Hybrid APC Assisted EMR for Large Colon Polyps to Reduce Local Recurrence : A Prospective Data Collection Study
Phase: NA
Conditions: Colon Polyp, Colon Adenoma, Colon Cancer
Sponsor: Milton S. Hershey Medical Center

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HRP-591 - Protocol for Human Subject 
Research 
Protocol Title:
Hybrid APC assisted EMR for large colon polyps to reduce local recurrence, a prospective data collection Study
Principal Investigator:
Name: John M. Levenick, MD
Department:  Medicine/ Gastroenterology & Hepatology
Telephone: 717-531-3834
E-mail Address: jlevenick@pennstatehealth.psu.edu
Version Date:
 4/26/2018
Clinicaltrials.gov Registration #:
N/A
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Table of Contents
1.0
Objectives
2.0
Background
3.0
Inclusion and Exclusion Criteria
4.0
Recruitment Methods
5.0
Consent Process and Documentation
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.0
Study Design and Procedures
8.0
Subject Numbers and Statistical Plan
9.0
Confidentiality, Privacy and Data Management
10.0
Data and Safety Monitoring Plan
11.0
Risks
12.0
Potential Benefits to Subjects and Others
13.0
Sharing Results with Subjects
14.0
Subject Stipend (Compensation) and/or Travel Reimbursements
15.0
Economic Burden to Subjects
16.0
Resources Available
17.0
Other Approvals
18.0
Multi-Site Research
19.0
Adverse Event Reporting
20.0
Study Monitoring, Auditing and Inspecting
21.0
Future Undetermined Research: Data and Specimen Banking
22.0
References
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1.0
Objectives
1.1
Study Objectives
The aim of this study to evaluate and examine, whether use of Hybrid Argon Plasma Coagulation (APC) 
as adjunct to endoscopic mucosal resection (EMR), will reduce the risk of residual or recurrent neoplasia 
at 6 months. Hybrid APC is an existing FDA approved device for ablation of abnormal tissue anywhere in 
GI tract. We hypothesis that with Hybrid APC assisted EMR there  will be a decrease in recurrence rate 
after 6 months and it would be more effective compare to the  standard EMR procedure.
1.2
Primary Study Endpoints
Measure Recurrent rate and efficacy of Hybrid APC assisted EMR. Assess rate of local recurrent or 
residual neoplasia at the EMR scar using optical and histologic classification at 6 months.
1.3
Secondary Study Endpoints
Evaluate rate of post-polypectomy bleeding and post-polypectomy syndrome and compare it to 
standard procedure.
2.0
Background
2.1
Scientific Background and Gaps
Colon Cancer is a major disease that effecting more than 1 million people per year globally. 
Adenomatous polyps have been identified as the main precursor in lesions leading to colorectal cancer.1
                             Colon cancer screening the best way to detect and remove large, often asymptomatic polyps. Early 
                        detection and resection of these colorectal polyps can prevent the development of colon cancer. 
                              Endoscopic polypectomy introduced in 1970’s, is an effective technique to prevent of colorectal cancer, 
                              as demonstrated in National Polyps Study. Endoscipc mucosal resection (EMR) is a technique
                        used for resection of medium to large colon polyps. In this technique, fluid is injected into the 
                        submucosal creating a cushion between the mucosa and the muscolaris propria. An electrocautery 
                             snare is then deployed to resect the polyp in a single (en-bloc) or multiple (piecemeal) pieces. Most of 
                             polyps > 2cm are resected in piecemeal way.  Although EMR is now considered standard of care with 
                              successful rate resection of 85 % and low risk of complication (3-10% bleeding and 1% perforation), this  
                             technique has inherent deficiencies, especially piecemeal EMR. This is particularly important if the polyp 
                        contains cancer. Resection of scarred polyps using this technique is particularly challenging due to the  
                             non-lifting of the polyp. Recurrence rates following piecemeal EMR can be as high as 20%.1,2
                             Endoscopic submucosal dissection (ESD) is an alternative approach that aims to remove non- 
pedunculated precancerous or cancerous lesions over 20 mm in one piece (en-bloc resection rate of 
89.95% and lesion recurrence rate of 0.7%). However, due to its technical complexity and high 
complication risk (mainly bleeding and perforation, with complication rates approximately 8%), it is not 
the current standard of care and only performed by experts in the technique.1 
Hybrid Argon plasma coagulation (APC) is a new technique in which the endoscopist reinjects the 
submucosal  with fluid  to create a cushion (normal saline/ diluted adrenaline and /or sodium 
hyaluronate solution) to protect the muscle layer and is  then ablated using spray argon coagulation to 
treat any microscopic residual disease that is the seed for local recurrence .3 Previous studies have 
shown that this technique is a safe and easily applicable technique to complete resection for recurrent 
polyps after first EMR.
In this present time there is no study to evaluate the safety and recurrence rate of the Hybrid-APC 
assisted EMR for large colon polyps at their initial resection attempt
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2.2
Previous Data
In 2012 Tsiamoulos et.al. in a single-center, retrospective case series report their experience in regards 
to   endoscopic mucosal ablation (EMA) technique that can be used to complement the eradication of 
recurrent fibrotic colon polyps. In this study, of consecutive patients referred for endoscopic excision of 
recurrent benign colon polyps with severe submucosal fibrosis, fourteen patients (mean age 73 years; 9 
men, 5 women) with 15 recurrent colon adenomas (mean polyp size 30 mm, 9 proximal/6 distal) were 
included. EMA with a mean APC power setting of 55 W was applied. Complete polyp eradication was 
achieved in 9 of 11 patients (82%) at first or second completed follow-up. One patient needed 
laparoscopic colectomy because of cancer, and 1 underwent transanal endoscopic microsurgery for 
benign massive recurrence. The other 3 patients with small, easily treatable recurrence (≤3 mm) were 
followed by 1-year-surveillance. No perforations and no postpolypectomy syndrome were reported. 
They concluded that EMA appears to be a safe and easily applicable technique to assist the complete 
eradication of recurrent fibrotic colon polyps.3
A systematic review and meta-analysis by Arezzo et.al in 2016 compares the safety and efficacy of 
endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) in the treatment of 
flat and sessile colorectal lesions >20mm. They reviewed the literature published between January 2000 
and March 2014. Pooled estimates of the proportion of patients with en bloc, R0 resection, 
complications, recurrence, and need for further treatment were compared. A total of 11 studies and 
4678 patients were included. The en bloc resection rate was 89.9% for ESD vs 34.9% for EMR patients 
(RR 1.93 p<0.001). The R0 resection rate was 79.6% for ESD vs 36.2% for EMR patients (RR 2.01 
p<0.001). The rate of perforation was 4.9% for the ESD group and 0.9% for EMR (RR 3.19, p<0.001), 
while the rate of bleeding was 1.9% for ESD and 2.9% for EMR (RR 0.68, p=0.070). Therefore, the overall 
need for further surgery, including surgery for oncologic reasons and surgery for complications, was 
7.8% for ESD and 3.0% for EMR (RR 2.40, p<0.001). They concluded that ESD achieves a higher rate of en 
bloc and R0 resection compared to EMR, at the cost of a higher risk of complications.4
Manner et.al in 2015 performed a prospective study, which evaluating the efficacy and safety of the new 
technique of Hybrid-APC which combines submucosal injection with APC in patients with dysplastic 
Barrett’s esophagus. In this study Patients who had a residual Barret’s Esophagus (BE) segment of at 
least 1 cm after endoscopic resection of early Barrett's neoplasia underwent thermal ablation of BE by 
Hybrid-APC. Prior to thermal ablation, submucosal injection of sodium chloride 0.9% was carried out 
using a flexible water-jet probe. Surveillence upper GI endoscopy was carried out 3 months after 
macroscopically complete ablation including biopsies from the neo-Z-line and the former BE segment, 
and recording of stricture formation. Total of 60 patients were included in the study [55 pt male (92%); 
mean age 62 ± 9 years, range 42-79]. Ten patients were excluded from the study. In the remaining 50 
pt., Hybrid-APC ablation and surveillence endoscopy at 3 months were carried out. Forty-eight out of 50 
pt. achieved macroscopically complete remission after a median of 3.5 APC sessions]. Freedom from BE 
was histopathologically observed in 39/50 patients (78%). There was one treatment-related stricture 
(2%). Minor adverse events of Hybrid-APC were observed in 11 patients (22%). It concluded that Hybrid-
APC was effective and safe for BE ablation in a tertiary referral center. The rate of stricture formation 
was only 2%.5
2.3
Study Rationale
EMR has a recurrence rate of up to 20% in large ≥20 mm lesions with a relatively low risk profile. ESD 
has a low 1-4% recurrence rate but higher risk profile. We are assessing if adjuvant hybrid APC with EMR 
drop the recurrence rate near ESD levels while maintaining the safety profile of EMR.
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3.0
Inclusion and Exclusion Criteria
3.1
Inclusion Criteria
• Adult patient aged ≥18 and ≤89 of any gender, ethnicity and race referred to endoscopy for resection     
   of large colon polyps
•   Patients with a ≥20mm colon non-pedunculated polyp

Ability to give written informed consent
3.2
Exclusion Criteria

Patients with known (biopsy proven) invasive carcinoma in a potential study polyp

Pedunculated polyps (as defined by Paris Classification type Ip or Isp) 

Patients with ulcerated depressed lesions (as defined by Paris Classification type III)

Patients with inflammatory bowel disease

Patients who are receiving an emergency colonoscopy

Poor general health (ASA class>3)

Patients with coagulopathy with an elevated INR ≥1.5, or platelets <50

Poor bowel preparation

Target sign or perforation during initial EMR

Need for ESD for complete resection prior to APC

Pregnancy and breast feeding
3.3
Early Withdrawal of Subjects
3.3.1
Criteria for removal from study
A patient will be removed from the study for any following reasons:
• The patient desires to discontinue participation
• The investigator believes that discontinuation is in the best interest of patient
3.3.2
Follow-up for withdrawn subjects
Patients will be informed that participation in this study is voluntary and that they do not to 
have to participate in this research. If patients choose to participate, they have the right to stop 
any time. If a patient decides not to take part in the research or decides to stop taking part in 
the research at later date, there will be no penalty or loss benefits to which he/she is entitled.
The PI of this study has the right to remove patients from the study without their permission. If 
the investigator determines that the subject does not fulfill the criteria to be in the study, or the 
subject’s condition becomes worse, he may remove the subject from the study. 
Information obtained prior to withdrawal may continue to be used if is necessary for the 
soundness of the overall research. Furthermore, records of the care that we provided will be 
retained as long as the law requires.
As this is a single point of care investigation, the process of withdrawal may occur between the 
time of consent and the administration of sedative. Withdrawal may occur either with a written 
or vocalized desire to retract one’s consent.
If a subject is removed from the study prior to completion, the reason for doing so and the date 
the subject is discontinued will be documented.
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4.0
Recruitment Methods
4.1
Identification of subjects
We will recruit patients presenting with a known ≥ 20mm polyp prior colonoscopy and referred for 
resection of this polyp to Hershey Medical Center.               
4.2
Recruitment process
All patients in our institute with a known ≥ 20mm polyp detected at a prior colonoscopy who are  
referred for colonoscopy procedure will be identified as potential study participants.                         
4.3
Recruitment materials
Not applicable
4.4
Eligibility/screening of subjects
All prospective subjects undergoing colonoscopy with a ≥ 20mm colon non-pedunculated polyp 
will be seen prior to the procedure to discuss and review the details of the study. Interested individuals 
will be screened to ensure that they meet inclusion and exclusion criteria.
5.0
Consent Process and Documentation
5.1
Consent Process 
 
5.1.1
Obtaining Informed Consent
5.1.1.1
Timing and Location of Consent
Consent and basic demographics will be garnered by the PI, one of the  
co-investigators or research associate prior to bringing the patient into
 the endoscopy suite, discussions about the research and obtaining 
                                                                         informed consent will occur in curtained endoscopy pre-procedure room.
 Patients will be giving adequate time to review consent form and consult 
 with family if they wish. Patients are not sedated at the time of consent.
5.1.1.2
Coercion or Undue Influence during Consent
 Patients will have time to review the consent form and ask questions.   
 Patients will be informed that Colonoscopy procedure will take place 
 even if the patient chooses not to participate in the study.
5.1.2
Waiver or alteration of the informed consent requirement
Partial Waiver of informed consent is requested pre – recruitment purpose. The chart and 
Medical record review pre-recruitment poses no more than minimal harm to
subject (i.e. loss of confidentiality/privacy). Given the number of subjects and the
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possibility that  not all subjects that look at their medical record may not eligible for the study 
this part of research would not be practical without waiver
5.2
Consent Documentation
5.2.1
Written Documentation of Consent
Consent will be performed by the PI, co-investigators or research associate prior to the
procedure. A discussion about the research study will be initiated prior to bringing the patient 
into the endoscopy suite. Written consent will be obtained by the PI, co-investigators or 
research associate prior to the procedure and that a copy of the signed consent form will be 
given to the subject. Patients will be informed that colonoscopy procedure will take place even if 
they chose to decline participation.
5.2.2
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.)
Not applicable
5.3
Consent – Other Considerations 
5.3.1
Non-English Speaking Subjects
Not planned at this time, although, if subjects who do not speak English will be enrolled, short 
form and oral translation process will be used to obtain informed consent.
5.3.2
Cognitively Impaired Adults
5.3.2.1 Capability of Providing Consent
Not applicable
5.3.2.2
Adults Unable To Consent
Not applicable
5.3.2.3 Assent of Adults Unable to Consent
Not applicable
5.3.3
Subjects who are not yet adults (infants, children, teenagers) 
5.3.3.1 Parental Permission
Not applicable
5.3.3.2 Assent of subjects who are not yet adults
Not applicable
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
6.1
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
Check all that apply:
 
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
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Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3]
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3]
6.2
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual
6.2.1.1 Plan to protect PHI from improper use or disclosure
Not applicable
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers 
Not applicable
6.2.2
Explanation for why the research could not practicably be conducted without access to and 
use of PHI
The information to be gathered is just for the recruitment purpose. Without it the PI could not 
identify the eligible subjects. This partial waiver is only for recognize the eligibility of study 
subjects. Obtaining consent from every subjects come for EMR would be prohibitive, resource 
exhaustive, and potentially cause confidentiality issues for the ones not be eligible for the study.
6.2.3
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization
The projects requires look at medical records to identify eligible subjects. 
Obtaining consent from every subjects come for EMR would be prohibitive, resource exhaustive, 
and potentially cause confidentiality issues for the ones not be eligible for the study.
6.3
Waiver or alteration of authorization statements of agreement
Not applicable
7.0
Study Design and Procedures
7.1
Study Design
This is a prospective data collection study which patients with non-pedunculated large polyps ≥ 20mm 
undergoing endoscopic mucosal resection (EMR with adjuvant Hybrid Argon Plasma Coagulation (APC) 
of the base and edges of the polypectomy site to fulgurate any potential microscopic residual disease. 
Resected polyps will be sent to the pathology laboratory where pathologist determine the final 
diagnosis of the polyps as per standard of care. We will collect the detail of the procedure, including, 
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general procedure details, polyp characteristic, details of any adverse event may happen and the details 
of 6 months follow up colonoscopy procedure. 
7.2
Study Procedures
Consent and basic demographics will be garnered by the PI, Co-investigators or research associate in the 
pre-procedure area prior to bringing the patient to the endoscopy unit.
Whether or not the patients choose to participate in this study, subject will undergo the scheduled 
colonoscopy in the same manner as any patient presently referred for resection of 
large polyps. Patients will have undergone colonoscopy prep as it is standard at each center. All exams 
will be performed using high-definition colonoscopes with digital chromoendoscopy capability (e.g. 
Olympus 190 series). 
Lesions will be identified using conventional colonoscopic views. Polyp characteristics will be recorded. 
Endoscopic mucosal resection (EMR) will be used for all resections: the polyp will be submucosally 
injected, so that the lesion will lift and demarcate from the submucosal layer. The submucosal injection 
creates a “cushion” between the mucosa and the muscularis propria. The idea is that mucosal lesions 
can be more safely removed. The applied injectate fluid will contain a lifting agent e.g. NaCl 0.9% and a 
dye agent e.g. methylene blue. The polyp will be resected with electrocautery snare. Following the 
resection of the polyp with the snare the submucosal area will be reinjected with saline (NaCl 0.9%) and 
then thermally ablated using APC (Erbe Hybrid APC). Finally thermal ablation of the resection site with 
the hybrid APC will occur using start settings. Once resection is considered complete the mucosal defect 
may be closed with clips for situations include but not limited to control bleeding during the polyp 
resection. Patients will be monitored continuously as is routine for any colonoscopy performed in our 
institution. Patients will be observed for in the recovery room before discharge for any sign of 
complications. (See appendix 1) We will collect the detail of the procedure, including, general procedure 
details, polyp characteristic, details of any adverse event may happen and the details of 6 months follow 
up colonoscopy procedure. 
7.2.1
EXAMPLE: Visit 1 or Day 1 or Pre-test, etc. (format accordingly)
Patients will be contacted by phone 30 days post procedure to assess for any possible  
 complications. (See appendix 2).
7.2.2
EXAMPLE: Visit 2 or Day 2 or Post-test, etc. (format accordingly)
A follow-up colonoscopy will be scheduled 6 months following the EMR procedure to evaluate    
for any recurrent polyp. 
This is a standard of care for resection of large polyps 
7.3
Duration of Participation
For all of the subjects it will be take 6 months to complete the study. A follow up colonoscopy will  
schedule and preform 6 months post-procedure to assess recurrence rate.
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.
8.0
Subject Numbers and Statistical Plan
8.1
Number of Subjects
We’re going to enroll 40 patients with detected colon polyps ≥20 mm that referred to Hershey 
Medical Center for EMR colonoscopy.
8.2
Sample size determination
We shall assume a recurrent rate of 5% for the APC assisted EMR. A sample size of 40 subjects provide 
60% power of rejecting 
 in a one-sided test, which is reasonable for a pilot study.
𝑯𝟎: 𝝅= 𝟏𝟓%
8.3
Statistical methods
The statistical plan for this study was designed with the assistance of Dr. Jason Liao with Penn State 
Public Health Sciences. The primary end point is the rate (proportion of patients) of local recurrent or 
residual neoplasia at 6 months for the Hybrid Argon Plasma Coagulation (APC) assisted EMR. Estimate of 
this recurrent rate will provided with 95% exact binomial confidence limits, which will then be compared 
to the historical rate of 15-20% recurrent rate for EMR alone. Statistical significance will be declared if 
the upper limit is smaller than 15%.  Even when significance is not reached, the confidence interval 
provides the plausible range of the local recurrent rate of the APC assisted EMR and helps to decide if a 
future study with a larger sample size is warranted. 
Summary statistics such as percentage of male/female patients, percentage of polyps within the 
different location of colon, mean diameter of polyps, percentage rate of neoplasia recurrence after 6 
months , the percentage of each type of Polyps (Ip, IIa, IIb, IIc,  etc), and Percentage of successful 
resection will also be provided. SPSS 22 statistical software shall be used to perform statistical analysis.
9.0
Confidentiality, Privacy and Data Management 
See the Research Data Plan Review Form
9.1
Confidentiality
9.1.1
Identifiers associated with data and/or specimens
9.1.1.1 Use of Codes, Master List
9.1.2
Storage of Data and/or Specimens
9.1.3
Access to Data and/or Specimens
9.1.4
Transferring Data and/or Specimens
9.2
Subject Privacy
10.0 Data and Safety Monitoring Plan
10.1
Periodic evaluation of data
                           The study involves minimal risk to subjects as it involves evaluate Hybrid APC assisted EMR, 
                               which is FDA approved equipment and standard care  procedure in U.S. for resection of 
                               large polyps.
                Oversight for the conduct of the study will be provided by the PI, John M. Levenick, MD 
                and the clinical research associate.  Any adverse event may occurring will 
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                be documented and reported according to HSPO policies and procedures. The principal 
                investigator and co-investigators will be responsible for data collection and verification, and 
                review of cumulative adverse events. Confidentiality will be protected by utilizing a code 
                number as the only identifier for each subject and the master list will be kept under lock and 
                key with access limited to the PI and research associate. Cumulative adverse events and study 
                progress summary will be communicated to the IRB at the time of continuing review.  
       
10.2
Data that are reviewed
All adverse events will be documented and entered into the Redcap® data management system for
centralized data storage and documentation. The following information will be entered: adverse event      
              type, onset/resolution date and time, intensity/severity, action taken, and outcome. All deaths on the  
              study, not related to progression of underlying disease will be reported to the IRB immediately. All 
              unanticipated AE’s related or possibly related to  study will be reported by PI to the IRB according to 
HSPO policies and procedures.
10.3
Method of collection of safety information
Patient demographics, risk factors, EMR procedural elements, Pathology results, complications, and all
follow up data will be entered into the Redcap® data management system for centralized data storage
and documentation.
10.4
Frequency of data collection
Data will be collected at the time of enrollment, the initial procedure, 30 days post
procedure phone call (adverse events), 2-3  weeks post-procedure pathology
results and  6 month follow-up colonoscopy examination .
10.5
Individuals reviewing the data
                          The PI and clinical research associate will review cumulative adverse events and accrual every 
                             3 months and report any issues requiring modification of the study or alternation of the risk: 
                             benefit ratio to IRB immediately. A summary of adverse events, study progress and protocol
                             modification will be included for IRB review in the continuing progress report.
10.6
Frequency of review of cumulative data
The PI and the clinical research associate will review cumulative adverse events and accrual every 3 
months.
10.7
Statistical tests
Not applicable
10.8
Suspension of research
The study team will make decisions regarding cessation of accrual. This trial will be suspended for
review for any patient death during, or up to 30 days after participating in the trial if felt to be causally
related to participation in this trial. The study team and the Office of Human Protection will then decide
after review whether it is safe to continue the trial. 
11.0 Risks
The research involves no more than minimal risk to participants because it involves prospective review of the 
patient’s medical records, procedure details and any adverse events may occur for limited and in-sensitive 
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information. The only risk is the loss of patient confidentiality and the risk will be minimized by coding the 
research data and keeping separate list that links code number with identifiers.
12.0 Potential Benefits to Subjects and Others
12.1
Potential Benefits to Subjects
There are no guarantees that subjects will benefit from participating in a research study, however, we 
hope there is a benefit of reducing recurrence rate while maintaining safety.
12.2
Potential Benefits to Others
The results of this research may lead to a technique for better way of complete resection of large polyps 
and safer one for future patients. 
13.0 Sharing Results with Subjects
Data and results of the study outcome will not be shared with either the patient, primary provider, or 
               referring provider. The results of the colonoscopy will be shared as per normal routine of the endoscopist.
14.0 Subject Stipend (Compensation) and/or Travel Reimbursements
Not Applicable
15.0 Economic Burden to Subjects
15.1
Costs 
Participant will not bear any costs which are not part of standard care. 
15.2
Compensation for research-related injury
Subjects will not receive any compensation for being in this research study. As this is a low risk study, 
the like-hood of complications or injury is very small. Is it possible however, that the subject could 
develop complications or injuries as a result of participating in this research study. In the event of injury 
resulting from this research, medical treatment is available but will provide at the usual charge.
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers. 
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16.0 Resources Available
16.1
Facilities and locations
All study procedures including colonoscopy will be conducted at Gastrointestinal Endoscopy and Motility 
Center at UPS (suite 2000) at Hershey Medical Center. The fully-staffed Gastrointestinal Endoscopy and 
Motility Center features 8 endoscopy rooms with state of the art Olympus endoscopes. Two of the room 
designed to accommodate advanced therapeutic procedures, and have fluoroscopic capabilities. The 
suite has several onsite anesthesiologists, nurses and physicians. Measures in place to maintain patient 
privacy include: procedures that are performed in private studios or rooms and recovery that occurs in 
curtained rooms. If required, continuous emergency care is available. The primary investigator Dr. John 
Levenick is an Assistant Professor of Medicine. He has extensive experience with colonoscopy and EMR 
procedures. Additionally Dr. Levenick has several years of research experience as PI or Co-Investigator.
  
16.2
Feasibility of recruiting the required number of subjects
A total of 40 patients are needed for this study. Approximately, 170 colonic EMR performed at Hershey 
medical center per year. 100-125 of these EMR are done to remove polyps >2cm. We anticipate 
complete enrollment in 6 months.
16.3
PI Time devoted to conducting the research
 As the principal investigator, Dr. Levenick has devoted a set amount of time to oversee the 
administration and surveillance of this study and to perform the procedures. He has been given a 
dedicated amount of academic time to pursue research, and while limited, it is sufficient to oversee and 
execute this trial safely and effectively.
16.4
Availability of medical or psychological resources
 Patients will have continuous monitoring of vital signs during and after the colonoscopy  
 procedure as is standard of care for this procedure as outlined in the protocol. Continuous 
 emergency medical care is available for any patient undergoing colonoscopy and to this study 
 population as standard of care. Physician, nursing, and support staff are available continuously   
  while the patient is in the endoscopy suite.
16.5
Process for informing Study Team
The study team will meet to review the study procedures every month at the therapeutic pod meeting. 
All team members will be up to date on the progress of the study and any adverse events that may 
occur.
17.0 Other Approvals
17.1
Other Approvals from External Entities
Not applicable
17.2
Internal PSU Committee Approvals
Check all that apply:
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library.
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  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy). 
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body 
fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that had 
been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of HRP-901 
- Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library.
  Clinical Research Center (CRC) Advisory Committee– All campuses – Research involves the use of 
CRC services in any way.  
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest.
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload a copy 
of HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library.
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE.
  Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The scientific 
review requirement may be fulfilled by one of the following: (1) external peer-review process; (2) 
department/institute scientific review committee; or (3) scientific review by the Clinical Research Center 
Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute Scientific Review 
Committee is required if the study involves cancer prevention studies or cancer patients, records and/or 
tissues. For more information about this requirement see the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/investigator 
18.0 Multi-Site Research
18.1
Communication Plans
Not Applicable
18.2
Data Submission and Security Plan
Not Applicable
18.3
Subject Enrollment
Not Applicable
18.4
Reporting of Adverse Events and New Information
Not Applicable
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18.5
Audit and Monitoring Plans
               Not Applicable
19.0 Adverse Event Reporting
19.1
Adverse Event Definitions
For device studies, incorporate the following definitions into the below responses, as written:
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.
19.2
Recording of Adverse Events
All adverse events (serious or non-serious) and abnormal test findings observed or reported to   
                             study team believed to be associated with the study drug(s) or device(s) will be followed until  
the event (or its sequelae) or the abnormal test finding resolves or stabilizes at a level 
                             acceptable to the investigator.
 An abnormal test finding will be classified as an adverse event 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
                             Note: Simply repeating a test finding, in the absence of any of the other listed criteria,  
                             does not constitute an adverse event.   
• The test finding leads to a change in study drug dosing or discontinuation of subject  
    participation in the clinical research study
• The test finding is considered an adverse event by the investigator.
19.3
Causality and Severity Assessments
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event.
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history.
19.4
Reporting of Adverse Reactions and Unanticipated Problems to the FDA  
19.4.1 Written IND/IDE Safety Reports
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The Sponsor-Investigator 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 Sponsor-Investigator 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 Sponsor-Investigator 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 Sponsor-Investigator 
will submit additional information concerning the reported adverse effect as requested by the 
FDA.
19.4.2 Telephoned IND Safety Reports – Fatal or Life-threatening Suspected Adverse Reactions
Not Applicable
19.5
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures.
19.6
Unblinding Procedures
Not Applicable
19.7
Stopping Rules
  Not Applicable
20.0 Study Monitoring, Auditing and Inspecting
20.1
Study Monitoring Plan
20.1.1 Quality Assurance and Quality Control
                           The study involves minimal risk to subjects as it involves evaluate Hybrid APC assisted EMR, 
                               which is FDA approved equipment and EMR is standard care  procedure in U.S. for resection of 
                               large polyps.
                Oversight for the conduct of the study will be provided by the PI, John M. Levenick, MD 
                and the clinical research associate.  Any adverse event may occurring will 
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                be documented and reported according to HSPO policies and procedures. The principal 
                investigator and co-investigators will be responsible for data collection and verification, and 
                review of cumulative adverse events. Confidentiality will be protected by utilizing a code 
                number as the only identifier for each subject and the master list will be kept under lock and 
                key with access limited to the PI and research associate. Cumulative adverse events and study 
                progress summary will be communicated to the IRB at the time of continuing review.  
20.1.2 Safety Monitoring
All adverse events will be documented and entered into the Redcap® data management system 
for centralized data storage and documentation. The following information will be entered: 
adverse event type, onset/resolution date and time, intensity/severity, action taken, and 
outcome. All deaths on the study, not related to progression of underlying disease will be 
reported to the IRB immediately. All unanticipated AE’s related or possibly related to study will 
be reported by PI to the IRB according to HSPO policies and procedures.
The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the 
AE case report forms by the coordinator; be available to answer any questions that the 
coordinators may have concerning AEs; and will notify the IRB, FDA, sponsor and/or DSMB of all 
applicable 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 complete the appropriate report form and logs; assist the PI to 
prepare reports and notify the IRB, FDA and/or DSMB of all Unanticipated Problems/SAE’s.
21.0 Future Undetermined Research: Data and Specimen Banking
21.1
Data and/or specimens being stored
Not applicable
21.2
Location of storage
Not applicable
21.3
Duration of storage
                             Not applicable
21.4
Access to data and/or specimens
               Not applicable
21.5
Procedures to release data or specimens
               Not applicable
21.6
Process for returning results
Not applicable
22.0 References
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1.
Von Renteln D, Bouin M, Barkun AN. Current standards and new developments of colorectal polyp 
management and resection techniques. Expert Rev Gastroenterol Hepatol. 2017 Sep; 11(9):835-842.
2.
Kandiah K, Subramaniam S1, Bhandari P. Polypectomy and advanced endoscopic resection. Frontline 
Gastroenterol. 2017 Apr;8(2):110-114
3.
Tsiamoulos ZP, Bourikas LA, Saunders BP. Endoscopic mucosal ablation: a new argon plasma 
coagulation/injection technique to assist complete resection of recurrent, fibrotic colon polyps (with video). 
Gastrointest Endosc. 2012 Feb; 75(2):400-4.
4.
 Arezzo A, Passera R, Marchese N., et.al. Systematic review and meta-analysis of endoscopic submucosal 
dissection vs endoscopic mucosal resection for colorectal lesions. United European Gastroenterol J. 2016 
Feb; 4(1):18-29.
5.
Manner H, May A, Kouti I, et.al. Efficacy and safety of Hybrid-APC for the ablation of Barrett's esophagus. 
Surg Endosc. 2016 Apr;30(4):1364-70
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Appendix 1: Schedule of events/study calendar, including screening, treatment, and follow-up
TimeLine
Before Colonoscopy 
During Colonoscopy
30 days  post 
EMR Procedure
6 months follow up 
Colonoscopy 
procedure
Tasks
-Screen patient for 
eligibility from Medical 
records and previous 
reports.
- Explain study and 
obtain informed 
consent prior to 
colonoscopy
-Assess polyp 
 eligibility
-Decide whether
  to resect or not
include patient in the 
study 
- Perform    
  EMR
  Followed by 
Hybrid APC 
  
-Follow up 
phone call and 
pt. interview
-Assesse interim 
events
 Assess the 
resection site
Location
Endoscopy unit
Endoscopy unit
         
 Phone
Endoscopy unit
Data
Patient characteristic 
and 
See checklist for 
inclusion/ exclusion 
criteria. Upload data 
into RedCap®
See checklist. Polyp characteristic data 
+ EMR procedure details using Hybrid 
APC study Data Acquisition Form. 
Upload data into RedCap®
Minor and major 
complications 
(Bleeding, 
abdominal pain, 
etc.)+ Pathology 
results.  Upload 
data into 
RedCap®
Resection site 
procedure details 
using Hybrid APC 
study Data 
Acquisition Form. 
Upload data into 
RedCap® 
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Appendix 2: Following questions will ask from the patients at the time of the 30 days follow up.  The answer from 
patients and information from medical records will be transfer to Hybrid APC study Data Form and upload into RedCap®  
1.
Did you have any bleeding within 30 days following the EMR colonoscopy?
                                                                                                                                                       Yes
                                                                                                                                                       No
2.
If yes when did this start? Date of AE start: ___ ___/ ___ ___/___ ___ (mm/dd/yy)
       3.
If yes when did this end? Date of AE end: ___ ___/ ___ ___/___ ___ (mm/dd/yy)
4.
If yes how much bleeding did you have?
5.
 If yes did you need a treatment?
                                                                    No treatment
                                                                    Outpatient treatment
                                                                    Inpatient treatment, specify days of admission: N= ____
                                                                    Other, specify 
6.
 Did you need Blood transfusion:                     Yes
                                                                                              No
                                                                                       Don’t know 
a.
If yes, number of transfused units: N= ______
7.
Did you have any fever within 30 days following the EMR colonoscopy?
                                                                                                                                                   Yes
                                                                                                                                                   No
8.
If yes when did this Start?  Date of AE start: ___ ___/ ___ ___/___ ___ (mm/dd/yy)
9.
If yes when did this End? Date of AE End: ___ ___/ ___ ___/___ ___ (mm/dd/yy)
10.  What was you temperature during this time?
11.       If yes did you need a treatment?
                                                                    No treatment
                                                                    Outpatient treatment
                                                                    Inpatient treatment, specify days of admission: N= ____
                                                                    Other, specify 
12. Did you have any abdominal pain within 30 days following the EMR colonoscopy?
                                                                                                                                                                  Yes
                                                                                                                                                                   No
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13. If yes what is the score of your pain from 0-10 (10 is the worst pain)?
14. If yes where was the location?
15. If yes did you need a treatment?
                                                                    No Intervention
                                                                    Outpatient treatment
                                                                    Inpatient treatment, specify days of admission: N= ____
                                                                    Other, specify 
16. If yes did a Colonoscopy performed?          Yes
                                                                                          No
                                                                                    Don’t know 
17. If yes did a CT performed?                                Yes
                                                                                              No
                                                                                       Don’t know
18. If yes did surgery required to repair/ resect your colon?
                                                                                                                       Yes
                                                                                                                       No
                                                                                                                Don’t know
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