assessments 
Technical success will be defined as bilateral prostatic artery embolization. This 
will be determined during the procedure. Clinical success will be defined as an 
IPSS score reported at the 6-month visit that is equal to or less than the pre-PAE 
baseline score. The size of the prostate will be measured by MRI at 6-month  
follow-up visit. IPSS, QoL, PVR and Qmax will be measured at 3, 6 and 12-
month follow-ups. 
4.3 
Time and Events Table 
 
 
 
5.0 
DEVICE 
 
 
Visit 1 
(Screening) 
Visit 2 
(Procedure) 
Visit 3 
(1 Day) 
Visit 4  
(1 week) 
Visit 5  
(3 month) 
Visit 6  
(6 Month) 
Visit 7 
(12 month) 
Informed Consent 
X 
 
 
 
 
 
 
MRI 
X 
 
 
 
 
X 
 
PAE procedure 
 
X 
 
 
 
 
 
IPSS w/QOL 
X 
 
 
 
X 
X 
X 
Qmax 
X 
 
 
 
X 
X 
X 
PVR 
X 
 
 
 
X 
X 
X 
Medication 
History 
Questionnaire 
X 
X 
 
 
X 
X 
 
AE Assessment 
 
 
X 
X 
X 
X 
 

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5.1 
Name of Device 
HydroPearl® compressible microspheres (75 to 400 µm) 
  
5.2 
Intended Use of the Device 
HydroPearl® compressible microspheres (75 to 400 µm) will be used for prostatic 
artery embolization in patients with BPH consistent with labeling. 
5.3 
Description of the Device  
HydroPearl® compressible microspheres are part of a family of embolic materials 
based on Microvention's proprietary microsphere technology. These spheres are 
designed to offer controlled, targeted embolization. HydroPearl microspheres are 
made using Poly-Ethylene Glycol and are precisely calibrated, non-resorbable, 
hydrophilic, compressible, and biocompatible. HydroPearl® microspheres are 
available from 75-1100 μm and are provided in a sterile syringe pre-filled with 
microspheres in phosphate buffered saline. 
 
The HydroPearl® compressible microspheres are intended for the embolization of 
arteriovenous malformations and hypervascular tumors, including uterine fibroids 
and benign prostatic hyperplasia. 
 
• HydroPearl® compressible microspheres are contained in a sterile 20 cc 
pre-filled syringe and packaged in a pre-formed tray with Tyvek peel-
away lid.  
• Each syringe contains approximately 2 ml of HydroPearl compressible 
microspheres in non-pyrogenic, sterile, transport solution of physiological 
buffered saline. 
• The product is packaged sterile. Do not use if the unit package is opened 
or damaged. 
• Each syringe is intended for a single patient use only. Do not re-sterilize. 
Discard any unused material.  
 
Once a catheter has been fluoroscopically guided into the target vessel, the 
embolization spheres are then injected, causing obstruction at the arteriole level 
until the desired degree of embolization has occurred. The embolization spheres 
used during the study will be unchanged. 
5.4 
Expected Risks 
A recent meta-analysis of PAE data from 662 patients in nine studies reported 
only two major complication (0.3% major complication rate) involving bladder 
ischemia requiring surgery and severe urinary sepsis requiring hospitalization. 
Among minor complications transient rectalgia and/or dysuria (9.1%), acute 
urinary rentention (7.9%) and transient hematuria (4.4%) were the most common 
(1). 
 
Detailed risk analysis is below: 
 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
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Risk or Side Effect 
Source of 
Risk or Side 
Effect 
Possible 
Less 
Possibl
e 
Rare 
Events 
Potential 
Risks 
Associated 
Study 
Enrollment 
& Study 
Procedures 
Discomfort 
Blood draw for 
lab test, 
ultrasound or 
MRI 
X 
Thrombophlebitis, bruising, 
bleeding, blood clot, Pre- 
syncope or Syncope (i.e. 
Fainting) 
Blood draw for 
lab tests 
X 
Anxiety or Claustrophobia 
MRI scan 
X 
Psychological Discomfort 
Clinical 
Trial 
X 
Infection 
Blood draw for 
lab tests 
X 
Allergic Reaction 
MRI 
contrast 
X 
Gadolinium contrast 
adverse reaction (i.e. 
Nephrogenic Systemic 
Fibrosis or severe skin 
reaction from contrast 
agent only reported in 
patients with kidney 
dysfunction) 
MRI 
Contrast 
injection 
X 
Confidentiality breach 
from Medical Records 
Medical Record 
Keeping 
X 
Groin/Anesthetic 
Injection/Neurologic Injury/ 
Pressure 
during 
arterial 
access and 
X 
Discomfort/Pain 
after catheter 
removed at 
the 
leg/femoral 
artery site 
X 
Risks of the 
PAE 
Radiation Exposure Injury 
PAE procedure 
X 
Kidney Dysfunction 
Contrast 
injected 
during 
procedure 
X 
Infection 
PAE Procedure 
X 

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Non-Oncology Imaging Protocol Template 
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Procedure 
and Post- 
operative 
care 
Adverse or Allergic Reaction 
Intravenous 
contrast agent or 
medications 
administered as 
part of 
procedure or 
follow-up care 
(ie. MRI 
contrast) 
X 
Tissue damage to Skin, 
Muscle, Skin or other 
structure in legs and groin 
(Non-target Embolization) 
PAE procedure 
X 
Minor Bruising or Bleeding 
PAE procedure 
X 
Bleeding requiring 
Transfusion or surgery 
PAE procedure 
X 
Post Embolization 
Syndrome, including 
fever, malaise, 
headache, and myalgia 
(body aches) 
PAE procedure 
X 
Internal bleeding, 
such as 
Gastrointestinal  
bleeding 
Medications 
taken after the 
procedure 
(i.e. 
Ibuprofen) 
X 
Infection 
Catheter site 
in the 
leg/groin 
X 
Arterial 
injury/trauma, 
laceration, 
bruising/pseudo 
aneurysm 
Procedure/ 
Closure 
device 
(clip) 
on the artery 
X 
Pulmonary embolism (clot 
in lung), Thrombophlebitis 
(clot in artery or vein) 
PAE procedure  
X 
Myocardial Infarction 
(Heart attack) 
PAE procedure 
including 
moderate 
sedation/sedative 
medication 
X 
Stroke 
PAE procedure 
including 
moderate 
sedation/sedative 
medication 
X 

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Non-Oncology Imaging Protocol Template 
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Disability 
PAE procedure 
including 
moderate 
sedation/sedative 
X 
Death 
PAE procedure 
including 
moderate 
sedation/sedative 
medication 
X 
 
 
5.5 
Risk Minimization 
The PAE procedure will be performed by board-certified interventional 
radiologists who have expertise in endovascular techniques, particularly in 
selective catheterization and transcatheter embolization techniques. Analgesia 
during the procedures will be provided through the use of conscious sedation if 
required. The risks of conscious sedation will be minimized by continuous 
monitoring of heart rate, blood pressure, oxygen saturation, and cardiac rhythm.  
The dose area product projected for the procedure is thought to be less than 30 
gray/cm2 which is about 2-4 years of background radiation and significantly less 
than that of a cardiac catheterization. Radiation exposure will be minimized to 
subjects under the principal of ‘as low as reasonably achievable’ (ALARA). 
 
Sterile instruments with a sterile technique will be used to minimize infection risk 
at the arterial access site.  Pre-operative antibiotic(s) will be administered to 
reduce risk of other infections, such as urinary tract. The arterial access site 
discomfort will be minimized by administration of local anesthesia into the 
overlying skin and adjacent tissues. Catheter access into the appropriate artery 
may be performed using ultrasound-guided arterial puncture to prevent 
inadvertent vessel puncture with subsequent bleeding. Real-time fluoroscopic 
monitoring of all catheter/wire manipulations will be used to prevent vascular 
injury. 
 
The subject will be monitored for the risk of an allergic response to iodinated 
contrast. To minimize the risk of renal dysfunction there will be use of non-ionic 
contrast agents, and appropriate pre-procedure hydration, when necessary.  
Subjects who report an allergic reaction to iodinated contrast will be pre-
medicated as per routine allergy prophylaxis per standard of care. 
5.6 
Receiving, Storage, Dispensing and Return 
5.6.1 Receipt of Supplies 
Terumo will provide, at no charge, up to 10 boxes (5 vials/box) of HydroPearl® 
microspheres for the Study (“Devices”).  HydroPearl® microspheres will be 
stored within the Interventional Radiology Department in a separate area.  
Embolic devices will be labeled ‘for investigational use only’ and will be reserved 
for use in the clinical trial. 

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5.6.2 Storage 
HydroPearl® microspheres must be stored in a cool, dark, dry place in their 
original packing. 
5.6.3 Dispensing 
No study specific dispensing techniques will be used. 
5.6.4 Return or Destruction of Device 
The Institution and Sponsor-Investigator shall, return any such Product to 
Company promptly if requested by the Company upon the completion or 
termination of the Study for which such Product was being utilized, or promptly 
dispose of or destroy, as the Company may reasonably direct, all of its remaining 
stocks of Product. All Devices supplied by Terumo to Institution for the Study 
shall be used by Institution only as specified in the Protocol and the Clinical Trial 
Agreement. No other use of the Devices is authorized.   
 
Disposable syringes, which spherical particulate is stored in, will be discarded as 
medical waste and packaging will be kept in a secure location until the study is 
completed. Packages will be disposed of upon completion of the study. 
 
Lot numbers of the device used will be recorded in the CRFs for the study 
procedure. 
6.0 
UNANTICIPATED CONCERNS (DEVICES) 
6.1 
Unanticipated Adverse Device Effect (UADE) 
The investigational device exemption (IDE) regulations define an unanticipated 
adverse device effect (UADE) as “any serious adverse effect on health or safety 
or any life-threatening problem or death caused by, or associated with, a device, if 
that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects” 
(21 CFR 812.3(s)). 
6.2 
Unanticipated Problems (UP) 
As defined by UNC’s IRB, unanticipated problems involving risks to study 
subjects refers to any incident, experience, or outcome that: 
• Is unexpected (in terms of nature, severity, or frequency) given (a) the 
research procedures that are described in the protocol-related documents, 
such as the IRB-approved research protocol and informed consent 
document; and (b) the characteristics of the subject population being 
studied; 
• Is related or possibly related to a subject’s participation in the research; 
and  

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• Suggests that the research places subjects or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) related 
to the research than was previously known or recognized. 
6.3 
Reporting 
6.3.1 UADEs 
UADEs must be reported by the clinical investigator to the sponsor and the 
reviewing IRB, as described below:  
 
For this device study, investigators are required to submit a report of a UADE to 
the FDA, the manufacturer of the device and the UNC IRB as soon as possible, 
but in no event later than 10 working days after the investigator first learns of the 
event (§ 812.150(a)(1)), using the MedWatch Form 3500A.   Sponsors  must 
immediately conduct an evaluation of a UADE and must report the results of the 
evaluation to FDA, the UNC IRB, and participating investigators within 10 
working days after the sponsor first receives notice of the effect (§§ 812.46(b), 
812.150(b)(1)).  
 
For this device study, we will submit a report of a UADE to the manufacturer and 
the IRB as soon as possible, but no later than 10 working days after the 
investigators first learn of the event. 
6.3.2 UP 
Any events that meet the criteria for “Unanticipated Problems” as defined by 
UNC’s IRB must be reported by the clinical investigator using the IRB’s web-
based reporting system.   
 
Any unanticipated problem that occurs during the conduct of this study and that 
meets at least the first two criteria listed in section 6.2 must be reported to the 
UNC IRB using the IRB’s web-based reporting system.  
7.0 
ADVERSE EVENTS (DRUGS- CONTRAST AGENTS) 
7.1 
Definitions  
7.1.1 Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence (e.g., an abnormal 
laboratory finding, symptom, or disease temporally associated with the use of a 
drug) in a patient or clinical investigation subject administered a pharmaceutical 
product and which does not necessarily have a causal relationship with this 
treatment.  An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not related to the 
medicinal product.   
 

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Hospitalization for elective surgery or routine clinical procedures that are not the 
result of an AE (e.g., surgical insertion of central line) need not be considered 
AEs and should not be recorded as an AE.  Disease progression should not be 
recorded as an AE, unless it is attributable by the investigator to the study therapy. 
7.1.2 Suspected Adverse Reaction (SAR) 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable 
possibility that the drug is the cause.   Reasonable possibility means that there is 
evidence to suggest a causal relationship between the drug and the AE.  A 
suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug.   
 
Causality assessment to a study drug is a medical judgment made in consideration 
of the following factors: temporal relationship of the AE to study drug exposure, 
known mechanism of action or side effect profile of study treatment, other recent 
or concomitant drug exposures, normal clinical course of the disease under 
investigation, and any other underlying or concurrent medical conditions.  Other 
factors to consider in considering drug as the cause of the AE: 
• Single occurrence of an uncommon event known to be strongly associated 
with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson 
Syndrome) 
• One or more occurrences of an event not commonly associated with drug 
exposure, but otherwise uncommon in the population (e.g., tendon 
rupture); often more than once occurrence from one or multiple studies 
would be needed before the sponsor could determine that there is 
reasonable possibility that the drug caused the event.   
• An aggregate analysis of specific events observed in a clinical trial that 
indicates the events occur more frequently in the drug treatment group 
than in a concurrent or historical control group 
7.1.3 Unexpected AE or SAR 
An AE or SAR is considered unexpected if the specificity or severity of it is not 
consistent with the applicable product information (e.g., Investigator’s Brochure 
(IB) for an unapproved investigational product or package insert/summary of 
product characteristics for an approved product).  Unexpected also refers to AEs 
or SARs that are mentioned in the IB as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation.   
7.1.4 Serious AE or SAR 
An AE or SAR is considered serious if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: 
• Death; 
• Is life-threatening (places the subject at immediate risk of death from 
the event as it occurred); 

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• Requires inpatient hospitalization (>24 hours) or prolongation of 
existing hospitalization; 
• Results in congenital anomaly/birth defect; 
• Results in a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions; 
• Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered a serious 
adverse drug experience when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed 
in the definition.  For reporting purposes, also consider the occurrences 
of pregnancy as an event which must be reported as an important 
medical event. 
 
7.2 
Documentation of non-serious AEs or SARs 
For non-serious AEs or SARs, documentation must begin from day 1 of study 
treatment and continue through the 30-day follow-up period after treatment is 
discontinued.   
 
Collected information should be recorded in the Case Report Forms (CRF) for 
that patient.  Please include a description of the event, its severity or toxicity 
grade, onset and resolved dates (if applicable), and the relationship to the study 
drug.    Documentation should occur at least monthly.  
7.3 
SAEs or Serious SARs  
7.3.1 Timing 
After informed consent but prior to initiation of study medications, only SAEs 
caused by a protocol-mandated intervention will be collected (e.g. SAEs related to 
invasive procedures such as biopsies, medication washout.  
 
For any other experience or condition that meets the definition of an SAE or a 
serious SAR, recording of the event must begin from day 1 of study treatment and 
continue through the 30 day follow-up period after treatment is discontinued.   
7.3.2 Documentation and Notification 
These events (SAEs or Serious SARs) must be recorded within 24 hours of 
learning of its occurrence.  
7.3.3 Reporting  
IRB Reporting Requirements: 
The UNC-IRB will be notified of all SAEs that qualify as an Unanticipated 
Problem as per the UNC IRB Policies using the IRB’s web-based reporting 
system within 7 days of the Investigator becoming aware of the problem.   

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8.0 
STATISTICAL CONSIDERATIONS 
 
8.1 
Study Design/Study Endpoints  
The primary study aim is to determine if PAE is as effective as medication (non-
inferiority) in reducing urinary symptoms due to BPH at 6 months. 
    
This will be a single arm, non-blinded study of PAE using HydroPearl Beads in a 
small population with BPH to assess a clinically significant reduction in 
medications at 6 months.  After IRB approval of a written informed consent and 
over, approximately a 24 month duration, N=30 subjects will be recruited.  Only 
subjects ≥ 40 years will be screened for study recruitment.  Clinical procedures 
and evaluations will consist of a preoperative screening assessment to determine 
if the potential study subject meets the inclusion and exclusion criteria, 
enrollment, surgical procedure for prostatic artery embolization (PAE), and 
follow-up visits at 24 hours, 1 week, 3, 6, & 12 months.  An MRI will be 
performed after the 6-month visit in those patients who underwent embolization 
to detect a change in prostatic volume and perfusion and to exclude complication. 
 
The study will be stopped if there is greater than one major complication (Grade 
D, E or F) as defined by the Society of Interventional Radiology Classification 
System for Complications by Outcome (29). 
8.2 
Sample Size Rationale 
Prior studies have demonstrated larger decreases in IPSS scores using PAE, 
compared to medication alone.  Abt found the mean decrease in IPSS to be 9.23 
for PAE with standard deviations of IPSS scores being 5.7 at baseline and after 
treatment (18).  Lepor found a decrease in IPSS attributable to medications of 6.6 
(17). 
 
We set a 10% non-inferiority margin and expect the correlation of IPSS scores 
between screening and 6-months to be high.  Assuming a correlation of .65.we 
will have 81.2% power to test the non-inferiority hypothesis with an alpha of 
0.025 for our 30 budgeted pairs, assuming 20% dropout (pairs=subjects given 
single subject study design). 
 
Power calculations used PROC POWER, SAS, Version 9.4.  This sample size is 
adequately large to address the study’s primary aim with reasonably large power.    
8.3 
Data Analysis Plans 
A patient will be considered an evaluable study subject evaluable for data analysis 
per the following criteria, a written informed consent was obtained, he meets the 
inclusion and exclusion criteria, and received the PAE study procedure.  All 
subjects with 12-month follow-up data will be included for analysis even if some 
follow up data is incomplete. Every attempt will be made to ensure that there is as 

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little missing data as possible including reminder phone calls and follow-up phone 
calls, if a subject misses a visit. 
 
The primary aim is to demonstrate non-inferiority of PAE compared to 
medication with respect to the outcome measure IPSS.  We assumed a non-
inferiority margin of 10%, in line with the FDA’s recommendations, since similar 
prior non-inferiority trials were unavailable.  The null hypothesis states that in the 
target population mean IPSS is at least 10% greater at 6 months post-treatment 
than at baseline (pre-treatment). The alternative hypothesis will be that the mean 
IPSS at 6 months is less than or equal to 10% greater than the mean IPSS at 
screening.   
 
To address this hypothesis we will implement a random effects linear model, 
modeling IPSS score as a function of time and the indicator of whether 
medication had stopped by the time of the 3-month follow-up.  We will include an 
R-side compound symmetric random effect to account for patient-level 
correlation.  We will compute the predicted mean and standard deviation(SD) of 
IPSS at screening and 6 months; the difference of the predicted mean IPSS score, 
defined as the mean IPSS at 6 months minus the mean IPSS at screening; and the 
SD of this difference.  Point estimates of these values will be reported along with 
95% confidence intervals for the mean difference.   
 
A non-inferiority p-value <0.05 testing whether the difference in the predicted 
mean at screening is at least 10% greater than the predicted mean of IPSS at 
screeningwill be considered evidence against the null hypothesis of inferiority of 
PAE, compared to treatment.  A non-inferiority p-value >0.05 will be considered 
inconclusive evidence against inferiority. 
 
As a sensitivity analysis for the primary aim, we will repeat the same model 
outlined above after removing patients from the analysis who were still taking 
medications at the 3-month follow-up.   Point estimates, confidence intervals, and 
p-values will be compared against those obtained in the primary analysis.  
 
To address the secondary aim, we will tabulate the proportion of patients AEs pre- 
and post-PAE, comparing the proportion using McNemar’s test.   A p-value <0.05 
for McNemar’s test will be considered evidence that the proportion of AE’s 
differs for medication, compared to PAE.  A p-value >0.05 will be considered 
inconclusive.  We will assume that the adverse events that occur following PAE 
will be attributed to the procedure and not medication.    
 
We will present the percentage of prostate infarcted at 6 months and the incidence 
of minor complications at 1 month descriptively, and calculate 95% confidence 
intervals.  Post-acquisition segmentation software will be used to measure infarct 
volume. 
 

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9.0 
STUDY MANAGEMENT 
9.1 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in 
accordance with federally mandated regulations.  The IRB should approve the 
consent form and protocol. 
 
In obtaining and documenting informed consent, the investigator should comply 
with the applicable regulatory requirement(s), and should adhere to Good Clinical 
Practice (GCP) and to ethical principles that have their origin in the Declaration 
of Helsinki. 
 
 
 
Before recruitment and enrollment onto this study, the patient will be given a full 
explanation of the study and will be given the opportunity to review the consent 
form. Each consent form must include all the relevant elements currently required 
by the FDA Regulations and local or state regulations. Once this essential 
information has been provided to the patient and the investigator is assured that 
the patient understands the implications of participating in the study, the patient 
will be asked to give consent to participate in the study by signing an 
IRB-approved consent form. 
 
Prior to a patient’s participation in the trial, the written informed consent form 
should be signed and personally dated by the patient and by the person who 
conducted the informed consent discussion. 
9.2 
Registration Procedures 
Study participants will be registered into REDCap®, a web based clinical 
research platform by one of the Study Coordinators. 
9.3 
Monitoring/Auditing 
9.3.1 Data and Safety Monitoring Plan 
Data and Safety Monitoring will be performed by a licensed physician who is not 
a study investigator. 
 
The CRFs and any relevant source documents will be sent to the Study Monitor 
(as above) who will review them after treatment is complete for subjects 1, 10, 20 
and 30. 
 
Complications will be assessed by the co-PIs, categorized into major and minor 
categories and recorded on the CRF. CRFs and appropriate source documents will 
be made available to this individual for annually (every 12 months) review to 
ensure completeness of data collection. Any discrepancies will be immediately 
addressed by the co-PIs.  All adverse events will be recorded and then 
summarized for inclusion in the final manuscript.  Relatedness to the study 

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procedure will be assessed by an appropriately delegated investigator based on 
licensure. 
 
Data monitoring will be performed by Study Monitor listed above. CRFs and 
appropriate source documents will be made available to this individual for bi-
monthly review to ensure completeness of data collection. Any discrepancies will 
be immediately addressed by the co-PIs. 
 
Because this is a small study with only 30 subjects, no DSMB will be used for 
this study.  Data and safety monitoring will be conducted by an individual (Study 
Monitor) who is not an investigator on this study (see above). 
9.3.2 Safety Monitoring 
The research coordinator will complete the appropriate report form and logs; 
assist the PI to prepare reports and notify the IRB, FDA, and/or safety monitor of 
all Unanticipated Problems/SAE’s. 
 
The research coordinator and co-principal investigators will confirm that all 
Adverse effects (AE) are correctly entered into the AE log by the coordinator; be 
available to answer any questions that the coordinators may have concerning AEs; 
notify the IRB and FDA of all Unanticipated Problems/SAEs and AEs as 
appropriate. All assessments of AEs will be made by a licensed medical 
professional who is an investigator on the research. 
 
The research coordinator will confirm that the AEs are correctly entered into the 
AE log. The Study Monitor will confirm that the adverse events are consistent 
with the source documents and are reported to the appropriate regulatory bodies, 
as required. 
9.3.3 Monitoring Activities 
A safety monitor who is not a study investigator (see section 9.3.1) will 
conduct safety monitoring after treatment is complete for subjects 1, 10, 20, and 
30. Adverse events will be documented and reported as described above. 
 
The following issues will be addressed quarterly or more frequently as necessary: 
• Verify receipt of all documents and supplies needed to conduct study 
• Informed consent obtained for each participant 
• CRF completion 
• Investigational product accountability 
• Check and review of the regulatory binder and all essential documents 
• Clinical supply inventory 
• SAE reporting 
• Enrollment issues and targets 
• Protocol amendment and their approval by the IRB 
• Significant protocol deviations 
• Personnel changes 

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• Updated regulatory documentation 
• Any other issue as deemed important to the conduct of the study 
9.3.4 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by 
the Research Quality Assurance Office, IRB, the sponsor, and government 
regulatory bodies, of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.).  The 
investigator will ensure the capability for inspections of applicable study-related 
facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
9.3.5 Study Closure 
Upon study closure a final evaluation of the data will ensure that all forms are 
present and complete. Data will be maintained in a secure location for the 
appropriate duration as described in section 9.4.6. At the conclusion of this term, 
all forms will be shredded and destroyed.   
 
9.4 
Data Management  
The online REDCap software system provided by UNC’s TraCS Institute will be 
used for data collection and management, which will ensure that data collected 
are consistent and follow standardized coding. Data will be entered into REDCap 
by the study coordinator within 5 business days. 
9.4.1 Data Quality  
The study team will adhere to the Department of Radiology Internal Monitoring 
and Quality Assurance Standard Operating Procedures to ensure data quality is 
maintained for this study. The Department of Radiology’s Internal Monitoring 
and Quality Assurance program will verify a random selection of at least 25% of 
all source documents for accuracy and completeness. 
 
9.4.2 Missing Value Documentation  
The study case report form (CRF) is the primary data collection instrument for the 
study.  All data requested on the CRF must be recorded.  All missing data must be 
explained.  If a space on the CRF is left blank because the procedure was not done 
or the question was not asked, write “N/D”.  If the item is not applicable to the 
individual case, write “N/A”.  All entries should be printed legibly in black ink.  If 
any entry error has been made, to correct such an error, draw a single straight line 
through the incorrect entry and enter the correct data above it.  All such changes 
must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, 
then initial and date it. 
 
Every attempt will be made to ensure that there is as little missing data as possible 
including reminder phone calls and follow-up phone calls, if a subject misses a 

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visit.  If subjects withdraw, the reason for subject withdrawal will be documented 
in the study database. 
 
9.4.3 Database Documentation  
Copies of completed CRFs with subject IDs will be scanned and sent to the lead 
study coordinator at UNC for verification through the study database.  All study 
data should be entered in REDCap within 5 business days to ensure timely entry. 
9.4.4 Software  
The online REDCap software system provided by UNC’s TraCS Institute will be 
used for this study.  
9.4.5 Documentation  
The research coordinator will monitor the study files on a monthly basis to ensure 
the appropriate regulatory and IRB documentations are on file and up to date. The 
research coordinator will also be responsible for ensuring proper study 
documentation in order to verify compliance with Institutional policy, IRB, FDA 
and GCP guidelines in the following areas: Informed consent, Protocol, Source 
Documents and Electronic Case Report Forms. 
 
The co-principal investigators and research coordinator will be responsible for 
maintaining IRB correspondence. IRB approved forms maintained, as part of the 
study will include the subject consent form and the HIPAA authorization form. 
9.4.6 Data archival and data sharing 
It is the investigators’ responsibility to retain study essential documents during the 
investigation and for a period of 2 years after the latter of the following two dates: 
The date on which the investigation is terminated or completed, or the date that 
the records are no longer required for purposes of supporting a premarket 
approval application or a notice of completion of a product development protocol. 
These documents should be retained for a longer period if required by an 
agreement with the sponsor.  In such an instance, it is the responsibility of the 
sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained. 
 
Research records and original signed consent forms are to be retained by principal 
investigator for at least 6 years if the form includes authorization for use of 
private health information.   Investigators may need to retain these documents for 
a longer period if required by an agreement with a sponsor or per other applicable 
regulatory requirements.  The 6 year minimum retention of authorizations 
complies with the privacy regulation requirements. 
 

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9.5 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, 
and well-being of the study patient requires alternative treatment, the study shall 
be conducted exactly as described in the approved protocol.   
9.5.1 Emergency Modifications 
UNC investigators may implement a deviation from, or a change of, the protocol 
to eliminate an immediate hazard(s) to trial subjects without prior UNC’s 
IRB/IEC approval/favorable opinion.   
 
For any such emergency modification implemented, an IRB modification form 
must be completed by UNC Research Personnel within five (5) business days of 
making the change.   
9.5.2 Protocol Deviations and Violations 
According to UNC’s IRB, a protocol deviation is any unplanned variance from an 
IRB approved protocol that:  
• Is generally noted or recognized after it occurs 
• Has no substantive effect on the risks to research participants 
• Has no substantive effect on the scientific integrity of the research plan 
or the value of the data collected  
• Did not result from willful or knowing misconduct on the part of the 
investigator(s).  
 
An unplanned protocol variance is considered a violation if the variance meets 
any of the following criteria:  
• Has harmed or increased the risk of harm to one or more research 
participants. 
• Has damaged the scientific integrity of the data collected for the study. 
• Results from willful or knowing misconduct on the part of the 
investigator(s). 
• Demonstrates serious or continuing noncompliance with federal 
regulations, State laws, or University policies. 
 
If a deviation or violation occurs please follow the guidelines below: 
 
Protocol Deviations: UNC personnel will record the deviation and report to any 
sponsor or data and safety monitoring committee in accordance with their 
policies.  Deviations should be summarized and reported to the IRB at the time of 
continuing review. 
 
Protocol Violations: Violations should be reported by UNC personnel within one 
(1) week of the investigator becoming aware of the event using the same IRB 
online mechanism used to report Unanticipated Problems.   
 
Unanticipated Problems: 

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Any events that meet the criteria for “Unanticipated Problems” as defined by 
UNC’s IRB must be reported by the study team using the IRB’s web-based 
reporting system.   
9.6 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be 
originated and documented by the Principal Investigator at UNC.  It should also 
be noted that when an amendment to the protocol substantially alters the study 
design or the potential risk to the patient, a revised consent form might be 
required.   
 
The written amendment, and if required the amended consent form, must be sent 
to UNC’s IRB for approval prior to implementation.  
9.7 
Record Retention 
Study documentation includes all eCRFs, data correction forms or queries, source 
documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and 
approval, signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical 
activities and all reports and records necessary for the evaluation and 
reconstruction of the clinical research study. 
 
Government agency regulations and directives require that all study 
documentation pertaining to the conduct of a clinical trial must be retained by the 
study investigator.  In the case of a study with a drug seeking regulatory approval 
and marketing, these documents shall be retained for at least two years after the 
last approval of marketing application in an International Conference on 
Harmonization (ICH) region.  In all other cases, study documents should be kept 
on file until three years after the completion and final study report of this 
investigational study. 
9.8 
Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the 
site in accordance with Title 21 of the Code of Federal Regulations and/or the 
Declaration of Helsinki.  The Principal Investigator is responsible for personally 
overseeing the treatment of all study participants.  The Principal Investigator must 
assure that all study site personnel, including sub-investigators and other study 
staff members, adhere to the study protocol and all FDA/GCP/NCI regulations 
and guidelines regarding clinical trials both during and after study completion. 
 
10.0 PLANS FOR PUBLICATION 

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Study results will be submitted to a peer-reviewed journal for publication. This 
study will also be listed on Clinicaltrials.gov and study results will be posted in 
accordance with appropriate regulations and ICJME requirements.  
 
Neither the complete nor any part of the results of the study carried out under this 
protocol, nor any of the information provided by the sponsor for the purposes of 
performing the study, will be published or passed on to any third party without the 
consent of the study sponsor. Any investigator involved with this study will be 
obligated to provide the sponsor with complete test results and all data derived 
from the study. 
 
11.0 REFERENCES 
1. 
Parsons JK. Benign Prostatic Hyperplasia and Male Lower Urinary Tract 
Symptoms: Epidemiology and Risk Factors. Current bladder dysfunction reports. 
2010;5(4):212-8. 
2. 
Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, et al. 
Morbidity, mortality and early outcome of transurethral resection of the prostate: a 
prospective multicenter evaluation of 10,654 patients. The Journal of urology. 
2008;180(1):246-9. 
3. 
Uchida T, Ohori M, Soh S, Sato T, Iwamura M, Ao T, et al. Factors influencing 
morbidity in patients undergoing transurethral resection of the prostate. Urology. 
1999;53(1):98-105. 
4. 
Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. 
EAU guidelines on the treatment and follow-up of non-neurogenic male lower 
urinary tract symptoms including benign prostatic obstruction. European urology. 
2013;64(1):118-40. 
5. 
Kuntz RM, Lehrich K, Ahyai SA. Holmium laser enucleation of the prostate versus 
open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of 
a randomised clinical trial. European urology. 2008;53(1):160-6. 
6. 
Carnevale FC, Antunes AA. Prostatic Artery Embolization for Enlarged Prostates 
Due to Benign Prostatic Hyperplasia. How I Do It. Cardiovascular and 
interventional radiology. 2013. 
7. 
Pisco JM, Rio Tinto H, Campos Pinheiro L, Bilhim T, Duarte M, Fernandes L, et al. 
Embolisation of prostatic arteries as treatment of moderate to severe lower urinary 
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particles and calibrated microspheres. Radiology. 2002;224(2):436-45. 

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11. Sun F, Sanchez FM, Crisostomo V, Diaz-Guemes I, Lopez-Sanchez C, Uson J, et 
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hyperplasia: randomised, open label, non-inferiority trial. BMJ. 2018 Jun 
19;361:k2338. doi: 10.1136/bmj.k2338. 
 
 
12.0 APPENDICES 

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL 
Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
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12.1 
International Prostate Symptom Score (IPSS) 
 

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Non-Oncology Imaging Protocol Template 
DEPARTMENT OF RADIOLOGY 
 
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Non-Oncology Imaging Protocol Template 
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12.2 
Adverse Event Questionnaires