A Randomized Trial Comparing the Effectiveness of Polyp Resection Treatments (Hot Snare vs Cold Snare vs Hot EMR vs Cold EMR)
Phase: NA
Conditions: Colon Cancer, Colon Polyp, Colon Adenoma
Sponsor: Indiana University

02/24/20 
 
 
 
 
 
 
A randomized trial comparing the effectiveness of polyp resection 
treatments (hot snare vs cold snare vs hot EMR vs cold EMR) 
 
NCT03462706 

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A randomized trial comparing the efficacy of polyp resection techniques for polyps sized 6-
15mm (Hot snare vs. cold snare vs. hot EMR vs. cold EMR) 
 
Primary Investigator:  
 
 
Dr. Douglas Rex 
Indiana University Hospital 
Indianapolis, IN 46202 
 
Sub-Investigators: 
 
 
 
Dr. Fadi Antaki, MD 
 
 
 
 
 
 
John D. Dingell VA Medical Center 
4646 John R St 
Detroit, MI 48201 
 
 
 
 
 
 
 
 
Dr. Kirthi Lilley, MD 
John D. Dingell VA Medical Center 
4646 John R St 
Detroit, MI 48201 
 
 
 
 
 
 
 
Dr. Stephanie Judd, MD 
John D. Dingell VA Medical Center 
4646 John R St 
Detroit, MI 48201 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dr. Joseph Anderson, MD 
 
 
 
 
 
White River Junction VA Medical Center 
215 North Main Street 
White River Junction, VT  05009 
 
Dr. Heiko Pohl, MD 
White River Junction VA Medical Center 
215 North Main Street 
White River Junction, VT  05009 
 
 
Introduction:  
The optimal method for removal of polyps 6-9 and 10-15 mm in size is not established.  
In recent years, the use of cold resection techniques (resection without the use of electrocautery) 
has been demonstrated to be effective and safer than techniques utilizing electrocautery (hot 
techniques) for diminutive polyps that are 1-5 mm in size.  However, the effectiveness of cold 
techniques for 6-15 mm polyps has been questioned. Recent studies have shown that cold snare 
endoscopic mucosal resection (EMR) is non-inferior to hot EMR for 6-9 mm polyps 1-3. Another 
trial showed that hot EMR was superior to cold snaring 4.  Cold EMR, or EMR in general, are 
both more time consuming than non-EMR techniques.  EMR refers to a submucosal injection that 
takes place prior to the removal of a polyp with a snare.  In this study, we propose to evaluate 
four different treatments for polyps (sized 6mm-15mm).  The four treatments are cold snaring 

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without injection, hot snaring without injection, cold EMR, and hot EMR. Previous published 
failure rates for 6-9 mm polyps are shown in the attached table. 
 
 
Methods:  
 
A member of the research team will approach a potential subject to discuss 
participation in the study, including background of the proposed study, inclusion and 
exclusion criteria, benefits and risks of the procedures and follow-up. If this is of interest to 
the subject, the informed consent form will be discussed and presented. The subject must sign 
the consent form prior to enrollment.  
All of the colonoscopies will be performed by Dr. Douglas Rex or one of the Sub-
Investigators listed above.  During the procedure, once a polyp has been identified and its size fits 
within the range of the target groups (Group 1: 6-9mm or Group 2: 10-15mm), each subject will be 
randomized to one of the four resection techniques in a 1:1:1:1 ratio using a computer generated 
randomization sequence. This treatment will be applied to additional polyps found within either 
of the target groups (correct size ranges) at the discretion of the physician in that patient. The PI 
has no preference and actively uses all four of the treatments and is expert in all four of the 
proposed treatments.   
Data will be collected by research team members authorized to be on the study. Data that 
will be assessed from each polyp include its size, a photograph, location of the polyp in the colon, 
shape (Paris classification), removal time (in seconds) of each polyp resection, prediction of 
complete resection, prediction of pathology, actual pathology, and efficacy of resection.  Efficacy 
of resection will be assessed by biopsies in four quadrants of the perimeter of the defect and one 
biopsy from the center of the defect.   
Subjects will receive a follow-up phone call 30 ± 7 days after their colonoscopy. 

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Objectives: 
  
The primary endpoint of the study will be the efficacy of resection.  The hypothesis 
centers on hot EMR as the gold standard, with an estimated effective resection rate of 97% 
(Table 1).  The trial will be powered for non-inferiority, that is, each of the other arms will be 
non-inferior compared to hot EMR within a > 7% margin2. Complications will be recorded, 
but the study will not be powered for complications. 
The study will help to establish the optimal resection technique for 6-9 and 10-15 mm 
polyps.  Although previous studies have compared two of the potential resection methods1-4, no 
previous study has evaluated all four of the resection methods.   
 
Criteria:  
 
 
Inclusion Criteria:  
 
• 
Aged 40 years or older 
• 
Ability to provide informed consent 
 
Exclusion Criteria:  
• 
Subjects with a history of inflammatory bowel disease 
• 
Lesions less than 6mm or greater than 15mm in largest dimension 
Randomization: 
Once a polyp has been identified and its size fits within the range of the target groups 
(Group 1: 6-9mm or Group 2: 10-15mm), each subject will be randomized in a 1:1:1:1 ratio using 
a computer generated randomization sequence. Randomization outcomes include: cold snaring 
without injection, hot snaring without injection, cold EMR, and hot EMR. The randomized 
treatment will be applied to additional polyps found within either of the target groups (correct 
size ranges) at the discretion of the physician in that patient. 
The randomization list will include 324 treatments. These randomized treatments will be 
printed and placed into sealed envelopes pertaining to the randomization number and will be 
opened following confirmation that the patient is eligible. Randomization will occur on a per 
procedure basis.  Not all 324 randomization numbers generated will be used in the study. Instead, 
enrollment will be competitive and each site will continue to enroll until a total of 264 patients 
have been randomized study-wide. 
Statistical Analysis & Sample Size:  
A sample size of 66 polyps per treatment (264 total subjects) will have 80% power to 
detect a non-inferiority margin difference of 7% for the cold EMR, hot snare, and cold snare 
treatments compared to the hot EMR treatment with an alpha of 0.05.  
Data Integrity and Safety 
All paper charts pertaining to the patient will be kept under lock and key in 

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coordinators office away from the endoscopy area. Each VA site will securely transfer their 
data to the main site electronically in a manner that is approved by their local IRBs (ie 
REDCap, Azure AMS System, faxed over a secure line to research office).  Only de-identified 
data from external sites will be added to the database (no HIPAA identifiers will be collected 
from external sites besides procedure dates).  Virtual data will be stored on an internal network 
drive with encryption and password security. Only approved personnel by the IRB will have 
access to the file storage.  This file will also not have any identifiable patient information.  A 
study log with the identifiable information will be kept in a separate folder to enable the 
investigators to assist in any research audit. No procedural data except the date of examination 
will be entered into this log. There will be regular back-ups of the data.  
 
The Data Safety Monitoring Board will consist of Dr Michael Gleeson and Dr. Charles 
Kahi. Dr. Gleeson will chair the DSMB which will meet every six months to review study related 
data. Additionally, Dr. Rex's research team will provide him up to date information regarding the 
status of patients and any reportable events. All SAEs and Unanticipated or Unexpected problems 
will be reported to the DSMB. 
Any subject who wishes to withdraw from this investigation on his/her own accord and 
for whatever reason is entitled to do so without obligation and prejudice to further treatment. In 
addition, the Investigator may decide for reasons of medical prudence, to withdraw a subject. In 
either event, the Investigator will clearly document the date and reason(s) for the subject’s 
withdrawal from this investigation in the CRF and should indicate whether or not he considers it 
was related to the study interventions. 
 
1. 
Aslan, F., et al. Cold SNARE polypectomy versus standard SNARE polypectomy in 
endoscopic treatment of small polyps. GIE May 2013; 77(5s): AB561. 
2. 
Papastergiou, V., et al. Cold versus hot endoscopic mucosal resection for 
nonpedunculated colorectal polyp sized 6-10 mm: a randomized trial.  Endoscopy 2017; doi: 
10.1055/s-0043-118594. 
3. 
Kawamura, T,. Comparison of the resection rate for cold and hot snare polpectomy from 
4-9 mm colorectal polyps: a multicenter randomized controlled trial (CRESCENT study). GUT 
2017; 0:1-8; doi: 10.1136/gutjnl-2017-314215. 
4. 
Zhang, Q., et al. Polypectomy for complete endoscopic resection of small colorectal 
polyps. GIE 2017; doi: 10.1016/j.gie.2017.06.010.