RCT of Gastric ESD With or Without Epineprhine Added Solution

The Chinese University of Hong Kong

Status and phase: Completed; Phase 3

Conditions: Early Gastric Cancer; Gastric Neoplasm

Treatments: Procedure: Endoscopic submucosal dissection; Drug: Epinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT04032119

EPI-ESD RCT01

Details and patient eligibility

About

This is an international multi-center randomised controlled study comparing outcomes of gastric endoscopic submucosal dissection (ESD) with or without addition of epinephrine in the submucosal injection solution.

Full description

Endoscopic submucosal dissection (ESD) is an endoscopic technique aiming to achieve en-bloc resection of mucosal neoplastic lesion in the gastrointestinal tract. It is now considered as the standard of treatment for early gastric cancer confined to the mucosa, achieving an excellent overall survival comparable to that of surgical resection.

Important adverse events associated with gastric ESD include hemorrhage (intraoperative or delayed) and perforation. The reported incidence of intraprocedural and delayed hemorrhage of gastric ESD is generally higher than that of esophageal or colorectal ESD5. This is likely due to the rich blood supply of the stomach penetrating from the muscularis to the submucosal layer. Bleeding during ESD would result in difficulty in visualizing the correct plane of dissection from blood clots obscuring view of the endoscope. As a result, prolonged procedural time may be required to achieve hemostasis and obtain adequate view for dissection.

There are currently different options of the solution for submucosal injection during gastric ESD. Epineprhine has often been added into these solutions with the aim of causing vasoconstrictive effect and potentially reduce bleeding during the procedure. The use of epinephrine has been recommended when removing larger pedunculated polyps with endoscopic mucosal resection (EMR)6. However the exact clinical benefit of adding epinephrine during gastric ESD has not been proven in the literature. On the other hand, when larger dose of epinephrine is absorbed systemically it may rarely cause significant tachycardia and generalized vasoconstriction, putting patients at risk of myocardial infarction or cerebrovascular accident.

A retrospective propensity score analysis was previously performed in one of our Japanese center (Presented at JGCA 2019, Shizuoka). After adjustment of important confounding factors including age, sex, tumor location, specimen size, depth of tumor invasion, presence of histological ulcer or scar and operators' experience, the addition of epinephrine into submucosal solution was associated with a significantly shorter procedural time upon multivariate analysis. The mean procedural time was 72±54 minutes versus 93±62 minutes with and without epinephrine respectively. (p<0.001) With the encouraging result from a single center retrospective study, we plan to conduct a prospective multicenter randomized controlled study to confirm the benefit of adding epinephrine into the submucosal solution during gastric ESD.

Enrollment: 800 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Selection criteria: Presence of intramucosal neoplastic lesions in the stomach planning for endoscopic submucosal dissection (Vienna Classification Category 3 and 4 lesion)
• Target subjects receiving sufficient briefing from the attending physician regarding the content of this study and providing informed consent for participation

Exclusion criteria

• Recurrent / remnant lesion after previous endoscopic resection
• Lesions arising from surgical anastomotic site, such as gastrojejunostomy / gastroduodenostomy.
• Marked electrolyte abnormalities
• Hemostatic or coagulative abnormalities
• Patient on anti-coagulant agents, including warfarin and other direct oral anti-coagulants (those on antiplatelet can be included)
• Failure of vital organ (heart, lungs, liver, or kidneys) function
• Allergic to components of injection solutions: Epinephrine, hyaluronic acid etc
• Other cases deemed by the examining physician as unsuitable for safe treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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800 participants in 2 patient groups

Epinephrine

Experimental group

Description:

0.2ml 1:10000 epinephrine diluted into each 20ml of the original solution for submucosal injection

Treatment:

Drug: Epinephrine

Procedure: Endoscopic submucosal dissection

Non-epinephrine

Active Comparator group

Description:

No epinephrine would be added into the solution

Treatment:

Procedure: Endoscopic submucosal dissection