Randomized Controlled Trial Investigating Use of Submucosal Injection of EverLift in Rates of Complete Resection of Nonpedunculated Polyps 4-9mm
Phase: NA
Conditions: Colo-rectal Cancer, Polyp of Colon, Adenomatous Polyp of Colon
Sponsor: Stanford University

Evaluation of EverLift in the Performance of Polypectomy for 
Polyps 4-9mm 
NCT04551014 
May 4, 2021 
Shai Friedland, Principal Investigator 
Stanford University 
Stanford, California 94305 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
It is important to optimize complete resection of polyps as residual tissue may play a role in interval 
cancers. The US Multi-Society Task Force recommends diminutive (<5 mm) and small (6–9 mm) polyps 
be removed by cold snare polypectomy (CSP). Use of viscous submucosal agents has not been evaluated in 
CSP. In this trial, we investigate the potential role of EverLiftTM (GI Supply, Pennsylvania) in CSP. 
b. 
Objectives 
This study is a single-center, prospective noninferiority randomized clinical trial evaluating CSP for 
nonpedunculated polyps 4-9mm, with or without submucosal injection of EverLiftTM. The primary outcome 
is complete resection rate, defined by absence of residual polyp in the margin biopsies. 
c. 
Rationale for Research in Humans 
There are no effective animal endoscopy models that would allow real-time assessment of efficacy of polypectomy. 
 
2. 
STUDY PROCEDURES 
a. 
Procedures 
If a polyp 4-9mm is to be removed as part of routine clinical care during the endoscopy procedure, we will remove half 
of the polyps using cold snare with submucosal injection of EverLiftTM and the other half without submucosal injection 
of EverLiftTM. Biopsies will be performed at the margins of the polypectomy site. This will allow us to assess whether 
cold biopsy forceps or cold snare is more effective at adequately removing polyps. While biopsies are routinely 
performed in clinical practice to check for completeness of resection, the biopsies performed at the margins of the 
polypectomy site are done for research purposes. However, biopsies of the margins are of minimal increased risk. 
b. 
Procedure Risks 
 
The participants will have their regularly scheduled endoscopy procedures. Polyps will be removed as part of routine 
clinical practice. While biopsies are routinely performed in clinical practice to check for completeness of resection, the 
biopsies performed at the margins of the polypectomy site are done for research purposes. However, biopsies of the 
margins are of minimal increased risk. 
c. 
Use of Deception in the Study 
There is no deception in the study.  

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d. 
Use of Audio and Video Recordings 
 
Endoscopy videos will be obtained. There will be no patient-identifying information on these videos. The videos may 
be shown at scientific meetings and will be kept as part of the study data. 
e. 
Alternative Procedures or Courses of Treatment 
 
The alternative is not to participate. In this case only the standard medically indicated endoscopic procedure will be 
performed. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the participant(s) 
after the conclusion of the study? 
Yes. All patients will continue to receive their appropriate medical therapy. 
g. 
Study Endpoint(s) 
The primary outcome measured was completeness of resection, defined as absence of polyp tissue in both 
polypectomy site margin biopsies. This outcome was tested for noninferiority. Secondary outcomes included 
polypectomy time, number of snare attempts for polyp removal, use of hemostatic clips, complication rates.  
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
There is limited data looking at use of submucosal injection in polyps <10mm. In work 
by Zhang et al in 2018 evaluating CSP of polyps 6-9mm with or without submucosal 
injection of normal saline/epinephrine/indigo carmine, incomplete resection rate was 
significantly lower in the group with submucosal injection. However, in 2020 Shimodate 
compared CSP with or without submucosal injection of normal saline/indigo 
carmine/epinephrine for polyps 3-10mm. In this study, there was no difference in rates of 
complete muscularis mucosal resection. To date, there has been no study evaluating 
viscous submucosal lifting agents.7 
 
Findings from Past Animal Experiments 
There are no prior relevant animal experiments.  
 
Radioisotopes or Radiation Machines 
b. 
Standard of Care (SOC) Procedures 
Identify Week/Month of Study 
Name of Exam 
Identify if SOC or Research 
N/A 
N/A 
N/A 
c. 
Radioisotopes 
i. 
Radionuclide(s) and chemical form(s) 
N/A 
ii. 
Total number of times the radioisotope and activity will be administered (mCi) and 
the route of administration for a typical study participant 
N/A 

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iii. 
If not FDA approved: dosimetry information and source documents (package insert, 
Medical Internal Radiation Dose [MIRD] calculation, and peer reviewed literature) 
N/A 
d. 
Radiation Machines – Diagnostic Procedures 
i. 
Examination description (well-established procedures) 
N/A 
ii. 
Total number of times each procedure will be performed (typical study participant) 
N/A 
iii. 
Setup and techniques to support dose modeling 
N/A 
iv. 
FDA status of the machine and information on dose modeling (if procedure is not 
well-established) 
N/A 
e. 
Radiation Machines – Therapeutic Procedures 
i. 
Area treated, dose per fraction/number of fractions, performed as part of normal 
clinical management or due to research participation (well-established procedures) 
N/A 
ii. 
FDA status of the machine, basis for dosimetry, area treated, dose per fraction and 
number of fractions (if procedure is not well-established) 
N/A 
4. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
N/A 
b. 
IDE-Exempt Devices 
N/A 
5. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
N/A 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
N/A 

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6. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
N/A 
7. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
Papastergiou et al found that cold snare endoscopic mucosal resection of polyps 
6-10mm had complete resection 92.8% of polypectomies. Using this data, in our 
sample size calculation we determined 115 polyps would be needed in each group 
to achieve an alpha value of 0.05, power of 90%, and non-inferiority margin of -
10%.  
b. 
Age, Gender, and Ethnic Background 
Age > 18, including all genders and ethnic backgrounds.  
c. 
Vulnerable Populations 
No vulnerable subjects.  
d. 
Rationale for Exclusion of Certain Populations 
Children are not included because the endoscopy units only serve adult patients  
e. 
Stanford Populations 
N/A 
f. 
Healthy Volunteers 
N/A 
g. 
Recruitment Details 
Patients who are scheduled for endoscopy by one of the investigators will be asked if they are interested in 
participating in the study. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
Patients 18 years or older undergoing colonoscopy, who had 1 or more polyps 
of the correct size 4-9mm that were removed.  
ii. 
Exclusion Criteria 
Patients <18 or >80; patients with inflammatory bowel disease or polyposis 
syndromes; patients who did not have consent form; patients in whom polyps 
were not removed.  
i. 
Screening Procedures 

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Patients scheduled for endoscopy by one of the investigators will be asked if they would like to participate in 
the study. If they are interested, then they will be enrolled. 
j. 
Participation in Multiple Protocols 
We will ask all patients if they are participating in any other studies. If they are participating in any other 
studies then we will ask them for more information to determine whether there could be any harm from 
participating in both studies and if there is then they will not be enrolled. 
k. 
Payments to Participants 
No payment. 
l. 
Costs to Participants 
No costs.  
m. 
Planned Duration of the Study 
1 year.  
8. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
N/A 
ii. 
Investigational drugs 
N/A 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
N/A 
iv. 
Procedures 
There is a very low (< 1 in 5000) risk of perforation of the gastrointestinal tract and a low (< 1 in 1000) risk 
of bleeding during the study portion of the endoscopy. There is a very low risk of an adverse event from the 
blood draw (< 1 in 1000). There is a very low risk of an adverse event from biopsies of resection site (<1 in 
1000 risk of bleeding, <1 in 1000 risk of infection). There is a very low risk of adverse event from 
polypectomy of a small polyp - there is no evidence to suggest either technique (cold snare or cold biopsy) is 
safer than the other.  
v. 
Radioisotopes/radiation-producing machines 
N/A 
vi. 
Physical well-being 
With the exception of the rare potential complications described above, we do not expect any harm to the 
participants' physical well-being. 
vii. 
Psychological well-being 
The patients are sedated during their medically-necessary endoscopy procedures and we do not expect any 
harm to their psychological health. 

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viii. 
Economic well-being 
No expected effect 
ix. 
Social well-being 
No expected effect 
x. 
Overall evaluation of risk 
Low 
b. 
International Research Risk Procedures 
N/A 
c. 
Procedures to Minimize Risk 
 
All of the patients undergo continuous vital signs monitoring by trained endoscopy nurses during the 
procedure. They are monitored continuously during the procedure and during recovery for any evidence of 
complications. 
 
d. 
Study Conclusion 
The study will be completed during the endoscopy procedure. 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
Complications from the endoscopy, including any complications that could potentially be due to the 
study. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The investigators and protocol director will be responsible for monitoring the data 
iii. 
Frequency of DSMB meetings 
Possible adverse events will be reviewed daily. 
iv. 
Specific triggers or stopping rules 
If any adverse events occur, the protocol will be suspended until the PD investigates the event and determines 
whether or not it is related to the study. 
v. 
DSMB Reporting 
The PD will inform the IRB if any adverse events relating to the study occur. 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
The Protocol Director will be the only monitoring entity for this study. 
vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
No 

May 4, 2021 
 
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f. 
Risks to Special Populations 
N/A 
9. 
BENEFITS 
 
This study will potentially improve our ability to treat premalignant disorders of the GI tract. 
 
10. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, 
Stanford Health Care, and Stanford Children’s Health.