Effect of Epinephrine on Immediate Post-polypectomy Pain in Colorectal Lesions Larger Than 20 mm
Phase: PHASE4
Conditions: Colonic Polyp
Sponsor: Indiana University

10/19/20 
 
 
 
 
 
 
Effect of epinephrine on immediate post-polypectomy pain in colorectal 
lesions larger than 20 mm 
 
NCT04065451 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 1 of 9 
 
 
 
Effect of epinephrine on immediate post-polypectomy pain 
in colorectal lesions larger than 20 mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Douglas Rex MD,  
#4100 University Hospital, 550 University Blvd, Indianapolis, 
Indiana 46202 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 2 of 9 
 
Table of Contents: 
 
Study Schema 
1.0 
Background & Rationale 
2.0 
Objective 
3.0 
Outcome Measures 
3.1 
Primary Outcome Measure 
3.2 
Secondary Outcome Measures 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
4.2 
Exclusion Criteria 
5.0 
Study Design 
6.0 
Enrollment/Randomization 
7.0 
Reportable Events 
8.0 
Data Safety Monitoring 
9.0 
Study Withdrawal/Discontinuation 
10.0 Statistical Considerations 
11.0 Data Management 
12.0 References 
 
 
 
 
 
 
Abbreviations 
This page is optional. The list below includes some common abbreviations. However, this list should be 
customized for each protocol (i.e., abbreviations not used should be removed and new abbreviations used 
should be added to this list). 
 
AE 
Adverse Event 
IRB Institutional Review Board 
PI 
Principal Investigator 
US 
United States 
 
 
 
 
 
 
 
 
 
 
 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 3 of 9 
 
 
1.0 
Background & Rationale 
 
Polypectomy is an important aspect of colonoscopy for colorectal cancer prevention1. Large 
sessile polyps (≥20 mm in any dimension) are particularly challenging to remove. Endoscopic 
mucosal resection (EMR) is an effective therapy for patients with large laterally spreading colon 
neoplasms measuring greater than 20 mm2. Main complications of endoscopic resection include 
bleeding, perforation, transmural injury and recurrence3.. Our anecdotal observation is that most 
patients with large colorectal lesions complain of pain immediately after polypectomy when 
using epinephrine. 
Epinephrine is sometimes used as an additive to submucosal injection fluid primarily to reduce 
immediate (intra-procedural) hemorrhage2. The submucosal injection generally consists of non-
allergenic viscous solution to raise the polyp away from the submucosa thereby reducing the 
chance of submucosal injury and perforation. Adding epinephrine to this solution is generally 
accepted and left to endoscopist discretion. We hypothesize that the complaint of pain in patients 
with polypectomy of colorectal lesions might be due to the use of epinephrine. Epinephrine 
reduces the propensity for immediate bleeding by contracting the blood vessels in the 
surrounding area where it’s injected, causing a degree of ischemia. Any relative ischemia might 
be the cause of the patients’ pain. 
 
 
2.0 
Objective 
 
To identify if epinephrine use during EMR will result in a change in patient pain perception 
 
 
 
 
3.0 
Outcome Measures/Endpoints 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 4 of 9 
 
 
3.1 
Primary Outcome Measure 
 
The primary outcome measure is the mean of the two pain scores assessed on a visual 
analog scale (VAS, 10 cm vertical line, appendix 1) at 30 minutes and one hour after 
colonoscopy. 
 
3.2 
Secondary Outcome Measures 
 
We will also collect information on the ease of polypectomy (Sydney resection quotient, 
en bloc resection, quality of mound) and frequency of immediate bleeding among both 
groups. 
 
 
4.0 
Eligibility Criteria 
 
4.1 
Inclusion Criteria 
 
1. Patients aged 18 years and over 
2. Patients scheduled for treatment of large (≥ 20 mm) colorectal polyps  
3. Able to sign informed consent 
 
4.2 
Exclusion Criteria 
 
1. Patients previously enrolled in the study 
2. Pedunculated polyps 
3. Polyps not amenable to endoscopic resection 
4.  Patients allergic or sensitive to epinephrine 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 5 of 9 
 
5.  Patients with coronary artery disease who have had a myocardial infarction in the past 
year, or had coronary stenting in the past year, or had angina in the past year. 
6.  Patients electing anesthesia other than monitored anesthesia care with propofol (MAC) 
for colonoscopy 
 
 
 
 
5.0 
Study Design 
 
All patients scheduled for the resection of a colorectal polyp ≥ 20 mm in diameter under MAC 
with propofol will be approached and explained the purpose of the study. If the patient is 
eligible, and willing to participate in the study and signs an informed consent, patient will be 
enrolled in the study. Randomization will be performed after Dr. Rex measures the polyp as ≥ 20 
mm in diameter and decides on employing EMR for polypectomy. 
 
If EMR is not employed, the patient will not be randomized and will be excluded from the study. 
Randomization is computer generated using a 1:1 ratio for the two arms in the study.  
 
Patients in the epinephrine arm will receive a submucosal injection of hetastarch and indigo 
carmine dye with diluted epinephrine (1:200,000, 5µg/ml) 5. Patients in the no epinephrine arm 
will receive submucosal injection of hetastarch and indigo carmine dye but no epinephrine. 
Submucosal injection will be prepared by a registered nurse in the technicians’ area away from 
the endoscopy room and the endoscopist will not be aware of the randomization. The 
endoscopist will administer the submucosal fluid. The total volume of injected fluid will be 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 6 of 9 
 
determined by the lesion and the need for fluid volume to achieve adequate lift before snare 
resection, and will not exceed 100 ml. 
 
 
 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
Visit 1 
Time Point  
 
 
 
 
 
6.0 
Enrollment/Randomization 
 
The subject will be randomized to one of the 2 arms – Epinephrine arm and non-epinephrine arm 
after the PI inspects the polyp for EMR potential. The research coordinator at this point will 
break the randomization by opening a sealed envelope. The PI will be blinded to the injection 
solution throughout the study. 
 
 
7.0 
Reportable Events 
 
All adverse events meeting prompt reporting criteria will be reported to the IRB within 5 
business days of the study team becoming aware of the event. An adverse event for this study is 
N=20 
Perform all assessments 
EMR with Epinephrine in the submucosal injection fluid or EMR with no epinephrine in the 
submucosal injection fluid 
                        VAS score at 30 minutes and one hour 
Arm: No Epinephrine 
N = 10 
Arm: Epinephrine 
N = 10 
Randomize 
1:1 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 7 of 9 
 
defined as any event assessed by the PI, or appropriately trained and qualified designee, as (1) 
unexpected, (2) related or possibly related to study participation, AND (3) suggesting that the 
research places subjects or others at greater risk of harm than was previously known. The period 
for assessing AE’s will be from the point of injecting submucosal fluid till the patient is 
discharged.  
 
 
8.0 
Data Safety Monitoring 
 
The PI, Dr. Rex has a large practice of resecting large polyps and we hope to recruit the 20 
patients as quickly as possible. Although this is a randomized trial, both arms of the study are 
currently commonly used in clinical practice and both are within the standard of care. Dr. Rex 
also uses both approaches in his practice. The use of epinephrine (1:200,000 as generally used in 
colon polypectomy) does not add significantly to the cost of the procedure and doesn’t raise 
important safety issues. All safety precautions for large polyp resection will be followed. Dr. Rex 
will monitor adverse events including delayed hemorrhage, post-polypectomy syndrome and 
perforations. 
 
 
9.0 
Study Withdrawal/Discontinuation 
  
Any patient who likes to withdraw from the study at any point can do so. The data collected until 
the patient withdraws consent will be used to maintain data integrity.  
 
 
10.0 
Statistical Considerations 
 
We hope to recruit 10 patients into each arm of the study. Our anecdotal observation is that using 
epinephrine dramatically increases the post-procedure pain perception of patients. To our 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 8 of 9 
 
knowledge, there is no literature comparing these two groups with pain outcome measure. The 
visual analog score is widely used for pain during colonoscopy procedures but there are no 
relevant publications testing whether epinephrine affects pain after EMR. We calculated that the 
total sample size of 20 will have 90% power to detect a 50% decrease in mean pain scores at a 2-
sided type 1 error rate of 0.05 using a student’s t-test (a decrease of mean VAS from 90 with 
epinephrine to 45 without epinephrine, with a standard deviation of 30 in each group). Sydney 
resection quotient and quality of mound will be analyzed using Wilcoxon rank sum tests. The 
proportion of patients who have an en bloc resection and immediate bleeding will be compared 
using chi-square tests. 
 
 
11.0 
Statistical Data Management 
 
Primary data will be collected via paper charts and stored electronically on the S-drive located on 
IUSM Gastroenterology servers. Access will be limited and password controlled. Data on S-
drive is backed up continuously and copies transferred to secure storage every 30 days. We will 
use Microsoft Excel for data entry and storage. Paper charts will be stored in the administration 
area away from the endoscopy suite. Charts will be stored for a period of 5 years from the end of 
the study recruitment. As part of quality control, Excel file will be checked for data entry errors 
at recruitment of 10 patients. 
 
 
12.0 
References 
 
1.         Pohl H, Srivastava A, Bensen SP, et al. Incomplete polyp resection during colonoscopy-
results of the complete adenoma resection (CARE) study. Gastroenterology 
2013;144:74-80 e1. 
2. 
Committee AT, Hwang JH, Konda V, et al. Endoscopic mucosal resection. Gastrointest 
Endosc 2015;82:215-26. 

IRB#: 1908473351 
Version 3; 10/19/2020  
 
Page 9 of 9 
 
3. 
Klein A, Bourke MJ. How to Perform High-Quality Endoscopic Mucosal Resection During 
Colonoscopy. Gastroenterology 2017;152:466-471. 
4. 
 
5. World Health Organization. Epinephrine (for use with local anaesthetics). Model Prescribing 
Information: Drugs Used in Anaesthesis, Geneva, 1989:33