Endoscopic Application of Tranexamic Acid and Sucralfate in Gastrointestinal Tumor Bleeding: A Randomized Controlled Trial

Background Gastrointestinal bleeding is a common disease among the population in Taiwan, with gastrointestinal tumor bleeding accounting for 3-5% of cases. The pathophysiology of gastrointestinal tumor bleeding is unique, involving fragile surface mucosa, abnormal vascular proliferation, and malformation, making endoscopic hemostasis challenging. Conventional endoscopic hemostasis methods such as hemostatic injections, clips, or thermal coagulation have suboptimal success rates below 80%, with recurrence rates exceeding 50%. Recent clinical trials have demonstrated that hemostatic powder spraying effectively enhances hemostasis for gastrointestinal ulcers and reduces recurrence rates. Our previous research repurposed tranexamic acid in a powder form to enhance hemostasis for peptic ulcer and applied sucralfate powder to prevent postpolypectomy wound bleeding.

Study aim Our research team combines previous experience by using tranexamic acid and sucralfate drug powders to spray onto bleeding gastrointestinal tumors to achieve hemostatic effects. Additionally, tumor-derived exosomes are associated with tumor angiogenesis and growth, so we hypothesize that gastrointestinal tumor bleeding may be linked to VEGF and miR-21 expression within gastrointestinal tumor exosomes.

Study method This study is a clinical randomized controlled trial conducted at National Cheng Kung University Hospital. We will recruit 60 patients with gastrointestinal tumor bleeding undergoing endoscopic hemostasis. Patients in the experimental treatment group will receive additional topical administration of 1.5 g of tranexamic acid and 3 g of sucralfate drug powder. Immediate hemostasis and 30-day bleeding recurrence will be observed. Enrolled patients will also provide blood and tumor specimens for exosome analysis, evaluating the predictive effect of extracted tumor exosomes' VEGF and miR-21 on bleeding risk. This study will explore the association between specific tumor exosome expression levels and bleeding, serving as a basis for bleeding risk assessment and innovative therapies.

Study Overview

• Status: Recruiting
• Conditions: Bleeding After GI Endoscopy
• Intervention / Treatment: Drug: 3g of sucralfate powder and 1.5g of tranexamic acid powder; Drug: Standard Treatment

Detailed Description

Upper gastrointestinal (GI) cancer bleeding is a challenging scenario in clinical practice, including esophageal cancer, gastric cancer, and duodenal cancer. Upper GI cancer bleeds because the growing tumor erodes into the gastrointestinal lining and blood vessels, creating ulcers or damaging capillaries. Certain risk factors contribute to upper GI tumor bleeding, including advanced tumor stage, male gender, older age, usage of certain medications (NSAIDs, anticoagulants, antiplatelets), and comorbidities like thrombocytopenia, coagulopathy, and chronic kidney disease.

Furthermore, angiogenesis in upper GI tumors increased the fragility of new tumor blood vessels, leading to slow oozing or severe hemorrhage. Upper GI cancer exosomes play a significant role in gastric cancer progression, influencing metastasis, drug resistance, and the tumor microenvironment. Exosomes contain and transport a wide range of DNA, mRNA, and miRNA molecules. Tumor-derived exosomes carry pro-angiogenic factors like vascular endothelial growth factor (VEGF) and miR-21, enhancing vessel permeability and clot instability in bleeding sites. In tumors, VEGF drives pathological angiogenesis, enabling tumor growth, invasion, and metastasis by forming leaky vessels. VEGF is transported via exosomes, leading to GI tumor bleeding risks. High serum VEGF also correlates with poor prognosis in gastric cancers. MiR-21 acts as an oncomiR in tumors, overexpressed across many cancers to promote proliferation, invasion, and metastasis by targeting tumor suppressor genes. In gastric cancers, elevated miR-21 correlates with advanced stages, angiogenesis, and bleeding risks through vessel instability.

Gastrointestinal tumor bleeding represents approximately 3-5% of all gastrointestinal bleeding cases, posing significant clinical challenges due to its unique pathophysiology and treatment complexity. The management of such bleeding is particularly difficult because malignant lesions have distinct characteristics compared to benign etiologies of bleeding. Gastrointestinal tumors often exhibit invasive growth patterns, causing disruption of the normal tissue architecture. They frequently develop multiple ulcerations on their surface, which serve as persistent bleeding sites. Additionally, local blood vessels within or adjacent to the tumor can be damaged or fragile, further complicating hemostasis.

In this situation, conventional endoscopic treatment, such as epinephrine injection, clipping, or heat coagulation for tumor bleeding, is challenging and less effective. Cohort studies have reported initial endoscopic hemostasis rates ranging from 31% to 86%, with rebleeding rates between 28% and 80% when using conventional endoscopic hemostatic methods. Hemostatic powder spray, introduced in clinical practice since around 2011, represents a novel endoscopic technique for managing active GI bleeding. The hemostatic powder is delivered through a spraying system under endoscopic visualization. When applied to the bleeding site, the hemostatic powder absorbs water and swells to create an adhesive barrier that covers the lesion and promotes hemostasis. Hemospray has been proven to achieve immediate hemostasis and decrease 30-day rebleeding rates in gastrointestinal tumor bleeding. However, current hemostatic powders on the market are expensive, and some case reports have indicated a risk of perforation in the gastrointestinal tract associated with Hemospray.

Tranexamic acid (TXA) is a well-known antifibrinolytic agent that inhibits fibrin degradation by binding to tissue plasminogen, thereby preventing blood clot lysis and reducing bleeding. Our recent study evaluating the effect of topical TXA powder on bleeding peptic ulcers demonstrated that the precise endoscopic administration of TXA powder can enhance the stop-bleeding effect. This study involved 60 patients (30 in each group) with peptic ulcer bleeding. The application of topical TXA reduced the early treatment failure rate (6.7% vs 30%, P = 0.042).

Sucralfate, a complex of aluminum hydroxide and sucrose octa sulfate, can bind to the wound base. Sucralfate has been widely used for wounds and ulcer treatment, e.g., skin wounds, oral ulcers, and peptic ulcers. Our recent study proved the protective effect of topical sucralfate in preventing postpolypectomy bleeding. This study involved 160 patients (80 in each group) who underwent polypectomy. The application of topical sucralfate reduced the delayed bleeding rate (0% vs 6.4%, P = 0.029).

In combination with TXA powder in stabilizing the clotting, we expect the rebleeding event will be reduced. Our recent clinical trials applying the combination powder (TXA 1g + sucralfate 2g) in all upper GI bleeding have shown promising efficacy in immediate hemostasis. Between October 2024 and May 2025, a total of 60 patients with upper GI bleeding were enrolled. Among these patients, 54 patients (90%) had peptic ulcer bleeding with major SRH, 2 (3.3%) had tumor ulcer bleeding, 2 (3.3%) had Dieulafoy lesion, and 2 (3.3%) had angiodysplasia. Adding the combination powder demonstrated a significantly lower rebleeding rate (10.0% vs 36.7%, P=0.030). In this recent study, two patients with tumor bleeding were successfully treated with the drug powder after conventional therapy failed. Therefore, this study aimed to investigate whether the combination therapy of topical administration of TXA and sucralfate can achieve immediate hemostasis and decrease 30-day rebleeding rates in gastrointestinal tumor bleeding.

Gastrointestinal tumor-derived exosomes transport pro-angiogenic factors like VEGF, which promote abnormal blood vessel formation, increasing permeability, and destabilizing clots at bleeding sites. This mechanism contributes to tumor bleeding by creating leaky, immature vessels prone to rupture. Current evidence shows uncertainty in whether serum or tumor exosome levels directly correlate with bleeding incidence. To investigate the relationship between upper GI tumor exosomes and tumor bleeding, this study will identify specific exosomes from upper GI tumors and measure their serum levels in cancer cohorts, correlating them with bleeding events for non-invasive hemorrhage risk prediction. Such insights enable proactive clinical monitoring and evaluation of recurrent bleeding. Targeting these pro-angiogenic exosomes via neutralizing antibodies or RNA interference offers a novel therapeutic method to stabilize vessels and mitigate gastric tumor bleeding

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hsueh-Chien Chiang, MD; Phone Number: 9118 8862353535; Email: scion456scion@gmail.com

Study Locations

• Taiwan
  • Not Required For This Country
    • Tainan, Not Required For This Country, Taiwan, 704
      • Recruiting
      • National Cheng Kung University Hospital
      • Contact: Hsueh-Chien Chiang, MD; Phone Number: 9118 8862353535; Email: scion456scion@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• patients aged ≥ 18 years who accept endoscopy for upper GI tumor bleeding

Exclusion Criteria:

• patients with no need for endoscopic hemostasis, allergy to sucralfate, tranexamic acid, pregnancy, and patients with hollow organ perforation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention group; For patients in both the standard group and intervention group, epinephrine injection, clipping, and heat coagulation will be applied. The decision for the choice of standard therapy was left to the discretion of the endoscopist in the absence of any recommendations or proof of superiority of one modality over another in the initial endoscopic approach to use in patients presenting with malignant bleeding. For patients in the intervention group, we will additionally deliver 3g of sucralfate powder and 1.5g of tranexamic acid powder through the endoscopy precisely on the bleeding site after conventional therapy.	Drug: 3g of sucralfate powder and 1.5g of tranexamic acid powder; For patients in the intervention group, we will additionally deliver 3g of sucralfate powder and 1.5g of tranexamic acid powder through the endoscopy precisely on the bleeding site after conventional therapy. After endoscopic treatment, 5 minutes of observation time is needed for the immediate hemostasis confirmation. After endoscopic hemostasis, patients with upper gastrointestinal lesions received an intravenous 80-mg bolus of proton pump inhibitors followed by 8 mg/h continuously for at least 72 hours.
Active Comparator: Standard group; For patients in both the standard group and intervention group, epinephrine injection, clipping, and heat coagulation will be applied. The decision for the choice of standard therapy was left to the discretion of the endoscopist in the absence of any recommendations or proof of superiority of one modality over another in the initial endoscopic approach to use in patients presenting with malignant bleeding.	Drug: Standard Treatment; Epinephrine injection, clipping, and heat coagulation will be applied. The decision for the choice of standard therapy was left to the discretion of the endoscopist in the absence of any recommendations or proof of superiority of one modality over another in the initial endoscopic approach to use in patients presenting with malignant bleeding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day rebleeding	Rebleeding was defined by any of the following criteria: (1) hematemesis or bloody nasogastric tube drainage occurring more than 6 hours after endoscopy; (2) melena recurring after initial normalization of stool color; (3) hematochezia occurring after normalization of stool color or melena; (4) development of tachycardia (heart rate ≥110 beats/min) or hypotension (systolic blood pressure ≤90 mm Hg) after at least 1 hour of stable vital signs without other identifiable cause; (5) a hemoglobin drop of ≥2 g/dL following two consecutive stable hemoglobin measurements; (6) tachycardia or hypotension persisting beyond 8 hours after the index endoscopy despite appropriate resuscitation, without alternative explanation, accompanied by ongoing melena or hematochezia; or (7) a persistent hemoglobin decline of >3 g/dL within 24 hours together with ongoing melena or hematochezia.	30 days
immediate hemostasis	no evidence of further bleeding after 3 minutes of observation during the index endoscopy, with elapsed time measured by a stopwatch.	3 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rebleeding in need of TAE or surgery	rebleeding in need of TAE or surgery	30 days
all cause mortality	all cause mortality	30 days
hospitalization day	hospitalization day	30 days

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital

Publications and helpful links

General Publications

• Chiang HC, Chen PJ, Yang EH, Hsieh MT, Shih IC, Cheng HC, Chang WL, Chen WY, Chiu HC, Kuo HY, Tsai WC, Lo YN, Yang KC, Chiang CM, Chen WC, Huang KK, Tseng HH, Chen CY, Lin XZ, Chuang CH. Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video). Gastrointest Endosc. 2023 Nov;98(5):755-764. doi: 10.1016/j.gie.2023.06.013. Epub 2023 Jun 24.
• Chiang HC, Chen PJ, Yang EH, Kuo TL, Hsieh MT, Kang JW, Cheng HC, Chang WL, Chen WY, Chiu HC, Lin MY, Hong TC, Chiang CM, Chen WC, Huang KK, Lu MH, Wu MH, Chen CY, Lin XZ, Chuang CH. Clinical Trial: Precise Administration of Sucralfate Powder in Prevention of Delayed Postpolypectomy Bleeding. A Randomized Controlled Trial. Clin Transl Gastroenterol. 2025 Apr 1;16(4):e00818. doi: 10.14309/ctg.0000000000000818.
• Ceci C, Atzori MG, Lacal PM, Graziani G. Role of VEGFs/VEGFR-1 Signaling and its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models. Int J Mol Sci. 2020 Feb 18;21(4):1388. doi: 10.3390/ijms21041388.
• Fu M, Gu J, Jiang P, Qian H, Xu W, Zhang X. Exosomes in gastric cancer: roles, mechanisms, and applications. Mol Cancer. 2019 Mar 15;18(1):41. doi: 10.1186/s12943-019-1001-7.
• Wang M, Shu H, Cheng X, Xiao H, Jin Z, Yao N, Mao S, Zong Z. Exosome as a crucial communicator between tumor microenvironment and gastric cancer (Review). Int J Oncol. 2024 Mar;64(3):28. doi: 10.3892/ijo.2024.5616. Epub 2024 Jan 19.
• Zheng Z, Zhai Y, Yan X, Wang Z, Zhang H, Xu R, Liu X, Cai J, Zhang Z, Shang Y, Zhang J, Yin J. Functions and Clinical Applications of Exosomes in Gastric Cancer. Int J Biol Sci. 2025 Feb 28;21(5):2330-2345. doi: 10.7150/ijbs.98087. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gastric tumor; Tumor bleeding
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: A-BR-114-065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After paper accept
• IPD Sharing Time Frame: After paper accept
• IPD Sharing Access Criteria: Email PI for information
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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