Precise Delivery of Tranexamic Acid to Enhance Endoscopic Hemostasis for Peptic Ulcer Bleeding

NCT05248321 | Completed

• 1 other identifier: A-BR-110-085
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Peptic ulcer bleeding is a common emergency for patients who need therapeutic endoscopy. According to international guidelines and Taiwan consensus, the standard therapy included proton pump inhibitor (PPI) and endoscopic therapy. For high-risk peptic ulcers, such as active spurting, oozing bleeding, a nonbleeding visible vessel or ulcers with adherent clots, we apply endoscopic hemostasis with epinephrine injection in combination with either heater probe coagulation, hemoclipping and/or rubber band ligation. Parenteral high-dose PPI is administered after endoscopic hemostasis. Though current standard endoscopic therapy plus PPI infusion are highly effective, 5%-10% of the patients still experience recurrence of bleeding after the initial treatment. It is still an important issue to reduce recurrent peptic ulcer bleeding after standard endoscopic therapy. Tranexamic acid reduces bleeding by inhibiting clot breakdown by inhibiting the degradation of fibrin by plasmin. It is effective to be used topically to reduce bleeding during surgery. However, the effect of application of tranexamic acid orally or intravenously for gastrointestinal bleeding was still controversial, probably because that the route of tranexamic acid use is not precise at the bleeding site. Tranexamic acid has anti-fibrinolytic effects at the bleeding site, so it is possible that use of tranexamic acid locally may have better efficacy than via intravenous or oral route. We propose to investigate the effectiveness and safety when using tranexamic acid locally under endoscopic guidance in patients with peptic ulcer bleeding after standard endoscopic therapy.

Conditions

Peptic Ulcer Hemorrhage

Keywords

Peptic ulcer; Tranexamic acid powder spray; Recurrent ulcer bleeding

Outcome Measures

Primary Outcomes (1)

• Rate of the early treatment failure of the index ulcer

  We monitor if early treatment failure of the peptic ulcer occurs after the first endoscopic therapy within 4 days. Early treatment failure was defined as (1) continuous melena, hematochezia, bloody drainage from a nasogastric tube, hemodynamic instability (systolic blood pressure \<90 mm Hg, heart rate \>120 bpm), or a drop in serum hemoglobin \>2 g/dL with the subsequent EGD confirmation of index ulcer with major SRH, or (2) index ulcer with major SRH in need of repeated endoscopic hemostasis during the second-look EGD.

  4 days

Secondary Outcomes (6)

• Rate of the recurrent bleeding from the index ulcer

  28 days

• PRBC transfusion units

  28 days

• The length of hospitalization

  28 days

• Recurrent ulcer bleeding requiring transarterial embolization or emergent surgery

  28 days

• The mortality

  28 days

Study Arms (2)

Extra treatment (ET) group

EXPERIMENTAL

In the extra treatment (ET) group, standard endoscopic therapy will be performed to the bleeding peptic ulcer by local injection of diluted epinephrine 1:10 000 in combination with either heater probe coagulation, hemoclipping and/or rubber band ligation. Afterwards, we will apply 1.25g tranexamic acid powder via the endoscopy to the peptic ulcer before the end of endoscopic exam. After the first endoscopy, the patient will receive a 3-day continuous high-dose (8 mg/h) PPI infusion and Rockall score assessment as current guideline's recommendation. In patients with Rockall scores ≥6, after 3-day intravenous PPI infusion, we will apply oral twice-daily PPI for 11 days followed by once-daily PPI after then. In patients with Rockall scores \<6, we will apply once-daily PPI after 3-day intravenous PPI infusion. A second-look esophagogastroduodenoscopy (EGD) will be performed 2-3 days after the initial endoscopy, aiming to survey if major SRH of peptic ulcer persists.

Drug: Tranexamic Acid Powder

standard treatment (ST) group

NO INTERVENTION

In the standard treatment (ST) group, the endoscopic exam ends after standard endoscopic therapy. After the first endoscopy, the patient will receive a 3-day continuous high-dose (8 mg/h) PPI infusion and Rockall score assessment as current guideline's recommendation. In patients with Rockall scores ≥6, after 3-day intravenous PPI infusion, we will apply oral twice-daily PPI for 11 days followed by once-daily PPI after then. In patients with Rockall scores \<6, we will apply once-daily PPI after 3-day intravenous PPI infusion. A second-look esophagogastroduodenoscopy (EGD) will be performed 2-3 days after the initial endoscopy, aiming to survey if major SRH of peptic ulcer persists.

Interventions

Tranexamic Acid Powder DRUG

2g tranexamic acid powder will be given via the endoscopy directly to the peptic ulcer

Also known as: Tranexamic acid powder spray from endoscopy

Extra treatment (ET) group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with peptic ulcer with major stigmata of recent hemorrhage receiving EGD therapy

You may not qualify if:

• Poor renal function (serum creatinine \> 2.9mg/dL)
• Tumor ulcer bleeding
• Patients allergy to tranexamic acid
• Whose antiplatelet agent/anticoagulation agent could not be transiently withdrawn

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (1)

National Cheng-Kung University Hospital

Tainan, NONE Selected, 704, Taiwan

Location

Related Publications (12)

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  PMID: 7717312 RESULT

• Sheu BS, Wu CY, Wu MS, Chiu CT, Lin CC, Hsu PI, Cheng HC, Lee TY, Wang HP, Lin JT. Consensus on control of risky nonvariceal upper gastrointestinal bleeding in Taiwan with National Health Insurance. Biomed Res Int. 2014;2014:563707. doi: 10.1155/2014/563707. Epub 2014 Aug 14.

  PMID: 25197649 RESULT

• Yang EH, Wu CT, Kuo HY, Chen WY, Sheu BS, Cheng HC. The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores >/= 6. Surg Endosc. 2020 Apr;34(4):1592-1601. doi: 10.1007/s00464-019-06919-3. Epub 2019 Jun 20.

  PMID: 31222633 RESULT

• Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, Rotondano G, Hucl T, Dinis-Ribeiro M, Marmo R, Racz I, Arezzo A, Hoffmann RT, Lesur G, de Franchis R, Aabakken L, Veitch A, Radaelli F, Salgueiro P, Cardoso R, Maia L, Zullo A, Cipolletta L, Hassan C. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015 Oct;47(10):a1-46. doi: 10.1055/s-0034-1393172. Epub 2015 Sep 29.

  PMID: 26417980 RESULT

• Lee JH, Kim BK, Seol DC, Byun SJ, Park KH, Sung IK, Park HS, Shim CS. Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring. Endoscopy. 2013 Jun;45(6):489-92. doi: 10.1055/s-0032-1326375. Epub 2013 Apr 11.

  PMID: 23580408 RESULT

• Yang EH, Cheng HC, Wu CT, Chen WY, Lin MY, Sheu BS. Peptic ulcer bleeding patients with Rockall scores >/=6 are at risk of long-term ulcer rebleeding: A 3.5-year prospective longitudinal study. J Gastroenterol Hepatol. 2018 Jan;33(1):156-163. doi: 10.1111/jgh.13822.

  PMID: 28497645 RESULT

• Picetti R, Shakur-Still H, Medcalf RL, Standing JF, Roberts I. What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies. Blood Coagul Fibrinolysis. 2019 Jan;30(1):1-10. doi: 10.1097/MBC.0000000000000789.

  PMID: 30585835 RESULT

• Hunt BJ. The current place of tranexamic acid in the management of bleeding. Anaesthesia. 2015 Jan;70 Suppl 1:50-3, e18. doi: 10.1111/anae.12910.

  PMID: 25440395 RESULT

• Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013 Jul 23;2013(7):CD010562. doi: 10.1002/14651858.CD010562.pub2.

  PMID: 23881695 RESULT

• HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jun 20;395(10241):1927-1936. doi: 10.1016/S0140-6736(20)30848-5.

  PMID: 32563378 RESULT

• Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut. 2014 Dec;63(12):1864-72. doi: 10.1136/gutjnl-2013-306531. Epub 2014 Mar 21.

  PMID: 24658598 RESULT

• 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.

  PMID: 37356632 DERIVED

MeSH Terms

Conditions

Peptic Ulcer Hemorrhage; Peptic Ulcer

Condition Hierarchy (Ancestors)

Gastrointestinal Hemorrhage; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Duodenal Diseases; Intestinal Diseases; Stomach Diseases

Study Officials

• Xi-Zhang Lin, M.D.

  National Cheng-Kung University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: February 21, 2022
• Study Start: March 24, 2022
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

TW (1)