Post-market, Prospective Evaluation of PHOTO-oxidized Decellularized Bovine Pericardium Used as a Patch in Vascular Repair and Reconstruction Surgery
Phase: NA
Conditions: Vascular Diseases, Peripheral Arterial Disease, Hemodialysis Access Failure (Disorder), Carotid Artery Diseases, Abdominal Aortic Aneurism
Sponsor: Artivion Inc.

Study Title: 
Post-market, prospective evaluation of PHOTO-
oxidized decellularized bovine pericardium used as a patch in 
Vascular repair and reconstruction surgery: PHOTO-V  
 
NCT03669042 
 
June 2018 
 

CryoLife, Inc. 
iii 
Confidential 
 
 
 
 
 
 
1655 Roberts Blvd., NW 
Kennesaw, GA  30144 
 
 
 
 
June 2018 
 
 
 
 
 
Project Number: 
PHF1801.000-M (04/18) 
Study Title:  
Post-market, prospective evaluation of PHOTO-oxidized 
decellularized bovine pericardium used as a patch in Vascular repair 
and reconstruction surgery: PHOTO-V 
Study Article Name:  
PhotoFix® 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized d.ecellulanzed 
PHFI 80 l.000-M(D-1/18) 
bovine pcncard,um used as c pntch in vascular n:p,ur and recon.{trucuon surgery 
SPONSOR SIGNATURE PAGE 
The signatures below constitute the approval oflhis protocol and the attachments. 
oln [
s/ao1 o
Erin Hurley, Project Manager, Clinical Research 
Date 
.L'iff· f_  
oh (M {?-a 19 
Scott B. Capps, Vice President,linical Research 
Date 
/ for/l;yv	/ 
J
n 
o 00 /;)01 r
William Northrup, M.D., Vice President Physician Relations and Education 
ate 7 
Virendra Patel, MD, MPH, Medical Expert 
Date 
CONFIDENTIALITY STATEMENT 
This document is a confidential communication of CryoLife's Clinical Research Department. Acceptance of this 
document constitutes the agreement by the recipient that no unpublished infom1ation contained within will be 
published or disclosed without prior written approval, except that this document may be disclosed to an institutional 
review board under the condition that it is requested that they keep it confidential. 
STATEMENT OF COMPLIANCE 
This study will be carried out in accordance with Good Clinical Practice (GCP) as required by the U, S. Code of
Federal Regulations applicable to clinical studies (45 CFR 46).
CryoLife, Inc. 
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7/9/2018

Post-market, prospective evaluation of photo-oxidized decellularized 
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
 
 
CryoLife, Inc. 
  iii 
Confidential 
SIGNATURE PAGE 
The signatures below constitute the approval of this protocol and the attachments, and provide 
the necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local and legal and 
regulatory requirements and applicable US federal regulations and GCP guidelines. 
 
 
Site Investigator:  
 
 
Signed: _________________________________________  
Date: __________________ 
 
Name:   
 
 
Title:  Primary Investigator 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized 
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
 
 
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TABLE OF CONTENTS 
 
1 
INTRODUCTION ................................................................................................................. 1 
1.1 
Abbreviations ................................................................................................................... 1 
1.2 
Protocol Summary ............................................................................................................ 1 
1.3 
Study Title ........................................................................................................................ 2 
1.4 
Study Objective ................................................................................................................ 2 
1.5 
Clinical Background ......................................................................................................... 2 
2 
GENERAL INFORMATION ............................................................................................... 4 
2.1 
Device Generic Name ...................................................................................................... 4 
2.2 
Device Trade Name .......................................................................................................... 5 
2.3 
Device Manufacturer ........................................................................................................ 5 
2.4 
Study Sponsor Contact ..................................................................................................... 5 
2.5 
Device Description ........................................................................................................... 5 
2.6 
Identification of Critical Components .............................................................................. 5 
2.7 
Materials Used.................................................................................................................. 6 
2.8 
Intended Use ..................................................................................................................... 6 
2.9 
Regulatory Status ............................................................................................................. 6 
3 
EXPERIMENTAL DESIGN ................................................................................................ 7 
3.1 
Type of Study ................................................................................................................... 7 
3.2 
Study Size & Duration ..................................................................................................... 7 
3.3 
Study Population .............................................................................................................. 8 
3.4 
Study Activities ................................................................................................................ 8 
4 
ANTICIPATED COMPLICATIONS AND ADVERSE EVENTS ................................. 12 
4.1 
Anticipated Complications ............................................................................................. 12 
4.2 
Consequences of Morbid Events: ................................................................................... 13 
4.3 
Reporting Expectations .................................................................................................. 13 
5 
RISK/BENEFIT ANALYSIS.............................................................................................. 14 
5.1 
Benefits........................................................................................................................... 14 
5.2 
Risks ............................................................................................................................... 14 
5.3 
Minimization of Foreseeable Risks ................................................................................ 14 
6 
DATA COLLECTION ........................................................................................................ 14 
6.1 
Study Endpoints & Variables ......................................................................................... 15 
6.2 
Records and Reporting ................................................................................................... 16 
6.3 
Electronic Case Report Forms........................................................................................ 16 
6.4 
Data Reporting ............................................................................................................... 16 
6.5 
Data Review ................................................................................................................... 17 
6.6 
Data Quality Control ...................................................................................................... 17 
6.7 
Statistical Analysis Plan ................................................................................................. 17 
6.8 
Privacy of Patient Data & Patient De-identification ...................................................... 18 
6.9 
Record Maintenance ....................................................................................................... 18 

Post-market, prospective evaluation of photo-oxidized decellularized 
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
 
 
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7 
SITE MANAGEMENT PLAN AND MONITORING ..................................................... 18 
8 
PATIENT WITHDRAWAL ............................................................................................... 19 
9 
DEVIATION FROM PROTOCOL ................................................................................... 19 
10 STUDY REPORT ................................................................................................................ 19 
11 STUDY ADMINISTRATION ............................................................................................ 20 
11.1 
Institutional Review Board Information ..................................................................... 20 
11.2 
Patient Informed Consent ........................................................................................... 20 
11.3 
Publication Policy ....................................................................................................... 20 
11.4 
Confidentiality ............................................................................................................ 21 
APPENDIX A: HIPPA ............................................................................................................... 22 
APPENDIX B:  INFORMED CONSENT ................................................................................ 24 
APPENDIX C:  IFU .................................................................................................................... 24 
APPENDIX D:  DATA VARIABLES (BY FORM) ................................................................ 37 
APPENDIX E:  DEFINITIONS AND ACRONYMS .............................................................. 55 
APPENDIX F:  REFERENCES ................................................................................................ 59 
APPENDIX G: PROTOCOL DEVIATION REPORT FORM ............................................. 61 

Post-market, prospective evaluation of photo-oxidized decellularized                     
    PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
 
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1 
INTRODUCTION 
 
1.1 
Abbreviations 
 AAA:  
abdominal aortic aneurysm 
 BMI:  
body mass index 
 CAS:  
carotid artery stenosis 
 CEA:  
carotid endarterectomy 
 CTA:  
computed tomography angiography 
 DSA:  
digital subtraction angiography 
 eCRFs: 
electronic case report forms 
 EDC:   
electronic data capture 
 ESRD: 
end stage renal disease 
 FDA:  
food and drug administration 
 HAR:  
hemodialysis access repair 
 IFU:  
instructions for use 
 IRB:  
institutional review board 
 MRA:  
magnetic resonance angiography 
 PTFE:  
polytetrafluoroethylene 
 PAD:  
peripheral arterial disease 
 RRT:  
renal replacement therapy 
 SDV:  
source document verification 
 SOP:  
standard operating procedure 
 TIA:  
transient ischemic attack 
 UDI:  
unique device identifier 
 
1.2 
Protocol Summary 
The objective of this post-market clinical follow-up study is to evaluate safety endpoints in 
patients receiving PhotoFix® Decellularized Bovine Pericardium (PhotoFix) as a patch within a 
vascular repair or reconstruction procedure.  PhotoFix is prepared from bovine pericardium, 
which is stabilized using a dye-mediated photo-oxidation process and sterilized using aseptic 
processing techniques.  The primary endpoint for patients with carotid artery stenosis (CAS) 
undergoing carotid endarterectomies (CEA) will be rate of ipsilateral central neurologic events; 
the primary endpoint for all other vascular procedures will be primary patency.  The secondary 
endpoints include all-cause reoperation rate, device-related reoperation rate, explant rate, 
restenosis rate, secondary patency (hemodialysis access repair (HAR) only) and survival.  A goal 
of 100 patients will be enrolled at approximately 10 sites.  The enrollment period will span a 
minimum of 8 months from Institutional Review Board (IRB) approval and site activation.  
Candidates for this study are adults who require vascular repair or reconstruction surgery that 
necessitates the use of a patch.  Patients will be consented pre-operatively and enrolled patients 
will be followed for approximately 6 months after PhotoFix surgery.  Data will be collected at 5 
time points: baseline (pre-operatively), intra-operatively, 1 month post-operatively, 3 months 
post-operatively, and 6 months post-operatively.  Patients will be required to return to the office 
for the 3 visits occurring after hospital discharge.  Follow-up data collection will focus on the 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
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safety endpoints; data will be abstracted from the patient’s medical record and collected from 
patient self-report.  Study specific testing, including imaging and laboratory testing, will not be 
required. 
 
1.3 
Study Title 
Post-market, prospective evaluation of photo-oxidized decellularized bovine pericardium used as 
a patch in vascular repair and reconstruction surgery (PHOTO-V). 
 
1.4 
Study Objective 
The objective of this post-market clinical follow-up study is to evaluate the clinical outcomes of 
patients receiving PhotoFix as a patch within a vascular repair or reconstruction procedure. 
 
1.5 
Clinical Background  
Vascular disease is a prevalent medical issue, which can require affected patients to undergo 
surgery.  The need for surgery is dependent on the indication, but can be required to reestablish 
blood flow, repair weakened artery walls, or create hemodialysis access.  These surgeries can 
require the use of a vascular patch to close or repair defects; primary suture closure is not always 
an option.   
 
Incidence Rates: 
Vascular surgery is required for a variety of indications.  A large percentage of vascular surgeries 
are performed due to CAS, peripheral artery disease (PAD), abdominal aortic aneurysm (AAA) 
and HAR in patients with end stage renal disease (ESRD).  These combined conditions represent 
a large population of individuals.  Not all patients require surgical intervention; however, many 
patients, including those who are asymptomatic, will undergo surgery to prevent potential long 
term complications.   
 
The prevalence of CAS has been reported to affect 3.4% and 4.2% of females and males, 
respectively.1 The prevalence of CAS varies by race, with increased risk in Caucasians and 
Native Americans.1 The worldwide prevalence of PAD has been estimated at greater than 200 
million people.2 A recent meta-analysis estimated a pooled prevalence for AAA to be 4.8%, with 
obvious global variance, with higher prevalence in Australia compared to America and Europe.3   
 
Lastly, the worldwide number of patients who received renal replacement therapy (RRT) was 
recently estimated as 2.6 million.  A conservative estimate determined that the number who 
received RRT vastly underestimates the total who need it; an estimated 4.9 million people need 
RRT.4 For those requiring hemodialysis, a type of RRT, arteriovenous fistula and arteriovenous 
graft are generally preferred over long-term central venous catheter.  However, these options 
require surgical interventions to create and maintain access.  In these cases, patches may be 
required to repair and reconstruct defects. 
 
The intention of vascular patching is to improve blood flow, vessel geometry and biomechanics. 
 

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Alternative Treatments for Vascular Surgery Requiring Patch Material:  
Currently available patch materials include vein patches (saphenous or neck veins) and synthetic 
patches (polytetrafluoroethylene (PTFE), Dacron, or bovine pericardium).  Selection of the ideal 
patch material is a debated topic; anatomical characteristics, availability, comorbidities, and 
patch indication are considered within the selection process.  The theoretical benefit of 
autologous patches include an increase in luminal size, provision of endothelialized tissue to the 
patch site,  less thrombogenicity, and increased resistance to infection.5 However, issues with 
availability, increased operative time, harvesting-related morbidity, and late aneurysmal 
dilatation have been reported with autologous patch use.5  Synthetic patches have been used as an 
alternative; early criticisms of these patches included prolonged hemostasis time and increased 
thrombosis.5   
 
Clinical Results in Alternative Treatments: 
There are numerous studies reporting results of vascular patches for cases of CAS requiring 
CEA.  These studies have compared outcomes between patches and direct suture, as well as 
outcomes between different patch materials. 
 
A recent systematic review and meta-analysis compared CEA outcomes over multiple studies.6 
Results from 10 studies comparing primary closure to patch closure were included in one of the 
meta-analyses.  Amongst the 10 studies, patches included saphenous vein patches (n=3), 
synthetic patches (n=3), and combined vein and synthetic (PTFE or Dacron) (n=4).6   Procedures 
using patches significantly reduced the risk of perioperative stroke and long-term stroke (OR = 
0.49, p = 0.02).6  The use of patches also reduced the risks of perioperative arterial occlusion (OR 
= 0.18, p < 0.0011) and long-term recurrent stenosis (OR = 0.24, p < 0.01).6  Aggregate results 
from 9 studies were also compared in a meta-analysis; studies reported the comparison of vein 
and PTFE patches.  Perioperative and long term rates of stroke, ipsilateral stroke, combined 
stroke and death and mortality were not different between groups.6    Aggregate results from 4 
studies compared Dacron to other synthetic patches.6    At 30 days, Dacron was associated with 
higher risk of perioperative stroke and transient ischemic attack (TIA) (p=0.03) and restenosis 
(p=0.004).6  There was also significantly more strokes (p=0.03), combined stroke and death 
(p=0.02), and arterial restenosis (p<0.001) with Dacron during longer term follow-up. 
 
Marien et al. compared peri and post-operative outcomes between CEA patients who received 
bovine pericardium (n=51) and Dacron (n=44).7 Suture line bleeding at 3 minutes and 4 minutes 
was significantly higher in the Dacron group (55% vs. 14%, p<0.001, 30% vs. 4%, p=0.001 
respectively).7 The surgeons also reported that bovine pericardium had superior handling 
characteristics compared to Dacron.7   
 
There is limited published data comparing vascular patch outcomes in surgeries for AAA, PAD 
or HAR.  One small retrospective study compared patency outcomes in HAR with stenting 
(n=34) vs. patch angioplasty (n=15).8 Initial post-interventional patency and patency after 
secondary reintervention were not statistically different between patients who received a patch 
and those who were stented; however, patch angioplasty trended towards reduced patency after 
second reintervention.8 
 
 

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PhotoFix Decellularized Bovine Pericardium: 
There is still a need for vascular patches with mechanical properties that mimic natural tissue, 
resist deterioration and do not increase the risk for restenosis and other device-related 
complications.  PhotoFix offers another option to vein patches and other synthetic patches, 
specifically, glutaraldehyde treated xenografts.  PhotoFix tissue is treated through dye-mediated 
photo-oxidation; the processing stabilizes the internal collagen structure while eliminating toxic 
by-products which allow calcium to bind to the tissue.  Dye-mediated photo-oxidation was first 
described in the medical literature in the 1990’s.9 The treated tissue was described as “stable 
toward chemical, enzymatic, and in vivo degradation while maintaining physical properties of 
natural tissue”.9 Moore expanded on the PhotoFix process in 2001 by further describing the 
material as “biostable, biocompatible, relatively nonclacific, and flexible”.10  
 
Biomechanical Testing Results: 
PhotoFix mechanical testing has demonstrated that the patch is either superior or comparable to 
currently marketed patches in terms of tear resistance strength, ultimate tensile strength, suture 
retention, and ball burst strength.  Testing was completed on CryoLife-manufactured product and 
evaluated the device’s average force of failure.  The average maximum load for suture retention, 
ultimate tensile strength, ball burst strength, and tear resistance were 8.39 N, 15.6 N, 309.85 N, 
and 7.3 N, respectively.  
 
Biocompatibility Results: 
Biocompatibility testing was performed under the guidance from ISO 10993-1.  The specific 
biocompatibility testing performed for PhotoFix is consistent with the exposure duration of the 
product and its intended use (i.e. permanent exposure of product in contact with blood).  The full 
battery of tests supports the biocompatibility of the device. 
 
Preclinical Results: 
PhotoFix (formerly CardioFix) was implanted in a rat subcutaneous study which concluded that 
the test article had excellent biostability (greater than 71%) and low to minimal calcification.  
PhotoFix was also examined in a 20-week sheep study.  PhotoFix was implanted within the 
pericardial sac, in the atrial septal, and the ascending and descending aortic positions.  There was 
no evidence of creep or stretching, structural degradation, or collagen degradation.  There was 
also no evidence of thrombogenicity, infection, excessive inflammation or intrinsic calcification.  
Overall, the testing demonstrated acceptable in vivo performance in cardiovascular and 
pericardial repair applications.  These results in a cardiac model can be considered applicable to 
its use in peripheral or non-cardiac vascular indications since cardiac conditions represent more 
exaggerated conditions of pressure, contractility and stretching. 
 
The PhotoFix biocompatibility data, photo-fixation data, pre-clinical data, and clinical literature 
of equivalent devices support the safety of the device.  Post-market clinical follow-up through a 
clinical study will support active surveillance efforts to identify any residual risk. 
 
2 
GENERAL INFORMATION  
 
 
 
 
 
 
 
 
 
2.1 
Device Generic Name  
 
 
Decellularized Bovine Pericardium 

Post-market, prospective evaluation of photo-oxidized decellularized   
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bovine pericardium used as a patch in vascular repair and reconstruction surgery 
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2.2 
Device Trade Name 
 
 
 
PhotoFix® 
 
2.3 
Device Manufacturer  
 
 
CryoLife®, Inc. 
1655 Roberts Blvd., NW 
Kennesaw, GA  30144 
 
2.4 
Study Sponsor Contact  
 
Erin Hurley 
 
1655 Roberts Blvd., NW 
Kennesaw, GA  30144 
Phone: 678-290-4627 
Fax: 770-590-3749 
Email: hurley.erin@cryolife.com 
 
2.5 
Device Description 
PhotoFix is prepared from bovine pericardium, which is stabilized using a dye-mediated photo-
oxidation process; it is processed using ethylene oxide and sterilized using aseptic processing 
techniques.  No aldehyde chemistry is used during any phase of pericardium manufacturing, 
including the tissue fixation and sterilization processes.  All available patch sizes, with respective 
product codes, are listed in Table 1. 
 
Table 1: PhotoFix Patch Sizes and Product Codes 
 
Description/ Patch Size 
Product Codes 
PhotoFix 6cm x 8cm 
PFP6X8 / PFP6X8-G 
PhotoFix 0.8cm x 8cm 
PFP0.8X8 / PFP0.8X8-G 
PhotoFix 1cm x 6cm 
PFP1X6 / PFP1X6-G 
PhotoFix 4cm x 4cm 
PFP4X4 / PFP4X4-G 
PhotoFix 1cm x 10cm 
PFP1X10 
PhotoFix 2cm x 9cm 
PFP2X9 
PhotoFix 1cm x 14cm 
PFP1X14 
 
2.6 
Identification of Critical Components 
The PhotoFix primary packaging system consists of the container (Nalgene bottle), which stores 
the tissue in 22% buffered ethanol solution, and the closure (screw on cap using a torque limited 
closure device) which prevents leakage of the solution.  A tamper evident shrink band is then 
applied around the bottle and the cap.  

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The PhotoFix secondary packaging consists of a PhotoFix shelf box, temperature indicator, and 
freeze-watch indicator.  The secondary packaging also holds additional unique device identifier 
(UDI) labels and the Instructions for Use (IFU).  Figure 1 illustrates the packaging configuration 
for PhotoFix. 
 
Figure 1: PhotoFix Packaging Configuration 
 
 
2.7 
Materials Used 
PhotoFix is manufactured from bovine pericardium derived from bovines born in Australia, New 
Zealand, or the United States. 
 
2.8 
Intended Use 
PhotoFix is indicated for the following uses: vascular repair and reconstruction (for example: the 
carotid, iliac, femoral, and tibial blood vessels and arteriovenous access revisions). 
 
2.9 
Regulatory Status 
United States: 
PhotoFix is classified as Class II per 21 CFR 870.3470- Intracardiac patch or pledget made of 
polypropylene, polyethylene terephthalate, or polytetrafluoroethylene. 

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3 
EXPERIMENTAL DESIGN 
 
3.1 
Type of Study 
This study is a prospective, multicenter, post-market clinical follow-up study to evaluate 
PhotoFix safety outcomes in vascular repair and reconstruction surgery.  This is an observational 
study on a currently marketed device; no study activities are experimental. 
 
3.2 
Study Size & Duration 
Patients will be enrolled at approximately 10 sites.  The enrollment period will span the time 
needed to consent approximately 166 patients.  The target sample size is 100; projected 
enrollment considers a screen failure rate of 33% and an early termination rate of 10%.  
Enrollment is estimated to take a minimum of 8 months from Institutional Review Board (IRB) 
approval and site activation.  Enrollment will begin at the principal investigator’s site and in 
agreement with all central and local IRB requirements.  The enrollment period will continue until 
the Sponsor decides to stop enrollment.  The Sponsor will activate additional sites at their 
discretion. 
 
A singular anatomical region will be selected for patch use.  More than one patch can be used 
within the repair or reconstruction of this target region.  However, patients requiring patches at 
distinct anatomical regions will be excluded.  Additionally, patients undergoing concomitant 
procedures requiring additional prosthetics (e.g. stents) will be excluded.  For complex cases, 
where clarification on these criteria is required, the Sponsor should be contacted prior to 
obtaining consent.    
 
Patients undergoing a vascular procedure which falls within the indications for use and requires 
the use of PhotoFix will be screened and consented for the study, pre-operatively.   
 
The study will collect prospective data at 5 time points; data will be collected pre-operatively, 
intraoperatively/immediately post-operatively, 1 month post-operatively, 3 months post-
operatively, and 6 months post-operatively.  All study patients will be expected to participate in 
all study required evaluations.  Patients will be expected to come into the office at the 3 follow-
up visits, post hospital discharge.  For all post-operative visits outside the hospital, a +/- 14 day 
window is allowed for schedule fluctuations, but visits should ideally remain at the intended 
intervals.  Data will also be collected on any unscheduled events (i.e. reoperation, explants, etc.) 
which may occur during the study period. 
 
Patient demographics and medical history, including medications, comorbidities, pertinent 
surgical history, and fundamental vascular diagnosis, will be collected at time of consent. 
Medications will only include drugs of interest and will not require a complete listing.  Adverse 
events will be collected after surgery on all patients consented and enrolled into the study.  The 
investigation will be conducted for a period necessary to collect all follow-up, as needed on each 
patient, but will not exceed 7 months after surgery.  The total time a patient will be followed will 
be determined by their date of surgery; dates of surgery should occur within 60 days of consent.  
If the patient’s surgery is scheduled after 60 days, a re-screen request must be submitted to the 
Sponsor.  The anticipated final follow-up will be conducted in November 2019, but will 
ultimately be determined by IRB approvals, site activation, and by rate of patient enrollment.  

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3.3 
Study Population 
Candidates for this study are adults who require vascular repair or reconstruction surgery that 
necessitates the use of a patch.  Examples of vascular procedures include the repair and 
reconstruction of the carotid, iliac, femoral, and tibial blood vessels, as well as arteriovenous 
access procedures. 
 
Study patients will be evaluated by medical history, disease process, and anatomic suitability for 
the study.  To be enrolled in the study, candidates must meet the following Inclusion and 
Exclusion Criteria.  
 
3.3.1 Inclusion Criteria: 
 Patient is undergoing a vascular procedure which falls within the 
indications for use and requires the use of PhotoFix Decellularized Bovine 
Pericardium 
 Patient’s surgery is anticipated to occur within 60 days of consent 
 Patient is ≥18 years old 
 Patient is willing and able to comply with the protocol and follow up 
period 
 Patient is willing and able to give written informed consent 
 
3.3.2 Exclusion Criteria: 
 Patient’s procedure is a revision of a prior arteriotomy or venotomy 
 Patient’s procedure requires multiple vascular patches in anatomically 
distinct regions or other prosthetics (e.g. stents) 
 Patient has a medical history of abnormal coagulopathy, bleeding, or 
thromboembolic disease 
 Patient has a medical history of severe immunodeficiency disease 
 Patient has a medical history of cancer 
 Patient has severe visceral disease in heart or active liver disease or icterus 
 Patient has a history of cerebrovascular accident (completed stroke) within 
3 months of planned surgery 
 Patient has a history of atrial fibrillation and requires a patch for carotid 
endarterectomy repair 
 Patient has an active or potential infection at the surgical site 
 Patient has used or plans to use immunomodulatory drugs for ≥ 6 months 
 Patient has a sensitivity to products of bovine origin 
 Patient is currently enrolled in another study 
 Patient has a life expectancy of less than 12 months 
 Patient is pregnant or breastfeeding or planning on becoming pregnant or     
unwilling to use medically acceptable methods of birth control 
 Patient’s procedure is emergent 
 
3.4 
Study Activities 
Patients will be carefully evaluated before being consented into the study.  Patients will be 
considered for screening after diagnostic evaluation has confirmed that the patient is a candidate 

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for vascular surgery and it is determined that the surgery will require the use of a patch.  
Diagnostic evaluation may include known patient history, presentation with symptomology 
associated with need for surgery, and imaging (Computed Tomography Angiography (CTA), 
Magnetic Resonance Angiography (MRA), Duplex imaging, Digital Subtraction Angiography 
(DSA), etc.). 
 
Screening and follow-up assessments will be performed in accordance with the schedule 
provided in Table 2.  These screening assessments will evaluate the patient’s medical and 
surgical history for inclusion in the study.  The follow-up assessments will evaluate post-
operative outcomes. 
 
3.4.1 Patient Enrollment 
Patients who provide written informed consent and meet the eligibility requirements will 
be consented into the study.  This is an open-label single arm study, so no randomization 
will be performed.  
 
Table 2:  Schedule of Activities 
PROTOCOL 
ACTIVITIES 
#1:     
Pre-Op 
#2: Intra-Op/ 
Immediately 
Post-Op 
#3:        
1 month 
Post-Op4 
#4:        
3 months 
Post-Op4 
#5:        
6 months 
Post-Op4 
Informed Consent 
X 
 
 
 
 
Eligibility Evaluation 
X 
 
 
 
 
Baseline Assessments1 
X 
 
 
 
 
Imaging Evaluation2 
X 
X 
X 
X 
X 
Medication 
X 
X 
X 
X 
X 
Operative Assessment 
 
X 
 
 
 
Adverse Event3 
 
X 
Explant Evaluation3 
 
X 
Follow-Up Evaluation 
 
 
X 
X 
X 
End of Study 
 
 
 
 
X 
1Includes the following: Demographics, Medical History, Surgical History, and Social History. 
2If available, pre, peri, and post-operative imaging data (specific to the study) will be extracted from the 
patient’s medical records by the site. 
3Only reported if applicable and can happen at any point peri or post-operatively. 
4Office visits windows are +/-14 days; however, visits should ideally remain at specified intervals. 
 
3.4.2 Informed Consent  
Prior to screening for the study, all patients will be informed in detail about the nature of 
the clinical study, as well as its risks, potential benefits and anticipated discomforts.  All 
patients will also be informed about the use and disclosure of the patient’s health 
information, referred to as “Protected Health Information (PHI),” for the clinical study.  
Patients will also be informed about their rights with respect to their PHI, and will be 
informed of the study site’s legal duties under the Health Insurance Portability and 
Accountability Act (HIPAA, see Appendix A), and any local requirement.   
 
The basic elements of HIPAA Authorization will be followed, as specified by 45 CFR 
164.508, and any local requirement(s).  HIPAA authorization will be incorporated into 
the Informed Consent Form (ICF).   

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The basic elements of informed consent will be followed, as specified by 21 CFR 50.25, 
and any local requirement(s).  Written informed consent will be obtained from each 
patient to be involved in the clinical study using the IRB approved ICF.  The primary 
investigator, or his/her designee, or a witness will verify consent as mandated by the 
site’s IRB requirements.   
 
All patients must provide written informed consent in accordance with the overseeing 
IRB regulations.  The study site must use the ICF approved by the IRB and CryoLife.  A 
sample ICF can be found in Appendix B. 
 
3.4.3 Screening, Eligibility and Enrollment 
All consented patients will be screened for potential inclusion in the study at a pre-
operative visit.  Any potential re-screens will need to be approved by CryoLife prior to 
reconsent.  Patients will be assigned a unique, de-identified Screening ID.  The ID will 
include a two-character site assigned ID, followed by a two-digit consecutive number.  
The Eligibility Evaluation will be used to assess eligibility at screening.   
 
All data will be captured and entered into electronic case report forms (eCRFs).  The 
following eCRFs will be completed at time of screening: 
  
 Informed Consent 
 Eligibility Evaluation 
 Demographics 
 Medical History 
 Surgical History 
 Social History 
 Medication  
 Imaging Evaluation (if applicable) 
 
The patient will have undergone a comprehensive vascular assessment prior to screening, 
which may include diagnostic imaging and surgical consult.  The Imaging Evaluation 
form will be used to capture all retrospective and prospective variables which are 
documented on available imaging reports, as it relates to the patient’s PhotoFix surgery.   
 
3.4.4 Surgical Procedures 
All patients will undergo a vascular repair or reconstruction surgery, which requires the 
use of PhotoFix.  The surgical procedures will vary by patient and by underlying 
etiology.  Therefore, PhotoFix implant sites will also vary.  In all cases, PhotoFix will be 
implanted per the Instructions for Use (IFU) (Appendix C). 
 
Photographs may be taken perioperatively and will capture the patch site, before, during 
and after PhotoFix implant.  A minimum of 3 photographs may be taken to include: the 
prepped target artery/vein, a point during the process of implanting PhotoFix, and after 
PhotoFix has been implanted (before surgical site closure). 
   

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3.4.5 Intraoperative Evaluation 
Patients that meet the study criteria will receive PhotoFix as a vascular patch, per the 
IFU.  A patient will remain eligible for continuation if PhotoFix remains implanted at the 
conclusion of their vascular surgery; patients would be considered enrolled at this point.  
Peri-operative and post-operative (<24 hours after surgery) data will be collected on all 
enrolled patients; this data will be entered into the Operative Assessment eCRF 
(Appendix D).  The following measures will be monitored and documented per 
indication, but may include: 
 
 Surgery date 
 Implanting surgeon 
 Number of PhotoFix Patches Used 
 PhotoFix lot number(s) 
 PhotoFix patch size(s) (indicated on box(es)) 
 Patch implant site 
 Surgical procedure description 
 Concomitant procedure description 
 Any adverse events, device malfunctions, or intraoperative mortality 
 Peri-operative imaging data 
 
Any intraoperative adverse events will be captured on the Adverse Event eCRF 
(Appendix D).  Patients will be told to contact the investigator in the event of any 
complications which occur during the study.  The contact information for the Principle 
Investigator is included in the copy of the signed ICF each consented patient will have 
received.   
 
3.4.6 Follow-up Visits 
The patients will be asked to return for 3 post-operative visits at 1, 3, and 6 months after 
surgery.  Available data from post-operative imaging reports will be collected, as is 
applicable to the study and entered into the Imaging Evaluation eCRF (Appendix D); the 
imaging is not a requirement of the study.  Clinical data for all follow-up visits will be 
entered into the Follow-Up Evaluation eCRF (Appendix D).  This form will collect data 
on post-operative recovery.  The following measures will be monitored and documented 
per indication, but may include: 
 
 Visit date 
 Study status 
 Loss of patency/ Evidence of restenosis 
 Reoperations / vascular surgeries required post-op 
 Any adverse events, explants, or other mortality 
 Post-operative imaging data 
 
 
 

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4 
ANTICIPATED COMPLICATIONS AND ADVERSE EVENTS 
 
4.1 
Anticipated Complications 
For this study, a complication is defined as the following:  morbid event or consequences of a 
morbid event.  While all complications will be summarized in the final report, the primary focus 
of the analysis will be complications involving the vascular system, such as transient ischemic 
attack (TIA), amaurosis fugax, stroke, symptomatic carotid occlusion, thrombosis, bleeding, and 
death.  The terms “adverse event” and “complication” will be used interchangeably. 
 
An Adverse Event (AE), Unanticipated Adverse Effect (UAE) and Serious Adverse Event (SAE) 
are defined in Appendix E.  All AEs, UAEs and SAEs that occur during the course of the study 
(until the completion of the final follow-up visit), whether observed by the investigator or by the 
patient, and whether or not thought to be PhotoFix related, will be reported in detail on the 
Adverse Event eCRF and followed to a satisfactory resolution.  The investigator will follow the 
patient until the event resolves.  In the unusual circumstance that the event has not resolved by 
the time of the patient’s completion of the study, an explanation will be entered on the Adverse 
Event eCRF; the circumstance may be determined to be a permanent condition, and will be 
documented as such.   
 
Secondary morbid events will not be included in the calculation of device-related complication 
rates.  A morbid event should be documented only once unless there are multiple occurrences of 
that event.  
 
Consequences of morbid events, such as explant, mortality, and reoperation will be captured on 
the Adverse Event eCRF, which details the associated event.  In the case of an explant, 
additional information will be captured on the Explant eCRF (Appendix D). 
 
Potential complications that may occur with any vascular surgery include, but are not limited to:  
 Allergic reaction to medication 
 Bleeding 
 Breathing difficulty 
 Chest pain 
 Heart attack 
 Infection (ex. pneumonia, urinary tract infection, wound infection) 
 Irregular heartbeat 
 Lung or kidney failure 
 Memory loss 
 Pain 
 Sickness/ nausea   
 Stroke 
 Thrombosis 
 
Complications specific to the use of the PhotoFix may include, but are not limited to the 
following:   
 Abscess 
 Adhesion 

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 Blood leakage through suture line, holes, or tears 
 Calcification/mineralization 
 Complete heart block (arrhythmia) 
 Death 
 Inflammatory immune response 
 Infection 
 Intimal hyperplasia 
 Rejection 
 Tissue damage/degradation 
 Tissue failure or rupture 
 Toxic response/reaction 
 TSE transmission/ variant Creutzfeldt-Jakob disease 
 
The likelihood of any complication is specific to the indication of surgery. 
 
4.2 
Consequences of Morbid Events: 
Morbid events can result in mortality or the permanent cessation of all vital bodily functions.   
Morbid events can also require reoperation.  Reoperation includes any operation that repairs, 
alters, or replaces a PhotoFix patch.  Morbid events can also require explant.  Explant includes 
any removal of the patch for any reason.  Details on the consequences of any morbid event will 
be captured in the Adverse Event eCRF and Explant eCRF, as applicable (Appendix D). 
 
4.3 
Reporting Expectations 
Adverse events will be reported per the following guidelines for all enrolled patients:   
 
1. 
Any (potential) AE must be reported to CryoLife as soon as possible, but no later  than 10 
 
working days after knowledge of occurrence, by entry into the EDC. 
2. 
Any UAE, SAEs or AEs of special interest (i.e. vascular complications) must be reported 
to CryoLife within 24 hours after gaining knowledge of the event, by email or telephone, 
in addition to entry into the EDC. 
3. 
De-identified source documentation (i.e., physicians/nurse notes or summaries) regarding 
an AE, UAE or SAE should be provided in addition to the eCRF.  The source documents 
can be uploaded into the eCRF (as a single file) or sent by e-mail to CryoLife. 
4. 
Any patient death will also be reported on the Adverse Event eCRF (requested death 
certificate and autopsy report, if performed, should also be provided). 
5. 
Additionally, all events shall be reported to the reviewing IRB per their reporting 
 
requirements (definitions and timelines).   
 
Report all (potential) AE, UAE or SAE to: 
 
 
Erin Hurley   
 
 
Clinical Research Project Manager 
 
 
CryoLife 
 
 
Phone: 678-290-4627 
 
 
E-mail:  hurley.erin@cryolife.com 
 

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5 
RISK/BENEFIT ANALYSIS 
 
5.1 
Benefits 
A decellularized, photo-oxidized bovine pericardium potentially offers benefits similar to 
autologous pericardium (i.e., similar texture, nonimmunogenic, and biocompatible) without the 
disadvantages of glutaraldehyde treated tissue; the additional (not naturally-occurring) aldehyde 
residue from glutaraldehyde can interact with surrounding tissue, which leads to membrane 
damage and trapping of calcium (Ca2+) on residues.11  Design features of PhotoFix may increase 
the durability and functionality of the device: 
 
 Photo-oxidation: Processing creates crosslinks and stabilizes the internal collagen 
structure, while eliminating toxic by-products that create sites where calcium can bind to 
the tissue. 
 
The calcification potential of glutaraldehyde-fixed bovine pericardium is well known.12 ,13 
Preclinical results have shown that PhotoFix implanted in a cardiac sheep model demonstrated 
no evidence of collagen degradation, thrombogenicity, infection, excessive inflammation or 
intrinsic calcification in the 20-week follow-up period.  PhotoFix may have enormous potential 
for clinical use.  The long-term benefits of the unique features of PhotoFix are currently 
hypothetical. 
 
5.2 
Risks 
Risks and complications related to vascular surgery are extensively documented in the medical 
literature.  Complications specific to the use of PhotoFix may include, but are not limited to, the 
following: abscess, adhesion, blood leakage through suture line/holes/tears, calcification 
/mineralization, complete heart block (arrhythmia), death, inflammatory immune response, 
infection, intimal hyperplasia, rejection, tissue damage /degradation, tissue failure /rupture, toxic 
response/reaction, and TSE transmission/ variant Creutzfeldt-Jakob disease.  The likelihood of 
each event is dependent on the specific surgical indication. 
 
5.3 
Minimization of Foreseeable Risks 
Each physician must consider all the risks and benefits to the patient on an individual basis, 
when choosing a vascular patch.  Efforts will be made to minimize these risks by selecting 
Investigators who are experienced in vascular surgery.  In addition, efforts will be made to 
ensure that the treatment and follow-up of all patients will be consistent with current medical 
practice. 
 
All procedures will be performed on patients who are candidates for vascular surgery, requiring 
the use of a patch.  Patients will be carefully monitored throughout the follow-up period  and any 
complications related to the study will be documented and evaluated. 
 
 
6 
DATA COLLECTION  
 
All data will be entered by site personnel into an electronic data capture (EDC) system, 
(ArisGlobal) which will utilize eCRFs.  The Investigator at the site will be expected to review 

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and approve eCRFs.  All data will be subject to source document review by the Sponsor’s 
(CryoLife) personnel or its representatives.  Any corrections made to the eCRFs will be done so 
by a designated study coordinator or Investigator. 
 
The eCRFs and patient’s corresponding medical records (source documents) are to be fully 
available for review by the Sponsor’s representatives at the scheduled site visits.  These reviews 
verify adherence to the study protocol and data accuracy in accordance with federal regulations.  
All related electronic records at this site are subject to inspection by the Sponsor, its agents, and 
regulating authorities.   
 
In accordance with ICH E6, Section 6.10, source documents include, but are not limited to the 
following:  
 Clinic, office, hospital charts; 
 Copies or transcribed health care provider notes which have been certified for accuracy 
after production; 
 Recorded data from automated instruments such as Interactive Voice-response Systems, 
x-rays, and other imaging reports, e.g., Duplex Ultrasound (DUS), sonograms, CT scans, 
magnetic resonance images, and radioactive images (regardless of how these images are 
stored, including microfiche and photographic negatives);  
 Correspondence regarding a study patient memorandum sent to IRB(s). 
 
6.1 
Study Endpoints & Variables 
In the case of CEAs, the primary endpoint of the study will be rate of ipsilateral central 
neurologic events. 
 Ipsilateral central neurologic events: Transient ischemic attack, amaurosis fugax, stroke, 
and symptomatic carotid occlusion.   
 
In the case of all other (non-CEA) vascular procedures, the primary endpoint of the study will be 
primary patency in the target artery or vein. 
 Primary patency (of target vessel):  Loss of patency will be determined by the loss of 
previously palpable pulses, patients presenting with recurrent symptoms, a drop in 
ABI>0.15 in the case of lower limb artery repair, Doppler ultrasound findings of 
occlusion, angiography of the affected vessel or a combination of these. 
 
The secondary endpoints of the study will include: overall survival rate, all-cause reoperation 
rate, device-related reoperation rate, explant rate, restenosis rate, adverse event rate, and 
secondary patency (HAR only). 
 
 Overall Survival: 
o Early mortality:  Death < 30 days following PhotoFix implantation.   
o Late mortality: Death ≥ 30 days following PhotoFix implantation, until last day of 
follow-up. 
 All-Cause Reoperation Rate: The total number of reoperations required in patients over 
the follow-up period, which include the repair or alteration of the surgical area around the 
patch.   

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 Device-Related Reoperation Rate: The total number of unplanned reoperations required 
in patients over the follow-up period, which are determined by the surgeon to be device-
related. 
 Explant Rate: The total number of device explants over the course of follow-up.  
Explants will include the removal of PhotoFix for any reason after implantation. 
 Restenosis Rate:  The total number of documented cases of stenosis documented as the 
recurrence of abnormal narrowing of a vessel after corrective surgery. 
 Adverse Event Rate:  The total number of any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporarily associated 
with the use of a device, whether or not related to the device.   
 Secondary Patency (HAR only):  The time from implantation to the point where the 
access is abandoned. 
 
Statistical analysis will be used to assess all study endpoints as applicable. 
 
6.2 
Records and Reporting 
The Investigator must maintain adequate records for the study including, without limitation, 
access to original source documents, medical records, laboratory reports, signed informed 
consent forms, adverse event reporting to the Sponsor, information regarding patients who no 
longer choose to be in the study or were withdrawn, all correspondence with the IRB and/or 
Privacy Board and CryoLife, and other pertinent data. 
 
Data will be collected within eCRFs designed specifically for this study.   
 
6.3 
Electronic Case Report Forms 
The clinical data collected for the study will be obtained from patient records, source documents, 
and existing databases and reported to the sponsor via eCRFs, within the electronic database.  
Data variables to be obtained are outlined in Appendix D and are organized by eCRF.  All data 
collected must be supported by source documents.  Patient medical records, hospital charts, 
operative reports, laboratory and diagnostic testing results, office visits, and other relevant 
documents are to be utilized for collection of relevant data.  The general time points for data 
collection include pre-operative screening, during/ immediately following the operation, and 
post-operative follow-up visits (Table 2).  The electronic database will store all data within the 
following eCRFs: Informed Consent, Eligibility Evaluation, Baseline Assessments 
(Demographics, Medical History, Surgical History, and Social History), Imaging Evaluation, 
Medication, Operative Assessment, Follow-Up Evaluation, Adverse Event, Explant Evaluation, 
and End of Study. 
 
6.4 
Data Reporting 
All data will be entered by site personnel into eCRFs.  The Investigator at the site will be 
expected to review and approve eCRFs.  Any corrections made to the forms at a study site will 
be done so by a designated study coordinator (or Investigator).  Form changes will be tracked in 
the EDC.  
 

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6.5 
Data Review 
The completed eCRFs will be reviewed for completeness and clarity by the Sponsor’s data 
manager and the Sponsor’s representative clinical research associates.  Throughout the study, the 
data manager and clinical research associates will issue queries for any information inadvertently 
omitted, inconsistent, not supported by source documents, or not answered within the EDC.  The 
data manager may request further documentation when data issues, complications, device 
malfunctions, or explants are observed and reported.  The site will be responsible for clarification 
and resolution of all queries.  The data manager will close queries after sufficient clarification 
and resolution is achieved.   
 
6.6 
Data Quality Control 
Site investigators will sign off on all study forms prior to data lock.  Additionally, data will be 
100% source document verified by the Sponsor or a representative of the Sponsor, as deemed 
necessary. 
 
6.7 
Statistical Analysis Plan 
Enrolled patients will be described in aggregate and by indication (as deemed appropriate); 
baseline characteristics will include, but not limited to, age, sex, race, ethnicity, body mass index 
(BMI), comorbidities, fundamental diagnosis/etiology, and pertinent surgical history.  Operative 
details will be described in aggregate and include a summary of the types of procedures 
performed, by relevant category.  Parameters with continuous data types will be summarized 
using descriptive statistics, i.e., mean, standard deviation, and range.  Categorical clinical 
parameters will be summarized based on percentages.   
 
Ipsilateral central neurologic event rate, overall survival, re-operation rate, explant rate, and 
restenosis rate (≥ 50% stenosis) will be summarized based on percentages of affected patients 
and included in a table, which will summarize the endpoints in aggregate and by surgical 
indication (ex. CAS, ESRD, PAD, AAA, etc.).  The summary of ipsilateral central neurologic 
event rates will include all events (transient ischemic attack, amaurosis fugax, stroke, and 
symptomatic carotid occlusion), as well as the incidence of each event individually. 
 
Additional analysis of follow-up data will also be performed with the Kaplan-Meier method, as 
deemed appropriate by the incidence of events.  Kaplan-Meier plots may be generated for 
endpoints including overall survival, primary patency, secondary patency, as well as freedom 
from ipsilateral central neurologic event rate, re-operation, explant, and restenosis (≥ 50% 
stenosis).  Kaplan-Meier plots for survival will include the following mortality classifications:  
all causes of mortality, vascular-related mortality and device-related mortality (as applicable).  
The remaining plots will be specific to indication, if the sample sizes allow for the creation of 
meaningful plots. 
 
The incidence of adverse events will be categorized and summarized with percentages for the 
aggregate sample.  Adverse events will be divided into early and late post-operative events to 
represent the distribution of occurrences.  Events will be considered as early events if the event 
occurs <30 days after the operation, while late post-operative events will be considered to be all 
events happening after this time period.  Early and late events will be presented by indication for 
surgery, seriousness of event, and relation to PhotoFix.  Adverse events occurring secondary to 

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another complication will be collected, but not included in the calculation of adverse event rates.  
Adverse events occurring prior to PhotoFix implant will not be reported. 
 
An interim analysis of the data will be performed approximately 6 months after the initiation of 
enrollment.  The sample size will be dependent on enrollment rate; follow-up could range from 0 
days to 5 months.  This analysis will be used to assess the interim performance and safety of 
PhotoFix.  The analysis of this data will also be used to address the planned enrollment of the 
study and to determine if any modifications to the study are necessary. 
 
6.8 
Privacy of Patient Data & Patient De-identification 
All patient data will remain confidential.  Patient names, social security number, addresses, or 
any other identifying information will not be reported.  Patients and their data will be de-
identified with the use of a Screening ID.  Patients will sign a HIPAA waiver acknowledging that 
their information will remain confidential.  The sample HIPAA waiver is attached in Appendix 
A. 
 
The site will be provided with a patient log that they will use to record the Screening ID and 
patient information at the time of each screening.  The site is responsible for maintaining the log. 
The unique 4-digit Screening ID will be assigned per the following scheme: the first two digits 
are the site assigned abbreviation, followed by the sequential number in which the patient was 
consented.   
 
Example: The 1st patient screened at site CR  
Site (2 letter) 
Patient Enrolled (2 digit) 
C 
R 
0 
1 
 
 
6.9 
Record Maintenance 
All correspondence related to this study should be kept in appropriate study files.  Patient 
records, source documents, and IRB and Sponsor correspondence pertaining to the study must, 
be kept on file.   
 
 
7 
SITE MANAGEMENT PLAN AND MONITORING 
 
It is the responsibility of CryoLife to ensure proper management of the clinical study.  Frequency 
of site visits will be determined by any of the following criteria: patient volume at a site, site 
compliance with the study protocol, and study duration.  Site visits may be completed in person 
or remotely.  One hundred percent source document verification (SDV) is intended for this study. 
Exceptions to this monitoring goal will include screen failures.  One hundred percent SDV for 
screen failures will be restricted to the following eCRFs: Informed Consent, Eligibility 
Evaluation, and Demographics.  
 
 
 

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Study management will be performed by appropriately trained personnel appointed by the 
Sponsor and will be documented per standard operating procedures (SOPs) to ensure that the 
clinical study is conducted in accordance with:  
 The signed Investigator Agreements 
 The protocol 
 Food and Drug Administration (FDA) regulations (as applicable) and Good Clinical 
Practice (GCP) 
 
 
8 
PATIENT WITHDRAWAL 
 
At the discretion of the physician, a patient can be removed from the study at any time without 
the patient’s consent for the following reasons: a) it is in the best interest of the patient to be 
withdrawn from the study; b) patient non-adherence to the study protocol requirements; c) 
patient, sponsor or investigator request; d) the investigator may also elect to withdraw the patient 
from the study at any time based on their medical judgment.  
 
A patient will be considered Lost to Follow-up and therefore terminated from the study when the 
following criteria are met: failure to complete two consecutive follow-up visits (without due 
cause) AND documentation of three unsuccessful attempts by the investigator or his/her 
designees to contact a patient or next of kin, including at least one registered letter. 
 
Subjects who request discontinuation from the study prior to completion will be encouraged to 
complete their study follow-up visits, particularly the 6-month visit; at a minimum, the patients 
can be followed per protocol for safety.  
 
It is the responsibility of the treating physician to notify the Sponsor of any patients removed 
from the study. 
 
 
9 
DEVIATION FROM PROTOCOL 
 
If a protocol deviation occurs, notifications to the Sponsor must be made within 10 working days 
of the occurrence of a deviation.  Details of the deviation must be documented in writing and 
provided to CryoLife with a copy maintained in the Investigator’s file.  All deviations must be 
documented on the provided Protocol Deviation Form (Appendix G).  If the deviation affects the 
rights, safety or welfare of the patients (and it is not an emergency), or the scientific soundness 
of the investigation, prior approval must be obtained from CryoLife, the reviewing IRB, and 
FDA or applicable Regulatory Authorities (when required).  For all other deviations, prior 
approval must be obtained from CryoLife.   
 
 
10 STUDY REPORT 
 
CryoLife will generate a final study report within 4 months after termination or completion of 
the clinical study. 

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11 STUDY ADMINISTRATION 
 
11.1 
Institutional Review Board Information 
The Investigator is responsible for submitting the appropriate study documentation to the 
Institutional Review Board (IRB) for review and approval in accordance with federal 
regulations.  A copy of the written approval for the protocol and informed consent form must be 
submitted to Sponsor before patient enrollment can begin.  The Investigator will be held 
responsible for keeping the IRB informed of all significant findings throughout the course of the 
study.  The Investigator will be required to notify the IRB in accordance with the Board’s written 
procedures if any of the following should occur: 
 
 Amendments to the protocol or informed consent form. 
 Safety updates generated by the Sponsor. 
 UAE, SAEs and AEs (See Appendix E) of special interest must be reported to the Sponsor 
within 24 hours of a site first becoming aware of an event, and additionally to the IRB per 
their reporting guidelines. 
 Any deviations from the protocol. 
 Any information related to patient safety. 
 
11.2 
Patient Informed Consent 
All patients must voluntarily provide signed informed consent, prior to the collection of 
prospective assessments, which would not have been performed as part of normal patient care.  
Informed consent must be obtained in accordance with the FDA regulation 21CFR Part 50 (see 
Appendix B).  Prior to obtaining written consent, the Investigator or delegate must give each 
patient a written explanation of the study.  This must be accompanied by a verbal explanation, 
including the purpose and nature of the study, potential benefits and risks, and patient rights as a 
study participant.  Adequate time must be allowed for each patient to consider the diagnostic and 
treatment options and to ask questions.  The Investigator will retain the original signed consent 
form, which must be made available for review by interested parties.  A copy will be made 
available to each patient.  
 
Informed consent forms must be approved prior to the study initiation by both the IRB and 
CryoLife.  The informed consent form must be written in language readable to each patient.  A 
sample informed consent form is attached in Appendix B. 
 
11.3 
Publication Policy 
The conduct and results of this study will be documented in study reports prepared by CryoLife, 
or a representative of CryoLife, in accordance with SOPs.  It is intended that the clinical results 
from this study will be published and/or presented at a scientific forum.  The Investigator will 
not publish or present results without prior consent from CryoLife.  Additionally, CryoLife 
reserves the right to future discussions with the Investigator including, but not limited to, 
continuance of current study and/or combining the study data with other data series with the 
intent of creating a multi-center evaluation of PhotoFix.  The study will be registered on 
https://www.clinicaltrials.gov.   
 

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11.4 
Confidentiality 
This protocol is a confidential communication of CryoLife.  Acceptance of this document 
constitutes the agreement by the recipient that no unpublished information contained within will 
be published or disclosed without prior written approval, except that this document may be 
disclosed to the IRB under the condition that it is requested that they keep it confidential. 
 
The privacy of patients who participate in this study will be protected by all reasonable means.  
The Principal Investigator is responsible for study records at study sites.  Access to study 
records, and especially patient information, will be limited to the Investigator, the Sponsor and 
its representatives, and Regulating Bodies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 22 of 61 
Confidential 
APPENDIX A: HIPPA 
 
Confidentiality 
 
While you are in this study, information about you and your progress will be kept in a private file 
by your study doctor, and a private file at the corporate headquarters of CryoLife.  The privacy 
of patients or patients who participate in this study will be protected by all reasonable means.  
During the reviews, representatives or designees of CryoLife, <<Insert Investigator Name>> and 
members of the support staff and clinical team, U.S. Food and Drug Administration (FDA), and 
Sterling Institutional Review Board may have access to medical records that contain your 
identity.  However, no information by which you can be identified will be released or published.  
Your file will be kept as private as the HIPAA law allows. 
 
Data Privacy – Confidentiality – Authorization to Disclose Health Information 
 
Release of Health Information – If you decide to participate in this study, information about your 
health may be used or disclosed for the purposes of conducting this study.  This information may 
include information from your medical record that is relevant to this study, such as your medical 
history, medications, test results, diagnoses, treatments, operative reports (reports from 
operations that you have undergone), and discharge summaries.  Information collected by the 
study doctor and/or research staff specifically for this study, such as test results, blood samples, 
physical examinations, information about possible side effects, and surveys you might be asked 
to complete could also be used or disclosed. 
 
Individual’s that may use or release this information include:  physician’s, physician’s office 
staff, hospital staff, the study doctor, and authorized members of the study doctor’s research 
staff.  These individual’s may release this information to the study doctor, authorized members 
of <<Insert Investigator Name>>staff, the sponsor (CryoLife) of the study, sponsor’s agents and 
representatives, Sterling, FDA representatives, and other regulatory agencies. 
 
The information released to the above listed individuals will not contain your name, social 
security number, or any other personal information.  However, authorized representatives of the 
sponsor, IRB, FDA or other regulatory agencies may review records containing personal 
information that can identify you, to make sure that the study information is correct.  Because of 
the need to provide information to these parties, absolute confidentiality cannot be guaranteed. 
 
Use of Information – This information may be used to monitor your healthcare during the study, 
to enable the sponsor to answer the scientific questions for which the study was designed, and to 
ensure that the study has been done properly.  Examples of the use of this information are as 
follows:  the sponsor may use the information for reporting adverse events to regulatory 
agencies, such as the FDA; the sponsor may also transfer the information to business partners or 
companies it hires to provide study-related services; both the sponsor and the study doctor may 
use the information to prepare reports or publications of the study results; the sponsor may also 
provide overall study results, including your information, to other study doctors; the sponsor may 
reanalyze the data from this study in the future or combine it with data from other studies for 
analysis. 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 23 of 61 
Confidential 
 
Once your information has been released, it is no longer protected by US federal regulations 
relating to data privacy and could be used or re-disclosed in ways other than those listed in this 
section of the consent form.   
 
You have the right to see and receive a copy of your records related to the study for as long as 
the study doctor has this information in his/her possession.  However, you might not be allowed 
to see these records until after the study has been completed. 
 
Authorization to Disclose – By signing this consent form, you authorize disclosure of 
information to the sponsor and review of your medical records by the sponsor and other 
authorized people, as described in this section of the consent form.  You do not have to authorize 
this disclosure of information.  However, if you do not, you will not be able to participate in this 
study. 
 
Expiration of Authorization – Because this information is being disclosed for research use, 
there is no expiration date for the authorization to disclose and use this information.  The 
sponsor may keep and continue to use your study information for many years.  Your study 
doctor may need to add to or correct information about you even after your study 
participation is over, including providing updates of your health status if that is important 
to the purpose of the study.  The review of your medical records (discussed above) may also 
take place after the study is over.  This authorization will remain in effect unless you 
revoke it. 
 
Revoking Authorization to Disclose – If you stop participating in this study, you also have the 
right to revoke (withdraw) your authorization to disclose information.  Revoking your 
authorization means taking back the permission you gave the study doctor to send information 
about you to the sponsor.  If you revoke your authorization, your study doctor will not use or 
release any more information about you after receiving your request, except to tell the sponsor 
that you have stopped early and have revoked your authorization.  However, the sponsor can still 
keep and use any information that it has already received. 
 
You may revoke your authorization at any time.  However, once you do so, you can no longer 
continue to participate in the study. 
 
If you want to revoke your authorization, you must do so in writing to the study doctor.  You can 
get a revocation form from your study doctor or you can write a letter to the study doctor.   
 
 
 
 
 
 

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     CryoLife, Inc. 
Page 24 of 61 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)
APPENDIX B: Informed Consent 

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CryoLife, Inc.
Page 25 of 61      
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

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CryoLife, Inc.                                   
 
 
Page 26 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

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CryoLife, Inc.                                   
 
 
Page 27 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

	

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CryoLife, Inc.                                   
 
 
Page 28 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

	


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CryoLife, Inc.                                   
 
 
Page 29 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

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CryoLife, Inc.                                   
 
 
Page 30 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

	

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CryoLife, Inc.                                   
 
 
Page 31 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

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CryoLife, Inc.                                   
 
 
Page 32 of 61      
 
 
 
 
Confidential
Post-market, prospective evaluation of photo-oxidized decellularized 
bovine pericardium used as a patch in vascular repair and reconstruction surgery
PHF1801.000-M(04/18)

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 33 of 61 
Confidential 
APPENDIX C:  IFU 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 34 of 61 
Confidential 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 35 of 61 
Confidential 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 36 of 61 
Confidential 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 37 of 61 
Confidential 
APPENDIX D:  DATA VARIABLES (BY FORM)  
 
Informed Consent eCRF 
Subject ID  
 
1.  Subject was fully informed regarding the study. 
 Yes 
 No 
2.  The consent form was signed and dated by the subject prior to 
any study procedures. 
 Yes 
 No 
3. Subject was given a copy of the signed consent form. 
 Yes 
 No 
ICF Version Date: 
 
_____/_____/__________ 
Month/Day/Year 
4. HIPPA was obtained. 
 Yes 
 No 
5.  Date Informed Consent and HIPPA forms signed by subject: 
 
_____/_____/__________ 
Month/Day/Year 
6.  Informed Consent and HIPPA obtained by (Full Name): 
 
 
*If any question is answered “No”, a detailed explanation must be provided.  The subject must be 
contacted immediately and consent process completed prior to any further study procedures being 
completed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 38 of 61 
Confidential 
Eligibility Criteria eCRF 
Study Subject ID  
Date of Screening: ____/_____/__________ 
Month/Day/Year 
Inclusion Criteria 
 
1. Patient is undergoing a vascular procedure which falls within the 
indications for use and requires the use of PhotoFix Decellularized 
Bovine Pericardium. 
 Yes 
 No 
2. Patient’s surgery is anticipated to occur within 60 days of consent. 
 Yes 
 No 
3. Patient is ≥18 years old. 
 Yes 
 No 
4. Patient is willing and able to comply with the protocol and follow up 
period. 
 Yes 
 No 
5. Patient is willing and able to give written informed consent. 
 Yes 
 No 
Exclusion Criteria 
 
6. Patient’s procedure is a revision of a prior arteriotomy or venotomy. 
 Yes 
 No 
7. Patient’s procedure requires multiple vascular patches in 
anatomically distinct regions or other prosthetics (e.g. stents). 
 Yes 
 No 
8. Patient has a medical history of abnormal coagulopathy, bleeding, or 
thromboembolic disease. 
 Yes 
 No 
9. Patient has a medical history of severe immunodeficiency disease. 
 Yes 
 No 
10. Patient has a medical history of cancer. 
 Yes 
 No 
11. Patient has severe visceral disease affecting the heart or active liver 
disease or icterus. 
 Yes 
 No 
12. Patient has a history of cerebrovascular accident (completed stroke) 
within 3 months of planned surgery. 
 Yes 
 No 
13. Patient has a history of atrial fibrillation and requires a patch for 
carotid endarterectomy repair. 
 Yes 
 No 
14. Patient has an active or potential infection at the surgical site. 
 Yes 
 No 
15. Patient has used or plans to use immunomodulatory drugs for ≥ 6 
months. 
 Yes 
 No 
16. Patient has a sensitivity to products of bovine origin. 
 Yes 
 No 
17. Patient is currently enrolled in another study. 
 Yes 
 No 
18. Patient has a life expectancy of less than 12 months. 
 
 Yes 
 No 
19. Patient is pregnant or breastfeeding or planning on becoming 
pregnant or unwilling to use medically acceptable methods of birth 
control. 
 Yes 
 No 
20. Patient’s procedure is emergent. 
 Yes 
 No 
Does the patient meet all inclusion and exclusion criteria and can be 
considered eligible for enrollment? 
 Yes 
 No 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 39 of 61 
Confidential 
 
 
Demographics eCRF 
Study Subject ID  
 
1. Date of Birth 
_____/_____/__________ 
Month/Day/Year 
2.   Sex 
  Male 
  Female 
3.   Race 
  American Indian or Alaska Native 
  Asian 
  Black or African American 
  Native Hawaiian or Pacific Islander 
  White 
  Unknown                    (select all that apply) 
4.  Ethnicity 
  Non-Hispanic 
  Hispanic 
  Unknown 
5.  Height (inches) 
Unknown 
 
6.  Weight (lbs) 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 40 of 61 
Confidential 
Medical History eCRF 
Study Subject ID  
 
1. Indication for Surgery 
 
  Abdominal aortic aneurysm (AAA) 
  Carotid artery stenosis (CAS) 
  Hemodialysis access repair (HAR) 
  Peripheral arterial disease (PAD) 
  Other:_____________________________ 
2. Symptom Status 
 
  Symptomatic 
  Asymptomatic 
3. (CEA only) Disease Grading 
*Refer to Appendix E: Definitions and Acronyms 
  Absent 
  Mild 
  Moderate 
  Severe 
  Unknown 
4. (PAD only) Rutherford Classification 
*Refer to Appendix E: Definitions and Acronyms 
  Category 0 
  Category 1 
  Category 2 
  Category 3 
  Category 4 
  Category 5 
  Category 6 
  Unknown 
5. Target Patch Location 
  Artery 
  Vein 
If Artery, please select the specific location: 
  Abdominal aorta 
  Anterior tibial 
  Axillary 
  Brachial 
  Common carotid 
  Common iliac 
  External iliac 
  Femoral 
  Internal iliac 
  Popliteal 
  Pulmonary 
  Renal 
  Subclavian 
  Superior mesenteric artery 
  Thoracic aorta 
  Other:_____________________________ 
If Vein, please select the specific location: 
  Anterior tibial 
  Axillary 
  Basilic 
  Cephalic 
  Common iliac 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 41 of 61 
Confidential 
Medical History eCRF 
  External iliac 
  External jugular 
  Femoral 
  Internal iliac 
  Internal jugular  
  Pulmonary 
  Renal 
  Subclavian 
  Superior mesenteric 
  Other:_____________________________ 
6. Side of Body 
  Right 
  Left                                                   
N/A 
7. History of Hypertension 
  None (cutoff point, diastolic pressure     
usually lower than 90 mm Hg) 
  Controlled (cutoff point, diastolic pressure 
usually lower than 90 mm Hg) with single drug 
  Controlled with two drugs 
  Requires more than two drugs or is 
uncontrolled 
  Unknown 
8. History of Hyperlipidemia 
  Cholesterol (low-density lipoprotein and 
total) and triglyceride levels within normal limits 
for age 
  Mild elevation, readily controllable by diet 
  Moderate elevation requiring strict dietary 
control 
  Moderate elevation but severe enough to 
require dietary and drug control 
  Unknown 
9. History of Diabetes 
  None 
  Adult onset, controlled by diet or oral agents 
  Adult onset, insulin-controlled 
  Juvenile onset 
  Unknown 
10. History of Coronary Artery Disease 
  Yes 
  No 
  Unknown 
11.   History of Congestive Heart Failure 
*Refer to Appendix E: Definitions and Acronyms 
  None 
  NYHA Class I 
  NYHA Class II 
  NYHA Class III 
  NYHA Class IV 
  Unknown 
12.   History of Myocardial Infarction 
*Refer to Appendix E: Definitions and Acronyms 
  None 
  Recent, < 4 weeks 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 42 of 61 
Confidential 
Medical History eCRF 
  Past, ≥ 4 weeks 
  Unknown 
13.   History of Renal Insufficiency 
  No known renal disease, normal serum 
creatinine level 
  Moderately elevated creatinine level, as high 
as 2.4 mg/dL 
  Creatinine level, 2.5 to 5.9 mg/dL 
  Creatinine level greater than 6.0 mg/dL, or 
on dialysis or with kidney transplant 
  Unknown 
14. History of Stroke 
  0 
  1 
  2 
  3 
 ≥4 
  Unknown 
If ≥1, indicate when the most recent 
stroke occurred. 
 
_____/_____/__________ 
Month/Day/Year 
15. History of Transient Ischemic Attack 
(TIAs) 
  0 
  1 
  2 
  3 
 ≥4 
  Unknown 
If ≥1, indicate when the most recent 
TIA occurred. 
 
_____/_____/__________ 
Month/Day/Year 
16.  History of radiation to patch site 
  Yes 
  No 
  Unknown                                          
17.  Describe of other significant medical 
condition 
 
 
  None 
18. (AAA/CAS/HAR only)                
History of Peripheral Arterial Disease 
  Yes 
  No 
  Unknown                                          
19. (CEA only) History of contralateral 
disease 
  Normal 
  < 50% 
  50 – 70% 
  > 70% 
  Unknown                                          
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 43 of 61 
Confidential 
Surgical History eCRF 
Study Subject ID  
 
1. History of any cardiovascular surgery 
  Yes 
  No 
  Unknown 
If yes, how many prior cardiovascular 
surgeries 
 
If yes, how would you classify the surgeries 
  Cardiac 
  Vascular                     (select all that apply) 
2. If yes, categorize the surgery (1) 
*List most recent first 
  Open 
  Endoscopic 
  Unknown 
If yes, describe surgery 
 
 
 
Date of surgery _____/_____/__________ 
Month/Day/Year 
3. If yes, categorize the surgery (2) 
  Open 
  Endoscopic 
  Unknown 
If yes, describe surgery 
 
 
 
Date of surgery _____/_____/__________ 
Month/Day/Year                                   
  N/A 
4. If yes, categorize the surgery (3) 
  Open 
  Endoscopic 
  Unknown 
If yes, describe surgery 
 
 
 
Date of surgery _____/_____/__________ 
Month/Day/Year                                   
  N/A 
5. If yes, categorize the surgery (4) 
  Open 
  Endoscopic 
  Unknown 
If yes, describe surgery 
 
 
 
Date of surgery _____/_____/__________ 
Month/Day/Year                                   
  N/A 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 44 of 61 
Confidential 
Social History eCRF 
Study Subject ID  
 
1. History of Tobacco Use 
  None or none for last 10 years 
  None current, by smoked in last 10 years 
  Current (includes abstinence < 1 year), less 
than 1 pack/day 
  Current, ≥ 1 pack/day 
  Unknown 
2. History of Alcohol Use 
  No 
  Past 
  Current 
  Unknown 
If past or current, approximately how 
many drinks/ per week 
 
 
  Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 45 of 61 
Confidential 
Imaging Evaluation eCRF 
Study Subject ID  
 
1. Date Imaging was Performed 
 
_____/_____/__________ 
Month/Day/Year 
2. Indicate Visit Associated with 
Abstraction of Imaging Data 
  Visit 1, Pre-op 
  Visit 2, Peri-Op/Immediately post-op 
  Visit 3, 1 month post-op 
  Visit 4, 3 months post-op 
  Visit 5, 6 months post-op 
  Unscheduled Visit 
3. Select Type of Imaging 
  Computed Tomography Angiography  
  Digital Subtraction Angiography  
  Duplex Ultrasound 
  Magnetic Resonance Angiography  
  Transcranial Doppler  
  Other:_____________________________ 
4. Reason for Imaging 
*If AE-related complete AE eCRF 
  Scheduled 
  Adverse Event 
  Other:______________________________ 
5. Evidence of 
Inflammation/Degeneration in Target 
Artery/Vein 
  Yes 
  No 
  Unknown 
If yes, does this finding affect the patch 
location? 
  Yes 
  No 
  Unknown 
6. Evidence of Stenosis in Target Artery 
or Vein 
  Yes 
  No 
  Unknown 
If yes, indicate degree of stenosis (%) 
 
 
  Unknown 
If yes, brief description of technique for 
determining degree of stenosis 
 
 
  Unknown 
If yes, location of stenosis 
 
 
  Unknown 
7. Evidence of Calcification in Target 
Artery/Vein 
  Absent 
  Mild 
  Moderate 
  Severe 
  Other:______________________________ 
  Unknown 
If mild, moderate, severe, or other, does 
  Yes 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 46 of 61 
Confidential 
Imaging Evaluation eCRF 
the calcification involve the patch area? 
  No 
  Unknown 
If yes, what percentage of the patch 
area was affected by calcification (%)? 
 
 
  Unknown 
 
8. (CEA only) Lesion length 
  No lesion 
  <15 mm 
  <15 mm but more than one lesion  
  >15 mm or if > 2 stents are required 
  More than one lesion > 15 mm 
  Unknown 
9. (CEA only) Lesion location 
  No lesion 
  Lower or mid-neck 
  Abnormal low below the clavicle 
  Midneck extending to C2 
  Upper neck (C2 or higher/string sign) 
  Unknown 
10. (CEA only) Peak systolic Velocity in 
Distal Target Common Carotid Artery 
 
 
  Unknown 
11. (CEA only) Peak systolic Velocity in 
Internal Target Carotid Artery 
 
 
  Unknown 
12. (CEA only) End Diastolic Velocity in 
Distal Target Common Carotid Artery 
 
 
  Unknown 
13. (CEA only) End Diastolic Velocity in 
Target Internal Carotid Artery 
 
 
  Unknown 
14.  (CEA only) Plaque morphology 
  No plaque 
  Fibrous plaque/web 
  Mild calcification 
  Mixed fibrous/ ulcerative plaques/ thin cap 
  Multiple large calcification or lipid/ 
necrotic cores 
  Unknown 
15. (AAA only) Size of AAA (mm) 
 
 
  Unknown 
16. Other Significant Imaging Findings 
 
 
 
  None 
 
 
 
 

Post-market, prospective evaluation of photo-oxidized decellularized   
PHF1801.000-M(04/18) 
bovine pericardium used as a patch in vascular repair and reconstruction surgery 
CryoLife, Inc. 
  Page 47 of 61 
Confidential 
Medication eCRF 
Study Subject ID: 
 
 
Study Visit: 
  Visit 1, Pre-op 
  Visit 2, Peri-Op/Immediately post-op 
  Visit 3, 1 month post-op 
  Visit 4, 3 months post-op 
  Visit 5, 6 months post-op 
  Unscheduled Visit 
1. Is the patient currently taking any blood 
thinners? 
  Yes 
  No 
  Unknown 
2. Is the patient currently taking a statin? 
  Yes 
  No 
  Unknown 
If yes to either question, please fill out the applicable medication details in the table. 
Drug Name 
Indication 
Dose 
per 
Admin. 
Dose Unit 
Route of 
Admin. 
Dosing 
Freq. 
Start 
Date 
Stop 
Date 
1.  
 
 
 
 
 
 
 
  
Unknown 
 mg 
 
 
 
 Other: 
_______________ 
 
_______________ 
 Oral 
 
 
 
 Other: 
______________ 
 
______________ 
 
 
 
 
 
 
  
Unknown 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
 Ongoing 
2.  
 
 
 
 
 
 
 
  
Unknown 
mg 
 
 
 
 Other: 
_______________ 
 
_______________ 
 Oral 
 
 
 
 Other: 
______________ 
 
______________ 
 
 
 
 
 
 
  
Unknown 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
 Ongoing 
3.  
 
 
 
 
 
 
 
  
Unknown 
mg 
 
 
 
 Other: 
_______________ 
 
_______________ 
 Oral 
 
 
 
 Other: 
______________ 
 
______________ 
 
 
 
 
 
 
  
Unknown 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
 Ongoing 
4.  
 
 
 
 
 
 
 
  
Unknown 
mg 
 
 
 
 Other: 
_______________ 
 
_______________ 
 Oral 
 
 
 
 Other: 
______________ 
 
______________ 
 
 
 
 
 
 
  
Unknown 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
Month:  
 
_______ 
Day: 
 
_______ 
Year: 
 
_______ 
 Ongoing 
 
 
 

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Operative Assessment eCRF 
Study Subject ID:  
 
1. Date of Surgery 
_____/_____/__________ 
Month/Day/Year 
2. Implanting Surgeon’s Name 
 
 
3. Description of Surgical 
Repair/Reconstruction Involving 
PhotoFix 
 
 
 
4. Concomitant Procedures Performed 
  Yes 
  No 
If yes, Description of any Concomitant 
Surgeries performed 
 
 
 
5. PhotoFix status at conclusion of 
surgery 
*If explanted, complete Explant eCRF. 
  Implanted 
  Explanted 
6. How many PhotoFix Patches were used 
in the surgery? 
 
7. PhotoFix Lot Numbers by Patch Size 
(Indicated on Packaging) 
  0.8 x 8 
 
  1 x 6 
 
  1 x 10 
 
  1 x 14 
 
  2 x 9 
 
  4 x 4 
 
  6 x 8              
*Select all that apply 
8. Were you able to detect a sidedness to 
the PhotoFix patch? 
  Yes 
  No 
  Did not check  
If yes, which patch side did you implant 
towards the bloodstream? 
  Smooth 
  Rough 
9. Perioperative or Post-Operative 
Adverse Events 
*If yes, fill out the Adverse Event eCRF. 
  Yes 
  No 
If yes, timing of event 
  Peri-Operative 
  Post-Operative 
10. Length of Implanted Patch (cm) 
 
  Unknown 
11.  Width of Implanted Patch (cm) 
 
  Unknown 
 

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Follow-Up eCRF 
Study Subject ID  
 
1. Date of Visit 
 
_____/_____/__________ 
Month/Day/Year 
2. Indicate Visit Number 
*If Visit 5, fill out End of Study eCRF. 
  Visit 3, 1 month post-op 
  Visit 4, 3 months post-op 
  Visit 5, 6 months post-op 
  Unscheduled Visit 
3. Indicate Current Subject Status 
*If withdrawn, fill out End of Study eCRF. 
  Active 
  Withdrawn 
4. Were there any post-operative Adverse 
Events since last study visit? 
*If yes, fill out the Adverse Event eCRF. 
  Yes 
  No 
5. Was patency lost in the target 
artery/vein since the last study visit? 
*If yes, fill out the Adverse Event eCRF. 
  Yes 
  No 
If yes, indicate the number of instances 
that patency was lost   
If yes, indicate date(s) patency was lost 
 
_____/_____/__________  (most recent) 
Month/Day/Year 
 
_____/_____/__________   
 N/A 
Month/Day/Year 
 
_____/_____/__________   
 N/A 
Month/Day/Year 
If yes, indicate reason(s) patency was 
lost 
  Aneurysm  
  Infection 
  Restenosis 
  Thrombosis 
  Other:_____________________________ 
                              *Select all that apply 
If yes, was a surgical (open or 
endovascular) procedure performed to 
re-establish patency? 
  Yes 
  No 
  Unknown 
If yes, was any loss of patency 
PhotoFix-related? 
  Definitely 
  Probably 
  Possibly 
  Unrelated 
If yes, was patency successfully re-
established for the most recent event? 
  Yes 
  No 
  Unknown 
6. Did the patient undergo any vascular 
  Yes 

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Follow-Up eCRF 
surgery (open or endovascular) since 
the last study visit? 
*If yes, fill out the Adverse Event eCRF. 
  No 
  Unknown 
If yes, date surgery occurred 
 
_____/_____/__________ 
Month/Day/Year 
If yes, indication for surgery? 
  Infection 
  Re-establish Hemodialysis Access Patency 
  Rupture  
  Stenosis 
  Thrombosis 
  Other:_____________________________ 
*Select all that apply 
 
If yes, describe the surgical procedure 
 
 
 
 
 
If yes, did the surgery involve PhotoFix 
or the surrounding patch area? 
  Yes 
  No 
If yes, was PhotoFix explanted? 
*If Partially or Completely, fill out Explant 
eCRF 
  No 
  Partially 
  Completely 
If yes, was the need for surgery related 
to PhotoFix? 
  Definitely 
  Probably 
  Possibly 
  Unrelated 
7. Has there been evidence of restenosis 
since the last study visit?   
  Yes 
  No 
  Unknown 
If yes, was an imaging evaluation 
performed  
*If yes, complete the Imaging Evaluation eCRF 
  Yes 
  No 
  Unknown 
If yes, indicate the degree of 
restenosis. 
 
 
  Unknown 
8. Describe any other significant events 
which have occurred since the last 
follow-up visit. 
 
 
 
  None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Adverse Event eCRF 
Study Subject ID  
 
1. Date Adverse Event Reported 
 
_____/_____/__________ 
Month/Day/Year 
2. Is this an update to a previously 
reported event? 
  Yes 
  No 
3. Start Date 
 
_____/_____/__________ 
Month/Day/Year 
4. Stop Date 
 
____/_____/__________ 
Month/Day/Year                             
 Ongoing 
5. Classify the event as one of the 
following (if multiple symptoms, 
classify by most severe) 
  Amaurosis Fugax 
  Bleeding event 
  Cardiac event 
  Endoleak 
  Infection 
  Inflammation/Edema 
  Pain 
  Paraparesis 
  Renal event 
  Stroke 
  Symptomatic Carotid Occlusion 
  Thrombosis 
  Trauma 
  Transient Ischemic Attack 
  Other:_____________________________ 
(Infection only), was a culture taken? 
 
  Yes 
  No 
(Infection only), If yes, what were the 
reported results?  
  Inconclusive 
  Positive (identify 
organisms):_____________________________ 
  Negative 
  Report not available 
6. Describe the Event 
 
 
 
 
 
7. Consequence of Adverse Event 
  Surgical Intervention 
  Hospitalization (New or Prolonged) 
  Death    
  Other:_____________________________ 
  None                           *Select all that apply 

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Adverse Event eCRF 
If death is indicated, provide cause of 
death 
 
 
 
  Unknown 
8. Required Drug Treatment 
*Update Medication eCRF, as applicable 
  Yes 
  No 
  Unknown 
9. Classify the Adverse Event. 
*Refer to Protocol Appendix E, Definitions 
  Adverse Event (AE) 
  Unanticipated Adverse Effects (UAE) 
  Serious Adverse Event (SAE) 
If SAE, select at least one of the 
following 
  Death 
  Life Threatening 
  Other Medically Important Serious Event 
  Persistent/ Significant Disability 
  Requires or Prolongs Hospitalization 
*Select all that apply 
10. Is the event related to the subject’s 
vascular surgery? 
  Yes 
  No 
 
11. Is the Adverse Event related to 
PhotoFix? 
  Definitely 
  Probably 
  Possibly 
  Unrelated 
12. Status of Adverse Event 
  Resolved  
  Resolved with Sequelae 
  Not Resolved 
  Fatal 
  Unknown 
13. Does the Adverse Event Require Study 
Discontinuation? 
If yes, complete the End of Study eCRF 
  Yes 
  No 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Explant eCRF 
Study Subject ID  
 
1. Date of Explant 
 
_____/_____/__________ 
Month/Day/Year 
2. Primary Reason for Explant  
*Complete Adverse Event eCRF 
  Infection  
  Patch Aneurysm 
  Patch Deterioration 
  Rupture 
  Suture Line Tear 
  Other:____________________________ 
3. Macroscopic evidence of the 
following: 
  Calcification 
  Fibrous Sheathing 
  Host Tissue Overgrowth 
  Infection 
  Inflammation 
  Thrombosis 
  Tissue Rejection 
  Other 
  Unknown 
*select all that apply 
If any macroscopic findings, provide 
additional detail. 
 
 
 
 
4. Was there a pathological analysis of 
the explanted specimen? 
  Yes 
  No 
  Unknown 
If yes, what were the documented 
pathology results? 
 
 
 
5. Explanting Surgeon 
 
 
6. Description of Surgical Procedure 
 
 
 
7. Was the entire PhotoFix patch 
removed? 
  Yes 
  No 
  Unknown 
8. Was peri-operative imaging 
completed? 
*If yes, complete the Imaging Evaluation eCRF 
  Yes 
  No 
  Unknown 
9. Were photographs taken of the explanted 
tissue? 
*If yes, please e-mail photographs to CryoLife 
  Yes 
  No 
  Unknown 
 

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End of Study eCRF 
Study Subject ID  
 
1. Date of Discontinuation 
 
_____/_____/__________ 
Month/Day/Year 
2. Indicate Associated Visit  
  Visit 1, Pre-op 
  Visit 2, Peri-Op/Immediately post-op 
  Visit 3, 1 month post-op 
  Visit 4, 3 months post-op 
  Visit 5, 6 months post-op 
  Unscheduled Visit 
3. Did the patient complete the study? 
  Yes 
  No 
If no, Reason for Discontinuation 
*Complete Adverse Event eCRF, as applicable 
  Adverse Event 
  Death 
  Did not meet inclusion/ exclusion criteria 
  Investigator Judgement  
  Lost-to-Follow-Up 
  Non-compliance 
  Pregnancy 
  Protocol Violation 
  Termination of Study by Sponsor 
  Withdrew Consent 
  Other:_____________________________ 
 
If no, provide Details on 
Discontinuation  
 
 
 
 
  No additional details 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX E:  DEFINITIONS AND ACRONYMS   
 
ADVERSE EVENT (AE) 
Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporarily associated with the use of a device, whether or not related to the device.   
 
ANIMAL ORIGIN INFECTIOUS AGENT TRANSMISSION 
Infection with any organism not commonly found in human beings which can be traced to the 
animal product by positive culture. 
 
ARRHYTHMIA 
An alteration of the heart’s rhythm from normal sinus rhythm which requires drug and/or 
pacemaker therapy. 
 
BLEEDING 
Extravascular blood loss requiring volume replacement of surgical interventions 
 
BLEEDING EVENT 
Any episode of major internal or external bleeding that causes death, hospitalization, or 
permanent injury (e.g., vision loss) or requires transfusion.  The complication “bleeding event” 
applies to all patients, whether or not they are taking anticoagulants or antiplatelet drugs, because 
bleeding events can occur in patients who are not anticoagulated.   
 
CARDIAC ARREST 
Permanent or temporary cessation of organized heart function, or precipitous drop in blood 
pressure sufficiently severe to require cardiopulmonary resuscitation (CPR) or emergency 
defibrillation. 
 
CAROTID ARTERY STENOSIS (CAS) GRADE 
Mild:   
Amaurosis fugax   
Moderate:  
TIA/minor stroke 
Major:  
Major stroke 
 
COMPLICATION 
An undesirable or unexplained clinical event experienced by the patient that results in death, 
injury, or invasive intervention.  Complications may or may not be related to the bypass conduit. 
 
EARLY MORTALITY 
Any mortality that occurs within the first 30 days postoperatively. 
 
ELECTRONIC CASE REPORT FORM (eCRF) 
An electronic form designed to record protocol required information that is to be reported to the 
Sponsor on a clinical study patient. 
 
EXPLANT 
Removal of the study device for any reason. 

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FDA 
Food and Drug Administration 
 
HEART FAILURE 
An event in which the heart fails to meet the circulatory requirements of the body under differing 
physiological circumstances, and/or a state in which cardiac output is reduced relative to the 
metabolic demands of the body, assuming the evidence of adequate venous return.   
 
INFECTION 
Bacterial or fungal proliferation confirmed by organism culture or systemic or localized reaction. 
 
INFORMED CONSENT 
A written document that contains relevant information about the clinical study and that is signed 
and dated by the patient or the patient’s legally acceptable representative. 
INSTITUTIONAL REVIEW BOARD (IRB) 
An independent body consisting of medical professionals and nonmedical members responsible 
for reviewing and providing initial and continuing approval of research in human patients and 
verifying that the safety, integrity, and human rights of patients participating in a particular 
clinical study are protected. 
 
MORTALITY 
Permanent cessation of all vital bodily functions. 
 
MYOCARDIAL INFARCTION 
An area of coagulation necrosis resulting from impaired oxygenation of the myocardium.  Events 
that are excluded are those patients who possess normal coronary arteries or if the patient is less 
than 40 years of age (will be reported as embolism events). 
 
NEW YORK HEART ASSOCATION CLASSIFICATION (NYHA) 
Classification system used to categorize a patient’s symptoms of heart failure. 
 
NSAID 
Nonsteroidal anti-inflammatory drug. 
 
NYHA CLASS I 
 
Patients with cardiac disease but without resulting limitations of physical activity.  Ordinary 
physical activity does not cause undue fatigue, palpitation, dyspnea, or angina pain. 
 
 
NYHA CLASS II 
 
Patients with cardiac disease resulting in slight limitation of physical activity.  They are 
comfortable at rest.  Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal 
pain. 
 
 
 

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NYHA CLASS III 
 
Patients with cardiac disease resulting in marked limitation of physical activity.  They are 
comfortable at rest.  Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or 
anginal pain. 
 
NYHA CLASS IV 
 
Patient with cardiac disease resulting in inability to carry on any physical activity without 
discomfort.  Symptoms of cardiac insufficiency or of the anginal syndrome may be present event 
at rest.  If any physical activity is undertaken, discomfort is increased.  
 
PRINCIPAL INVESTIGATOR 
An individual responsible for the conduct of the clinical investigation at a study site.  In the event 
the study is conducted by a team of individuals at a study site, the Principal Investigator is the 
responsible leader of the team. 
 
REOPERATION 
Any operation that repairs, alters, or replaces PhotoFix and/or the surrounding tissue. 
 
RUTHERFORD CLASSIFICATION FOR CHRONIC LIMB ISCHEMIA 
Category 0:  Asymptomatic—no hemodynamically significant occlusive disease 
Category 1:  Mild claudication 
Category 2:  Moderate claudication 
Category 3:  Severe claudication 
Category 4:  Ischemic rest pain 
Category 5:  Minor tissue loss—nonhealing ulcer, focal gangrene with diffuse pedal ischemia 
Category 6:  Major tissue loss—extending above transmetatarsal level, functional foot no longer 
salvageable 
 
SERIOUS ADVERSE EVENT (SAE) 
A serious adverse event (experience) or reaction is any untoward medical occurrence that at any 
dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of 
existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital 
anomaly/birth defect. 
 
SPONSOR 
An individual, device company, governmental agency, academic institution, private organization, 
or organization that takes responsibility for and initiates a clinical investigation. 
 
SUDDEN UNEXPECTED, UNEXPLAINED DEATH 
The cause of these deaths is unknown and the relationship to a bypass conduit is also unknown.  
These deaths should be reported as a separate category of bypass mortality if the cause cannot be 
determined by clinical data or autopsy. 
 
THIRTY-DAY MORTALITY 
Thirty-day Mortality (sometimes termed Operative Mortality) is death within 30 days of 
operation regardless of the patient's geographic location.  Hospital Mortality is any death within 

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any time interval after operation if the patient is not discharged from the hospital.  (Hospital-to-
hospital transfer is not considered discharge; transfer to a nursing home or rehabilitation unit is 
considered hospital discharge unless the patient subsequently dies of complications of the 
operation.) 
 
UNANTICIPATED ADVERSE EFFECTS (UAEs) 
Any serious adverse effect on health or safety or any life-threatening problem or death caused 
by, or associated with, a product, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the study protocol, or any other unanticipated serious 
problems associated with a product that relates to the rights, safety, or welfare of a Patient. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX F:  REFERENCES 
 
1. Rockman CB, Hoang H, Guo Y, Maldonado TS, Jacobowitz GR, Talishinskiy T, et al.  
The prevalence of carotid artery stenosis varies significantly by race. J Vasc Surg. 2013; 
57: 327-337. 
2. Criqui MH, Aboyans V.  Epidemiology of peripheral artery disease.  Circ Res. 2015; 116: 
1509-1526. 
3. Li X, Zhao G, Zhang J, Duan Z, Xin S.  Prevalence and Trends of the Abdominal Aortic 
Aneurysms Epidemic in General Population- A Meta-Analysis.  PLoS One.  2013; 
8(12):e81260. 
4. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, et al.  Worldwide access 
to treatment for end-stage kidney disease: a systematic review.  Lancet.  2015; 385 
(9981): 1975-1982. 
5. AbuRahma AF.  Processes of care for carotid endarterectomy: surgical and anesthesia 
considerations.  J Vasc Surg. 2009; 50: 921-933. 
6. Rerkasem K, Rothwell PM.  Systematic review of randomized controlled trials of patch 
angioplasty versus primary closure and different types of patch materials during carotid 
endarterectomy.  Asian J Surg. 2011; 34 (1): 32-40. 
7. Marien BJ, Raffetto JD, Seidman CS, LaMorte WW, Menzoian JO.  Bovine pericardium 
vs Dacron for patch angioplasty after carotid endarterectomy.  Arch Surg. 2002; 137:785-
788. 
8. Trinh KN, Wilson SE, Gordon IL, and Williams RA. Postintervention patency: a 
comparison of stenting versus patch angioplasty for dysfunctional hemodialysis access 
sites.  Ann Vasc Surg. 2016; 33: 120-125. 

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9. Moore MA, Bohachevsky IK, Cheung DT, Boyan BD, Chen W, Bickers RR et al. 
Stabilization of pericardial tissue by dye-mediated photooxidation.  J Biomed Mater Res. 
1994; 28(5): 611-618. 
10. Moore MA.  PhotoFix: Unraveling the Mystery.  J Long Term Eff Med Implants.  2001; 
11(3-4): 185-197. 
11. Kim KM, Herrera G, Battarbee HD. Role of Glutaraldehyde in Calcification of Porcine 
Aortic Valve Fibroblasts.  Amer J of Path. 1999; 154(3): 843–852. 
12. Schoen FJ and Levy RJ.  Calcification of Tissue Heart Valve Substitutes: Progress 
Toward Understanding and Prevention.  Ann Thorac Surg. 2005; 79: 1072-1080. 
13. Unmashankar PR, Mohanan PV, and Kumari TV.  Glutaraldehyde Treatment Elicits 
Toxic Response Compared to Decellularization in Bovine Pericardium.  Toxicol Int. 
2012 19(1): 51-58. 
 

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APPENDIX G: PROTOCOL DEVIATION REPORT FORM