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RCT of Gastric ESD With or Without Epineprhine Added Solution

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ClinicalTrials.gov Identifier: NCT04032119
Recruitment Status : Recruiting
First Posted : July 25, 2019
Last Update Posted : December 20, 2019
Sponsor:
Collaborators:
Osaka International Cancer Institute
Shizuoka Cancer Center
Fukuoka University
Changi General Hospital
Kyoto 2nd Red Cross Hospital
Ishikawa Prefectural Central Hospital
Kosin University Gospel Hospital
Information provided by (Responsible Party):
Hon Chi Yip, Chinese University of Hong Kong

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.

Condition or disease Intervention/treatment Phase
Gastric Neoplasm Early Gastric Cancer Procedure: Endoscopic submucosal dissection Drug: Epinephrine Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter Randomized Controlled Trial of Gastric Endoscopic Submucosal Dissection With or Without Epineprhine Added Solution
Estimated Study Start Date : January 10, 2020
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : June 30, 2022


Arm Intervention/treatment
Experimental: Epinephrine
0.2ml 1:10000 epinephrine diluted into each 20ml of the original solution for submucosal injection
Procedure: Endoscopic submucosal dissection
Endoscopic submucosal dissection

Drug: Epinephrine
Epinephrine

Active Comparator: Non-epinephrine
No epinephrine would be added into the solution
Procedure: Endoscopic submucosal dissection
Endoscopic submucosal dissection




Primary Outcome Measures :
  1. Overall procedural time [ Time Frame: During the endoscopic procedure ]
    From the beginning of mucosal incision till the end of submucosal dissection, excluding time for prophylactic homeostasis


Secondary Outcome Measures :
  1. Number of intra-procedural hemorrhage events [ Time Frame: During the endoscopic procedure ]
    The number of oozing or spurting bleeding events during a procedure, requiring hemostasis with coagulating forceps

  2. Maximum systolic blood pressure [ Time Frame: During the endoscopic procedure ]
    Maximum systolic blood pressure during ESD

  3. Maximum heart rate [ Time Frame: During the endoscopic procedure ]
    Maximum heart rate during ESD

  4. Adverse event - Delayed hemorrhage [ Time Frame: 30 days ]
    Delayed hemorrhage (Based on CTCAE definition)

  5. Adverse event - Perforation [ Time Frame: 30 days ]
    Perforation (Based on CTCAE definition)

  6. Adverse event - Cardiovascular event [ Time Frame: 30 days ]
    Cardiovascular event (Based on CTCAE definition)

  7. Adverse event - Cerebrovascular event [ Time Frame: 30 days ]
    Cerebrovascular event (Based on CTCAE definition)

  8. Other adverse event [ Time Frame: 30 days ]
    Based on CTCAE definition

  9. Pathology [ Time Frame: During the endoscopic procedure ]
    Final histology based on Vienna Classification

  10. Size of lesion [ Time Frame: During the endoscopic procedure ]
    Size of lesion

  11. Depth of invasion [ Time Frame: During the endoscopic procedure ]
    Depth of tumor invasion

  12. Vertical margin [ Time Frame: During the endoscopic procedure ]
    Vertical margin involvement

  13. Horizontal margin [ Time Frame: During the endoscopic procedure ]
    Horizontal margin involvement

  14. Differentiation [ Time Frame: During the endoscopic procedure ]
    Degree of differentiation for cancer of stomach

  15. Lymphovascular invasion [ Time Frame: During the endoscopic procedure ]
    Lymphovascular invasion on pathology



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04032119


Contacts
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Contact: Hon Chi Yip, MBChB, FRCSEd (Gen) +85235052627 hcyip@surgery.cuhk.edu.hk
Contact: Noriya Uedo, MD noriya.uedo@gmail.com

Locations
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Hong Kong
The Chinese University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Hon Chi Yip, MBChB, FRCSEd (Gen)    +85235052627    hcyip@surgery.cuhk.edu.hk   
Japan
Ishikawa Prefecture Central Hospital Not yet recruiting
Ishikawa, Japan
Contact: Hisashi Doyama       doyama.134@gmail.com   
Kyoto 2nd Red Cross Hospital Not yet recruiting
Kyoto, Japan
Contact: Takuji Kawamura       kawamura_takuji@yahoo.co.jp   
Osaka International Cancer Institute Not yet recruiting
Osaka, Japan
Contact: Noriya Uedo       uedou-no@mc.pref.osaka.jp   
Shizuoka Cancer Center Not yet recruiting
Shizuoka, Japan
Contact: Kohei Takizawa       k.takizawa@scchr.jp   
Korea, Republic of
Kosin University Gospel Hospital Not yet recruiting
Busan, Korea, Republic of
Contact: Kyoungwon Jung       forjkw@gmail.com   
Singapore
Changi General Hospital Not yet recruiting
Singapore, Singapore
Contact: James Weiquan Li       james.li.w.q@singhealth.com.sg   
Sponsors and Collaborators
Chinese University of Hong Kong
Osaka International Cancer Institute
Shizuoka Cancer Center
Fukuoka University
Changi General Hospital
Kyoto 2nd Red Cross Hospital
Ishikawa Prefectural Central Hospital
Kosin University Gospel Hospital
Investigators
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Principal Investigator: Hon Chi Yip, MBChB, FRCSEd Chinese University of Hong Kong

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Responsible Party: Hon Chi Yip, Associate Consultant, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT04032119    
Other Study ID Numbers: EPI-ESD RCT01
First Posted: July 25, 2019    Key Record Dates
Last Update Posted: December 20, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Hon Chi Yip, Chinese University of Hong Kong:
Gastric Endoscopic submucosal dissection
Epinephrine
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Epinephrine
Racepinephrine
Epinephryl borate
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Pharmaceutical Solutions
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents