Cold Snare Endoscopic Mucosal Resection Trial

Study Overview
=================
Brief Summary
-----------------
This study compares different approaches to endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (≥20mm) in a 2 x 2 randomized design. The first randomization will assign half of patients to polyp resection with electrocautery (hot snare EMR) and half of patient to polyp resection without electrocautery (cold snare EMR). The second randomization will assign half of patients to polyp removal using Eleview as the submucosal injection agent, and the other half using placebo (normal saline with methylene blue) as the submucosal injection agent.

Detailed Description
-----------------
Electrocautery, or hot snare resection has long been considered the standard approach to polyp resection. A major limitation is a 5 to 10% risk of major adverse events. Recent studies suggest that snare resection without electrocautery - so-called cold snare EMR - may be safer than hot snare EMR. The concern with cold snare resection is a potentially lower efficacy, because cold snare resection requires the removal of a large polyp in smaller and greater number of pieces than with hot snare resection. This may lengthen procedure time and increase the risk of incomplete resection. Furthermore, there is uncertainty about the optimal injection solution for lifting of the polyp prior to resection. Normal saline with methylene blue as the contrast agent is frequently used, but is limited by fast dissipation of the polyp lift. Eleview is a newly approved viscous solution (that contains methylene blue), which provides a longer polyp lift than normal saline. It is unclear how these two solutions compare with respect to resection efficacy and safety.

Official Title
-----------------
Cold Endoscopic Resection of Large Colorectal Polyps: A Randomized Trial

Conditions
-----------------
Colonic Polyp, Colonoscopy, Complication, Recurrence

Intervention / Treatment
-----------------
* Procedure: Cold snare EMR
* Procedure: Hot snare EMR
* Procedure: Eleview injection
* Procedure: Placebo injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any patient ≥18 who presents for a colonoscopy and who does not have criteria for exclusion Patients with a ≥20mm non-pedunculated colorectal polyp Exclusion Criteria: Pedunculated polyps (as defined by Paris Classification type Ip) Suspected adenocarcinoma with deep submucosal invasion Patients with ulcerated depressed lesions (as defined by Paris Classification type III) or confirmed adenocarcinoma 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 Inadequate bowel preparation (Boston Bowel Prep Scale, total score ≤2) Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: 2 x 2 randomized trial. First randomization: Among half of patients with a large polyp will be removed by electrocautery (hot) snare resection, and the other half will have their polyp removed by snare resection without electrocautery (cold). Second randomization: Among half of patients the large polyp will by lifted (submucosal injection before resection) with Eleview; among the other by Placebo (Normal Saline with Methylene Blue).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cold snare & Eleview injection<br>Polyp resection without electrocautery (cold snare EMR), and initial submucosal injection with Eleview | Procedure: Cold snare EMR<br>* Participants will have their large polyp removed without electrocautery<br>Procedure: Eleview injection<br>* Participants will have their polyp submucosally injected with Eleview<br>|
| Experimental: Cold Snare & Placebo injection<br>Polyp resection without electrocautery (cold snare EMR), and initial submucosal injection with Placebo | Procedure: Cold snare EMR<br>* Participants will have their large polyp removed without electrocautery<br>Procedure: Placebo injection<br>* Participants will have their polyp submucosally injected with placebo<br>|
| Active Comparator: Hot snare & Eleview injection<br>Polyp resection with electrocautery (hot snare EMR), and initial submucosal injection with Eleview | Procedure: Hot snare EMR<br>* Participants will have their large polyp removed with electrocautery<br>Procedure: Eleview injection<br>* Participants will have their polyp submucosally injected with Eleview<br>|
| Active Comparator: Hot snare & Placebo injection<br>Polyp resection with electrocautery (hot snare EMR), and initial submucosal injection with Placebo | Procedure: Hot snare EMR<br>* Participants will have their large polyp removed with electrocautery<br>Procedure: Placebo injection<br>* Participants will have their polyp submucosally injected with placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Adverse Events | Aggregate of all severe adverse events that occur at the time of the colonoscopy with resection of the large polyp or following the procedure | up to 30 days following the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subcategories of severe adverse events | Bleeding, post-polypectomy syndrome, perforation, abdominal pain | during the procedure and up to 30 days following the procedure | 
| Performance submucosal injectate | Injection performance | immediately following polyp resection during the colonoscopy | 
| Volume of submucosal injectate | volume of injection | immediately following polyp resection during the colonoscopy | 
| Efficacy of submucosal injectate | Sidney index | immediately following polyp resection during the colonoscopy | 
| Completeness of polyp resection | Complete polyp removal is defined as removal of all visible polyp tissue at the end of the EMR, as assessed by the endoscopist. | immediately following polyp resection during the colonoscopy | 
| Intraprocedural bleeding | bleeding that requires endoscopic intervention to stop the bleeding | at the time of polyp resection | 
| Polyp recurrence | Presence of biopsy proven neoplastic polyp tissue at the EMR resection site at surveillance colonoscopy following complete polyp resection | at surveillance colonoscopies up to 5 years following the initial polyp resection | 
| Crossover from cold to hot snare | Proportion of polyps in the cold snare group that could not be removed by cold snare and were removed by hot snare, categorized by size and morphology subtypes of polyps | at the time of polyp resection |