Geniculate Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis
Phase: NA
Conditions: Osteoarthritis Of Knee
Sponsor: University of North Carolina, Chapel Hill

 
Geniculate Artery Embolization for the Treatment of Knee Pain Secondary to 
Osteoarthritis 
 
 
NCT number NCT02850068 
Document Date May 31, 2017 
 

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Protocol Title: 
Geniculate Artery Embolization for the 
Treatment of Knee Pain Secondary to 
Osteoarthritis 
 
 
Sponsor: 
 
Ari J. Isaacson, MD 
Principal Investigators: 
Ari J. Isaacson, MD (UNC-Chapel Hill, Radiology) 
 
 
Sandeep Bagla, MD (UNC-Chapel Hill, Radiology) 
 
Co-Investigator: 
 
Daniel Del Gaizo, MD (UNC-Chapel Hill, Orthopaedics) 
 
 
 
Medical Device: 
Embozene Microspheres  
 
IDE Number:  
 
G160129 
 
Version Date:  
 
5/31/17 
 
 
 

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Table of Contents 
 
1.0 
Introduction 
1.1 
Study Conduct 
1.2 
Background 
1.3 
Medical Device 
1.3.1 Name of Investigational Device 
1.3.2 Intended Use of the Investigational Device 
1.3.3 Description of the Investigational Device 
1.4 
Preclinical Data 
1.5 
Clinical Data to Date 
2.0 
Study Objectives 
3.0 
Study Design  
3.1 
General Design 
3.2 
Primary Study Endpoints 
3.3 
Secondary Study Endpoints 
3.4 
Primary Safety Endpoints 
4.0 
Subject Selection and Withdrawal 
4.1 
General Characteristics of the Proposed Subject Population 
4.2 
Anticipated Number of Research Subjects 
4.3 
Inclusion Criteria 
4.4 
Exclusion Criteria 
4.5 
Subject Recruitment and Screening 
4.6 
Early Withdrawal of Subjects 
4.6.1 Criteria for removal from study 
4.6.2 Follow-up for Withdrawn Subjects 
5.0 
Study Treatment or Diagnostic Product Procedures 
5.1 
Description 
5.2 
Method for Assigning Subject to Treatment Groups 
5.3 
Subject Compliance Monitoring 
5.4 
Prior and Concomitant Therapy 
5.5 
Blinding of Study  
5.6 
Receiving, Storage, Dispensing and Return 
5.6.1 Receipt of Investigational Device Supplies 
5.6.2 Storage 
5.6.3 Dispensing 
5.6.4 Return or Destruction of Investigational Device 
6.0 
Study Procedures 
6.1 
Visit 1 Screening/Enrollment Visit 
6.2 
Visit 2 GAE Study Procedure 
6.3 
Visit 3 1 day followup 
6.4 
Visit 4 30 day followup 
6.5 
Visit 5 3 month followup 
6.6 
Visit 7 6 month followup 
6.7 
Study Procedure Flow Chart 
7.0 
Safety and Effectiveness Assessments 

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7.1 
Safety Assessments 
7.2 
Effectiveness Assessments 
8.0 
Statistical Plan 
8.1 
Sample Size Determination 
8.2 
Statistical Methods 
8.3 
Subject Population(s) for Analysis 
8.4 
Interim Analysis 
9.0 
Risk Analysis 
9.1 
Anticipated Risks 
9.2 
Adverse Event Definitions 
9.3 
Recording of Adverse Events 
9.4 
Causality and Severity Assessment 
9.5 
Reporting of Adverse Effects and Unanticipated Problems 
9.5.1 Reporting of Adverse Effects to the FDA 
9.5.2 Reporting Adverse Effects to the Responsible IRB 
9.6 
Stopping Rules 
9.7 
Medical Monitoring 
9.7.1 Data and Safety Monitoring Plan 
9.7.2 Data and Safety Monitoring Board 
10.0 
Data Handling and Record Keeping 
10.1 
Confidentiality 
10.2 
Source Documents 
10.3 
Case Report Forms 
10.4 
Record Retention 
10.5 
IRB Documentation 
11.0 
Study Monitoring, Auditing and Inspecting 
11.1 
Study Monitoring Plan 
11.1.1 Locations 
11.1.2 Study Staff Responsibilities and Training 
11.1.3 Quality Assurance and Quality Control 
11.1.4 Safety Monitoring 
11.1.5 Monitoring Activities 
11.1.6 Study Closure 
11.2 
Auditing and Inspecting 
12.0 
Ethical Considerations 
12.1 
Institutional Review Board (IRB) Approval 
12.2 
Ethical and Scientific Conduct of the Clinical Research Study 
12.3 
Subject Informed Consent 
13.0 
Study Finances 
13.1 
Funding Source 
13.2 
Conflict of Interest 
13.3 
Subject Stipends or Travel Reimbursements 
14.0 
Publication Plan 
15.0 
References 
16.0 
Attachments 
 
 

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1.0 Introduction 
1.1 Study Conduct 
This study will be conducted in compliance with the protocol approved by the 
Institutional Review Board, and according to Good Clinical Practice standards. No 
deviation from the protocol will be implemented without the prior review and approval 
of the IRB except where it may be necessary to eliminate an immediate hazard to a 
research subject. In such case, the deviation will be reported to the IRB according to its 
policies and procedures. 
 
1.2 Background 
 
Osteoarthritis (OA) is a common and major cause of pain and disability. An estimated 
26.9 million adults in the US suffer from OA (1) and nearly 50% of adults may 
develop symptomatic knee OA by age 85 (2).  Knee OA affects obese individuals at a 
higher rate with ⅔ of individuals developing symptomatic disease.  The treatment for 
knee osteoarthritis is broad and includes: exercise and patient education; 
pharmacologic therapies, including oral, topical, and intra-articular medications; and 
surgical interventions, including total joint arthroplasty.  Minor symptoms can be 
managed with non-opioid pain medications such as acetaminophen or nonsteroidal 
anti-inflammatory drugs (NSAIDs), which are the mainstay of pain management for 
OA. Severe and end- stage osteoarthritis can be treated with total joint arthroplasty.  
Unfortunately, NSAIDs can be a cause of renal failure, exacerbation of asthma and 
most notably, gastrointestinal hemorrhage.  Estimated number of deaths from 
NSAID-related gastrointestinal bleeding has been estimated at 16500 (3). With the 
significant morbidity associated with treatment of OA, there is a need to develop a 
new, effective, minimally invasive and safe treatment for pain related to osteoarthritis 
of the knee.   
 
The principal symptom of OA, pain, is mediated by a number of factors. However, 
angiogenesis resulting in neovascularity, neural sensitization and inflammation has 
been described as a potential pathophysiological pathway of the deep joint pain 
described by many OA patients (4, 5).  This increased vascularity in the setting of 
pain and OA has been the focus of recent endovascular investigation, with the 
proposed mechanism of embolization as a novel treatment.  
 
Particulate embolization of geniculate artery branches supplying hypervascular joint 
tissue, the same technique we are proposing to treat pain from OA, has been 
previously described as a safe treatment for hemorrhage after total knee arthroplasty 
in multiple reports (6-9). In 2008, three cases were reported using 150-355 
micrometer particles without any complications (6). In 2013, a Japanese group 
reported the use of 1000-2000 micrometer particles in the treatment of five patients, 
again without complication (9). In 2015, an author group that includes one of the Co-
PIs reported outcomes from 13 cases in which there were no major complications and 
two minor complications (transient cutaneous ischemia) (8). Finally, in 2016 a fourth 
report of 14 embolizations was published in which there were no major complications 
and, again, two minor complications (transient cutaneous ischemia) (7).  

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Embolization of hypervascular joint tissue for the treatment of pain has been 
pioneered by Dr. Okuna and his colleagues in Japan. They initially reported a case 
series in which they were able to reduce pain related to refractory tendinopathy and 
enthesopathy in multiple joints in 7 patients using an antibiotic particulate for 
embolization without major complication (10).  Subsequently, the same team 
published its experience with transcatheter embolization of hypervascular tissue 
within the shoulder joint in 7 patients diagnosed with adhesive capsulitis. The 
procedure successfully resulted in pain reduction with any complications (11). 
Finally, Okuno et al also published their results after synovial embolization in 
patients with painful OA. The procedure was performed on 14 patients and there were 
no major complications. There was significant pain reduction and decreased difficulty 
of movement at 4 months. Medication frequency also decreased after embolization 
(12).  
 
The current investigation teams have led efforts pioneering embolization procedures 
in novel targets that have proved successful (13-18).  We have also had experience in 
embolization of the knee, in particular with post-arthroplasty hemorrhage (8). With 
our proven experience in embolization, and in particular the local-regional anatomy, 
we have set forth to pursue a US study evaluating embolization as a treatment for OA 
related knee pain.  
 
1.3 Medical Device 
 
1.3.1 Name of Investigational Device 
Embozene Microspheres 
 
1.3.2 Intended Use of the Investigational Device 
Embozene Microspheres will be used for geniculate artery embolization (GAE) in 
subjects with knee osteoarthritis. 
 
1.3.3 Description of the Investigational Device 
 
CeloNova BioSciences Inc. Embozene® Microspheres and Embozene® Color 
Advanced Microspheres were found to be substantially equivalent and cleared 
medical devices (Premarket Notification K073417) to prior technologies: 
 
 
• 
Boston Scientific Contours SE ™ Microspheres (K032707), and  
• 
Biocompatible Bead Block ™ Microspheres (K033761).  
 
Identified in the Code of Federal Regulations 21 Part 870- Subpart D-
Cardiovascular Prosthetic Devices.  
 
Classification Name: Artificial Embolization Device. Class II Medical Device 
Common Name: Vascular Embolization Device Subpart D-Prosthetic Devices; 
Sec. 870.3300 
 
Indication for Use: A vascular embolization device is an intravascular implant 
intended to control hemorrhaging due to aneurysms, certain types of tumors (e.g., 

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nephroma, hepatoma, uterine fibroids), and arteriovenous malformations. This 
does not include cyanoacrylates and other embolic agents, which act by 
polymerization or precipitation.  Embolization devices used in neurovascular 
applications are also not included in this classification.  
 
Embozene Microspheres are tightly calibrated, sub-millimeter, hydrogel beads 
coated with inorganic perfluorinated polymer coating for biocompatibility. They 
are manufactured in multiple sub-millimeter sizes. They come in a liquid 
suspension that is mixed with iodinated contrast before use. Once a catheter has 
been fluoroscopically guided into the target vessel, the microspheres are then 
injected, causing obstruction at the arteriole level until the desired degree of 
embolization has occurred. The microspheres used during the study will be 
unchanged. 
 
1.4 Preclinical Data 
Embozene Microspheres have proven to be an effective embolization material with 
high biocompatibility in multiple non-human studies (19-23). In porcine model 
studies, Embozene Microspheres effectively embolized renal arteries without toxicity, 
with low immunoreactivity and associated inflammation of the surrounding tissue and 
with low rates of recanalization. Inflammation within porcine liver models was also 
seen to be low after Embozene embolization. 
  
1.5 Clinical Data to Date 
Embozene Microspheres have been safely used as an embolic agent to target 
hypervascular lesions throughout the body including hepatocellular carcinoma, 
meningioma, uterine fibroids and adenomyosis and benign prostatic hyperplasia (18, 
24-26). The investigators have also performed GAE for knee hemarthrosis with 
technical and clinical success using Embozene Microspheres (8). Recently, 
Embozene has been used safely and effectively for GAE to treat medial knee pain in 
the setting of osteoarthritis (12). Embozene Microspheres are FDA approved for the 
treatment of arteriovenous malformations and hypervascular tumors. 
 
2.0 Study Objectives 
The primary aims of this study are to determine if GAE will reduce the severity of 
pain as well as global disability (resulting from the combination of pain, stiffness and 
difficulty performing daily activities) caused by knee OA and if it can be performed 
safely. The secondary aim is to determine if GAE can result in the decreased 
necessity for ongoing conservative OA therapies such as medication therapy and joint 
injections. Another secondary aim to provide 'sample size data' for planning a future 
study. 
 
3.0 Study Design  
3.1 General Design 
This will be an open label pilot study with a small population undergoing GAE to 
determine safety and efficacy.  After IRB approval of a written informed consent and 
over, approximately a 24 month duration, N=20 subjects will be recruited within 2 
hospital clinic based settings.  Only subjects ≥ 40 years will be screened for study 
recruitment and will be un-blinded from study treatment.  Clinical procedures and 

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evaluations will consist of a preoperative screening assessment to determine if the 
potential study subject meets the inclusion and exclusion criteria, enrollment, surgical 
procedure for geniculate artery embolization, and follow-up visits at 24 hours, 1, 3 & 
6 months.  An MRI will be performed at the 1-month visit to detect a change in 
synovial vascularity and to exclude complication. 
 
3.2 Primary Study Endpoints 
1. Overall efficacy of treatment as determined by a minimal clinically significant 
reduction in global Western Ontario and McMaster University Osteoarthritis Index 
(WOMAC) questionnaire scoring of 16% (27) at 6 months follow-up. 
2. Minimal clinically important decrease of 15% on the pain VAS (28) at 6 month 
follow-up.  
 
3.3 Secondary Study Endpoints 
1. Reduction of previously initiated OA medical therapy (e.g. NSAIDs) at 6 months 
follow-up. 
 
3.4 Primary Safety Endpoints 
1. GAE without major complication. 
 
4.0 Subject Selection and Withdrawal 
4.1 General Characteristics of the Proposed Subject Population 
Study subjects will be men and women with knee osteoarthritis resulting in knee pain 
that is refractory to conservative therapies, who are not planning to undergo surgery 
within 6 months. 
 
4.2 Anticipated Number of Research Subjects 
Enrollment into the investigation will be defined as providing informed consent for 
study participation per IRB policies.  
 
Twenty (20) subjects will be enrolled between both sites and all are anticipated to 
complete the study. 
 
4.3 Inclusion Criteria 
1. Moderate to severe knee pain (VAS > 50 mm), and 
2. Pain refractory to at least 3 months* of conservative therapies (anti-inflammatory 
drugs, or physical therapy, or muscle strengthening, or intra-articular injections), and  
3. Kellgren-Lawrence grade 1, 2 or 3 on radiograph of the knee. 
4. Age > 40 years. 
 
*3 months was chosen because this time interval is thought adequate for knee pain to be 
considered refractory to conservative care.  
 
4.4 Exclusion Criteria 
1. Current local infection, or 
2. Life expectancy less than 6 months, or 

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3. Known advanced atherosclerosis, which is known lower extremity vascular or 
lower extremity symptoms thought to be secondary to arterial vascular disease (eg 
claudication, ischemic rest pain), or 
4. Rheumatoid or infectious arthritis, or 
5. Prior knee surgery, or 
6. Uncorrectable coagulopathy including INR > 2.5 or platelets < 30,000, or 
7. Iodine allergy resulting in anaphylaxis, or 
8. Renal dysfunction as defined by GFR (eGFR) of <45 obtained within the past 60 
days, or 
9. Contraindication for MR Imaging (such as claustrophobia, metallic fragment or 
foreign bones, implants or prosthesis), or 
10. IV contrast allergy characterized by anaphylaxis or anaphylactoid reactions. 
 
4.5 Subject Recruitment and Screening 
Subjects will be recruited from orthopedic and interventional radiology clinics at 
University of North Carolina Healthcare System and the Vascular Institute of 
Virginia. 
 
4.6 Early Withdrawal of Subjects 
4.6.1 Criteria for Removal from Study 
1. Subjects will be withdrawn from the study if  
a. a major complication occurs that prevents completion of GAE or the 
ability to complete the follow up visits, or 
b. at any point at their discretion. 
 
 
4.6.2 Follow-up for Withdrawn Subjects 
If a subject withdraws from the study, any recorded data will still be included 
in the analysis. Subjects will only be replaced if they withdrew prior to 
undergoing GAE. 
 
5.0 Study Treatment or Diagnostic Product Procedures 
5.1 Description  
 
Subjects will not initiate any new pain therapy or escalate current therapy for 1 month 
prior to GAE. They will be given an intravenous dose of antibiotics on the day of the 
procedure and continue with oral antibiotics for seven days after the procedure.  The 
subjects will be given the choice of receiving intravenous anxiolytic and analgesic 
medication during procedure or proceeding with local anesthetic only. 
 
Arterial access site will be prepped and draped using sterile technique. Ultrasound-
guided access may be used and arterial access will be obtained. An intra-arterial 
sheath will be placed. Through this sheath a guiding catheter will be used to perform 
lower extremity angiography on the targeted side either manually or robotically. 
Using the guiding catheter and a microcatheter, the geniculate arteries supplying 
hypervascular synovial tissue in the region of the knee joint will be catheterized. If 
there is uncertainty about the angiographic findings, pre-embolization simulation can 
be performed with contrasted cone beam CT on the procedure table. This will allow 

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the operators to know exactly what tissues will be receiving the microspheres. 
Embozene Microspheres ranging from 40-500 microns*, selected at the operator’s 
discretion based upon size of target vessels, will then be injected under fluoroscopic 
guidance to prevent reflux and non-target embolization. Injection will continue until 
an end point of at least ‘near stasis’ (slowed antegrade flow of contrast). Multiple 
geniculate arteries may be embolized until neovascularity is no longer seen. A repeat 
lower extremity angiogram will then be performed to evaluate for success of 
embolization and to exclude complication. The catheter and sheath will then be 
removed and hemostasis will be achieved with manual compression or a vascular 
closure device. The subject subsequently will be discharged home the same day (<23 
hours) unless a complication arises that requires inpatient admission for management 
of the complication.  Subjects may be discharged on pain medications as needed for 
post-operative care (<14 days). 
 
*The range in size of particles will allow the operators to discern the safest, most 
effective size for the vessels targeted. For example, if the catheter can be advanced all 
the way in to the branch supplying only the synovium, smaller particles can be safely 
used to induce ischemia in the target tissue. If the catheter cannot be advanced due to 
tortuous or small caliber vessels, a larger sized particle may be selected. This will 
allow for proximal embolization without distal penetration into the cutaneous 
branches, thereby allowing continued blood flow to the skin through collateral 
pathways (Fig 1-2). This concept is utilized routinely within embolization procedures 
are commonly performed. 
 

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Fig 1.-Geniculate artery angiogram after total knee arthroplasty demonstrating 
“contrast blush” denoting hypervascular synovium (bold arrow). Separate arterial 
branches are seen supplying the joint tissue (arrow) and skin (dotted arrow). At this 
point an attempt would be made to place a microcatheter in the synovial branch. If 
impossible due to the size of the target vessel, embolization would be performed from 
this catheter location using larger particles to preserve distal collateral supply to the 
skin. 
 

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Fig 2. Lateral angiogram of the knee with selective catheterization of the synovial 
branch of the geniculate artery. In this circumstance, smaller sized embolic particles 
would be appropriate because cutaneous branches are not seen. This could also be 
verified with cone beam CT prior to embolization. 
 
It is anticipated that less than 20 milliliters of Embozene will be required for 
embolization. Embozene Microspheres currently have FDA approval for 
embolization of hypervascular tumors and arteriovenous malformations. 
 
5.2 Method for Assigning Subject to Treatment Groups 
Because this is a pilot study to assess feasibility, all subjects will receive the study 
intervention (GAE). 
 
5.3 Subject Compliance Monitoring 
Study coordinators and physicians will inquire of the subjects to confirm that they 
have not initiated any new conservative therapies during the follow-up period. 
 

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5.4 Prior and Concomitant Therapy 
The subjects will be required to have been on conservative therapy for OA for at least 
three months prior to undergoing GAE. They will be allowed to continue previously 
initiated therapies throughout the study period, but no new or escalated therapies will 
be permitted, except post-operative medications (<14 days). 
 
5.5 Blinding of Study  
As a pilot study to assess feasibility, all subjects will receive GAE.  Therefore, neither 
the study physicians nor subjects will be blinded to the treatment protocol.   
 
5.6 Receiving, Storage, Dispensing and Return 
 
5.6.1 Receipt of Investigational Device Supplies 
Embozene Microspheres will be stored within the Interventional Radiology 
procedural suites.  Embolic devices will be labeled ‘for investigational use 
only’ and will be reserved for use in the clinical trial. 
 
5.6.2 Storage 
Embozene Microspheres must be stored in a cool, dark, dry place in their 
original packing. 
 
5.6.3 Dispensing 
No study specific dispensing techniques will be used. 
 
5.6.4 Return or Destruction of Investigational Device 
Embozene Microspheres can be used for other FDA approved indications and 
will not be destroyed or returned at the completion of the study. Disposable 
syringes which spherical particulate is stored in will be discarded as medical 
waste and packaging will be kept in a secure location until the study is 
completed. Packages will be disposed of upon completion of the study.  
 
6.0 Study Procedures 
6.1 Visit 1  
Potential enrollees will first be identified and will undergo a standard knee OA work-
up to include history and physical exam with emphasis on specific site of knee 
tenderness. The Western Ontario and McMaster University Osteoarthritis Index 
(WOMAC) questionnaire will be administered to assess difficulty as a result of pain, 
stiffness and overall decreased function secondary to knee pain in the past week. 
Current pain will also be assessed using a visual analog scale (VAS). A knee 
radiograph will be obtained and evaluated using the Kellgren-Lawrence grading 
scale. A baseline knee MRI will also be acquired to evaluate for concomitant 
pathology as part of routine orthopedic evaluation.  For patients that have had an MRI 
of the knee within the past 90 days, the previous knee MRI will be used as the 
baseline MRI and new imaging will not be obtained. 
 
If a patient qualifies to be a subject in the study based on the inclusion and exclusion 
criteria listed in section 4.3 and 4.4, the local study coordinator, co-principal 
investigator or designee will provide the candidate with a copy of the approved 

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informed consent and introduction letter for the candidates’ review. Written informed 
consent will be obtained if appropriate. If the patient wishes to take more time to 
review the study before enrolling, he/she may complete the consent process at the 
beginning of the next visit, prior to the study GAE procedure. Those candidates who 
are disqualified from study entry will be logged into the Screening Log with a reason 
for no study entry.  A copy of the consent will be provided to the subject and the 
original filed in the study files. 
 
6.2 Visit 2 GAE 
GAE will be performed as described in part 5.1 above within 4 weeks of Visit 1. 
Subjects will be given a pager number to reach a physician 24 hours a day to report 
any adverse symptoms and receive medical advice. 
 
6.3 Visit 3 -1 Day Follow-up 
Subjects will be seen in clinic or contacted by phone or by teleconference per the 
subject’s preference the day following GAE (+3 days). As most complications of the 
procedure will be evident within this time period, this visit is to evaluate for early 
AE’s. If AE is suspected based on change in pain scores or functionality, an MRI will 
be obtained for further evaluation. 
 
6.4 Visit 4 - 1 Month Follow-Up 
Subjects will be seen in clinic 30 +/- 7 days following GAE. The WOMAC 
questionnaire and VAS pain score will be completed and subjects will be evaluated 
for possible adverse events. An MRI of the treated knee will be acquired.* Subjects 
will also provide an update about the necessity/frequency of pre-established 
conservative therapies. 
 
*MRI is only scheduled at one month in order to evaluate for non-target ischemic 
injury. These types of injuries will become apparent as early as 24 hours after 
embolization. Infarcted tissue will still be detectable at one month. Based on our 
experience with embolization in other areas, it is thought extremely unlikely that new 
ischemic injury related to the procedure will develop after the one-month follow-up. 
Additionally, findings that would be detected on later scans may be unrelated to the 
procedure and confound the data. 
 
6.5 Visit 5 - 3 Month Follow-Up 
Subjects will be seen in clinic or contacted by phone or by teleconference per the 
subject’s preference 90 +/- 10 days following GAE. The WOMAC questionnaire and 
VAS pain score will be completed and subjects will be evaluated for possible adverse 
events. Subjects will also provide an update about the necessity/frequency of pre-
established conservative therapies. If AE is suspected based on change in pain scores 
or functionality, an MRI will be obtained for further evaluation. 
 
6.6 Visit 6 - 6 Month Follow-Up 
Subjects will be seen in clinic or contacted by phone or by teleconference per the 
subject’s preference 180 +/- 10 days following GAE. The WOMAC questionnaire 
and VAS pain score will be completed and subjects will be evaluated for possible 
adverse events. Subjects will also provide an update about the necessity/frequency of 

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pre-established conservative therapies. If an AE is suspected based on change in pain 
scores or functionality, an appropriate work-up will be performed which may include 
MRI. 
 

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6.7 Study Procedure Flow Chart
 
 
  

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7.0 Safety and Effectiveness Assessments 
7.1 Safety Assessments 
Subjects will be observed for several hours after GAE to monitor for immediate 
complications to include bleeding, infection and acute ischemia of the lower 
extremity. The subjects will be given a phone number that they can call to reach the 
principal investigator or designee if they believe they have developed a complication 
of the procedure. 
 
7.2 Effectiveness Assessments 
Technical success will be defined as devascularization of hypervascular synovium at 
the affected knee. This will be determined during the procedure. Clinical success will 
be defined as a 16% reduction of the baseline global WOMAC score at 6 month 
follow-up (primary outcome) and a 15% reduction of the baseline pain VAS score at 
6 month follow-up (secondary outcome). 
 
8.0 Statistical Plan 
8.1 Sample Size Determination 
Only one small study has examined the use of transcatheter arterial embolization for 
the treatment of knee pain secondary to OA (12). In that study, the baseline WOMAC 
total score (mean±SD) was 48.5±9.4. The primary outcome of this study is a 16% 
reduction in the baseline WOMAC total score. Using the baseline total score from 
that study, a sample size of 15 will have 80% power to detect a 16% difference (7.8 
points) in means, assuming a standard deviation of 10 points. Conservatively, to 
protect against a potential lost-to-follow-up of 30%, 20 total subjects will be enrolled. 
This sample size also will ensure adequate power for the secondary outcome, a 
reduction in the VAS by 15% at 6 months follow-up.  
 
8.2 Statistical Methods 
This is a pre-post analytical design and the primary statistical method will be a 
paired t-test, examining changes from baseline to 6 months. We will use a paired t-
test to statistically measure changes resulting from the GAE procedure.  Frequencies, 
including pre-post change, will be reported as percents with 95% confidence 
intervals. Continuous data will be reported as means with 95% confidence intervals. 
P≤0.05 will be considered to indicate statistical significance. All analyses will be 
performed using SAS software and confidence intervals will be reported as 
appropriate, including estimates for the appropriate sample size for a larger future 
study (v9.2, SAS Institute Inc., Cary, NC). 
 
Any deviations from the previously described statistical plan will be described and 
justified in a protocol amendment and/or in the final report submitted to the IDE 
application.  The causes of all missing values will be documented with the study data. 
 
8.3 Subject Population(s) for Analysis 
A patient will be considered an evaluable study subject evaluable for data analysis per 
the following criteria, a written informed consent was obtained, he/she meets the 
inclusion and exclusion criteria, and received the GAE study procedure.  All subjects 
with 6 month follow-up data will be included for analysis even if some follow up data 
is incomplete. Every attempt will be made to ensure that there is as little missing data 

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as possible including reminder phone calls and follow-up phone calls if a subject 
misses a visit. 
 
8.4 Interim Analysis 
An interim analysis will not be conducted. 
 
9.0 Risk Analysis 
 
9.1 Anticipated Risks 
Previous studies of lower extremity geniculate artery embolization for arthritis related 
pain have reported only one complication of moderate puncture site related hematoma 
(1/13), however this was a small population (12). A recent study of GAE for recurrent 
hemarthrosis completed by one of the co-PIs (Bagla) included 2/13 subjects who 
developed transient cutaneous ischemia that resolved within three weeks without 
intervention (8). Additional risks that are anticipated but occur infrequently after any 
arterial intervention include infection, pain, pseudoaneurysm formation, arterial 
dissection and distal non-target embolization resulting in ischemia or necrosis. 
Detailed risk analysis is below:  
 
 
Risk or Side Effect 
Source of Risk or 
 Side Effect 
Possible 
Less 
Possible 
 
Rare 
Event 
 
 
 
Potential 
Risks 
Associated 
Study 
Enrollment 
& Study 
Procedures 
 
Discomfort 
Blood draw for lab 
test, ultrasound or 
MRI 
X 
 
 
Thrombophlebitis, bruising, 
bleeding, blood clot, Pre-
syncope or Syncope (i.e. 
Fainting) 
Blood draw for lab 
tests 
 
X 
 
Anxiety or Claustrophobia 
MRI scan 
 
X 
 
Psychological Discomfort 
Clinical Trial 
Enrollment 
 
 
X 
Infection 
Blood draw for lab 
tests 
 
 
X 
Allergic Reaction 
MRI contrast 
injection 
 
 
X 
Gadolinium contrast adverse 
reaction (ie. Nephrogenic 
Systemic Fibrosis or severe 
skin reaction from contrast 
agent only reported in patients 
with kidney dysfunction) 
MRI Contrast 
injection 
 
 
X 
Confidentiality breach from 
Medical Records 
Medical Record 
Keeping 
 
 
X 
 
Groin/Anesthetic 
Injection/Neurologic Injury/ 
Discomfort/Pain 
Pressure during 
arterial access and 
after catheter 
removed at the 
leg/femoral artery 
site 
X 
 
 
 
 
Radiation Exposure Injury  
GAE procedure 
 
 
X 
Kidney Dysfunction 
Contrast injected 
during procedure 
 
X 
 

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Risks of the 
GAE 
Procedure 
and 
Postoperative 
care 
Joint Infection 
GAE Procedure 
 
X 
 
Adverse or Allergic Reaction 
Intravenous contrast 
agent or medications 
administered as part 
of procedure or 
follow-up care (ie. 
MRI contrast) 
 
X 
 
Tissue damage to Skin, 
Muscle, Skin or other structure 
in legs (Non-target 
Embolization) 
GAE procedure 
 
 
X 
Minor Bruising or Bleeding 
GAE procedure 
 
 
X 
Bleeding requiring 
Transfusion or surgery 
GAE procedure 
 
 
X 
Synovitis related symptoms 
including pain, stiffness or 
limited joint mobility 
GAE procedure 
X 
 
 
Post Embolization Syndrome, 
including fever, malaise, 
headache, and myalgia (body 
aches) 
GAE procedure 
 
X 
 
Internal bleeding, such as 
Gastrointestinal bleeding 
Medications taken 
after the procedure 
(ie. Ibuprofen) 
 
 
X 
Infection 
Catheter site in the 
leg/groin 
 
 
X 
Arterial injury/trauma, 
laceration, 
bruising/pseudoaneurysm 
Procedure/ Closure 
device (clip) on the 
artery 
 
 
X 
Pulmonary embolism (clot in 
lung),  Thrombophlebitis (clot 
in artery or vein) 
GAE procedure and 
immobility 
 
 
X 
Myocardial Infarction (Heart 
attack) 
GAE procedure 
including moderate 
sedation/sedative 
medication 
 
 
X 
Stroke 
GAE procedure 
including moderate 
sedation/sedative 
medication 
 
 
X 
Disability 
GAE procedure 
including moderate 
sedation/sedative 
medication 
 
 
X 
Death 
GAE procedure 
including moderate 
sedation/sedative 
medication 
 
 
X 
 
 
 
9.2 Risk Minimization 
The GAE procedure will be performed by board-certified interventional radiologists who 
have expertise in endovascular techniques, particularly in selective catheterization and 
transcatheter embolization techniques. Analgesia during the procedures will be provided 
through the use of conscious sedation if required. The risks of conscious sedation will be 
minimized by continuous monitoring of heart rate, blood pressure, oxygen saturation, and 

Page 19 of 29 
cardiac rhythm.  The dose area product projected for the procedure is thought to be less 
than 30 gray/cm2 which is about 2-4 years of background radiation and significantly less 
than that of a cardiac catheterization. Radiation exposure will be minimized to subjects 
under the principal of ‘as low as reasonably achievable’ (ALARA).  
 
Sterile instruments with a sterile technique will be used to minimize infection risk at the 
arterial access site.  Pre-operative antibiotic(s) will be administered to reduce risk of other 
infections, such as urinary tract.  The arterial access site discomfort will be minimized by 
administration of local anesthesia into the overlying skin and adjacent tissues. Catheter 
access into the appropriate artery may be performed using ultrasound-guided arterial 
puncture to prevent inadvertent vessel puncture with subsequent bleeding. Real-time 
fluoroscopic monitoring of all catheter/wire manipulations will be used to prevent 
vascular injury.   
 
Cone beam CT, which provides cross sectional anatomic detail prior to embolization, will 
be available to the operating interventional radiologist. This angiographic technique can 
mitigate the risk of non-target embolization.  The intent of this technique, as well as 
meticulous angiographic technique will be used to minimize the risk of non-targeted 
embolization, that could lead to skin or soft tissue/muscle injury. 
 
The subject will be monitored for the risk of an allergic response to iodinated contrast. To 
minimize the risk of renal dysfunction there will be use of non-ionic contrast agents, and 
appropriate pre-procedure hydration, when necessary.  Subjects who report an allergic 
reaction to iodinated contrast will be pre-medicated as per routine allergy prophylaxis per 
standard of care. 
 
9.3 Adverse Event Definitions 
Adverse effect. Any untoward medical occurrence in a clinical study of an 
investigational device; regardless of the causal relationship of the problem with the 
device or, if applicable, other study treatment or diagnostic product(s). 
 
Associated with the investigational device or, if applicable, other study treatment or 
diagnostic product(s).  There is a reasonable possibility that the adverse effect may 
have been caused by the investigational device or, if applicable, the other study 
treatment or diagnostic product(s). 
 
Disability.  A substantial disruption of a person’s ability to conduct normal life 
functions. 
 
Life-threatening adverse effect.  Any adverse effect that places the subject, in the 
view of the investigator-sponsor, at immediate risk of death from the effect as it 
occurred (i.e., does not include an adverse effect that, had it actually occurred in a 
more severe form, might have caused death). 
 
Serious adverse effect. Any adverse effect that results in any of the following 
outcomes: death, a life-threatening adverse effect, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, or a congenital anomaly/birth defect. 

Page 20 of 29 
● Hospitalization shall include any initial admission (even if less than 24 hours) 
to a healthcare facility as a result of a precipitating clinical adverse effect; to 
include transfer within the hospital to an intensive care unit.  Hospitalization 
or prolongation of hospitalization in the absence of a precipitating, clinical 
adverse effect (e.g., for a preexisting condition not associated with a new 
adverse effect or with a worsening of the preexisting condition; admission for 
a protocol-specified procedure) is not, in itself, a serious adverse effect. 
 
Unexpected adverse effect.  Any adverse effect, the frequency, specificity or severity 
of which is not consistent with the risk information described in the clinical study 
protocol(s) or elsewhere in the current IDE application, as amended. 
 
Unanticipated adverse device effect.  Any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or IDE application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
9.2 Recording of Adverse Events 
Research subjects will be questioned about adverse effects in person or by telephone 
the day following the procedure. In addition they will be given a pager number to 
reach a physician 24 hours a day to report adverse effects and receive medical advice. 
The subjects will also be questioned about possible adverse effects at each follow-up 
visit. 
 
All observed or volunteered adverse effects (serious or non-serious) and abnormal 
test findings, regardless of treatment group, if applicable, or suspected causal 
relationship to the investigational device or, if applicable, other study treatment or 
diagnostic product(s) will be recorded in the subjects’ case histories.  For all adverse 
effects, sufficient information will be pursued and/or obtained so as to permit 1) an 
adequate determination of the outcome of the effect (i.e., whether the effect should be 
classified as a serious adverse effect) and; 2) an assessment of the causal relationship 
between the adverse effect and the investigational device or, if applicable, the other 
study treatment or diagnostic product(s).    
 
Adverse effects or abnormal test findings felt to be associated with the investigational 
device or, if applicable, other study treatment or diagnostic product(s) will be 
followed until the effect (or its sequelae) or the abnormal test finding resolves or 
stabilizes at a level acceptable to the investigator-sponsor. 
 
An abnormal test finding will be classified as an adverse effect if one or more of the 
following criteria are met: 
 
● The test finding is accompanied by clinical symptoms 
● The test finding necessitates additional diagnostic evaluation(s) or 
medical/surgical intervention; including significant additional concomitant 
drug treatment or other therapy  

Page 21 of 29 
o Note: simply repeating a test finding, in the absence of any of the other 
listed criteria, does not constitute an adverse effect.   
● The test finding leads to a change in study protocol or discontinuation of 
subject participation in the clinical research study 
● The test finding is considered an adverse effect by the Sponsor-Investigator. 
 
9.3 Causality and severity assessment 
The investigator-sponsor will promptly review documented adverse effects and 
abnormal test findings to determine 1) if the abnormal test finding should be 
classified as an adverse effect; 2) if there is a reasonable possibility that the adverse 
effect was caused by the investigational device or, if applicable, other study treatment 
or diagnostic product(s); and 3) if the adverse effect meets the criteria for a serious 
adverse effect. 
 
If the investigator-sponsor’s final determination of causality is “unknown and of 
questionable relationship to the investigational device or, if applicable, other study 
treatment or diagnostic product(s)”, the adverse effect will be classified as associated 
with the use of the investigational device or study treatment or diagnostic drug 
product(s) for reporting purposes.  If the investigator-sponsor’s final determination of 
causality is “unknown but not related to the investigational device or, if applicable, 
other study treatment or diagnostic product(s)”, this determination and the rationale 
for the determination will be documented in the respective subject’s case history. 
 
9.4 Reporting of Adverse Effects and Unanticipated Problems 
9.4.1 Reporting of adverse reactions to the FDA 
The investigator-sponsor will submit a completed FDA Form 3500Ato the FDA’s 
Center for Devices and Radiological Health for any observed or volunteered adverse 
effect that is determined to be an unanticipated adverse device effect.  A copy of this 
completed form will be provided to all participating sub-investigators. 
 
The completed FDA Form 3500Awill be submitted to the FDA as soon as possible 
and in no event, later than 10 working days after the investigator-sponsor first 
receives notice of the adverse effect. 
 
If the results of the sponsor-investigator’s follow-up evaluation show that an adverse 
effect that was initially determined to not constitute an unanticipated adverse device 
effect does, in fact, meet the requirements for reporting; the investigator-sponsor will 
submit a completed FDA Form 3500Aas soon as possible, but in no event later than 
10 working days, after the determination was made. 
 
For each submitted FDA Form 3500A, the sponsor-investigator will identify all 
previously submitted reports that that addressed a similar adverse effect experience 
and will provide an analysis of the significance of newly reported adverse effect in 
light of the previous, similar report(s). 
 
Subsequent to the initial submission of a completed FDA Form 3500A, the 
investigator-sponsor will submit additional information concerning the reported 
adverse effect as requested by the FDA. 

Page 22 of 29 
 
9.4.2 Reporting Adverse Events to the Responsible IRB 
In accordance with applicable policies of the University of North Carolina and Inova 
Health System Institutional Review Board (IRB) the investigator will report, to the 
IRB, any observed or volunteered adverse effect that is determined to be (1) 
unexpected; (2) related or possibly related to the research; and (3) involves increased 
or greater risk of harm to participant(s) or others than was previously known or 
approved by the IRB. Adverse effect reports will be submitted to the IRB in 
accordance with the IRB policies and procedures.  
 
9.5 Stopping Rules 
The study will be stopped if there is greater than one major complication (Grade D,E 
or F) as defined by the Society of Interventional Radiology Classification System for 
Complications by Outcome (29). 
 
9.6 Medical Monitoring 
9.6.1 Data and Safety Monitoring Plan 
 Safety Monitoring will be performed by a licensed physician who is not a study 
investigator. The CRFs and any relevant source documents will be sent to the medical 
safety monitor (as above) who will review them after treatment is complete for 
subject 1, 5, 10 and 20. 
 
Complications will be assessed by the co-PIs, categorized into major and minor 
categories and recorded on the CRF. CRFs and appropriate source documents will be 
made available to this individual for bi-monthly (every 2 months) review to ensure 
completeness of data collection. Any discrepancies will be immediately addressed by 
the co-PIs.  All adverse events will be recorded and then summarized for inclusion in 
the final manuscript.  
 
Data monitoring will be performed by an individual who is not a study investigator. 
CRFs and appropriate source documents will be made available to this individual for 
bi-monthly review to ensure completeness of data collection. Any discrepancies will 
be immediately addressed by the co-PIs. 
 
9.6.2 Data and Safety Monitoring Board 
Because this is a pilot study with only 20 subjects, no DSMB will be used for this 
study.  Data and safety monitoring will be conducted by individuals who are not 
investigators on this study. 
 
10.1 
Data Handling and Record Keeping 
10.2 
Confidentiality 
Information about study subjects will be kept confidential and managed according to 
the requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Consistent with these regulations a signed authorization will be obtained 
that informs each subject of the following:   
● What protected health information (PHI) will be collected from subjects in 
this study 
● Who will have access to that information and why 

Page 23 of 29 
● Who will use or disclose that information 
● The rights of a research subject to revoke their authorization for use of their 
PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the 
investigator, by regulation, retains the ability to use all information collected prior to 
the revocation of subject authorization.  For subjects that have revoked authorization 
to collect or use PHI, attempts should be made to obtain permission to collect at least 
vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
 
10.3 Source Documents 
Source data are all information, original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the reconstruction and evaluation of the 
trial.  Source data are contained in source documents.  Examples of these original 
documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the 
pharmacy, at the laboratories, and at medical-technical departments involved in the 
clinical trial. 
 
10.4 Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the 
study.  All data requested on the CRF must be recorded.  All missing data must be 
explained.  If a space on the CRF is left blank because the procedure was not done or 
the question was not asked, write “N/D”.  If the item is not applicable to the 
individual case, write “N/A”.  All entries should be printed legibly in black ink.  If 
any entry error has been made, to correct such an error, draw a single straight line 
through the incorrect entry and enter the correct data above it.  All such changes 
must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, 
then initial and date it. 
 
Copies of completed CRFs with subject IDs will be scanned and sent to the lead 
study coordinator at UNC for entry in the study database.  CRFs should be sent 
within 5 business days to ensure timely entry. 
 
The coordinator at each site will complete the first CRF together with one of the Co-
PIs to verify that it is completed correctly. The coordinator at each site will then be 
responsible for completing the CRF moving forward.  Then, we will verify a 
randomly selected 25% of all source docs at the conclusion of data collection.  
Randomization will occur on a visit level and not per patient.  The randomization for 
this verification will be generated using a random number generator in Excel. 
 
10.4     Record Retention 
It is the investigators’ responsibility to retain study essential documents during the 
investigation and for a period of 2 years after the latter of the following two dates: 

Page 24 of 29 
The date on which the investigation is terminated or completed, or the date that the 
records are no longer required for purposes of supporting a premarket approval 
application or a notice of completion of a product development protocol.  These 
documents should be retained for a longer period if required by an agreement with 
the sponsor.  In such an instance, it is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.  
 
Research records and original signed consent forms are to be retained by principal 
investigator for at least 6 years if the form includes authorization for use of private 
health information.   Investigators may need to retain these documents for a longer 
period if required by an agreement with a sponsor or per other applicable regulatory 
requirements.  The 6 year minimum retention of authorizations complies with the 
privacy regulation requirements. 
 
10.5    IRB Documentation 
The co-principal investigators and research coordinator will be responsible for 
maintaining IRB correspondence. IRB approved forms maintained, as part of the 
study will include the subject consent form and the HIPAA authorization form. 
 
11.0 Study Monitoring, Auditing and Inspecting 
11.1 Study Monitoring Plan 
11.1.1   Locations 
Initial enrollment will occur at either an orthopedic clinic or in an 
interventional radiology clinic within the UNC Healthcare systems or 
Vascular Institute of Virginia. The procedures will be performed in UNC 
Interventional Radiology or Vascular Institute of Virginia. procedural suites. 
Follow-up visits will occur at UNC IR clinics, or Vascular Institute of 
Virginia, or via phone or teleconference. 
 
11.1.2   Study Staff Responsibilities and Training 
CITI Training: 
The investigators and all staff involved in the study will have completed their 
required Collaborative IRB Training Initiative (CITI) in the protection of 
human research subjects and Good Clinical Practice training. Alternate 
training modules, as requested by local IRB, may also suffice.  
 
Drs. Bagla and Isaacson (fellowship trained interventional radiologists with 
subspecialty board certification) will be the only primary operators for each of 
the GAE’s. Dr. Bagla has performed more than 600 arterial embolization 
procedures. Dr Isaacson has performed approximately 250 arterial 
embolization procedures. 
 
Any of the investigators may conduct follow-up visits as determined by the 
subjects’ and investigators’ availability.  
 
All subjects will be coded by an alphanumeric identifier (letters [initials] and 
site number) and subject identity will be kept confidential. Subjects will be 
apprised during the informed consent review that they have the right to 

Page 25 of 29 
voluntarily withdraw from the study at any time for any reason, and that his 
decision will not affect his medical care, but for attrition analysis subjects will 
be asked their reason for withdrawal .    
 
11.1.3   Quality Assurance and Quality Control 
The research coordinator will monitor the study files on a monthly basis to 
ensure the appropriate regulatory and IRB documentations are on file and up 
to date. The research coordinator will also be responsible for ensuring proper 
study documentation in order to verify compliance with Institutional policy, 
IRB, FDA and GCP guidelines in the following areas: Informed consent, 
Protocol, Source Documents and Electronic Case Report Forms. 
 
11.1.4   Safety Monitoring 
The research coordinator will complete the appropriate report form and logs; 
assist the PI to prepare reports and notify the IRB, FDA, and/or safety monitor 
of all Unanticipated Problems/SAE’s. 
 
The research coordinator and co-principal investigators will confirm that all 
Adverse effects (AE) are correctly entered into the AE log by the coordinator; 
be available to answer any questions that the coordinators may have 
concerning AEs; notify the IRB and FDA of all Unanticipated Problems/SAEs 
and AEs as appropriate. All assessments of AEs will be made by a licensed 
medical professional who is an investigator on the research. 
 
The research coordinator will confirm that the AEs are correctly entered into 
the AE log. The Monitor will confirm that the adverse events are consistent 
with the source documents and are reported to the appropriate regulatory 
bodies, as required. 
 
11.1.5 Monitoring Activities 
A safety monitor who is not a study investigator will conduct safety 
monitoring after treatment is complete for subject 1, 5, 10, and 20. Adverse 
events will be documented and reported as described above. 
 
The following issues will be addressed quarterly or more frequently as 
necessary: 
• Verify receipt of all documents and supplies needed to conduct study 
• Informed consent obtained for each participant 
• CRF completion 
• Investigational product accountability 
• Check and review of the regulatory binder and all essential documents 
• Clinical supply inventory 
• SAE reporting 
• Enrollment issues and targets 
• Protocol amendment and their approval by the IRB 
• Significant protocol deviations 
• Personnel changes 
• Updated regulatory documentation 

Page 26 of 29 
• Any other issue as deemed important to the conduct of the study 
 
11.1.6 Study Closure 
Upon study closure a final evaluation of the data will ensure that all forms are 
present and complete. Data will be maintained in a secure location for the 
appropriate duration as described in section 10.4.  At the conclusion of this 
term, all paper forms will be shredded and destroyed. All subjects will be 
contacted via phone to thank them for their participation and to discuss the 
study findings as well possible additional treatment options. 
 
11.2 Auditing and Inspecting 
 
The investigator will permit study-related monitoring, audits, and inspections by the 
Research Quality Assurance Office, IRB, the sponsor, and government regulatory 
bodies, of all study related documents (e.g. source documents, regulatory documents, 
data collection instruments, study data etc.).  The investigator will ensure the 
capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 
12.0 Ethics 
This study will be conducted in compliance with the protocol approved by the 
Institutional Review Board, the relevant federal regulations, and IRB policies and 
procedures and according to Good Clinical Practice standards. No deviation from the 
protocol will be implemented without the prior review and approval of the IRB 
except where it may be necessary to eliminate an immediate hazard to a research 
subject. In such case, the deviation will be reported to the IRB according to its 
policies and procedures. 
 
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for 
review and approval by the IRB for the study.  The formal consent of all subjects will 
be sought using the IRB-approved consent form. Before a subject undergoes any 
study procedure, an informed consent discussion will be conducted and written 
informed consent obtained with a consent form signed by the subject or legally 
acceptable surrogate if applicable. An investigator-designated research professional 
will obtain written informed consent from subjects. All subjects will be given a 
signed copy of the informed consent form. 
 
13.0 Study Finances 
13.1 Funding Source 
Grant from Boston Scientific Corporation. 
 
13.2 Conflict of Interest 
Any investigator who has a conflict of interest (COI) with this study as defined by the 
policies of the University of North Carolina will have the conflict reviewed by a 
properly constituted Conflict of Interest Review Committee with a committee-
sanctioned conflict management plan that has been reviewed and approved by the 

Page 27 of 29 
IRB prior to participation in this study.  All University of North Carolina 
investigators will follow the University conflict of interest policy. 
 
13.3 Subject Stipends or Travel Reimbursements 
Subjects will not be remunerated for study participation. 
 
14.0 Publication Plan 
Neither the complete nor any part of the results of the study carried out under this 
protocol, nor any of the information provided by the sponsor for the purposes of 
performing the study, will be published or passed on to any third party without the 
consent of the study sponsor. Any investigator involved with this study will be 
obligated to provide the sponsor with complete test results and all data derived from 
the study. 
 
15.0 Appendices  
1. Study Device (Embozene Microspheres) 
 
 
 
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non-specific non-steroidal anti-inflammatory drugs in osteoarthritic patients: a 
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