EMR Versus ESD for Barrett's Neoplasia (REMOVE-RCT)

Endoscopic Mucosal Resection Versus Endoscopic subMucosal Dissection fOr Removal of Visible Lesions in Barrett's Esophagus With Early Neoplasia: a Randomized Controlled Trial

Rationale:

The optimal technique for removal of visible dysplastic lesions in Barrett's esophagus remains controversial. Endoscopic mucosal resection (EMR) is safe, effective, easy to apply, and has been the most widely used technique since 2008. Endoscopic submucosal dissection (ESD) is a more controlled dissection method with potential improved efficacy, but at the cost of higher technical complexity.

Objective:

The investigators aim to compare EMR and ESD for removal of visible lesions in Barrett's esophagus.

Study design:

Randomized clinical trial

Study population:

Patients with Barrett's esophagus and a visible lesion with dysplasia and/or early cancer. Suspicion for submucosal invasion is an exclusion criterion.

Intervention:

Patients are randomized to receive either EMR or ESD, with follow-up and no ablation during 12 months after the resection.

Main study endpoint:

Primary endpoint is the proportion of patients with no evidence of residual or local recurrent neoplasia during 12 months follow-up after baseline.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Cancer; Barrett Adenocarcinoma; Barretts Esophagus With Dysplasia
• Intervention / Treatment: Other: ESD; Other: EMR

• Study Type: Interventional
• Enrollment (Anticipated): 331
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age: ≥ 18 years
• Willingness to undergo both EMR or ESD
• Ability to provide written, informed consent (approved by IRB) and understand the responsibilities of trial participation
• BE with a single visible lesion with absence of signs of submucosal invasion on endoscopy, after evaluation by the adjudication committee.

Exclusion Criteria:

• Patients with visible lesions with suspicion of submucosal invasion bases on assessment of the adjudication committee
• History of esophageal surgery other than fundoplication
• History of esophageal ablation therapy or endoscopic resection
• Multiple visible lesions in the BE segment at baseline
• Uncontrolled coagulopathy with INR >2.0, thrombocytopenia with platelet counts < 50,000
• Subject has a known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions related to informed consent, post-treatment in-structions, or follow-up guidelines
• Life expectancy <2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endoscopic submucosal dissection	Other: ESD; Endoscopic submucosal dissection, according to standard care
Active Comparator: Endoscopic mucosal resection	Other: EMR; Endoscopic mucosal resection, according to standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary endpoint is the proportion of patients with no evidence of residual or local recurrent neoplasia during 12 months follow-up after baseline.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complications	. Complications will be assessed on patient level (yes/no) and chi-square test will be used to compare the outcomes between the study arms. In the case > 25% of patients have multiple complications, assessment will be performed on complication level (n per patient) using Poisson-regression analysis.	12 months
Procedure times	a skewed continuous variable that will be compared using the Mann-Whitney U test.	12 months
Proportion of patients with endoscopically radical resection	assessed during the ER endoscopy, a proportion that will be compared using the chi2 test or Fisher's exact if the number of patients in a single category is <5.	12 months
The total number of ER endoscopies per patient	This number will be compared using Poison regression analysis.	12 months
The proportion of patients that shows neoplastic progression	This will be compared with a chi2 test or Fisher's exact if the number of patients in a single category is <5, and this analyses will be stratified for moment of detection (i.e. at baseline or later during the study duration).	12 months
Cost-effectiveness	Cost-effectiveness will be calculated by efficacy of both procedures (absence of residual or recurrent disease) divided by total costs in Euro associated with the procedures	12 months
Additional histopathologic evaluation may be performed to evaluate potential differences between the two techniques.	Interobserver agreement between the two techniques will be evaluated with Cohen's kappa, as well as a subjective score on ease of assessment on a NRS score ranging from 0-10.	12 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: University Medical Center Groningen; UMC Utrecht; Erasmus Medical Center; Catharina Ziekenhuis Eindhoven; Amsterdam UMC, location VUmc; St. Antonius Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Barrett's esophagus; Esophagheal adenocarcinom
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus
• Other Study ID Numbers: 001 (NavyGHB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No