RCT of Gastric ESD With or Without Epineprhine Added Solution

Early Gastric Cancer Clinical Trial

Official title:

Multicenter Randomized Controlled Trial of Gastric Endoscopic Submucosal Dissection With or Without Epineprhine Added Solution

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04032119
• Other study ID #: EPI-ESD RCT01
• Status: Completed
• Phase: Phase 3
• Start date: January 10, 2020
• Est. completion date: January 31, 2023

Study information

• Verified date: February 2023
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: January 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Early Gastric Cancer
• Gastric Neoplasm
• Stomach Neoplasms

Intervention

Procedure:
• Endoscopic submucosal dissection
Endoscopic submucosal dissection

Drug:
• Epinephrine
Epinephrine

Locations

Country	Name	City	State
Hong Kong	The Chinese University of Hong Kong	Hong Kong
Japan	Ishikawa Prefecture Central Hospital	Ishikawa
Japan	Kyoto 2nd Red Cross Hospital	Kyoto
Japan	Osaka International Cancer Institute	Osaka
Japan	Shizuoka Cancer Center	Shizuoka
Korea, Republic of	Kosin University Gospel Hospital	Busan
Singapore	Changi General Hospital	Singapore

Sponsors (14)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Changi General Hospital, Fukuoka University, Ishikawa Prefectural Central Hospital, Japan Community Healthcare Organization Osaka Hospital, JCHO Osaka Hospital, Kosin University Gospel Hospital, Kyoto 2nd Red Cross Hospital, Machida General Hospital, Nara City Hospital, Osaka International Cancer Institute, Sapporo Kinentou hospital, Shizuoka Cancer Center, Wakayama Red Cross Hospital

Countries where clinical trial is conducted

Hong Kong,  Japan,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall procedural time	From the beginning of mucosal incision till the end of submucosal dissection, excluding time for prophylactic homeostasis	During the endoscopic procedure
Secondary	Number of intra-procedural hemorrhage events	The number of oozing or spurting bleeding events during a procedure, requiring hemostasis with coagulating forceps	During the endoscopic procedure
Secondary	Maximum systolic blood pressure	Maximum systolic blood pressure during ESD	During the endoscopic procedure
Secondary	Maximum heart rate	Maximum heart rate during ESD	During the endoscopic procedure
Secondary	Adverse event - Delayed hemorrhage	Delayed hemorrhage (Based on CTCAE definition)	30 days
Secondary	Adverse event - Perforation	Perforation (Based on CTCAE definition)	30 days
Secondary	Adverse event - Cardiovascular event	Cardiovascular event (Based on CTCAE definition)	30 days
Secondary	Adverse event - Cerebrovascular event	Cerebrovascular event (Based on CTCAE definition)	30 days
Secondary	Other adverse event	Based on CTCAE definition	30 days
Secondary	Pathology	Final histology based on Vienna Classification	During the endoscopic procedure
Secondary	Size of lesion	Size of lesion	During the endoscopic procedure
Secondary	Depth of invasion	Depth of tumor invasion	During the endoscopic procedure
Secondary	Vertical margin	Vertical margin involvement	During the endoscopic procedure
Secondary	Horizontal margin	Horizontal margin involvement	During the endoscopic procedure
Secondary	Differentiation	Degree of differentiation for cancer of stomach	During the endoscopic procedure
Secondary	Lymphovascular invasion	Lymphovascular invasion on pathology	During the endoscopic procedure