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AzTrials

Gastric NeoplasmPhase 3NCT04032119

RCT of Gastric ESD With or Without Epineprhine Added Solution

A Phase 3 study testing Endoscopic submucosal dissection and Epinephrine in people with Gastric Neoplasm and Early Gastric Cancer, run by Chinese University of Hong Kong at 7 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Gastric Neoplasm, Early Gastric Cancer
What is being tested?
Endoscopic submucosal dissection and Epinephrine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
800 participants
Where
7 sitesin 4 countries
Study dates
10 Jan 2020to 31 Jan 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

7 sites in 4 countries.

7 sites in 4 countries

Japan4 sites

  • Ishikawa Prefecture Central Hospital

    Ishikawa

  • Kyoto 2nd Red Cross Hospital

    Kyoto

  • Osaka International Cancer Institute

    Osaka

  • Shizuoka Cancer Center

    Shizuoka

Other trials in Japan

Hong Kong1 site

  • The Chinese University of Hong Kong

    Hong Kong

Other trials in Hong Kong

Singapore1 site

  • Changi General Hospital

    Singapore

Other trials in Singapore

South Korea1 site

  • Kosin University Gospel Hospital

    Busan

Other trials in South Korea

About this study

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

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.

Read the 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.

Being tested
Endoscopic submucosal dissection, Epinephrine
Keywords
Gastric Endoscopic submucosal dissection, Epinephrine
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endoscopic submucosal dissectionProcedure or surgery

    Endoscopic submucosal dissection

  • EpinephrineDrug

    Epinephrine

Study groups in NCT04032119
Study groupRoleWhat they receive
EpinephrineExperimental0.2ml 1:10000 epinephrine diluted into each 20ml of the original solution for submucosal injection
Receives: Procedure: Endoscopic submucosal dissection; Drug: Epinephrine
Non-epinephrineActive comparatorNo epinephrine would be added into the solution
Receives: Procedure: Endoscopic submucosal dissection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall procedural time

    From the beginning of mucosal incision till the end of submucosal dissection, excluding time for prophylactic homeostasis

    Measured: During the endoscopic procedure

Secondary outcomes (15)

  1. Number of intra-procedural hemorrhage events

    The number of oozing or spurting bleeding events during a procedure, requiring hemostasis with coagulating forceps

    Measured: During the endoscopic procedure

  2. Maximum systolic blood pressure

    Maximum systolic blood pressure during ESD

    Measured: During the endoscopic procedure

  3. Maximum heart rate

    Maximum heart rate during ESD

    Measured: During the endoscopic procedure

  4. Adverse event - Delayed hemorrhage

    Delayed hemorrhage (Based on CTCAE definition)

    Measured: 30 days

  5. Adverse event - Perforation

    Perforation (Based on CTCAE definition)

    Measured: 30 days

  6. Adverse event - Cardiovascular event

    Cardiovascular event (Based on CTCAE definition)

    Measured: 30 days

  7. Adverse event - Cerebrovascular event

    Cerebrovascular event (Based on CTCAE definition)

    Measured: 30 days

  8. Other adverse event

    Based on CTCAE definition

    Measured: 30 days

  9. Pathology

    Final histology based on Vienna Classification

    Measured: During the endoscopic procedure

  10. Size of lesion

    Size of lesion

    Measured: During the endoscopic procedure

  11. Depth of invasion

    Depth of tumor invasion

    Measured: During the endoscopic procedure

  12. Vertical margin

    Vertical margin involvement

    Measured: During the endoscopic procedure

  13. Horizontal margin

    Horizontal margin involvement

    Measured: During the endoscopic procedure

  14. Differentiation

    Degree of differentiation for cancer of stomach

    Measured: During the endoscopic procedure

  15. Lymphovascular invasion

    Lymphovascular invasion on pathology

    Measured: During the endoscopic procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2019
  2. Study start10 Jan 2020
  3. Primary completion31 Dec 2022
  4. Study completion31 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
800 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04032119
Sponsor's protocol ID
EPI-ESD RCT01
Status last verified
Apr 2025
First submitted
23 Jul 2019
Last updated
4 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yip HC, Uedo N, Iwagami H, Waki K, Ohtsu K, Miyaoka M, Yao K, Akamatsu T, Konishi T, Nakano S, Nakanishi H, Doyama H, Machida H, Jung K, Chiu P, Iwasaki T, Uchita K, Kawamura T, Takizawa K, Kitamura Y, Li JW, Ang TL, Shimokawa T, Zhu Z, Yung MY. The use of diluted epinephrine during gastric endoscopic submucosal dissection: an international randomized controlled trial. Gastrointest Endosc. 2026 Sep;104(3):387-395.e1. doi: 10.1016/j.gie.2026.01.031. Epub 2026 Jan 29.

    PubMed 41620139

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Endoscopic submucosal dissection and Epinephrine in people with Gastric Neoplasm and Early Gastric Cancer, run by Chinese University of Hong Kong at 7 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Japan, Hong Kong, Singapore, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall procedural time (time frame: During the endoscopic procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04032119, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

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