Clinical trial NCT03350217
Conditions: Procedural Bleeding Delayed Bleeding Post-Polypectomy Syndrome Post Procedural Complication
Sponsor: Indiana University
Start date: 2017-10-09; Completion date: 2019-01-07
Enrollment: 160 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
EMR is a technique used for the removal of flat or sessile neoplasms confined to the superficial layers of the GI tract using a snare. Injection-assisted EMR is commonly used during resections of larger flat lesions as it provides submucosal lift of polyps, adenomas, other gastrointestinal mucosal lesions or early-stage cancers prior to EMR. This has been found to minimize mechanical or electrocautery damage to the deep layers of the gastrointestinal tract wall as the injectate provides a "safety cushion" as such between the area to be removed and healthy mucosal tissue.

Several solutions are used today for injecting lesions including saline, hyaluronic acid, and hydroxyethyl starch (Hetastarch). Saline solution has been found to dissipate within minutes, which may result in a lower quality lesion lift. Hyaluronic acid provides a longer lift, but is expensive and is not readily available in the U.S.

A new injectate known as Eleview has been developed for use in gastrointestinal endoscopic procedures and recently approved by the FDA. This injectate boasts a cushion of excellent height and duration through the use of an oil-in-water emulsion. However, the initial cost of this material is quite high ($80 per 10 ml).

Hetastarch, which is the current injectate used by Dr Rex, is a safe and considerably inexpensive solution that provides prolonged submucosal elevation and lowers procedure times. Our study will aim to compare Eleview to Hetastarch in the hopes of finding the ideal submucosal injectate.

This trial will focus on polyps of size ≥11 mm removed by snare EMR technique. Patients with lesions deemed not suitable for EMR due to features suggestive of sub-mucosal invasion will not be included.

Detailed description:
Injectate randomization:

Study patients will be randomly assigned to the Eleview or the Hetastarch treatment group in a 1:1 ratio. Randomization will occur at the site using envelopes provided by the Investigator. The envelope's contents will specify the treatment assignment for each patient and opened by the research team (PI will be blinded). The investigators will monitor the safety and effectiveness data. The appropriate solutions will be injected into the submucosal space beneath the lesion(s) to be excised before the lesion(s) is/are removed. Subjects in both groups will receive the appropriate volume of injectate deemed necessary by the PI for the individual patient.

Sample size and Statistical Analysis At least 200 patients will be enrolled. 100 of these patients will be randomized to Eleview injectate and 100 will be given the standard of care, Hetastarch injectate only. Efficacy and safety of Eleview injectate has only been reviewed in one previous study. Therefore, the planned sample size was not calculated using a statistical power analysis, but was regarded as sufficient to repeat the objectives of the COSMO study (2017) and satisfy the exploratory purposes of the present study.

Study personnel will carry out a simple randomization using a commonly used online generator. Randomization assignments will then be sealed until day of procedure until patient eligibility has been confirmed. The Principal Investigator will remain blinded and will perform all data analysis after completion of the study.

Data will be summarized and compared using classic descriptive statistics, i.e. mean, standard deviation, coefficient of variation (%), minimum, median and maximum values for quantitative variables, and frequencies for qualitative variables.

The Sydney Resection Quotient will be compared between treatment groups using a Wilcoxon Rank-Sum test. The proportion of subjects with en bloc resection of all endoscopically visible lesions will also be compared between treatment groups using a Fisher's exact test. A nominal alpha level of 0.05 will be used for both the comparisons.

No formal comparison will be performed for the secondary endpoints.

Arms: arm 1: This arm will be administered the Eleview Injectate (up to 50 mL's) solution upon randomization, provided the lesion is equal to or greater than 11 millimeters. arm 2: This arm will be administered Hetastarch (w/Methylene blue as a contrast agent) as the injection solution upon randomization, provided the lesion is equal to or greater than 11 millimeters.
Interventions: intervention 1: Eleview intervention 2: Hetastarch
Intervention descriptions: intervention 1: If a lesion in the colon is found to fit the description listed in the protocol, the subject will be randomized to Eleview or Hetastarch as the injectate solution for the procedure. The injectate solution is used, as needed, to aid in the resection of the target lesion. intervention 2: If a lesion in the colon is found to fit the description listed in the protocol, the subject will be randomized to Eleview or Hetastarch as the injectate solution for the procedure. The injectate solution is used, as needed, to aid in the resection of the target lesion.

Protocol documents:
Prot_SAP_000.pdf: 
 
OCT-16-2018 
 
 
 
A randomized, double-blind, comparative, effectiveness and safety study of 
Eleview vs. Hetastarch in subjects undergoing Endoscopic Mucosal Resection 
(EMR) of colonic lesions equal to or larger than 11mm 
 
 
 
 
 
NCT03350217 


A randomized, double-blind, comparative, effectiveness and safety study of 
Eleview vs. Hetastarch in subjects undergoing Endoscopic Mucosal 
Resection (EMR) of colonic lesions equal to or larger than 11mm 
 
Primary Investigator: 
 
 
Dr. Douglas Rex, 
Indiana University Hospital 
Indianapolis, IN 46202 
 
Introduction: 
EMR is a technique used for the removal of flat or sessile neoplasms confined to 
the superficial layers of the GI tract using a snare. Injection-assisted EMR is 
commonly used during resections of larger flat lesions as it provides submucosal 
lift of polyps, adenomas, other gastrointestinal mucosal lesions or early-stage 
cancers prior to EMR. This has been found to minimize mechanical or 
electrocautery damage to the deep layers of the gastrointestinal tract wall as the 
injectate provides a “safety cushion” as such between the area to be removed and 
healthy mucosal tissue (ASGE, 2008). 
Several solutions are used today for injecting lesions including saline, hyaluronic 
acid, and hydroxyethyl starch (Hetastarch). Saline solution has been found to 
dissipate within minutes, which may result in a lower quality lesion lift. 
Hyaluronic acid provides a longer lift, but is expensive and is not readily available 
in the U.S (Hwang, 2015).  
A new injectate known as Eleview has been developed for use in gastrointestinal 
endoscopic procedures and recently approved by the FDA. This injectate boasts a 
cushion of excellent height and duration through the use of an oil-in-water 
emulsion.  However the initial cost of this material is quite high ($80 per 10 ml). 
Hetastarch, which is the current injectate used by Dr Rex, is a safe and 
considerably inexpensive solution that provides prolonged submucosal elevation 
and lowers procedure times (Fasoulas, 2012). Our study will aim to compare 
Eleview to Hetastarch in the hopes of finding the ideal submucosal injectate. 
This trial will focus on polyps of size ≥11 mm removed by snare EMR technique. 
Patients with lesions deemed not suitable for EMR due to features suggestive of 
sub-mucosal invasion will not be included. 
 
Injectate randomization: 
Study patients will be randomly assigned to the Eleview or the Hetastarch 
treatment group in a 1:1 ratio. Randomization will occur at the site using envelopes 
provided by the Investigator. The envelopes contents will specify the treatment 
assignment for each patient and opened by the research team (PI will be blinded). 


We will monitor the safety and effectiveness data. The appropriate solutions will 
be injected into the submucosal space beneath the lesion(s) to be excised before the 
lesion(s) is/are removed. Subjects in both groups will receive the appropriate 
volume of injectate deemed necessary by the PI for the individual patient.  
 
Objectives: 
Primary objectives of the study are: 
 
 To evaluate the effectiveness of Eleview injection in comparison to 
Hetastarch, for EMR. Effectiveness will be evaluated by the Sydney Resection 
Quotient (SRQ), which is defined as the size of the polyp divided by the 
number of pieces resected. 
 
 To evaluate the safety of Eleview for EMR procedures in relation to adverse 
events and occurrence of complications during and after the EMR procedure in 
comparison to Hetastarch injectate. 
 
Secondary objectives: 
 
 To collect other effectiveness data regarding the administration of Eleview in 
comparison to Hetastarch, such as injectate amount required for efficient 
lesion lift and complete removal. 
 
End-points:  
 
Primary endpoints: 
 Effectiveness of  Eleview in comparison to Hetastarch for EMR in terms of: 
 
o Sydney Resection Quotient 
o Number of subjects with en bloc resection of lesions. 
 
 Safety outcomes as assessed by complications during or after the procedures 
including: 
o Intra-procedural bleeding (bleeding requiring therapeutic intervention 
during the EMR). 
o Early (<24h) and delayed (≥24h post EMR) post-procedural bleeding 
(bleeding post procedure that necessitates transfusion or endoscopic 
hemostasis because of hematemesis or a decrease of Hgb concentration 
of more than 2 g/dL after EMR). 
o Perforation  


o Post-Polypectomy Syndrome 
o Hospital admissions for any clinically relevant complications post-
procedure. 
 
Secondary endpoints: 
 Effectiveness of  Eleview compared to Hetastarch in terms of: 
 
o Injected volume needed for initial lesion lift 
o Injected volume needed for complete removal of lesion 
o Number of re-injections (number of times the injection device is passed 
down the scope). 
o Number of resected pieces 
o Ease of use for polyp removal and fluid behavior combined, and rated on 
a 5-point scale for: very easy, easy, neutral, difficult and very difficult. 
o Time (in minutes) to remove the lesion completely (measured from the 
first injection to final excision of the lesion), and total time of procedure. 
o Need for additional treatments such as avulsion, coagulation or ablation. 
o Pathological reports for negative lateral and/or deep margins (lateral 
margins only accurately assessed in en bloc resections) 
o Presence and number of deep resections containing muscularis propria. 
o En-bloc resections histologically examined for free-margins. 
o Recurrent or residual neoplasia rates examined by biopsy (if applicable) 
at the follow-up visit. 
 
Sample size and Statistical Analysis 
At least 200 patients will be enrolled. 100 of these patients will be randomized to 
Eleview injectate and 100 will be given the standard of care, Hetastarch injectate 
only. Efficacy and safety of Eleview injectate has only been reviewed in one 
previous study. Therefore, the planned sample size was not calculated using a 
statistical power analysis, but was regarded as sufficient to repeat the objectives of 
the COSMO study (2017) and satisfy the exploratory purposes of the present study. 
Study personnel will carry out a simple randomization using a commonly used 
online generator. Randomization assignments will then be sealed until day of 
procedure until patient eligibility has been confirmed. The Principal Investigator 
will remain blinded and will perform all data analysis after completion of the 
study. 
Data will be summarized and compared using classic descriptive statistics, i.e. 
mean, standard deviation, coefficient of variation (%), minimum, median and 
maximum values for quantitative variables, and frequencies for qualitative 


variables. 
The Sydney Resection Quotient will be compared between treatment groups using 
a Wilcoxon Rank-Sum test. The proportion of subjects with en bloc resection of all 
endoscopically visible lesions will also be compared between treatment groups 
using a Fisher's exact test. A nominal alpha level of 0.05 will be used for both the 
comparisons.  
No formal comparison will be performed for the secondary endpoints. 
 
Selection criteria 
Inclusion criteria: 
1. 
Sex and age: men and women > 18 years old 
2. 
Subjects referred for EMR of polyps of size ≥11 mm 
3. 
ASA score 1, 2 or 3. 
4. 
Contraception: Women of childbearing potential must have a negative 
pregnancy test (one is provided as the standard of care) or sign a waiver. 
Post-menopausal women must have been in that status for at least 1 year (per 
standard of care). 
5. 
Subject is willing and able to participate in the study procedures and to 
understand and sign the informed consent 
 
Exclusion criteria: 
1. 
Age: Subjects is under 18 years old 
2. 
Consent: Vulnerable subjects including those who are unable to consent 
3. 
Pregnancy: Pregnant or breastfeeding women 
4. 
ASA score <3 
5. 
Physical findings: Abnormal physical findings that may interfere with the 
study objectives 
Excluded lesions: 
• 
Lesions less than 11 mm in largest dimension 
• 
Lesions involving the muscularis propria (T2 lesions)  
• 
Ulcerated depressed lesions (Paris type III) or pathology proven invasive 
carcinoma 
• 
Proven malignant disease locally advanced or with metastasis 
• 
Active inflammatory bowel disease lesion, e.g ulcerative colitis, Crohn’s 
disease 
6. 
Endoscopic appearance of invasive malignancy 
7. 
Previous partial resection or attempted resection of the lesion 
8. 
Allergy: Proven or potential allergic reaction to study products or history of 
anaphylaxis to drugs  
9.     Severe liver disease.  


10. 
Known or suspected gastrointestinal obstruction or perforation, active 
diverticulitis, toxic megacolon, 
11.  
Inflammatory bowel disease e.g ulcerative colitis or Crohn’s disease 
12. 
Hemostasis disorders (eg Von Willebrand disease, factor V Leiden 
thrombophilia or haemophilia), known clotting disorder (INR>1.5). 
13. 
Subject with any other current serious medical conditions that would 
increase the risks associated with taking part in the study. 
14. 
Patients must be advised to stop anticoagulation medications prior to the 
procedure per local practice guidelines and should re-start as clinically 
indicated after the procedure. 
  
Visit 1 will be a screening appointment where the patient will be educated about 
the study and the informed consent document will be completed. The patient 
medical history will then be recorded, as well as current medications taken. The 
patient will also undergo a physical exam as standard of care. This visit can be 
combined with Visit 2 (Day of Procedure).  
During Visit 2, inclusion and exclusion criteria will again be confirmed and after 
the lesion has been measured and found to be ≥11mm and suitable for EMR, the 
patient will be randomized to the injectate.  Polyps will be documented by 
photographic record prior to randomization. The injectate will be prepared out of 
sight from the investigator performing the EMR so that the investigator will remain 
blinded to the injectate. Patient vital signs including BP, HR and SpO2 will be 
recorded prior to, during, and after the procedure. Once the lesion has been 
injected, only Boston Scientific Captivator snares measuring 15-20mm will be 
used to resect the polyps, however additional treatment modalities required will 
also be recorded. 
Visit 3 will consist of a follow up phone call 30 days±7 later. The occurrence or 
persistence of any adverse events will be recorded.  
 
Data integrity and safety: 
All paper charts pertaining to the patient will be kept under lock and key in 
coordinators office away from the endoscopy area. The data entry will be 
performed into an excel file which will be stored on an internal network drive with 
encryption and password security. Regular quality control checks of the data will 
be performed. Only approved personnel by the IRB will have access to the file 
storage. This file will also not have any identifiable information (name, DOB or 


mrn). A study log with the identifiable information will be kept in a separate folder 
(also encrypted) to enable the investigators to assist in any research audit. No 
procedural data except the date of examination will be entered into this log.  The 
data and safety will reviewed annually in addition to the continuous PI monitoring. 
Protocol revisions will be proposed, if needed, based on the results of the safety 
review including, but not limited to, stopping the randomization process. 
 
 
 
 
References: 
COSMO (2017). A randomized, double-blind, comparative, effectiveness and safety study of 
SIC 8000 in subjects undergoing Endoscopic Mucosal Resection (EMR) of 
colonic lesions equal to or larger than 2 cm