A Study Evaluating Intraoperative Application of Platelet-Rich Plasma to the Neurovascular Bundles During Nerve-Sparing Radical Prostatectomy: Initial Technical Description and Prospective Early Postoperative Outcomes Analysis
Phase: NA
Conditions: Prostate Cancer
Sponsor: Mayo Clinic

 
 
 
 
 
MC2051 / 16-001320 
 
 
A Study Evaluating Intraoperative Application of Platelet-Rich 
Plasma to the Neurovascular Bundles During Nerve-Sparing 
Radical Prostatectomy: Initial Technical Description and 
Prospective Early Postoperative Outcomes Analysis 
 
 
NCT02957149 
 
 
Document Date: 06/11/2018 

 
 
A Study Evaluating Intraoperative Application of Platelet-Rich Plasma to the 
Neurovascular Bundles During Nerve-Sparing Radical Prostatectomy:  Initial 
Technical Description and Prospective Early Postoperative Outcomes Analysis 
 
 
Regulatory Sponsor: 
Matthew T. Gettman, MD 
Mayo Clinic, Department of Urology 
200 First Street SW 
Rochester, MN  55905 
Phone:  507-284-2297 
 
 
Study Product: 
Platelet-Rich Plasma  
Protocol Number: (IRBe) 
 
16-001320  
 
IDE Number: 
16915 
 
 
     Initial version: 
 
 
[03/09/16] Version (1.0) 
 
 
 
 
[04/08/16] Version (2.0) 
 
 
 
 
[06/08/16] Version (3.0)  
 
 
 
 
[05/16/18] Version (4.0) 
[06/11/18] Version (5.0) 
Version 
No.  
Date 
Major Changes 
1 
09 Mar 16 
Initial 
2 
08 Apr 16 
UNK 
3 
08 Jun 16 
UNK 
4 
16 May18  
6.1: Updated baseline PSA and CBC w/differential documentation 
procedure; 6.2: AE assessment via medical record review; 6.3:  AE 
assessment and vitals collected via medical record review; 6.4: visit 4 
may be done on site or remotely  Outside records for physical exam 
and vitals will not be requested if visits are done remotely. 6.5: visit 5 
may be done on site or remotely. Outside records for physical exam 
and vitals will not be requested if visits are done remotely. Allowable 
PSA window is +/- 21d; 6.8: Protocol Schedule of Events was 

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Table of Contents 
 
STUDY SUMMARY ...................................................................................................................................... 5 
1 
INTRODUCTION ................................................................................................................................. 6 
1.1 
BACKGROUND .................................................................................................................................... 6 
1.2 
INVESTIGATIONAL AGENT .................................................................................................................... 6 
1.3 
PRECLINICAL DATA ............................................................................................................................. 7 
1.4 
CLINICAL DATA TO DATE..................................................................................................................... 7 
1.5 
DOSE RATIONALE AND RISK/BENEFITS .................................................................................................. 7 
2 
STUDY OBJECTIVES .......................................................................................................................... 8 
3 
STUDY DESIGN ................................................................................................................................... 8 
3.1 
GENERAL DESIGN ............................................................................................................................... 8 
3.2 
PRIMARY STUDY ENDPOINTS ................................................................................................................ 9 
3.3 
SECONDARY STUDY ENDPOINTS ........................................................................................................... 9 
4 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL ........................................................ 9 
4.1 
INCLUSION CRITERIA ........................................................................................................................... 9 
4.2 
EXCLUSION CRITERIA ........................................................................................................................ 10 
4.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING ....................................................................... 10 
4.4 
EARLY WITHDRAWAL OF SUBJECTS .................................................................................................... 10 
4.4.1 
When and How to Withdraw Subjects ........................................................................................ 10 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects .............................................................. 11 
4.4.3 
Replacement of Subjects ........................................................................................................... 11 
If subjects withdraw from the study, they will be removed from the final study cohort.  In the situation of a 
subject withdrawing from the study, we will continue to recruit subjects such that 20 total subjects complete 
the entire study with 18 months of followup. ............................................................................................ 11 
5 
STUDY DRUG .................................................................................................................................... 11 
5.1 
DESCRIPTION .................................................................................................................................... 11 
5.2 
TREATMENT REGIMEN ....................................................................................................................... 11 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ................................................................ 11 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ......................................................................... 11 
5.4.1 
Specifics of PRP Sample Preparation ........................................................................................ 13 
5.5 
SUBJECT COMPLIANCE MONITORING ................................................................................................... 13 
5.6 
PRIOR AND CONCOMITANT THERAPY .................................................................................................. 13 
5.7 
PACKAGING ...................................................................................................................................... 13 
5.8 
MASKING/BLINDING OF STUDY .......................................................................................................... 13 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN ................................................................................. 14 
5.9.1 
Receipt of Drug Supplies .......................................................................................................... 14 
5.9.2 
Storage ................................................................................................................................... 14 
5.9.3 
Dispensing of Study Drug ......................................................................................................... 14 
5.9.4 
Return or Destruction of Study Drug ......................................................................................... 14 
6 
STUDY PROCEDURES ...................................................................................................................... 14 
6.1 
VISIT 1; SCREENING AND BASELINE .................................................................................................... 14 
6.2 
VISIT 2; SURGERY ............................................................................................................................. 14 
updated 
5 
11 June 18 
6.4: visit 4 Outside records for physical exam and vitals will be 
requested if visits are done remotely. 6.5: visit 5  Outside records for 
physical exam and vitals will be requested if visits are done remotely 

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6.3 
VISIT 3:  POST-OPERATIVE DAY 2 (POD 2) ........................................................................................... 15 
6.4 
VISIT 4:  WEEK 1 ............................................................................................................................... 15 
6.5 
VISIT 5: WEEK 12 .............................................................................................................................. 15 
6.6 
VISIT 6:  MONTH 6 ............................................................................................................................. 15 
6.7 
VISITS 7, 8 AND 9: MONTHS 9, 12 AND 18 ............................................................................................. 16 
6.8 
PROTOCOL SCHEDULE OF EVENTS ....................................................................................................... 16 
7 
STATISTICAL PLAN ......................................................................................................................... 17 
7.1 
SAMPLE SIZE DETERMINATION ........................................................................................................... 17 
7.2 
STATISTICAL METHODS ..................................................................................................................... 17 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ............................................................................................. 17 
8 
SAFETY AND ADVERSE EVENTS ................................................................................................... 18 
8.1 
DEFINITIONS ..................................................................................................................................... 18 
8.2 
RECORDING OF ADVERSE EVENTS ....................................................................................................... 19 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS .......................................... 20 
8.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB ............................................................. 20 
8.3.2 
Sponsor-Investigator reporting: Notifying the FDA ..................................................................... 20 
8.4 
UNMASKING/UNBLINDING PROCEDURES ............................................................................................. 21 
8.5 
STOPPING RULES ............................................................................................................................... 21 
8.6 
MEDICAL MONITORING ..................................................................................................................... 21 
9 
DATA HANDLING AND RECORD KEEPING .................................................................................. 21 
9.1 
CONFIDENTIALITY ............................................................................................................................. 21 
9.2 
SOURCE DOCUMENTS ........................................................................................................................ 22 
9.3 
CASE REPORT FORMS ........................................................................................................................ 22 
9.4 
DATA MANAGEMENT......................................................................................................................... 22 
9.4.1 
Data Processing ...................................................................................................................... 22 
9.4.2 
Data Security and Confidentiality .............................................................................................. 22 
9.4.3 
Data Quality Assurance ............................................................................................................ 23 
9.4.4 
Data Clarification Process ....................................................................................................... 23 
9.5 
RECORDS RETENTION ........................................................................................................................ 23 
10 
STUDY MONITORING, AUDITING, AND INSPECTING ................................................................ 23 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 23 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 23 
11 
ETHICAL CONSIDERATIONS ......................................................................................................... 24 
12 
STUDY FINANCES ............................................................................................................................ 24 
12.1 
FUNDING SOURCE ......................................................................................................................... 24 
13 
PUBLICATION PLAN ....................................................................................................................... 24 
14 
REFERENCES ................................................................................................................................... 24 
14.1 
ATTACHMENTS ............................................................................................................................. 26 
14.1.1 
Expanded Prostate Cancer Index Composite (EPIC)  ............................................................. 26 
14.1.2 
Sexual Health Inventory for Men (SHIM) ............................................................................... 26 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DSMB 
Data and Safety Monitoring Board 
ED 
Erectile Dysfunction 
EPIC 
Expanded Prostate Cancer Index Composite 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug (Application) 
IRB 
Institutional Review Board 
NVB 
Neurovascular Bundle 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PRP 
Platelet rich plasma 
RP 
Radical Prostatectomy 
PSA 
Prostate-Specific Antigen 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SHIM 
Sexual Health Inventory for Men 
SOP 
Standard Operating Procedure 
 
 
 
 

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Study Summary 
Title 
A Study Evaluating Intraoperative Application of Platelet-Rich Plasma 
to the Neurovascular Bundles During Nerve-Sparing Radical 
Prostatectomy:  Initial Technical Description and Prospective Early 
Postoperative Outcomes Analysis 
Running Title 
PRP Application During RP  
Protocol Number 
16-001320 
Methodology 
Open label 
Overall Study 
Duration 
18 months  
Subject Participation 
Duration 
18 months  
Single or Multi-Site  
Single site 
Objectives 
To evaluate the safety, tolerability, feasibility and efficacy of using 
platelet rich plasma to facilitate early nerve healing and decrease erectile 
dysfunction after nerve-sparing radical prostatectomy.  
Number of Subjects 
20 
Diagnosis and Main 
Inclusion Criteria 
Post-surgical erectile and urinary dysfunction. Main inclusion criteria 
are men, aged 50-60 years, with normal sexual function and regular 
sexual partner, undergoing RP for newly diagnosed prostatic 
adenocarcinoma.  
Study Product, Dose, 
Route, Regimen 
Autologous Platelet-Rich Plasma  The dose is approximately 1,000,000 
platelets/mL and the product is applied topically to the neurovascular 
bundle once during radical prostatectomy  
Duration of 
Administration 
One time drug administration with duration of drug application is 
approximately 4 hours. 
Reference therapy 
None 
Statistical 
Methodology 
The safety evaluation will focus on the number of adverse events 
including local reactions, expected serious adverse events and 
unexpected serious adverse events.  All events will be collected, 
recorded and assessed for severity as a means to facilitate the reporting 
process.  All patients will undergo an assessment of sexual and urinary 
function and oncologic outcomes at 3, 6, 9, 12 and 18 months after 
surgery.  All patients will be evaluated for perioperative complications, 
length of stay, and need for blood transfusion.    
 
 

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1 Introduction 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the applicable United States government regulations and Mayo Clinic research 
policies and procedures. The described study will be conducted in compliance with the protocol 
and associated Federal regulations, and all applicable institutional research requirements.   
 
1.1 
Background 
Prostate cancer is a common problem worldwide with an estimated incidence of 1.1 million 
cases and 307, 000 deaths in 2012.  Advancing age, black race, and poor health literacy are 
known risk factors for development of prostate cancer.  Radical prostatectomy remains the most 
common surgical treatment for prostate cancer with excellent oncologic outcomes.   With the 
development of anatomic RP, ED after surgery has decreased but the risk is still a significant 
treatment concern.  Even with nerve-sparing RP, a significant proportion of man can experience 
transient or even permanent ED.  The etiology of ED after nerve-sparing RP is multifactorial, 
however common factors contributing to the problem related to nerve damage secondary to 
thermal or mechanical trauma.1-3 
 
Recovery of sexual function after RP may depend on nerve healing or nerve-regrowth from the 
remaining NVB.   Until now, this has been thought to be a time-dependent process.  New 
evidence suggests that growth factors play an important role in this process.  Platelets are known 
to contain many growth factors such as platelet-derived growth factor, insulin growth factor 1, 
vascular endothelial growth factor and transforming growth factor beta.  At the time of RP, 
whole blood containing platelets and other hemostatic substances is observed to have an 
intraoperative impact on repairing the neurovascular bundle.  At the time of RP, platelets are 
functioning in a homologous manner to counteract the surgical trauma required to remove the 
prostate.  At the time of surgery, the platelets demonstrate a physiologic response by releasing 
growth factors to help repair the NVB.   
 
Growth factors such as vascular endothelial growth factor, insulin growth factor -1, and brain-
derived growth factor have been shown to promote neuronal regeneration and increase the 
presence neuronal nitric oxide synthase in cavernosal nerve tissue.1    A prior report has evaluated 
the use of dehydrated human amnion/chorion membrane allograft nerve wrap as a means to 
deliver growth factors and anti-inflammatory substances during RP.  In this study, allograft 
enhanced functional recovery yet this approach required placement of a foreign body.4      
 
1.2 
Investigational Agent 
PRP is prepared by specialized centrifugation of a patient’s own whole blood.5    The PRP 
product that is created is a platelet concentrate of approximately 1,000,000 platelets/mL.  The 
morphology and function of the platelets in the whole blood sample used to create the product 
and morphology and function of the platelets in the prepared PRP sample are identical.  In both 
instances during RP, the platelets are activated to release growth factors that help repair the NVB 
that is traumatized during surgery. 
 

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In general, platelets are known to contain many growth factors such as platelet-derived growth 
factor, insulin growth factor 1, vascular endothelial growth factor and transforming growth factor 
beta that can have a healing effect and regenerative effect on nerve tissue.  By concentrating the 
number of platelets by volume, the healing and regenerative impact of PRP on the NVB is 
thought to be augmented.  The basic function of the platelet is not changed, but the repairing 
effect on the NVB is increased by the fact that the concentration of the platelets compared to 
whole blood has been increased.      
 
1.3 
Preclinical Data 
In animal models, application of PRP has promoted healing of cavernous nerves in an 
experimental nerve crush model when compared to controls.1-3   
 
1.4 
Clinical Data to Date 
To date, there is no available clinical research data on use of PRP application to the NVB intra-
operatively at the time of nerve-sparing RP.  Clinical application of PRP using a similar topical 
application, however, has been found to be safe and efficacious for a variety of musculoskeletal 
indications including osteoarthritis, chronic tendinopathy, nerve injury and ligamentous 
injuries.5-10     
 
1.5 
Dose Rationale and Risk/Benefits 
The PRP sample will be prepared in the operating room from a sample of whole blood while the 
patient is undergoing RP.  The PRP sample will be prepared by trained personnel from the Mayo 
Clinic Division of Transfusion Medicine using a commercially available, FDA-cleared, platelet 
concentration device in accordance with the manufacturer’s instructions ((510K# BK110046; 
Angel® Concentrated Platelet Rich Plasma [cPRP] System, Cytomedix, Inc.,  Gaithersburg, MD 
USA).  The Division of Transfusion Medicine has developed a detailed SOP that all staff using 
the 
Angel® 
system 
must 
follow 
in 
order 
to 
operate 
the 
Angel® 
device 
(http://mayoweb.mayo.edu/txmed-docs/documents/002696.pdf).  
  
At the present time, the Angel® device is used in routine clinical use in the department of 
orthopedics and physical medicine and rehabilitation at Mayo Clinic.  The Angel® system yields 
platelet concentrations of approximately 1,000,000 platelets/ mL of plasma.  This dose of PRP 
has been demonstrated to have clinical efficacy and safety for topical applications used in 
orthopedic and physical medicine and rehabilitation applications. 
 
Clinical experience with the Angel® device has demonstrated that a sample of 180 mL of whole 
blood will yield approximately 10 mL of PRP.  This dose would be divided equally and will 
permit even topical application to the NVB intra-operatively at RP.  The study proposes a one-
time dosage period and clinical studies to date report that the duration of action for PRP is 
approximately 4 hours.       
 
Risks from study participation may be related to obtaining the whole blood to produce the PRP 
sample or the effects of the PRP sample on the healing process after surgery.  The collection of 

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blood would be obtained under general anesthesia required for RP using sites needed for the 
general anesthetic.  Obtaining the whole blood could results in pain, bruising, and infection at the 
needle site.  Obtaining a collection of blood could also have an adverse effect the patient’s 
circulating blood volume and could result in lightheadedness or hypotension after surgery.  In 
some instances this could require that a blood transfusion be given.  Since the risk of blood 
transfusion for RP ranges from <1 to 5%, the independent risk of the blood collection alone 
requiring a postoperative blood transfusion is very low.   
 
Platelets contain growth factors and the hypothesis of the study is that the growth factors will 
augment healing of the NVB after surgery.  There is a possibility that the growth factors could 
cause adverse healing of the NVB.  There is also a possibility that if residual prostate tissue is 
present that growth of the tissue could occur.  There is a low risk that if the residual prostate 
tissue were cancerous that the growth factors could contribute to a higher chance of cancer 
recurrence.  The relatively short term effect (<4 hours) of PRP applied topically will significantly 
decrease the risk of promoting growth of prostate tissue.  It is also defined approximately 15-
20% of men undergoing radical prostatectomy can expect to have recurrence after surgery.  
Based on the physiology of growth factors, it is thought the risk of PRP independently increasing 
risk of prostate cancer recurrence is very unlikely.        
 
Benefits are thought to outweigh the risks of the study.  Topical application of autologous PRP at 
the time of RP will permit supraphysiologic doses of growth factors to be present on the NVB.  
The growth factors may help promote healing and/or decrease the surgical trauma associated 
with RP.  This may augment healing and recovery of erectile function after RP as measured 
during the 18 month study duration. Subjects will be asked to complete questionnaires regarding 
urological symptoms, quality of life (urinary control and ED) before and at 3, 6, 9, 12, and 18 
months following the procedure.   
2 Study Objectives 
Primary Objective:  To evaluate the safety and tolerability of using platelet rich plasma on the 
NVB after nerve-sparing radical prostatectomy. 
 
Secondary Objective(s):   
 To assess the feasibility of applying 1 dose of PRP intra-operatively at the time of 
bilateral nerve-sparing RP in 20 men with prostatic adenocarcinoma. 
 To assess preliminary clinical benefit/efficacy of using PRP in facilitating early nerve 
healing and decreasing ED at 3, 6, 9, 12 and 18 months after nerve-sparing RP.To assess 
change in urological function by measuring urinary control before and at 3, 6, 9, 12 and 
18 months after PRP treatment during nerve sparing surgery. 
 
3 Study Design 
3.1 
General Design 
This is an  open label, human study evaluating the safety and tolerability, feasibility, and 
efficacy, s of PRP applied in topical fashion intra-operatively during RP. Subjects will be 
screened at outpatient clinic visit appointments and interested qualified subjects will be 

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consented and offered participation in this trial.  The study aims to enroll 20 men with newly 
diagnosed prostatic adenocarcinoma that are planning to undergo bilateral nerve-sparing RP.  
Once written consent has been obtained baseline functional and laboratory assessments will be 
obtained and patients will be followed for the expected duration for study participation of 18 
months.   
 
Since the present study is a single-arm study, evaluation of safety and efficacy parameters will 
have to be performed using benchmark outcomes from historical controls.  At Mayo Clinic, all 
patients undergoing RP are included in the Mayo Clinic Prostatectomy Registry.  The 
prostatectomy registry is prospectively maintained by study nurses.  The prostatectomy registry 
maintains detailed oncologic and quality of life data using PSA testing and the same validated 
questionnaires proposed by the current study.  The comparator for the present study would be 
other subjects from the Mayo Clinic Prostatectomy Registry that underwent bilateral nerve-
sparing RP within the same study dates and met all of the other inclusion and exclusion criteria 
for the present study but did not have PRP applied intraoperatively to the neurovascular bundles.       
 
3.2 
Primary Study Endpoints 
 
Primary Objective:   
To evaluate the safety and tolerability of using platelet rich plasma on the NVB after nerve-
sparing radical prostatectomy. 
3.3 
Secondary Study Endpoints 
Secondary Objective(s):   
 To assess the feasibility of applying 1 dose of PRP intra-operatively at the time of 
bilateral nerve-sparing RP in 20 men with prostatic adenocarcinoma. 
 To assess preliminary clinical benefit/efficacy of using PRP in facilitating early nerve 
healing and decreasing ED at 3, 6, 9, 12 and 18 months after nerve-sparing RP. 
 To assess change in urological function by measuring urinary continence before and at 3, 
6, 9, 12 and 18 months after PRP treatment during nerve sparing surgery. 
 
4 Subject Selection Enrollment and Withdrawal 
4.1 
Inclusion Criteria 
The study involves men newly diagnosed with prostatic adenocarcinoma that are selecting RP 
for treatment.  The men identified for the study would be from the outpatient clinic setting and 
all men would be able to give appropriate informed consent.   
The following are inclusion criteria for the study: 
 
 Newly diagnosed, clinically localized prostatic adenocarcinoma 
 Age 50 – 60 years 
 Male gender 
 Normal preoperative sexual function (as defined by Sexual Health Inventory for Men 
questionnaire score > 19; see attachment) 

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 
Normal urinary continence (as defined by  Expanded Prostate Cancer Index Composite, 
question 5, response = none, see attachment)Regular sexual partner 
 
4.2 
Exclusion Criteria 
 
 Unable or unwilling to provide informed consent 
 Vulnerable study populations 
 Active systemic infection 
 Diabetes Mellitus diagnosis  
 Preexisting ED or urinary incontinence 
 Metastatic or locally advanced prostatic adenocarcinoma on preoperative evaluation 
 Men found grossly or pathologically to have locally advanced or metastatic disease at the 
time of RP 
 An estimated blood loss of >750 mL at the time of RP 
 Treatment prior to surgery with any form of hormones, antiandrogens or androgen 
deprivation therapy 
 Use of an antidepressant, beta blocker or ED medication at the time of study 
 Screening Men without a regular sexual partner 
 Use of aspirin or heparin 2 weeks before RP 
 Need for use of aspirin or heparin for 2 weeks or more after RP. 
 
4.3 
Subject Recruitment, Enrollment and Screening 
Subjects will be recruited for the study in the outpatient clinic environment by the PI and Co-
Investigators.  Identified subjects will discuss the study with a Study Coordinator.  At that time, 
the inclusion and exclusion criteria will be discussed as well as the rationale, the potential 
benefits, and potential risks associated with the study.  The recruitment, enrollment, and 
screening procedures will occur in the outpatient clinic setting.  If subjects want to proceed with 
the study, informed consent will be obtained by the study coordinator or investigator.  
4.4 
Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
A subject may withdraw at any time prior to RP. There are no adverse safety considerations in 
the study for those deciding to withdraw from the study.  Subjects may choose to discontinue 
study participation after RP surgery and will be counted as withdrawn     
 
A subject consenting to the study will receive PRP at the time of RP unless the surgical team 
decides intra-operatively to withdraw a subject from the study in the following situations:  
 
 Estimated blood loss greater than 750 mL 
 
 Evidence of disease grossly and/or pathologically that the prostate cancer is locally 
advanced or metastatic   

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 Documentation of the reason for withdrawal will be retained in the study files. 
4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
As part of normal clinical care, subjects that have withdrawn from the study will still have 
routine postoperative monitoring after RP.  Any collected study data from withdrawn subjects 
will not be included in the data analysis.  Since all patients have their outcomes tracked after RP 
at Mayo Clinic, postoperative data would be available should this be needed as part of another 
study protocol.   
 
4.4.3 Replacement of Subjects 
If subjects withdraw from the study, they will be removed from the final study cohort.  In the 
situation of a subject withdrawing from the study, we will continue to recruit subjects such that 
20 total subjects complete the entire study with 18 months of follow-up.   
 
5 Study Drug  
5.1 
Description 
The PRP product will appear as a liquid.  
5.2 
Treatment Regimen 
The PRP product will be created intra-operatively by personnel from the Division of Transfusion 
Medicine from a 180 mL sample of the patient’s whole blood.  An FDA-cleared platelet 
concentration device (Angel® Concentrated Platelet Rich Plasma [cPRP] System, Cytomedix, 
Inc., Gaithersburg, MD USA) in routine clinical use at Mayo Clinic in Rochester, MN will be 
used to create the sample of PRP that will be given one time in topical fashion onto the NVB 
during nerve-sparing RP.  The application of PRP will take approximately 1 minute to perform 
and the treatment duration for the PRP product is estimated at 4 hours.    
5.3 
Method for Assigning Subjects to Treatment Groups 
Not applicable. 
5.4 
Preparation and Administration of Study Drug 
The PRP sample will be prepared in the operating room from a sample of whole blood while the 
patient is undergoing RP.  The PRP sample will be prepared by trained personnel from the Mayo 
Clinic Division of Transfusion Medicine. The Division of Transfusion Medicine has developed a 
detailed SOP that all staff using the Angel® system must follow in order to operate the device 
(http://mayoweb.mayo.edu/txmed-docs/documents/002696.pdf).  At the present time, the 
Angel® device is used in routine clinical use in the department of orthopedics and physical 
medicine and rehabilitation at Mayo Clinic in Rochester, MN.  In many instances, the Angel® 
system yields platelet concentrations of approximately 1,000,000 platelets/ mL of plasma. 
During our planned study we will follow SOP 002696 prior to administration and confirm that 
the concentration of platelets over baseline be at least 2.   This dose of platelets has been 

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demonstrated to have clinical efficacy and safety for topical applications used in orthopedic and 
physical medicine and rehabilitation applications. 
       
In addition, the Division of Transfusion Medicine is accredited by the American Association of 
Blood Banks to perform perioperative activities at Mayo Clinic.  Perioperative activities by 
definition include the intraoperative preparation of PRP.  To achieve accreditation, an institution 
“shall have a structure that clearly defines and documents the parties responsible for the 
following activities:  intraoperative acute normovolemic hemodilution; collection, storage, and 
administration of autologous blood products obtained during intraoperative and postoperative 
autologous blood recovery; and perioperative autologous product production.  Products covered 
under these activities include but are not limited to autologous plasma for reinfusion, injection, 
or topical application, thrombin for topical application, and bone marrow aspirate concentrate for 
topical application.”  
     
The Angel® Concentrated Platelet Rich Plasma (cPRP) System is cleared for use in the U.S. by 
the FDA as an automated blood cell separator.  The device operator’s manual states it’s 
indications for use specifically include the following:  “To be used in the clinical laboratory or 
intra-operatively at the point of care for the safe and rapid preparation of platelet poor plasma 
and platelet concentrate (platelet rich plasma) from a small sample of whole blood or a small 
mixture of blood and bone marrow.  The platelet rich plasma can be mixed with autograft and/or 
allograft bone prior to applications to an orthopedic site.”  The Angel device is contraindicated in 
cases where there is active systemic infection or systemic heparinization. In preparation of this 
research application we have reviewed the United States government electronic CFR (accessed 
March 3, 2016 and current as of March 1, 2016) part 1271 entitled “Human Cells, Tissues, and 
Cellular and Tissue Based Products.” We believe that the PRP created in the study would be 
solely regulated under Section 361 of the Public Health Service Act on the basis of meeting all 
criteria included in part 1271.10:       
 The PRP product created by the Angel® device is minimally manipulated. 
 The PRP product created by the Angel® device is intended only for homologous use, 
following the labeling, advertising, or other indications of the manufacturer’s objective 
intent.     
 The PRP product created does not involve the combination of cells or tissues with 
another article except for water, crystalloid, or a sterilizing preserving or storage agent 
provided that addition of water, crystalloid, or the sterilizing, preserving, or storage agent 
does not raise new clinical safety concerns with respect to the product.  
 The PRP product created does not have a systemic effect and is not dependent upon the 
metabolic activity of living cells for its primary function. 
Furthermore, according to part 1271.15 from the CFR, we note that our proposed use of PRP 
would fulfill item (b) that states, “You are not required to comply with the requirements of this 
part if you are an establishment that removes human cell tissue/products (PRP is an example) 
from an individual and implants such human cell tissues/products into the same individual during 
the same surgical procedure.   
Since we meet all of the criteria established in part 1271.10 and also meet exception criteria 
listed in part 1271.15, we believe that the PRP created in this study would be solely regulated 

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under section 361 of the Public Health Safety Act and that regulation of the created product as a 
drug under section 351 of the Public Health Service Act would not apply.  Accordingly, the need 
to pursue an IND application for the proposed use was not felt to be applicable.  However, upon 
request for an exemption from IND regulations, FDA subsequently decided to regulate this study 
under an Investigational Device Exemption, (IDE) for the investigational use of an approved 
blood separation device.      
5.4.1 Specifics of PRP Sample Preparation  
To prepare the sample, 180 mL of whole blood will be obtained from the patient by venipuncture 
during the RP by Anesthesia personnel.  The whole blood will be placed in the platelet 
concentration device and centrifuged following manufacturer’s instructions.  After final 
processing, the final PRP sample will consist of 10 mL of product that will be used for intra-
operative application.  The PRP created intra-operatively would be placed into a syringe labeled 
“PRP.”  Samples of whole blood and PRP will also be sent to the laboratory for analysis for 
quality control purposes, in accordance with Division of Laboratory Medicine SOP.10    
 
During the RP procedure, PRP will be applied to the NVB after completion of the vesicourethral 
anastomosis and after conventional techniques have been performed to achieve adequate 
hemostasis.  Conventional techniques for hemostasis include the placement of surgical clips or 
suture as required to bleeding sites on the neurovascular bundle.    No additional hemostatic 
products will be applied to the neurovascular bundles during the study.  PRP will be applied 
evenly to the entire length of the NVB by mechanical transfer of product.  For robotic 
procedures, a laparoscopic spoon instrument will be used to deliver the PRP directly to the NVB.  
For open procedures, delivery of PRP will occur via PRP-labelled syringe.  After application of 
PRP, the surgical team will then complete RP in standard fashion.   
5.5 
Subject Compliance Monitoring 
Not applicable. 
5.6 
Prior and Concomitant Therapy 
The following concomitant medicines are not permitted during the study: 
 
 Any type of androgen deprivation therapy 
 
 Aspirin and heparin for 2 weeks before or 2 weeks after the date of PRP application 
 
  Use of an antidepressant, beta blocker or ED medication at the time of study screening 
5.7 
Packaging 
The PRP will be made intra-operatively and will be placed into a syringe labelled PRP.   The 
PRP will be created from the patient for autologous use and none of the created PRP will be 
removed from the operating room.   
5.8 
Masking/Blinding of Study  
Not applicable 

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5.9 
Receiving, Storage, Dispensing and Return 
5.9.1 Receipt of Drug Supplies 
Not applicable 
5.9.2 Storage 
Not applicable 
5.9.3 Dispensing of Study Drug 
Not applicable 
5.9.4 Return or Destruction of Study Drug 
Not applicable 
6 Study Procedures 
6.1 
Visit 1; Screening and Baseline 
Potential study subjects will be identified by study staff, will be provided ample time to review 
the informed consent document, discuss the study procedures and contents of the ICF, have all 
questions answered, have their medical history reviewed, vitals taken, and a physical 
examination performed.  The baseline quality of life assessments with Sexual Health Inventory 
for Men and the Expanded Prostate Cancer Index Composite will be completed by the subject at 
this visit, if not done earlier.  Baseline CBC with differential and platelet count and serum PSA 
samples will be obtained.  If a PSA and CBC with differential and platelet count have not been 
performed during clinic visits at Mayo Clinic within the year prior to the screening visit and the 
subject has scheduled clinical labs before the screening visit, an order will be placed for the 
baseline PSA and CBC with differential and platelet count to ensure there is proper record of test 
result in the Mayo Clinic medical record. If a PSA and CBC with differential and platelet count 
have been performed outside of Mayo Clinic within the year prior to the screening visit and the 
subject does not have scheduled clinical labs before the screening visit, outside results may be 
used to satisfy this study visit with copies retained in study files. The study coordinator will 
confirm the contact information of the outside laboratory facility at the time of the screening visit 
and will request outside laboratory results if not already available in the Mayo Clinic medical 
record. However, all study eligibility requirements; including a review of current medical 
conditions and medications as well as written informed consent must be documented by study 
staff and reviewed for acceptability by an Investigator prior to enrolling the subject into the 
study.   Documentation of any subjects who were consented but subsequently failed the 
screening requirements, including the reason for screen failure, will be retained in study files.   A 
screening/enrollment log will be maintained.  
6.2 
Visit 2; Surgery 
At the time of radical prostatectomy, topical PRP will be prepared and applied topically to the 
NVB. An assessment of adverse events will be conducted via medical record review by the study 
coordinator. 

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6.3 
Visit 3:  Post-operative Day 2 (POD 2) 
Subjects will undergo a review of their medical status and a physical examination. There will be 
a blood draw to assess CBC with differential and platelet count. An assessment of adverse events 
will be conducted by the study coordinator via medical record review. For visit 3 only, vital sign 
readings taken as part of standard of care will be abstracted via medical record review by the 
study coordinator. 
6.4 
Visit 4:  Week 1 
At approximately 1 week after surgery, the urinary catheter placed at the time of RP will be 
removed. This visit is timed at one week post RP to allow for the typical healing period prior to 
removal of catheter.  If clinically indicated, the healing period may require more than 7 days, 
therefore this study visit may occur up to 21 days following the RP. This visit may be completed 
remotely rather than on-site, if the subject decided to have urinary catheter removal done locally. 
Contact with the subject may be by telephone or email, depending upon subject preference. The 
subject will undergo a postoperative check by study staff where quality of life status will be 
assessed with questionnaires. The Questionnaires may be mailed to the subjects (if visit is done 
remotely) with a self-addressed, postage paid, return envelope for completion and return to the 
study site by email, fax or regular mail and will be retained with subject study files. A physical 
examination by a Study Investigator will be performed and vitals will be taken if visit is 
completed on-site. An assessment for adverse events and concomitant medications review will 
be conducted by the study coordinator. Outside records for physical exam and vitals will be 
requested if visit is done remotely. The RP date will be considered Day 0 for determining future 
study visit windows. Per protocol, serum PSA has not been collected at this point and will 
continue to not be collected for remote visit 
6.5 
Visit 5: Week 12 
At approximately 12 weeks after surgery, with an allowable visit window of +/- 14 days, subjects 
will undergo a postoperative check by study staff where quality of life status will be assessed 
with questionnaires. The Questionnaires may be mailed to the subjects with a self-addressed, 
postage paid, return envelope or emailed to the subjects for completion and return to the study 
site by email, fax or regular mail and will be retained with subject study files. This study visit 
may be completed remotely rather than on-site, if more convenient for the subject. Contact with 
subject may be by telephone or email, depending upon subject preference. Subjects will undergo 
a physical examination by a Study Investigator, have vitals taken, and have a serum PSA sample 
drawn. Adverse events will be assessed and concomitant medications will be reviewed by study 
coordinator. Outside records for physical exam and vitals will be requested by study staff if visit 
is done remotely. For subjects returning to the institution, the PSA sample will be drawn in the 
Mayo Clinic clinical laboratory. For subjects completing a remote visit, serum may be collected 
locally using a “mail-in” PSA kit mailed to the subject by study staff. This kit will be mailed 
back to Mayo Clinic for testing. The allowable PSA testing window is +/- 21d. 
6.6 
Visit 6:  Month 6 
At approximately 6 months after surgery, with an allowable visit window of +/- 14 days, subjects 
will undergo a study visit which may be completed remotely rather than on-site, if more 
convenient for the subject. Contact with subject may be by telephone or email, depending upon 
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postage paid, return envelope or emailed to the subjects for completion and return to the study 
site by email, fax or regular mail and will be retained with subject study files.  For remote visits, 
the subject will be contacted to assess changes in concomitant medications and to assess if any 
adverse events have occurred since the previous study visit. Information obtained during 
telephone calls or other contact will be documented in the subject’s study file.  A serum PSA 
sample will be obtained. For subjects returning to the institution, the PSA sample will be 
processed in the Mayo Clinic clinical laboratory.  For subjects completing a remote visit, serum 
may be collected locally using a “mail-in” kit to be mailed to the subject by study staff. This kit 
will be mailed back to Mayo Clinic for testing. Venipuncture may be obtained by a local 
physician or clinic. The allowable PSA testing window is +/- 21d. 
 
6.7 
Visits 7, 8 and 9: Months 9, 12 and 18 
At approximately 9, 12 and 18 months after surgery, with allowable visit windows of +/- 14 
days, subjects will undergo a study visit which may be completed remotely rather than on-site, if 
more convenient for the subject. For remote visits, the SHIM and EPIC Questionnaires may be 
sent to the subjects for completion and returned to the study site by mail, fax or email.   A 
telephone call to the subject will be made to assess changes in concomitant medications and if 
any adverse events have occurred since the previous study visit.  A serum PSA sample will be 
obtained. For subjects returning to the institution, the PSA sample will be analyzed in the Mayo 
Clinic clinical laboratory.  For subjects completing a remote visit, the PSA sample may be 
obtained with venipuncture obtain locally and returned using a “mail-in” kit with analysis to be 
performed by the Mayo Clinic laboratory. The allowable PSA testing window is +/- 21d. 
     
6.8 
Protocol Schedule of Events  
 
 
Study Activity 
Screen/ 
Baseline 
 RP 
POD 
2 
Wk 1  
 
Wk  12 
Mo  
62 
Mo   
92 
Mo  
122 
Mo  
182 
Visit number 
1 
 
2 
Day 0 
3 
 
4 
5 
6 
 
7 
 
8 
 
9 
 
Allowable Visit 
Window from RP 
 
 
 
+21d 
+/- 14d 
+/- 14d +/- 14d 
+/- 14d 
+/- 14d 
Consent 
       X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Concomitant Meds 
X 
 
 
X 
X 
X 
X 
X 
X 
Eligibility Review 
X 
 
 
 
 
 
 
 
 
Physical exam3 
 
X 
 
X 
X 
X 
 
 
 
 
Vital signs2,3 
X 
 
X 
X 
X 
 
 
 
 
Questionnaires1,4 
X 
 
 
 X 
X 
X 
X 
X 
X 

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CBC w/diff, 
platelets 
X 
 
X 
 
 
 
 
 
 
Serum PSA4 
X 
 
 
 
X 
X 
X 
X 
X 
PRP topical 
application 
 
X 
 
 
 
 
 
 
 
Adverse events 
evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
   1 SHIM and EPIC  
   2 Vitals will be abstracted from the medical record for visit 3, post-operative day 2 
3 Week 1 and week 12 visits may be done on-site or via telephone interview or email. Physical exam and vitals will 
be performed for these visits if participant is able to return to Mayo Clinic. Outside records for physical exam and 
vitals will be requested if visits are done remotely.  
4 The 6, 9, 12 and 18 Month visits may be done remotely via telephone interview or email. Completed SHIM/EPIC 
Questionnaires may be returned to study site by mail, email or fax.  PSA testing: A local clinic may be used for 
venipuncture, using mail in lab kit for sample return to Mayo Clinic. PSA testing window for week 12 and 6, 9, 12, 
18 month visit is +/- 21d 
 
7 Statistical Plan 
7.1 
Sample Size Determination 
For the proposed trial, a sample of 20 subjects is proposed.  This sample will permit a statistical 
description of that is required for the primary and secondary objectives.  Use of 20 subjects is in 
the range normally enrolled for trials of this nature.   
7.2 
Statistical Methods 
Descriptive Statistics 
Univariate descriptive statistics and frequency distributions will be calculated, as appropriate for 
all variables.  Baseline values for demographic, clinical, and outcome variables (primary and 
secondary) will be tabulated.  Temporal trends in recovery of erectile function and urinary 
continence will be assessed.  Normal sexual function will be defined as a Sexual Health 
Inventory for Men score of >19.  Normal urinary continence will be defined as a response of 
“none” on question 5 of the Expanded Prostate Cancer Index Composite. 
 
Handling of Missing Data 
Subjects that miss follow-up appointments where data is gathered will be contacted to forward 
missing data records.    
 
Multiplicity 
Not applicable 
 
 
7.3 
Subject Population(s) for Analysis 
Data from all subjects consented for the study and completing postoperative visits will be 
evaluated.   

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8 Safety and Adverse Events 
8.1 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  
 Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; (6) 
breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
 Unanticipated: (i.e. unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, not listed in the IB, or not 
part of an underlying disease. A problem or event is "unanticipated" when it was 
unforeseeable at the time of its occurrence. A problem or event is "unanticipated" when it 
occurs at an increased frequency or at an increased severity than expected, AND 
 Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
Adverse Event 
An untoward or undesirable experience associated with the use of a medical product (i.e. drug, 
device, biologic) in a patient or research subject. 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  Serious problems/events can be well 
defined and include; 
 death 
 life threatening adverse experience 
 hospitalization 
 inpatient, new, or prolonged; disability/incapacity 
 persistent or significant birth defect/anomaly 
 
and/or per protocol may be problems/events that in the opinion of the sponsor-investigator 
may have adversely affected the rights, safety, or welfare of the subjects or others, or 
substantially compromised the research data. 
 
All adverse events that do not meet any of the criteria for serious, should be regarded as non-
serious adverse events.  
 
Adverse Event Reporting Period 
For this study, the study treatment follow-up period is defined as 18 months following the topical 
application of PRP at the time of RP.     
 

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Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
should be recorded as an adverse event if the frequency, intensity, or the character of the 
condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an AE must also be recorded and documented as an AE.  
 
Post-study Adverse Event 
All unresolved AEs should be followed by the sponsor-investigator until the events are resolved, 
the subject is lost to follow-up, or the AE is otherwise explained.  At the last scheduled visit, the 
sponsor-investigator should instruct each subject to report, to the sponsor-investigator, any 
subsequent event(s) that the subject, or the subject’s personal physician, believes might 
reasonably be related to participation in this study.  
 
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an AE if the serum hemoglobin on 
postoperative day 2 is <8 g/dL.  If hemoglobin level is considered an AE, then patient should 
have hemoglobin monitored and if there is a downward trend or if clinical symptoms are 
associated with the value then blood transfusion should be considered.   
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any AE that results in rehospitalization or prolonged hospitalization (greater than 1 week) 
should be documented and reported as a serious AE unless specifically instructed otherwise in 
this protocol.  Any condition requiring surgery should be documented as an AE if the condition 
meets the criteria for an AE.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
AE in the following circumstances:  
 The planned hospitalization for RP. 
 The prolonged hospitalization for diagnosis not related specifically to RP.   
 Surgical procedure not related to RP.   
 
8.2 
Recording of Adverse Events 
At each contact with the subject, the study team must seek information on AE by specific 
questioning and, as appropriate, by examination.  Information on all adverse events should be 
recorded immediately in the source document, and also in the appropriate AE section of an 
electronic adverse event worksheet.  All clearly related signs, symptoms, and abnormal 
diagnostic, laboratory or procedure results should recorded in the document. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 

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events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious AE that occurs after the study period and is considered to be at least 
possibly related to the study treatment or study participation should be recorded and reported 
immediately. 
8.3 
Reporting of Serious Adverse Events and Unanticipated Problems 
When an AE has been identified, the study team will take appropriated action necessary to 
protect the study participant and then complete the Study Adverse Event Worksheet form and 
log.  The sponsor-investigator will evaluate the AE and determine the necessary follow-up and 
reporting required. 
8.3.1 Sponsor-Investigator reporting: notifying the Mayo IRB 
For any SAE, an AE worksheet will be sent to the IRB.  In this situation the PI and study 
coordinators will document the data related to the SAE on the event worksheet and notify the 
IRB using the standard reporting procedure.  The sponsor-investigator will specifically report to 
the Mayo IRB any UPIRTSOs and Non-UPIRTSOs according to the Mayo IRB Policy and 
Procedures. 
 
Information collected on the adverse event worksheet (and entered in the research database):  
 Subject’s name:  
 Medical record number:  
 The date the adverse event occurred:  
 Description of the adverse event:  
 Relationship of the adverse event to the research (drug, surgery, or other intervention):  
 If the adverse event was expected:  
 The severity of the AE: (use a table to define severity scale 1-5) 
 If any intervention was necessary:  
 Resolution: (was the incident resolved spontaneously, or after discontinuing treatment) 
 Date of Resolution:  
 
8.3.2 Sponsor-Investigator reporting: Notifying the FDA 
The sponsor-investigator will report to the FDA all unexpected, serious suspected adverse events 
and reactions according to the required safety reporting timelines, formats and requirements. 
 
Unexpected fatal or life threatening suspected adverse reactions where there is evidence to 
suggest a causal relationship between the study drug/placebo and the AE, will be reported as a 
serious suspected adverse reaction.  This will be reported to the FDA by telephone or by fax 
using FDA Form 3500A, no later than 5 calendar days after the sponsor-investigator’s initial 
receipt of the information about the event and the report will also be made in writing within 10 
days as required under 21 CFR 812.150.   
 
Other unexpected serious suspected adverse reactions where there is evidence to suggest a causal 
relationship between the study drug/placebo and the adverse event, will be reported as a serious 
suspected adverse reaction.  This will be reported to the FDA on FDA Form 3500A, no later than 

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15 calendar days after the sponsor-investigator’s initial receipt of the information about the 
event. 
 
Any clinically important increase in the rate of serious suspected adverse reactions over those 
listed in the protocol or product insert will be reported as a serious suspected adverse reaction.  
This will be reported to the FDA on FDA Form 3500A no later than 15 calendar days after the 
sponsor-investigator’s initial receipt of the information about the event. 
 
Findings from other studies in human or animals that suggest a significant risk in humans 
exposed to the drug will be reported.  This will be reported to the FDA on FDA Form 3500A, no 
later than 15 calendar days after the sponsor-investigators initial receipt of the information about 
the event. 
8.4 
Unmasking/Unblinding Procedures 
Not applicable 
8.5 
Stopping Rules  
Not applicable 
8.6 
Medical Monitoring 
It is the responsibility of the PI to oversee the safety of the study at his/her site.  This safety 
monitoring will include careful assessment and appropriate reporting of adverse events as noted 
above, as well as the construction and implementation of a site data and safety-monitoring plan 
(see section 10  “Study Monitoring, Auditing, and Inspecting”).  Medical monitoring will include 
a regular assessment of the number and type of serious adverse events. 
 
Since the present study is a single-arm study, evaluation of safety and efficacy parameters will 
also be performed using benchmark outcomes from historical controls.  At Mayo Clinic, all 
patients undergoing RP are included in the Mayo Clinic Prostatectomy Registry.  The 
prostatectomy registry is prospectively maintained by study nurses.  The prostatectomy registry 
maintains detailed oncologic and quality of life data using PSA testing and using the same 
validated questionnaires proposed by the current study.  By using other subjects from the Mayo 
Clinic Prostatectomy Registry that underwent bilateral nerve-sparing RP within the same study 
dates (and those that met all of the other inclusion and exclusion criteria for the present study but 
did not have PRP applied intraoperatively to the neurovascular bundles), another means to 
compare the safety and preliminary evidence of efficacy will be achieved.       
 
9 Data Handling and Record Keeping 
9.1 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of HIPAA.  Those regulations require a signed subject authorization informing the 
subject of the following:  
 What PHI will be collected from subjects in this study 
 Who will have access to that information and why 

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 Who will use or disclose that information 
 The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (long term survival status that 
the subject is alive) at the end of their scheduled study period. 
9.2 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.  Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
9.3 
Case Report Forms 
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 use “white-out” for errors.  For clarification 
of illegible or uncertain entries, print the clarification above the item, then initial and date it.  If 
the reason for the correction is not clear or needs additional explanation, neatly include the 
details to justify the correction. 
9.4 
Data Management 
The process for managing data will be standardized for each patient using Case Report Form.  
Information will be recorded on the CRF directly at the time of study visits or completed based 
on entries made in the electronic medical.  In situation where data is missing, subjects will be 
contacted to reconcile the missing data entries.   
9.4.1 
Data Processing 
Data will be maintained in accordance with institutional research standards in an electronic 
format.   
9.4.2 
Data Security and Confidentiality 
Data will be kept in an electronic format with confidentiality maintained by having only the 
study coordinators and investigators with access to the data.  Subjects will not have their name 
recorded on the database and identification will only be made by registration/study code number 
and/or subject initials.    

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9.4.3 
Data Quality Assurance 
Study staff will cross check the accuracy of the database to the CRFs entries and source data.   
9.4.4 
Data Clarification Process 
If there are concerns about the accuracy of the reported data, then the medical record will be 
reviewed for clarification.  Subjects may be contacted as part of ongoing regular clinical care as 
part of their postoperative management of prostate cancer.  
9.5 
Records Retention 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents. 
 
The sponsor-investigator will retain the specified records and reports for the longest of these time 
frames: 
1. If conducted under an IND, until 2 years after the marketing application is approved for 
the drug; or, if a marketing application is not submitted or approved for the drug, until 2 
years after shipment and delivery of the drug for investigational use is discontinued and 
the FDA has been so notified. OR 
2. As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy” http://mayocontent.mayo.edu/research-policy/MSS_669717   
10 Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
Periodic study monitoring will be provided on behalf of the Sponsor by staff from the Mayo 
Clinic Office of Research Regulatory Support. Monitoring may include but will not necessarily 
be limited to review of the study regulatory documents, source data and database entries 
throughout the duration of the study to help ensure the completeness, validity and integrity of the 
data.  Original signed informed consent forms will be reviewed. Written monitoring reports with 
findings and recommended and suggested corrective actions will be provided to the sponsor, who 
will subsequently provide them to the IRB at time of annual continuing review. 
 
The PI, assisted by delegated study staff, will also monitor study conduct and documents. PI and 
study staff meetings will be held bi-weekly.  
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, internal audits by the IRB, and external 
inspections governmental regulatory agencies, 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.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 

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11 Ethical Considerations 
This study is to be conducted according to United States government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the Approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject or the subject’s legally authorized representative, and the individual obtaining the 
informed consent. 
12 Study Finances 
12.1 Funding Source 
This study will be funded internally by Mayo Clinic.   
13 Publication Plan 
The primary responsibility for the publication of results will be the principle investigator.  No 
information from the study will be passed on to third parties.  The study will be registered to 
ClinicalTrials.gov prior to subject recruitment and results will also be reported within 12 months 
of final data collection for the primary outcome.   
 
 
 
 
 
 
 
14 References 
 
1.  
Ding XG, Li SW, Zheng XM, Hu LQ, Luo Y.  The effect of platelet-rich plasma on 
cavernous nerve regeneration in a rat model.  Asian J Androl 2009; 11: 215-21. 
 
2. 
Wu YN, Wu CC, Sheu MT, Chen KC, Ho HO, Chiang HS.  Optimization of platelet rich 
plasma and its effects on the recovery of erectile function after bilateral cavernous nerve injury 
in a rat model.  J Tissue Eng Regen Med 2013; Aug 16, doi 10.1002/term. 1806, epub ahead of 
print 
 

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3. 
Wu CC, Wu YN, Ho HO, Chen KC, Sheu MT, Chiang HS.  The neuroprotective effect of 
platelet rich plasma on erectile function in bilateral cavernous nerve injury rate model.  J Sex 
Med  2012; 9: 2838-48.   
 
4. 
Patel VR, Samavedi S, Bates AS, Kumar A, Coelho R, Rocco B, Palmer K.  Dehydrated 
human anmion/chorion membrane allograft nerve wrap around the prostatic neurovascular 
bundle accelerates early return to continence and potency following robot-assisted radical 
prostatectomy: propensity score-matched analysis.  Eur Urol 2015;67:977-980. 
 
5. 
Pourcho AM, Smith J, Wisniewski SJ, Sellon JL.  Intraarticular platelet-rich plasma 
injection in the treatment of knee osteoarthritis.  J Phys Med Rehabil 2014; 93 (suppl): S108-
S121. 
 
6. 
de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, et al.  Platelet-rich plasma 
injection for chronic Achilles tendinopathy: a randomized controlled trial.  JAMA 2010; 
303:144-9. 
 
7. 
Kalaci A, Cakici H, Hapa O, Yanat AN, et al:  Treatment of plantar fasciitis using four 
different local injection modalities: a randomized prospective clinical trial.  J Am Podiatr Med 
Assoc 2009; 99: 108-13. 
 
8. 
Mishra A, Pavelko T:  Treatment of chronic elbow tendinosis with buffered platelet-rich 
plasma.  Am J Sports Med 2006; 34: 1774-8 
 
9. 
Farrag TY, Lehar M, Verhaegen P, Carson KA, Byrne PJ.  Effect of platelet rich plasma 
and fibrin sealant on facial nerve regeneration in a rat model.  Laryngoscope 2007; 117: 157-65.   
 
10. 
Finnoff JT, Fowler SP, Lai JK, Santrach PJ, Willis EA, Sayeed YA, and Smith J.  
Treatment of chronic tendinopathy with ultrasound-guided needle tenotomy and platelet-rich 
plasma injection.  PM R 2011; 3: 900-11 
 
 

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14.1 Attachments 
 
14.1.1 Expanded Prostate Cancer Index Composite (EPIC)  
14.1.2 Sexual Health Inventory for Men (SHIM)