Prophylactic Double Thermal Ablation After Endoscopic Mucosal Resection of Large Non-Pedunculated Colorectal Polyps

Colorectal Cancer Clinical Trial

— ABLATION  

Official title:

Prophylactic Double Thermal Ablation After Endoscopic Mucosal Resection of Large Non-Pedunculated Colorectal Polyps: A Randomized Controlled Trial - (ABLATION Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06271941
• Other study ID #: HAPC-RCT
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: April 1, 2028

Study information

• Verified date: June 2024
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Large (≥20mm) colorectal polyps often harbor areas of advanced neoplasia, making them immediate colorectal cancer (CRC) precursors. Such polyps have to be completely removed to prevent CRC and to avoid surgery and/or adjuvant therapy. The laterally spreading lesions (LSLs) are removed via endoscopic mucosal resection (EMR). However, recurrence is common. Recent studies have found that the use of hybrid argon plasma coagulation (h-APC) for the ablation of the margin and base of resection post-EMR could significantly reduce the recurrence rate, and complete closure of the post-EMR defect can prevent other adverse pre- and post-procedure outcomes such as bleeding.

It is hypothesized that hypothesize that performing hybrid argon plasma coagulation (h-APC) margin and base ablation post-EMR for large (≥20mm) colorectal LSLs will demonstrate a lower recurrence rate compared to Snare Tip Soft Coagulation (STSC) margin ablation. It is also hypothesized that performing complete closure of the EMR defect will result in lower rates of adverse events compared to cases where no defect closure is performed.

Description:

This is a prospective, randomized controlled trial enrolling patients with non-pedunculated colorectal polyps ≥ 20mm who are referred for endoscopic mucosal resection (EMR). All primary EMRs will be randomized to either EMR with hybrid argon plasma coagulation (h-APC) ablation of the base and margins or EMR with Snare Tip Soft Coagulation (STSC) margin ablation groups. Additionally, each group will be randomized to either complete defect closure or not.

Patients will be enrolled in the study before the endoscopy procedure, or in the outpatient clinic.

Eligible patients who have consented to participate in the study will be asked to take a standard colonoscopy preparation regimen before their scheduled procedure.

EMR intervention will be performed for all eligible patients with a large laterally spreading lesions (LSLs) by expert endoscopists. Only if a polyp meets inclusion criteria, the study subject will be enrolled and randomized into one of these four groups:

• Group 1: EMR + h-APC margin and base thermal ablation

• Group 2: EMR + STSC of the margin

The standard EMR technique will be used for the primary removal of all polyps. Submucosal injection will be used to lift the polyp from the muscularis propria. Injection will be used as per the current standard of care using a contrast agent and a lifting agent (e.g., NaCl 0.9% or Voluven). Snare electrocautery resection will be facilitated until complete visible removal of the complete polyp. Electrocautery snare technique will be facilitated using standard microprocessor-controlled electrocautery. If residual polyp tissue cannot be removed by a snare, other means such as cold snare (i.e., for small residual polyp tissue that cannot be engaged into standard snares) or avulsive methods will be used. After the complete removal of the polyp, depending on the randomization group, h-APC or STSC techniques will be used for margin and base or only margin ablation of the post-EMR defect.

The polypectomy site will be tattooed with submucosal injection of approximately 1-2cc of India ink (standard of care to mark lesions) to allow recognition of the polypectomy site during follow-up endoscopy. Polyps will be sent to the pathology lab and evaluated according to standard practice by institutional pathologists. To determine the homogeneity and depth of h-APC margin ablation in the pathology lab, some ablated margins might be resected using the standard cold snare technique.

Telephone calls at 20-30 days following the EMR will be conducted to assess possible adverse events.

Follow-up 1: Surveillance colonoscopy at 6 months (± 2 months) after the EMR intervention for the assessment of recurrence (biopsy from the post-EMR site to be confirmed by pathology) following the intervention (h-APC) and the control (STSC) techniques.

Follow-up 2: Surveillance colonoscopy at 18 months (± 2 months) after the EMR intervention for the assessment of recurrence (biopsy from the post-EMR site to be confirmed by pathology) at FU1.

Patients with visible recurrence at the EMR site will undergo additional resection for complete eradication of recurrence. Patients with no visible but pathology-confirmed recurrence will be rescheduled for another colonoscopy with subsequent treatment of the post-EMR site and another follow-up colonoscopy for biopsies and confirmation of complete/incomplete eradication within 18 months after the initial EMR.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 892
• Est. completion date: April 1, 2028
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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);

• biopsy proven invasive carcinoma in a potential study polyp.

Related Conditions & MeSH terms

• Colonic Polyps
• Colorectal Cancer
• Polyp of Colon
• Polyps

Intervention

Procedure:
• Hybrid Argon Plasma Coagulation (h-APC)
The hybrid argon plasma coagulation (h-APC) combines an ablation technique (APC) with the option for submucosal saline injection using a high-pressure water jet. The technique allows for the lifting of dysplastic epithelium, creating a cushion under the mucosa to facilitate the ablation of larger areas more thoroughly and with higher energy settings, while posing a low risk for side effects or complications.
• Snare tip soft coagulation (STSC)
The Snare tip soft coagulation (STSC) involves using a snare to remove polyps, while simultaneously applying soft coagulation to the surrounding tissue using a specialized tip on the snare.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinically significant delayed bleeding after EMR with STSC or h-APC	Defined as blood per rectum resulting in emergency room visit, unplanned hospitalization; endoscopic, radiologic, or surgical intervention.	30 days
Other	Clinically significant delayed bleeding in the proximal colon after EMR with STSC or h-APC	Defined as blood per rectum resulting in emergency room visit, unplanned hospitalization; endoscopic, radiologic, or surgical intervention. Proximal defined as proximal to the splenic flexure.	30 days
Other	Delayed perforation after EMR with STSC or h-APC	Delayed perforation defined as endoscopic or radiologic evidence of air or luminal contents outside the gastrointestinal tract	30 days
Other	Factors associated with recurrence after colorectal EMR between the h-APC and STSC methods	Lesion recurrence at first follow-up after EMR of large (=20mm) colorectal LSLs when performing STSC margin ablation or h-APC margin and base ablation. Defined by pathology-confirmed hyperplastic, serrated or adenomatous histology of the same histology of the index lesion at the tattooed resection site on at least one of four random biopsies of resection scars. Factors such as age, sex, lesion size (20-29mm, =30mm; 20-39mm, =40mm), histology, location, difficulty (difficult defined as peri-appendiceal, on the ileocecal valve, resection previously attempted and failed by a referring endoscopist), use of epinephrine in submucosal injection, submucosal lifting solution, resection type (en bloc [i.e. in one piece] vs piecemeal), technical success, study site, endoscopist yearly EMR volume, presence of intraprocedural bleeding, utilization of adjunct resection methods, ileocecal or anus involvement, polyp histology/morphology will be evaluated.	4 years
Other	Factors associated with adverse event rates after EMR with STSC or h-APC	Adverse event rates after EMR of large (=20mm) colorectal LSLs when performing EMR with STSC margin ablation or h-APC margin and base ablation. Defined as either a) delayed bleeding (defined as blood per rectum resulting in emergency room visit, unplanned hospitalization; endoscopic, radiologic, or surgical intervention) or b) delayed perforation (defined as endoscopic or radiologic evidence of air or luminal contents outside the gastrointestinal tract). Factors such as age, sex, lesion size, morphology, histology, location, complete/incomplete/no defect closure, prophylactic vessel ablation, base ablation, anticoagulant use will be evaluated	30 days
Primary	Recurrence after colorectal EMR between the h-APC and STSC methods	Lesion recurrence at first follow-up after EMR of large (=20mm) colorectal LSLs when performing STSC margin ablation or h-APC margin and base ablation. Defined by visual recurrence or pathology-confirmed hyperplastic, serrated or adenomatous histology of the same histology of the index lesion at the tattooed resection site on at least one of four random biopsies of resection scars. These will be evaluated from an intention to treat and per protocol standpoint.	4 years
Secondary	Adverse event rates after EMR with STSC or h-APC	Adverse event rates after EMR of large (=20mm) colorectal LSLs when performing EMR with STSC margin ablation or h-APC margin and base ablation. Defined as either a) delayed bleeding (defined as blood per rectum resulting in emergency room visit, unplanned hospitalization; endoscopic, radiologic, or surgical intervention) or b) delayed perforation (defined as endoscopic or radiologic evidence of air or luminal contents outside the gastrointestinal tract). These will be evaluated from an intention to treat and per protocol standpoint.	4 years
Secondary	Technical success of STSC or h-APC	Technical success of STSC or h-APC defined as achieving a complete uninterrupted ring ofcircumferential margin ablation for STSC and h-APC, without crossover to complete the margin ablation, and achieving 100% surface ablation of the resection base for h-APC.	4 years
Secondary	Lesion recurrence at the 18-month follow-up after EMR with STSC or h-APC	Lesion recurrence at the 18-month follow-up after EMR with STSC or h-APC	4 years
Secondary	High-grade dysplasia or colorectal cancer occurence after EMR during the 18-month follow-up period.	High-grade dysplasia or colorectal cancer occurence after EMR during the 18-month follow-up period at the resection site.	4 years