Clinical trial NCT04032119: RCT of Gastric ESD With or Without Epineprhine Added Solution
Official title: Multicenter Randomized Controlled Trial of Gastric Endoscopic Submucosal Dissection With or Without Epineprhine Added Solution
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Neoplasm
Early Gastric Cancer
Keywords: Gastric Endoscopic submucosal dissection
Epinephrine
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Osaka International Cancer Institute
name: Fukuoka University
name: Changi General Hospital
name: Kyoto 2nd Red Cross Hospital
name: Ishikawa Prefectural Central Hospital
name: Kosin University Gospel Hospital
name: Machida General Hospital
name: Nara City Hospital
name: Wakayama Red Cross Hospital
name: JCHO Osaka Hospital
name: Sapporo Kinentou hospital
name: Japan Community Healthcare Organization Osaka Hospital
First posted: 2019-07-25
Enrollment: 800
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall procedural time
timeFrame: During the endoscopic procedure
Secondary outcomes:
measure: Number of intra-procedural hemorrhage events
timeFrame: During the endoscopic procedure
measure: Maximum systolic blood pressure
timeFrame: During the endoscopic procedure
measure: Maximum heart rate
timeFrame: During the endoscopic procedure
measure: Adverse event - Delayed hemorrhage
timeFrame: 30 days
measure: Adverse event - Perforation
timeFrame: 30 days
measure: Adverse event - Cardiovascular event
timeFrame: 30 days
measure: Adverse event - Cerebrovascular event
timeFrame: 30 days
measure: Other adverse event
timeFrame: 30 days
measure: Pathology
timeFrame: During the endoscopic procedure
measure: Size of lesion
timeFrame: During the endoscopic procedure
measure: Depth of invasion
timeFrame: During the endoscopic procedure
measure: Vertical margin
timeFrame: During the endoscopic procedure
measure: Horizontal margin
timeFrame: During the endoscopic procedure
measure: Differentiation
timeFrame: During the endoscopic procedure
measure: Lymphovascular invasion
timeFrame: During the endoscopic procedure
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Ishikawa
country: Japan
facility: Ishikawa Prefecture Central Hospital
city: Kyoto
country: Japan
facility: Kyoto 2nd Red Cross Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Hon Chi Yip, MBChB, FRCSEd
role: PRINCIPAL_INVESTIGATOR
References: