Esomeprazole Plus Sucralfate for Post-ESD Ulcer Healing (ESUS-ESD)

Intravenous Esomeprazole Combined With Sucralfate Suspension for Ulcer Healing and Complication Prevention After Gastric Endoscopic Submucosal Dissection: A Prospective, Randomized, Controlled Trial

Endoscopic submucosal dissection (ESD) is an established treatment for early gastric cancer and precancerous lesions. Post-ESD artificial ulcers may lead to complications including delayed bleeding (3-15%) and prolonged healing. Current guidelines recommend high-dose proton pump inhibitors (PPIs), but evidence for additional mucosal protective agents remains limited.

This study aims to evaluate whether combining sucralfate suspension with standard intravenous esomeprazole therapy improves ulcer healing and reduces complications after gastric ESD compared to esomeprazole alone.

This is a prospective, randomized, controlled, outcome-assessor-blinded trial. A total of 120 patients undergoing gastric ESD will be randomly assigned 1:1 to receive either:

• Intervention group: Intravenous esomeprazole 40mg twice daily (3 days) followed by oral esomeprazole 40mg once daily PLUS sucralfate suspension 1g twice daily for 8 weeks
• Control group: Intravenous esomeprazole 40mg twice daily (3 days) followed by oral esomeprazole 40mg once daily for 8 weeks The primary outcome is ulcer reduction rate at 4 weeks post-ESD, assessed by endoscopy. Secondary outcomes include complete ulcer healing rate at 8 weeks, delayed bleeding rate, symptom scores, and safety parameters.

This study will provide high-quality evidence regarding the role of sucralfate as an adjunctive therapy for post-ESD ulcer management and may inform future clinical guidelines.

Study Overview

• Status: Not yet recruiting
• Conditions: Early Gastric Cancer; Gastric Ulcer; Gastric Neoplasms; Gastric Dysplasia; Peptic Ulcer With Haemorrhage
• Intervention / Treatment: Drug: Esomeprazole (Intravenous); Drug: Esomeprazole (Oral); Drug: Sucralfate Suspension; Procedure: Gastric Endoscopic Submucosal Dissection (ESD)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qiangqiang Tian; Phone Number: 86+15009460497; Email: tianqq2023@lzu.edu.cn
• Study Contact Backup: Name: Zhaofeng Chen; Phone Number: 86+15009460497; Email: zhfchen@lzu.edu.cn

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
      • Contact: Qiangqiang Tian; Phone Number: 86+15009460497; Email: tianqq2023@lzu.edu.cn
      • Contact: Email: tianqq2023@lzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 years, male or female
2. Diagnosed with early gastric cancer or high-grade intraepithelial neoplasia planned for gastric ESD
3. Lesion location: Gastric corpus, antrum, or angle (cardiac lesions may be included but will require subgroup analysis)
4. Successful en bloc resection achieved by ESD
5. Post-ESD artificial ulcer diameter ≥2 cm
6. Complete coagulation of all visible vessels during ESD procedure
7. ECOG performance status 0-1
8. Able to comply with follow-up visits and endoscopic examinations
9. Voluntary participation with written informed consent

Exclusion Criteria:

1. Previous gastric surgery history
2. Active peptic ulcer disease (confirmed by pre-ESD endoscopy) within 1 month
3. Recent upper gastrointestinal bleeding (within 1 month, excluding tumor-related bleeding)
4. Severe heart, liver, or kidney dysfunction (Child-Pugh class C, NYHA class III-IV, or CKD stage 4-5)
5. Coagulation disorders (INR >1.5 or platelet count <50×10⁹/L)
6. Uncontrolled diabetes (HbA1c >9%)
7. Known allergy or hypersensitivity to PPIs or sucralfate
8. Use of PPIs, H2 receptor antagonists, or mucosal protective agents within 2 weeks prior to ESD
9. Long-term anticoagulant therapy that cannot be discontinued (e.g., warfarin, direct oral anticoagulants)
10. Long-term NSAIDs or aspirin (>100mg/day) that cannot be discontinued
11. Unsuccessful complete (en bloc) resection (piecemeal resection)
12. Intraoperative perforation
13. Uncontrolled active bleeding during ESD
14. Pregnancy or lactation
15. Women of childbearing potential not using adequate contraception
16. Concurrent participation in another clinical trial
17. Any condition that, in the investigator's opinion, makes the patient unsuitable for study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esomeprazole + Sucralfate (Intervention Group); Days 1-3: Esomeprazole 40mg intravenously every 12 hours; Days 4-56: Esomeprazole 40mg orally once daily (before breakfast) + Sucralfate suspension 1g orally twice daily (1 hour before breakfast and at bedtime on empty stomach)	Drug: Esomeprazole (Intravenous); Esomeprazole 40mg intravenously every 12 hours for 3 days (Days 1-3 post-ESD); Other Names: Esomeprazole Sodium; Drug: Esomeprazole (Oral); Esomeprazole 40mg orally once daily, taken before breakfast, for 8 weeks (Days 4-56); Other Names: Esomeprazole Magnesium; Drug: Sucralfate Suspension; Sucralfate suspension 1g (one sachet) orally twice daily for 8 weeks. Administered 1 hour before breakfast and at bedtime on empty stomach (2-3 hours after dinner). Should be taken separately from other medications (≥1-2 hours apart).; Procedure: Gastric Endoscopic Submucosal Dissection (ESD); Standardized gastric ESD procedure including lesion marking, submucosal injection, circumferential incision, submucosal dissection, and complete coagulation of all visible vessels at the ulcer base.
Active Comparator: Esomeprazole Alone (Control Group); Days 1-3: Esomeprazole 40mg intravenously every 12 hours; Days 4-56: Esomeprazole 40mg orally once daily (before breakfast)	Drug: Esomeprazole (Intravenous); Esomeprazole 40mg intravenously every 12 hours for 3 days (Days 1-3 post-ESD); Other Names: Esomeprazole Sodium; Drug: Esomeprazole (Oral); Esomeprazole 40mg orally once daily, taken before breakfast, for 8 weeks (Days 4-56); Other Names: Esomeprazole Magnesium; Procedure: Gastric Endoscopic Submucosal Dissection (ESD); Standardized gastric ESD procedure including lesion marking, submucosal injection, circumferential incision, submucosal dissection, and complete coagulation of all visible vessels at the ulcer base.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ulcer Reduction Rate at 4 Weeks Post-ESD	The percentage reduction in ulcer area from baseline (immediately post-ESD) to 4 weeks, calculated as: Ulcer Reduction Rate (%) = [(Baseline ulcer area - Week 4 ulcer area) / Baseline ulcer area] × 100	4 weeks after ESD procedure (±3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ulcer Reduction Rate at 8 Weeks Post-ESD	Same calculation method as primary outcome, assessed at 8 weeks	8 weeks after ESD procedure (±3 days)
Ulcer Stage at 4 Weeks (Sakita Classification)	Classification of ulcer healing stage according to Sakita classification: A1 (active with thick coat), A2 (healing with thinning coat), H1 (healing with regenerating epithelium, red), H2 (healing with thickened epithelium, red fading), S1 (scar stage, red), S2 (scar stage, white). Assessed by blinded endoscopists.	4 weeks after ESD procedure (±3 days)
Complete Ulcer Healing Rate at 8 Weeks	Proportion of patients achieving complete ulcer healing defined as scar stage (S1 or S2) on Sakita classification at 8 weeks post-ESD	8 weeks after ESD procedure (±3 days)
Incidence of Delayed Bleeding	Occurrence of delayed post-ESD bleeding defined as: hematemesis or melena accompanied by hemoglobin decrease ≥2 g/dL, or requiring blood transfusion or endoscopic hemostatic intervention. Time of bleeding occurrence will be recorded.	From 24 hours post-ESD up to 8 weeks
Change in Epigastric Pain Score	Severity of epigastric pain assessed using Visual Analog Scale (VAS) ranging from 0 (no pain) to 10 (worst imaginable pain). Change from baseline at each time point will be calculated.	Baseline (Day 0), Day 7, Week 4, and Week 8
Change in Bloating Score	Severity of bloating assessed using Visual Analog Scale (VAS) ranging from 0 (no bloating) to 10 (worst imaginable bloating). Change from baseline at each time point will be calculated.	Baseline (Day 0), Day 7, Week 4, and Week 8
Change in Acid Reflux Score	Severity of acid reflux assessed using Visual Analog Scale (VAS) ranging from 0 (no reflux) to 10 (worst imaginable reflux). Change from baseline at each time point will be calculated.	Baseline (Day 0), Day 7, Week 4, and Week 8
Change in Quality of Life Score	Quality of life assessed using EQ-5D-5L questionnaire, which evaluates five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with five levels each, plus a visual analog scale (0-100). Change from baseline will be calculated.	Baseline (Day 0), Week 4, and Week 8
Rate of Rehospitalization Due to ESD-Related Complications	Proportion of patients requiring rehospitalization due to post-ESD complications including delayed bleeding, severe pain, or other ESD-related adverse events	From Day 0 through Week 8
Need for Endoscopic Hemostatic Intervention	Proportion of patients requiring emergency or urgent endoscopic hemostatic procedures (such as hemoclipping, coagulation, or injection therapy) for post-ESD bleeding	From Day 0 through Week 8
Incidence of Adverse Events	Frequency and severity of all adverse events and serious adverse events, categorized by organ system and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	From Day 0 through Week 8
Medication Compliance Rate	Percentage of prescribed medication doses actually taken by the patient, calculated as: (Actual medication days / Expected medication days) × 100%. Assessed using medication diary and pill/sachet count. Compliance ≥80% will be considered good.	Throughout 8-week treatment period

Collaborators and Investigators

• Sponsor: LanZhou University

Publications and helpful links

General Publications

• Pimentel-Nunes P, Libanio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, Esposito G, Lemmers A, Maselli R, Messmann H, Pech O, Pioche M, Vieth M, Weusten BLAM, van Hooft JE, Deprez PH, Dinis-Ribeiro M. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2022 Jun;54(6):591-622. doi: 10.1055/a-1811-7025. Epub 2022 May 6.
• Tanaka S, Terasaki M, Kanao H, Oka S, Chayama K. Current status and future perspectives of endoscopic submucosal dissection for colorectal tumors. Dig Endosc. 2012 May;24 Suppl 1:73-9. doi: 10.1111/j.1443-1661.2012.01252.x.
• Takeuchi T, Ota K, Harada S, Edogawa S, Kojima Y, Tokioka S, Umegaki E, Higuchi K. The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection. BMC Gastroenterol. 2013 Sep 6;13:136. doi: 10.1186/1471-230X-13-136.

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 17, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Cancer; Endoscopic Submucosal Dissection; Proton Pump Inhibitor; Ulcer Healing; Post-ESD Ulcer; Early Gastric Neoplasm
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Hemorrhage; Duodenal Diseases; Peptic Ulcer; Gastrointestinal Hemorrhage; Pathological Conditions, Signs and Symptoms; Stomach Neoplasms; Stomach Ulcer; Peptic Ulcer Hemorrhage; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Omeprazole; Esomeprazole
• Other Study ID Numbers: LDYYczf2025121701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No