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Patients with EV bleeding often suffered from hematemesis, Tarry stool, and blood loss. Standard treatment for bleeding esophageal varices includes hemodynamic stabilization, pharmacological control, and endoscopic intervention. For endoscopic intervention, endoscopic variceal ligation (EVL) is the first-line therapy with 95% initial hemostasis success rate. However, after variceal ligation, esophageal ulcers form 3 days later. These ulcers expose underlying vessels in friable esophageal mucosa, exacerbated by portal hypertension and coagulopathy in cirrhosis patients. Bleeding peaks around day 5-10 when bands detach. Among these patients, 7-9% of patients experience recurrent bleeding as a result. Recurrent bleeding from esophageal ulcers carries an extremely high mortality rate, particularly in patients with advanced stage cirrhosis. Therefore, how to promote esophageal ulcer healing and prevent ulcer rebleeding is an important clinical issue.
Proton pump inhibitors (PPIs) are the primary drugs for preventing and treating gastric ulcers, but clinical evidence for their role in preventing post-ligation esophageal ulcers is insufficient. Sucralfate, a complex of aluminum hydroxide and sucrose octa sulfate, can bind to the wound base. This protective barrier can prevent the wound from further environmental injury. Sucralfate has been widely used for wounds and ulcer treatment, e.g., skin wounds, oral ulcers, and peptic ulcers. Our recent clinical trial also proved topical sucralfate can prevent postpolypectomy bleeding. Therefore, this study aimed to investigate whether the topical administration of sucralfate after standard endoscopic hemostasis can promote the esophageal ulcer healing and reduce the rebleeding event.
Liver cirrhosis is with high prevalence in Taiwan at around 1-2% of the adult population. Cirrhosis scars the liver, obstructing blood flow through the portal vein and raising pressure, so collateral veins dilate in the lower third esophagus. As a result, liver cirrhosis commonly leads to esophageal varices (EV) through portal hypertension. Up to 80-90% of cirrhotic patients develop varices. Esophageal varices may rupture and bleed when hepatic venous pressure gradient exceeds 12 mmHg. About one-third cirrhosis patients suffer from EV bleeding, which is associated with high mortality per episode and high rebleeding rates.
Patients with EV bleeding often suffered from hematemesis, Tarry stool, and blood loss. Standard treatment for bleeding esophageal varices includes hemodynamic stabilization, pharmacological control, and endoscopic intervention. For endoscopic intervention, endoscopic variceal ligation (EVL) is the first-line therapy with 95% initial hemostasis success rate. However, after variceal ligation, esophageal ulcers form 3 days later. These ulcers expose underlying vessels in friable esophageal mucosa, exacerbated by portal hypertension and coagulopathy in cirrhosis patients. Bleeding peaks around day 5-10 when bands detach. Among these patients, 7-9% of patients experience recurrent bleeding as a result. Recurrent bleeding from esophageal ulcers carries an extremely high mortality rate, particularly in patients with advanced stage cirrhosis. Therefore, how to promote esophageal ulcer healing and prevent ulcer rebleeding is an important clinical issue.
Proton pump inhibitors (PPIs) are the primary drugs for preventing and treating gastric ulcers, but clinical evidence for their role in preventing post-ligation esophageal ulcers is insufficient. Sucralfate, a complex of aluminum hydroxide and sucrose octa sulfate, can bind to the wound base. This protective barrier can prevent the wound from further environmental injury. Sucralfate has been widely used for wounds and ulcer treatment, e.g., skin wounds, oral ulcers, and peptic ulcers. Our recent clinical trial also proved topical sucralfate can prevent postpolypectomy bleeding. Therefore, this study aimed to investigate whether the topical administration of sucralfate after standard endoscopic hemostasis can promote the esophageal ulcer healing and reduce the rebleeding event.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention Group | Experimental | After the standard endoscopic EV ligation, patients will be randomly assigned to either a standard group (ST group) or an intervention group (ET group). After then, 3g of sucralfate powder will be delivered through the endoscopy precisely on the EV ligation bands in the intervention group. Followingly, patients in the intervention group will receive oral sucralfate suspension 1g four times a day for 5 days. On the 5th day after EV ligation, all enrolled patients will receive a 2nd-look endoscopy to evaluate the esophageal ulcers and the status of esophageal varices. |
|
| Standard group | No Intervention | After the standard endoscopic EV ligation, patients will be randomly assigned to either a standard group (ST group) or an intervention group (ET group). On the 5th day after EV ligation, all enrolled patients will receive a 2nd-look endoscopy to evaluate the esophageal ulcers and the status of esophageal varices. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sucralfate | Drug | 3g of sucralfate powder through the endoscopy precisely on the EV ligation bands in the intervention group. Followingly, patients in the intervention group will receive oral sucralfate suspension 1g four times a day for 5 days. |
| Measure | Description | Time Frame |
|---|---|---|
| post-EVL ulcers | total sum of size of post-EVL ulcers at the esophagogastric junction on the second-look EGD on day 5 | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| esophageal ulcer bleeding | esophageal ulcer bleeding requiring endoscopic hemostasis | 14 days |
| esophageal varices rebleeding | esophageal varices rebleeding within 14 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hsueh-Chien Chiang, MD | Contact | +886910890307 | scion456scion@gmail.com | |
| Hsueh-Chien Chiang | Contact | scion456scion@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Hsueh-Chien Chiang | National Cheng-Kung University Hospital | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36174643 | Background | Gralnek IM, Camus Duboc M, Garcia-Pagan JC, Fuccio L, Karstensen JG, Hucl T, Jovanovic I, Awadie H, Hernandez-Gea V, Tantau M, Ebigbo A, Ibrahim M, Vlachogiannakos J, Burgmans MC, Rosasco R, Triantafyllou K. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022 Nov;54(11):1094-1120. doi: 10.1055/a-1939-4887. Epub 2022 Sep 29. | |
| 29249128 |
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after publication
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| ID | Term |
|---|---|
| D004932 | Esophageal and Gastric Varices |
| ID | Term |
|---|---|
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D006975 | Hypertension, Portal |
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| ID | Term |
|---|---|
| D013392 | Sucralfate |
| ID | Term |
|---|---|
| D013865 | Thioglycosides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D013395 | Sucrose |
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After the standard endoscopic EV ligation, patients will be randomly assigned to either a standard group (ST group) or an intervention group (ET group). After then, patinet in the intervention group will receive 3g of sucralfate powder through the endoscopy precisely on the EV ligation bands. Followingly, patients in the intervention group will receive oral sucralfate suspension 1g four times a day for 5 days. On the 5th day after EV ligation, all enrolled patients will receive a 2nd-look endoscopy to evaluate the esophageal ulcers and the status of esophageal varices.
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| 14 days |
| total packed RBC transfusion during hospitalization | total packed RBC transfusion during hospitalization | 14 days |
| length of hospitalization | length of hospitalization | 14 days |
| cirrhosis related mortality | cirrhosis related mortality | 14 days |
| Background |
| Seo YS. Prevention and management of gastroesophageal varices. Clin Mol Hepatol. 2018 Mar;24(1):20-42. doi: 10.3350/cmh.2017.0064. Epub 2017 Dec 18. |
| 22666604 | Background | Maruyama H, Yokosuka O. Pathophysiology of portal hypertension and esophageal varices. Int J Hepatol. 2012;2012:895787. doi: 10.1155/2012/895787. Epub 2012 May 15. |
| 40993012 | Background | Chen CJ, Wu CC, Wei SL, Lin LJ, Lee WC, Chiang CJ, Chien RN, Lu SN. National strategy for elimination of liver diseases in Taiwan. J Formos Med Assoc. 2025 Dec;124 Suppl 2:S74-S83. doi: 10.1016/j.jfma.2025.09.008. Epub 2025 Sep 24. |
| D008107 | Liver Diseases |
| D004187 |
| Disaccharides |
| D009844 | Oligosaccharides |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D000073893 | Sugars |