Geniculate Artery Embolization for Knee Osteoarthritis
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: Anish Ghodadra

 
G190248 Supplement 001 
 
 
 
A. Cover Page 
 
Device Information : 
Device name: 
Teleflex Gel-Bead  
 
Intended use of device: 
The Gel-Bead embolization particles will be used to perform geniculate artery 
embolization (GAE) for the purposes of treatment of osteoarthritis-related knee pain. 
 
 
 
Device Information: 
Device name: 
Teleflex Gel-Bead  
 
Intended use of device: 
The Gel-Bead embolization particles will be used to perform geniculate artery embolization 
(GAE) for the purposes of treatment of osteoarthritis-related knee pain. 
 
Sponsor-Investigator and Correspondent Contact Information: 
Anish Ghodadra, MD 
University of Pittsburgh Medical 
Center 200 Lothrop St. Suite E200 
Pittsburgh, PA 15213 
412-647-0104 / Fax: 412-864-2452 
ghodadraa@upmc.edu 
 
Manufacturer Information: 
Teleflex (acquired Vascular Solutions, Inc. February 
2017) 3015 Carrington Mill Boulevard 
Morrisville, NC 27560 
Tel: 919-544-8000 
 
Distributed by Medtronic 
 
Referenced files: There are no referenced files. 
 
 
Protocol Ammendments:
Updated protocol to remove 6-minute walk test due to feasibility issues in performing
Study Title: Geniculate Artery Embolization for the Treatment of Knee Osteoarthritis
04/08/2025

 
B. Clinical Plan 
 
The primary goal of our investigation is to determine if geniculate artery embolization (GAE) will 
result in a decrease in pain and disability caused by knee osteoarthritis. The investigation will be 
conducted as two distinct studies: 
 
1. 
A pilot study of GAE for the treatment of knee osteoarthritis 
a. 
A series of up to 30 subjects undergoing geniculate artery embolization will be 
included in this arm with the explicit purpose to demonstrate safety and efficacy. 
 
 
The primary endpoint of this study is overall efficacy of treatment as determined by a minimal 
clinically significant improvement in KOOS pain score of 10 based on the KOOS Pain 
questionnaire at 6 months. 
Secondary outcomes will be improvement in functionality and quality of life based on the 
KOOS Function in Sport and Recreation, and KOOS Quality of Life Scales. Secondary 
outcomes will also include changes in quantitative functional metrics as well as reduction in 
medication use. 
Technical success will be defined as the performance of diagnostic angiography of the knee with 
delivery of the Gel-Bead particles to a region of hypervascularity within the knee resulting in 
reduced flow/occlusion of the target vessels. Clinical success will be defined by a decrease in pain of 
10 points per the KOOS questionnaire at 6 months.  
 
C. Report of Prior Investigations of the Device 
 
Name of the Investigational Device: Gel-Bead Microspheres 
Intended Use of the Device: Geniculate artery embolization (GAE) for patients with osteoarthritis 
of the knee. 
Description of the Investigational Device 
Gel-Bead embolization spheres were found to be substantially equivalent and cleared medical 
devices (Premarket Notification K133237) to prior technologies: 
• 
Embosphere Microspheres (Biosphere Medical, Inc/Merit Medical Systems, Inc, K021397) 
• 
Gel-Block Embolization Pledgets (Vascular Solutions, Inc, K113266) 
 
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: Gel-Bead embolization spheres is intended for use in embolization of 
hypervascular tumors. 
 
Gel-Bead embolization spheres (Gel-Bead) consist of biodegradable gelatin spheres pre-filled in 
20ml syringes. Each syringe contains 1 ml of spheres suspended in 5 ml of saline. There are four size 
ranges for Gel-Bead offered: 100-300 um, 300-500 um, 500-700 um and 700-1000 um. The spheres 
are intended to be delivered via a delivery catheter with an inner diameter that is appropriately sized 
for sphere delivery (not included). The product is intended for single use and is sterilized by Gamma 
irradiation. The liquid suspension is mixed with iodinated contrast before use to allow visualization 
under fluoroscopy. Once a catheter has been fluoroscopically guided into the target vessel, the 
microspheres are injected and cause obstruction at the arteriole level until the desired degree of 

 
embolization is reached. The microspheres used during this study will be unmodified. 
 
A Gel-Bead implantation GLP animal study in twelve mature miniature swine, with animals 
survived up to 12 weeks following implantation was performed (13). Eight animals received Gel-
Bead and four animals were implanted with the control (Embosphere). Gel-Bead spheres were 
implanted in the selected target arteries with angiography confirmation. There were similar well-
demarcated foci of infarction, indicative of successful embolization, observed in the target organs of 
both test article and control article animals. No clinically significant abnormalities were identified in 
the clinical pathology blood results. No systemic abnormalities were identified. Verification, animal 
study, and biocompatibility test results met the specified acceptance criteria and did not raise new 
safety or performance issues. Gel-Bead was therefore deemed substantially equivalent to the 
predicate device (Embosphere). 
 
The technological differences between the Gel-Bead and predicate device have been evaluated 
through bench tests to provide evidence supporting the substantial equivalence of the 100-300 μm 
and 300-500 μm size embolization spheres. The 100-300 μm and 300-500 μm sizes are substantially 
equivalent to the specified predicate device based on comparisons of the device functionality, 
technological characteristics, and indications for use. The device design has been verified through 
the following tests: deliverability, sphere diameter, sphericity. Gel-Bead received 510(k) clearance 
from the FDA in April 2014 for the user of embolization of hypervascular tumors. Early trials have 
shown transcatheter embolization of abnormal neovasculature with particles can be effective in the 
treatment of mild to moderate knee osteoarthritis refractory to conservative management in select 
cases (5). 
 
Transcatheter arterial embolization with microparticles has been shown to be safe in early trials for 
treatment of knee osteoarthritis as well as in patients being treated for hemarthrosis, with small trials 
showing no major complications related to particle embolization (5, 8-9). Additionally, 
complications do not increase with repeat embolizations (9). A theoretical advantage of Gel-Bead is 
the biodegradable nature, in contrast to other permanent microsphere devices, which remain 
permanently inside the patient. 
Bibliography 
Okuno Y, Korchi AM, Shinjo T, Kato S, Kaneko T. Midterm Clinical Outcomes and MR Imaging 
Changes after Transcatheter Arterial Embolization as a Treatment for Mild to Moderate 
Radiographic Knee Osteoarthritis Resistant to Conservative Treatment. J Vasc Interv Radiol. 2017 
Jul;28(7):995-1002. 
Guevara CJ, Lee KA, Barrack R, Darcy MD. Technically Successful Geniculate Artery 
Embolization Does Not Equate Clinical Success for Treatment of Recurrent Knee Hemarthrosis 
after Knee Surgery. J Vasc Interv Radiol. 2016 Mar;27(3):383-7. 
Van Baardewijk LJ, Hoogeveen YL, van der Geest ICM, Schultze Kool LJ. Embolization of 
the Geniculate Arteries Is an Effective Treatment of Recurrent Hemarthrosis Following 
Total Knee Arthroplasty That Can Be Safely Repeated. J Arthroplasty. 2018 
Apr;33(4):1177-1180.e1. 
www.accessdata.fda.gov >pdf13. Gel-Bead 510(k) summary  
 
D. Investigational Plan 
 

 
1.0 Purpose of the Investigation 
 
Osteoarthritis is an increasingly prevalent disease and often results in functionally limiting joint pain. In 
2015, an estimated 54 million adults (22.7%) in the United States had doctor-diagnosed arthritis, with 
43.5% of those patients reporting lifestyle and activity limitations (1). 
 
The knee is a commonly affected joint and results in an annual healthcare expenditure of $27 billion (2). 
Definitive therapy for knee osteoarthritis is total knee arthroplasty. An estimated 54% of patients with 
knee osteoarthritis require a total knee arthroplasty within their lifetime, and 658,000 people undergo 
surgery annually (2-3). The goal of conservative management is to delay or eliminate the need for a total 
knee arthroplasty in patients. Currently, patients manage their pain with conservative management for an 
average of 13 years (2). 
 
First line conservative management is treatment with physical therapy, weight loss, non-steroidal anti-
inflammatory medications, and corticosteroid injections. Opiate medications are being prescribed with 
increasing frequency, despite evidence that they do not effectively treat osteoarthritis pain (4). 
 
Early trials have shown transcatheter embolization of abnormal neovasculature with microparticles can be 
effective in the treatment of mild to moderate knee osteoarthritis refractory to conservative management 
in select cases (5). This therapy aims to treat the angiogenesis and inflammatory component involved in 
the pathophysiology of osteoarthritis (6-7). 
 
Thickening and hypertrophy of the knee synovium has a similar appearance on angiography to 
hypervascular tumors. Transcatheter arterial embolization with permanent and resorbable particles has 
been shown to be safe in early trials for treatment of knee osteoarthritis as well as in patients being treated 
for hemarthrosis, with small trials showing no major complications and 8-20% having minor self-
resolving skin or puncture site complications (5, 8-9). Additionally, complications do not increase with 
repeat embolizations (9). The use of resorbable particles has a theoretical advantage as the particles will 
not permanently reside within tissue. 
 
1.1 
Trial Objective 
 
The purpose of this study is to perform a pilot to determine efficacy of transcatheter arterial embolization 
of the geniculate arteries in treating knee osteoarthritis related pain using the Gel-Bead embolization 
particles. This trial will assess reduction in pain, functional improvement, and reduction of medication 
usage in patients with mild to moderate knee osteoarthritis who have failed conservative management. 
 
2.0 GAE Study Clinical Protocol 
 
2.0 
Title and Version Date of Clinical Protocol: 
Geniculate artery embolization for the treatment of osteoarthritis of the knee 
Version date: 4/18/2023  
 
2.2  
Study Design: 
 
2.2.1 
General Study Design 
A series of 15 patients undergoing geniculate artery embolization will be included in this arm with 
the explicit purpose to demonstrate safety and efficacy. 
 
This trial will assess reduction in pain, functional improvement, and reduction of conservative 
medical therapy in patients with mild to moderate knee osteoarthritis who have failed conservative 

 
management, for 6 months and for up to two years following embolization. 
 
 
2.2.2 
Study Design Schematic 
 
 
 
2.3 
Subject Selection: 
 
2.3.1 
General characteristics of the proposed subject population 
Similar to prior studies conducted on GAE, subjects included in the study will be those with mild to 
moderate knee osteoarthritis with moderate to severe pain that is refractory to conservative 
management. These are patients who have significant symptoms but are not ideal candidates for 
total knee replacement. 
 
2.3.2 
Anticipated number of research subjects 
For the Pilot Study, 30 patients are expected to enroll (defined as completion of the informed 
consent process as per University IRB policies) and all are expected to complete the study. 
 
2.3.3 
Inclusion Criteria: 
1. 
Patients between ages 18 and 75 with moderate/severe knee pain secondary to 
primary osteoarthritis. Moderate/severe pain will be defined as pain 30 mm to 
Pilot Group
(n = 30)
Screening Visit
Pre-procedure 
MRI
GAE Procedure
1 Month Visit
3 Month Visit
6 Month Visit and at 12 and 24 months

 
100 mm on the Visual Analog Pain Scale (where 0 denotes ‘no pain’ and 100 
mm denotes worst pain imaginable’) 
2. 
Grade 1, 2, or 3 osteoarthritis on the Kellgren-Lawrence grading scale on knee x-ray in 
the last 12 months 
3. 
Pain must be refractory to 3 months of medical management (which may include a 
combination of oral analgesics, intraarticular steroids, viscosupplementation, 
opioid therapy, etc) 
4. 
Patients willing and able to consent to the study 
2.3.4 
Exclusion Criteria: 
1 Kidney dysfunction defined as an estimated GFR < 60 mL/min 
2 Acute knee injury 
3 Current local infection 
4 Prior ipsilateral knee replacement surgery 
5 Infectious or inflammatory arthritis 
6 History of contrast allergy resulting in anaphylaxis 
7 INR (International Normalization Ratio) > 1.6 
8 Platelets < 50,000 
9 Significant atherosclerosis that would limit angiography 
10 Active malignancy 
11 Active pregnancy 
12 Appropriate candidate for knee replacement surgery determined by clinical and physical 
examination 
13 Recent within 3 months, or active cigarette user 
14 Any other condition that in the opinion of the investigator would preclude the patient from 
participation. 
 
2.4 
Study Procedures: 
 
2.4.1 
Patient Recruitment: 
Patients will be recruited from sports medicine, family medicine, orthopedic, geriatric, and 
rheumatology clinics. Participating clinicians and research partners will identify patients with 
moderate or severe pain secondary to primary osteoarthritis (using the Kellgren-Lawrence Scale) 
who have persistent knee pain refractory to all attempted medical therapies and lifestyle 
modifications. The clinician will notify one of the GAE research team members. The patient will 
then be scheduled for consultation in the Interventional Radiology (IR) clinic. A thorough 
description of the research study will be provided. Informed consent will be obtained at this visit for 
any patient who chooses to participate. Pre-procedure work-up will also take place at this time (see 
below). Once the bloodwork and imaging are reviewed, the patient will be scheduled for the 
procedure following this clinic visit if they meet criteria and the patient is willing to proceed. 
 
 
 
 Visit 1 - Screening: 
The screening period may take up to 8 weeks to complete.  Some of the tests and assessments will be 
performed at the time of the consultation in Interventional Radiology (IR).  Other tests and assessments 

 
will be scheduled at appropriate facilities within the 8-week period.  The following will be performed for 
screening: 
1) 
Obtain informed consent 
2) 
Collect demographics including age, sex, and race 
3) 
Medical history and co-morbidities 
4) 
Physical exam to include height, weight, BMI and vital signs 
5) 
Evaluation for moderate sedation 
6) 
Knee MRI with or without contrast. If performed within 12 months will not need to be repeated. 
Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire 
7) 
Frequency/dosage of analgesic questionnaire 
8) 
100 mm visual analog pain scale 
9) 
Knee x-ray.  If performed within 12 months will not need to be repeated. 
10) 
30 second chair stand test 
11) 
Pre-procedure labs – If performed within 1 month will not need to be repeated: 
o CBC with Platelets 
o GFR 
o INR 
o PTT 
 Pregnancy test for women of child-bearing potential 
Remote consenting may be used as opposed to in person consenting where possible to reduce unnecessary 
in person encounters. In the event remote consenting is utilized, subjects will be provided with a copy of 
the informed consent prior to the teleconsent meeting either via email, fax, mail or previously provided 
during an in-person visit. After the physician investigator and subject review the consent form via video 
conferencing (e.g., telephone, conference call, videoconference, telemedicine, etc.), the subject will be 
offered the opportunity to ask any questions and have those questions answered. The subject will sign and 
date the informed consent. 
The physician investigator will verify the subject physically signed the consent document either by 
viewing via video conference or obtaining a photo of the complete signed consent signature page or 
obtaining verbal confirmation from the subject that he/she signed the consent form or agreed to 
participate electronically. The signed document is then mailed, emailed, photo/scanned to text or faxed to 
the study team. 
If the signed consent is provided as an electronic copy (emailed, photo/scanned, or faxed), the subject will 
return the original signed document on their first in person visit or by mail. If the signed consent form is 
mailed to the study team, the physician investigator will sign their copy which they possess after the 
subject has acknowledged signature on their copy. Once the subject’s original copy is received the study 
team’s copy will be attached to make a single document. 
The study team will document the remote consent process, including the date and time the conversation 
occurred, how it occurred (e.g., telephone, video conference), the names of the participants, confirmation 
that the subject received the informed consent, and confirmation of informed consent to participate. 
Visit 2 GAE Procedure: 
Subjects should withhold pain medication 24 hours prior to visit for the evaluation of VAS  
 or other measures. 
 
Subjects will be treated with a genicular artery embolization (GAE) procedure performed with Gel Bead 
Microspheres. The microspheres will be delivered in a saline-contrast medium solution and will be 
delivered to the arteries supplying the areas of the subject’s pain.  

 
Subjects will not initiate new pain therapy or escalate current therapy for 1 month prior to GAE. A 
dose of intravenous antibiotic will be given in the peri-procedural period and oral antibiotics may be 
continued for up to 7 days. Anti-inflammatory medications will also begin 1 day prior to and up to 7 
days after the procedure. 
On the day of the procedure, the subject will be brought to the angiography suite and positioned in 
the supine position. Anxiolytic medications and analgesics will be administered per patient and 
provider discretion. After appropriate local anesthesia, arterial access will be obtained using a 
standard micropuncture kit. The femoral artery ipsilateral to the affected knee will be catheterized. A 
subsequent angiogram will be used to identify abnormal neovascularization arising from the 
geniculate artery branches. The affected geniculate artery branches will be catheterized with a 
microcatheter and the abnormal vessels will be embolized with a suspension of the Gel-Bead 
particles ranging in size from 100 to 500 micrometers at the physician’s discretion. The suspension 
will slowly be injected into the vessel until there is stasis of forward flow. All guidewires, catheters 
and microcatheters will be removed. Hemostasis will be obtained either with manual compression or 
a closure device. 
 
The following data will be collected during each GAE procedure: 
 
Technical success of GAE, defined as successful catheterization and embolization 
 
Procedure time, duration of hospitalization, duration of catheterization, fluoroscopy dose, volume of 
embolic delivered, arteries embolized. 
 
Post-procedure Care and Disposition: 
Following the procedure, the patient will be observed in the post-procedure area. Routine post- 
angiography care will be provided and routine precautions followed (lying flat for up to 6 hours post 
procedure, adequate post-procedure hydration with intravenous fluids). No additional lab work will 
be routinely drawn at this time. Any additional labs drawn will be left to the discretion of the 
attending physician. All complications, minor and major, will be documented and managed 
appropriately at the physician’s discretion. Patient may be deemed appropriate discharge on the same 
day if: 
1. There are no access site complications (e.g. groin hematoma) 
2. Pain is adequately controlled 
3. Patient is ambulatory 
4. Distal perfusion to the bilateral lower extremities is confirmed by physical examination and/or 
Doppler waveforms 
5. There are no signs of active bleeding or hemorrhage 
6. Patient has a safe ride home 
 
After GAE, follow-up will occur at 1 week (± 4 days), 1 month (± 2 weeks), 3 months (± 2 weeks), 6 
months (± 2 weeks) from the date of treatment.  
 
Visit 3 – 1 week (± 4 days) Post Procedure Phone Call  
 
One week after the GAE procedure, a phone follow-up call will be made to check the on status of the 
subject.  Standard post surgical questions pertaining to infection and pain will be asked.  If there are any 
concerns, an in-person evaluation will be scheduled. 
 
Visit 4 – 1 month (± 2 weeks) Post Procedure  
 

 
Subjects will have the following assessments performed: 
• 
Physical examination including vital signs 
• 
KOOS and VAS questionnaires  
• 
30 second chair stand test 
• 
Review of adverse events 
 
Visit 5 – 3 months (± 2 weeks) Post Procedure 
 
Subjects will have the following assessments performed: 
• 
Physical examination including vital signs 
• 
KOOS and VAS questionnaires  
• 
30 second chair stand test 
• 
Review of adverse events 
 
Visit 6 – 6 months (± 2 weeks) Post Procedure 
 
Subjects will have the following assessments performed: 
• 
Physical examination including vital signs 
• 
KOOS and VAS questionnaires  
• 
30 second chair stand test 
• 
Review of adverse events 
 
Whenever possible, follow-up phone calls\tele-medicine visits will be made to subjects at 12 and 24-
months post procedure to obtain updated information on pain.  
 
2.4.2.1 
Study Compliance 
Subjects will be required to avoid escalation of conservative therapy during the study period. A 
review of current and prior conservative treatment measures will be reviewed with each subject 
during follow-up visits. Any patient that significantly elevates conservative therapy (e.g. initiation of 
a new medication or therapy not previously used) will be withdrawn from the study. 
 
Early Withdrawal of Subjects: 
Subjects will be withdrawn from the study under the following conditions: 
1 
At any point at the patient’s discretion 
2 
Any major complication that occurs that prevents the ability to perform/complete the 
GAE procedure 
3 
Patient is unable to complete at least one follow-up visit 
2.5 
Statistical Methods and Data Analysis 
 
2.5.1 
Study Endpoints 
 
2.5.1.1 
Primary Endpoints 
The primary endpoint of this study will be overall efficacy of treatment as determined by an 
improvement in pain of at least 10 points based on the KOOS Pain questionnaire at 6 months. 
The null and alternative hypotheses respectively will be: H0:  MeanGAE   =  MeanSham and HA: 
MeanGAE  ≠  MeanSham, with a two sided test. 

 
2.5.1.2 
Secondary Endpoints 
Secondary outcomes will be improvement in functionality and quality of life based on the KOOS 
Function in Sport and Recreation KOOS, and Quality of Life Scale at 6 months as well as the 
quantitative functional measures and changes in medication use. To adjust for multiple comparisons, 
the Holm-Bonferroni correction method will be implemented. 
 
2.5.2 
Sample Size Determination 
The Knee Injury and Osteoarthritis Outcome (KOOS) Score which is a primary outcome measure is 
a measure of patients’ knee and associated problems and functionality. It is endorsed by the 
American Academy of Orthopedic Surgeons, the US Food and Drug Administration, and the 
International Cartilage Repair Society and has demonstrated reliability for both clinical and research 
purposes (11). The Visual Analog Scale (VAS) for pain will be used as a secondary outcome 
measure. This scale is also well-validated and has demonstrated reliability for patients with 
osteoarthritis (12). The Minimal Clinically Important Difference (MCID) for KOOS has been 
reported to be ~10. Data on the KOOS indicates a population standard deviation of 15 (koos.nu). 
Assuming we wish to detect an MCID of 10 points in this population, our targeted effect size is 0.66. 
A power calculation for a paired t-test (baseline vs 6-month KOOS Pain scores) shows our pilot 
study of 15 patients would have 22% power.  
 
 
2.5.3 
Efficacy Analysis 
Comparison of semi-quantitative and quantitative outcome measures will be performed with the 
appropriate statistics testing. For the pilot group, baseline and endpoint scores will be compared 
using paired t-tests.  
 
2.5.4 
Safety Analysis 
Differences in the occurrence of adverse events between groups will be assessed with chi-square tests 
with a significance level p < 0.05. Descriptive statistics will be used to report occurrence of adverse 
events in the pilot group. 
 
3.0 Risk Analysis 
3.1 Anticipated Risks 
To mitigate risk to patient confidentiality, data will be kept in encrypted files on a secure UPMC server. 
The identifying patient information will be kept in a second document separate from the clinical data 
gathered, and a non-identifying code will be assigned to each patient. The data collected will not be 
shared with any person(s) not included in the study investigator list. Should a breach of conduct occur, the 
IRB will be notified immediately by one of the principal investigators. 
 
Participants in the intervention arm will undergo an invasive procedure and will be subjected to moderate-
to-high risk. Risks include but are not limited to bleeding at the puncture site, infection, damage to nearby 
structures, synovitis, worsening of groin hematoma, and nontarget embolization. A qualified, board-
certified interventional radiologist will perform the procedure.  Sterile technique will always be followed. 
Radiation exposure to the patient will be minimized using standard strategies (e.g. aggressive collimation, 
minimizing fluoroscopy time). All adverse events will be thoroughly documented and reported to the 
UPMC IRB immediately. 
 
Because the study population has osteoarthritis-related knee symptoms refractory to conservative 
management, the next treatment option traditionally available is knee replacement surgery.  Transarterial 
embolization, while still an invasive procedure, has a much lower risk profile that knee replacement 
surgery. 

 
 
This trial will include 15 initial patients to confirm safety and initial efficacy of the treatment. Patients 
will include both male and female and range from age 18-75 who meet the inclusion criteria as detailed 
above. GAE will be performed by the trained investigating Interventional Radiologists who have 
significant experience in performing endovascular embolization procedures. 
 
3.2 Adverse Event Recording/Reporting 
 
3.2.1 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. 
 
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 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. 
 
3.2.2 Eliciting Adverse Effect Information 
Clinical subjects will be routinely questioned about adverse effects at study visits. 
 
3.2.3 Recording and Assessment of Adverse Effects 
All observed or volunteered adverse effects (serious or non-serious) and abnormal test findings, 
regardless of treatment group 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 casual relationship between the adverse effect and the 
investigational device or, if applicable, other study treatment or diagnostic product(s).   
 
Adverse effects or abnormal test findings felt to be associated with the investigational device or 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. 
 
3.2.3.1 Abnormal Test Findings 
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 or other therapy. (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 dosing or exposure or discontinuation of subject 
participation in the clinical study. 
• 
The test finding is considered an adverse effect by the investigator-sponsor. 
 
3.2.3.2 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. 
 
3.2.4 Reporting of Adverse Effects to the FDA 
The investigator-sponsor will submit a completed FDA Form 3500A to 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. 
 
3.2.5 Reporting of adverse effects to the responsible IRB 
In accordance with applicable policies of the University of Pittsburgh Institutional Review Board (IRB), 
the investigator-sponsor will report, to the IRB, any observed or volunteered adverse effect that is 
determined to meet all of the following criteria: 1) associated with the investigational device or, if 
applicable, other study treatment or diagnostic product(s); 2) a serious adverse effect; and 3) an 
unexpected adverse effect. Adverse event reports will be submitted to the IRB in accordance with the 
respective IRB procedures. 
 
Applicable adverse effects will be reported to the IRB as soon as possible and, in no event, later than 10 
calendar days following the investigator-sponsor’s receipt of the respective information. Adverse effects 
which are 1) associated with the investigational drug or, if applicable, other study treatment or diagnostic 
product(s); 2) fatal or life-threatening; and 3) unexpected will be reported to the IRB within 24 hours of 
the investigator-sponsor’s receipt of the respective information. 
 
Follow-up information to reported adverse effects will be submitted to the IRB as soon as the relevant 
information is available. If the results of the sponsor-investigator’s follow-up investigation show that an 
adverse effect that was initially determined to not require reporting to the IRB does, in fact, meet the 
requirements for reporting; the investigator-sponsor will report the adverse effect to the IRB as soon as 
possible, but in no event later than 10 calendar days, after the determination was made. 
 
3.3 Withdrawal of Subjects due to Adverse Effects 
 
During evaluation of subjects and visits after the procedure, any adverse effects due to treatment 
will be evaluated and monitored. Subjects will not be withdrawn from the study due to adverse 
effects. 
 
4.0 Description of Investigational Device: 
Trade Name: Gel-Bead 
Common / Usual Name Embolization spheres 
Classification Name Class II – 21 CFR 870.3300; 
KRD – Device, vascular, for promoting embolization 
Predicate Device Gel-Bead embolization spheres, Vascular Solutions 
(K133237 cleared April 25, 2014; K171946 cleared October 25, 2017) 
 
Gel-Beads are embolic particles made from purified porcine skin gelatin. The product is crosslinked with 
glutaraldehyde, which improves the mechanical strength of the spheres and provides controlled 
degradation over time. These particles are intended for embolization of hypervascular tumors.  
 
The embolization spheres product consists of biodegradable gelatin spheres pre-filled in a 20 ml syringe. 
The syringe contains either 1 ml or 2 ml of spheres suspended in 5 ml or 4 ml of saline, respectively. 
Offered in five nominal size ranges (100-300 μm, 300-500 μm, 500-700 μm, 600-800 μm, and 700-1000 
μm), the spheres are intended to be used with a delivery catheter with an inner diameter that is adequate 
for sphere delivery (not included). The finished product is sterilized by Gamma irradiation and is intended 
for single use only. 
 

 
The technological differences between the subject and predicate device have been evaluated through 
bench tests to provide evidence supporting the substantial equivalence of the 100-300 μm size 
embolization spheres. The 100-300 μm size is substantially equivalent to the specified predicate device 
based on comparisons of the device functionality, technological characteristics, and indications for use. 
The device design has been verified through the following tests: deliverability, sphere diameter, 
sphericity. 
 
The verification test results demonstrate that the Gel-Bead embolization spheres (100-300 μm) met the 
specified acceptance criteria and did not raise new safety or performance issues. Therefore, the 100-300 
μm embolization spheres product is substantially equivalent to the predicate devices.  
 
For additional device details refer to Appendix 1 of the IDE application for Vascular Solutions’ 510k 
summary for the Gelbead embolization spheres and Appendix 2 of the IDE application for the instructions 
for use. 
 
5.0 Monitoring Procedures: 
 
Independent monitoring of the clinical study for clinical protocol and IDE application compliance will be 
conducted periodically (i.e., at a minimum of annually) with assistance from qualified staff of the 
University of Pittsburgh’s Education and Compliance Support – Human Subject Research (ECS-HSR).  
 
The investigator-sponsor and the University of Pittsburgh and University of Pittsburgh Medical Center 
will permit direct access of the study monitors and appropriate regulatory authorities to the study data and 
to the corresponding source data and documents to verify the accuracy of this data. 
 
A data and safety monitoring plan will be implemented by the Principal Investigator (PI) to ensure that 
there are no changes in the risk/benefit ratio during the study and that confidentiality of research data is 
maintained. Each member of the study team will meet with the PI and review confidentiality issues and 
complete a confidentiality agreement, prior to having access to the identifiable medical record 
information. Investigators and study personnel will meet monthly to discuss the study (e.g. study goals 
and modifications of those goals; data collection; progress in data coding and analysis; documentation, 
identification of adverse events; violations of confidentiality) and address any issues or concerns at that 
time. Minutes will be kept for these meetings and will be maintained in the study regulatory bonder. Any 
instances of adverse events will be reported immediately to the University of Pittsburgh IRB using 
standard forms and/or procedures that have been established by the IRB. The IRB renewal for this study 
will include a summary report of the Data and Safety Monitoring Plan findings from the prior renewal 
period. 
 
The Sponsor-investigator (Anish Ghodadra, MD) will be responsible for the monitoring of the study. 
 
6.0 Labeling 
Refer to section K. of the IDE application. 
 
7.0 Consent Materials 
Refer to Appendix 3 of the IDE application. 
 
8.0 IRB Information 
Refer to Section H. of the IDE application. 
 
9.0 Other Institutions 
Refer to Section I. of the IDE application.