Complete Closure After Endoscopic Mucosal Resection of Large Non-Pedunculated Colorectal Polyps (Closure-RCT)

Complete Closure After Endoscopic Mucosal Resection of Large Non-Pedunculated Colorectal Polyps: a Randomized Controlled Trial

The goal of this clinical trial is to compare adverse even rates after EMR for large (≥20mm) flat colorectal polyps (so-called laterally spreading lesions, LSLs) when performing complete or no defect closure. It will also evaluate lesion recurrence after EMR for large colorectal LSLs.

The hypothesis is that performing complete defect closure following EMR of large colorectal LSLs will result in lower rates of adverse events compared to cases where no defect closure is performed.

For participants with planned EMR, endoscopists will perform EMRs as per standard of care and:

• prophylactic defect closure will either not be performed (control group), or will be performed (experimental group);
• then, patients will be called between 14 and 44 days after EMR to assess for possible adverse events, and electronic medical files will be verified for emergency room visits and healthcare received for an adverse event;
• finally, patients will undergo follow-up colonoscopy 6 months and 18 months after randomization.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Polyp of Colon
• Intervention / Treatment: Procedure: Prophylactic defect closure; Procedure: No prophylactic defect closure

Detailed Description

This trial is an open-label, two-arm, parallel-group, multicenter, randomized controlled superiority trial. Patients undergoing EMR will be randomized in a 1:1 ratio and assigned to undergo no closure (control group) vs complete defect closure (experimental group).

Participants with planned EMR procedures will be approached by a research assistant before the EMR to request study participation. To mitigate loss to follow-up, patients will be questioned on their preferred contact method with multiple contact methods obtained to adequately reach patients. The importance of follow-up after EMR to detect and treat recurrence will also be highlighted both verbally and in the consent forms during initial patient contact.

Despite being experienced, all endoscopist participants will review dedicated teaching videos showing the standardized EMR approach. Videos demonstrating key technical details defect closure will also be circulated across sites to ensure a standardized approach for both procedures as described in the literature.

- Control group: EMR will be performed as per standard of care with submucosal injection and electrocautery resection of all visually visible polyp tissue using a snare. After performing EMR with thermal ablation, prophylactic defect closure will not be performed. Endoscopists can chose to close defects if there are significant concerns for risk of perforation or active perforation after EMR. When the endoscopist determines that the resection is complete, a tattoo will be placed 3 cm distal to the resected lesion to allow for better identification of the resection site in case of follow-up colonoscopy for delayed bleeding. If multiple large polyps are found and removed, the largest lesion (study polyp) will be marked with two tattoos 3 cm distal and 3 cm proximal to the lesion, to clearly identify the study polyp resection site.

- Experimental group: EMR will be performed as per standard of care with submucosal injection and electrocautery resection of all visually visible polyp tissue using a snare.

After performing EMR with thermal ablation, prophylactic defect closure will be performed. The choice of the number and types of closure devices used to achieve defect closure will be left to endoscopist discretion. If multiple large polyps are found and removed, the largest lesion (study polyp) will be marked with two tattoos 3 cm distal and 3 cm proximal to the lesion, to clearly identify the study polyp resection site. As per standard of care, endoscopists will take a photograph of the lesion before resection for documentation; a photograph of the EMR resection site will be taken before and after defect closure; a photograph of the defect will be taken if emergency colonoscopy is performed to treat delayed bleeding. When more than one lesion meeting inclusion criteria is present in a patient, all lesions 20mm or larger will be photographed next to an open snare to aid in size measurement.

- 6-month & 18-month follow-up colonoscopies: To mitigate loss to follow-up, patients will be questioned on their preferred contact method with multiple contact methods obtained to adequately reach patients. The importance of follow-up after EMR to detect and treat recurrence will also be highlighted both verbally and in the consent forms during initial patient contact. Patients will be sent a reminder that they will soon receive an invitation to undergo follow-up through their preferred contact method. If patients do not undergo follow-up after invitation, a research assistant will contact patients by phone to answer any concerns they might have at that time.

At follow-up colonoscopies, endoscopists will identify the resection scar tangential to the tattoo placed at the initial EMR. The resection scars will be observed under white light and digital chromoendoscopy to assess for visual recurrence. For all patients, four random biopsies will be taken at the resection scar. If visual recurrence is present, the lesions will be resected using the method deemed most appropriate by the endoscopist at the time and pathologically evaluated for histologic recurrence.

• Study Type: Interventional
• Enrollment (Estimated): 686
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal
      • Contact: Samira Hanin; Phone Number: 30916 514-890-8000; Email: samira.hanin.chum@ssss.gouv.qc.ca
      • Contact: Daniel Von Renteln, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult ≥18 years old
• patients undergoing EMR for a large (≥20mm) colorectal LSL
• patients providing written and informed consent for study participation.

Exclusion Criteria:

• inflammatory bowel disease;
• non-elective colonoscopy;
• poor general health (American Society of Anesthesiologists classification >III);
• coagulopathy or thrombocytopenia (international normalized ratio ≥1.5 or platelets <50 x 109/L);
• pedunculated polyps (Paris class Ip, Isp);
• overt signs of deep submucosal invasive cancer (JNET 3);
• appendiceal orifice or terminal ileum invasion;
• pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic Mucosal Resection (EMR) + prophylactic defect closure (defect closure); Prophylactic defect closure will be performed using at least one new generation closure device.	Procedure: Prophylactic defect closure; Endoscopists will use at least one new generation closure device to approximate the healthy mucosal surrounding the submucosal defect to ensure complete defect closure. Adequate apposition of the mucosal defect margins will be achieved when no visible submucosal areas >3 mm along the closure line are present.
Active Comparator: Endoscopic Mucosal Resection (EMR); After performing EMR with thermal ablation, prophylactic defect closure will not be performed.	Procedure: No prophylactic defect closure; After performing EMR with thermal ablation, prophylactic defect closure will not be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed bleeding	Defined as blood per rectum resulting in emergency room visit, unplanned hospitalization; endoscopic, radiologic, or surgical intervention.	14 days
Delayed perforation	Defined as endoscopic or radiologic evidence of air or luminal contents outside the gastrointestinal tract	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any delayed bleeding	Defined as blood per rectum after the procedure	14 days
Clinically significant delayed bleeding in the proximal colon	Defined as proximal to the splenic flexure	14 days
Clinically significant delayed bleeding in the distal colon	The distal colon is defined as splenic flexure and distal	14 days
Lesion recurrence	Lesion recurrence at 6 months' follow-up defined by pathology-confirmed hyperplastic, serrated or adenomatous histology at the tattooed resection site	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Defect closure time	Time for defect closure	14 days
Technical success for complete defect closure	Defined as adequate apposition of the mucosal defect margins without visible submucosal areas >3 mm along the closure line	6 months
Procedure costs	Costs associated with procedures	18 months
Technical success of margin and/or base ablation	Defined as achieving a complete uninterrupted ring of circumferential margin ablation for margin ablation, and achieving 100% surface ablation of the resection base for base ablation	18 months
Colonoscopies required to achieve lesion clearance	Defined as no histologic recurrence at the resection scar on follow-up	18 months
Loss to follow-up	Number of patients lost to follow-up	18 months
EMR procedure time	Duration of the EMR procedure	During procedure
Margin and/or base ablation time	Duration of the margin and/or base ablation	During procedure

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: January 29, 2025
• First Submitted That Met QC Criteria: January 29, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Polyps; Polyps; Colonic Polyps
• Other Study ID Numbers: 2025-12350

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices).
• IPD Sharing Time Frame: Beginning 12 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Proposals should be directed to daniel.von.renteln.med@ssss.gouv.qc.ca . To gain access, data requestors will need to sign a data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No