Tranexamic Acid During Upper GI Endoscopic Resection Procedures

NCT ID: NCT05688020

Last Updated: 2023-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2026-02-28

Brief Summary

Endoscopic resection of gastrointestinal lesions may prevent cancer. However, resection is associated with adverse events such as bleeding. Tranexamic acid (TXA) is a synthetic derivative of lysine that exerts antifibrinolytic effects and may prevent bleeding. The investigators aim to evaluate the effect of local TXA on preventing intraprocedural and postprocedural bleeding in patients undergoing endoscopic mucosal resection (EMR) of upper gastrointestinal lesions.

Detailed Description

Endoscopic resection (ER) is an endoscopic technique used for the removal of sessile or flat neoplasms confined to the superficial layers (mucosa and submucosa) of the gastrointestinal (GI) tract.

This technique is not without risk, and clinically significant intraprocedural bleeding and post-ER bleeding remain the most frequently encountered serious adverse event.

The bleeding rate associated with ER varies for the different regions of the GI tract. This is most probably due to differences in the vascularity within the wall of the GI tract in each region.

Intraprocedural bleeding in the stomach and duodenum is more frequent and may be as high as 11.5% and 19.3%, respectively. Delayed bleeding has been reported at about 5% for these sites.

Management of bleeding is often resource intensive and may necessitate hospitalization, blood transfusion, and repeat intervention. Some techniques, such as soft coagulation with the tip of a snare; epinephrine injection; hemoclip placement or proton-pump inhibitor treatment, are used to decrease the risk of bleeding or treat active bleeding.

Diluted epinephrine, which causes vasoconstriction, is often added to the submucosal injection fluid because of the theoretical benefit of decreasing bleeding. However, epinephrine has a short time-of-action and for long procedures it requires multiple doses to be injected. This can result in systemic effects such as severe hypertension, ventricular tachycardia, and intestinal ischemia, and may also increase postprocedural pain and prolong patient observation after the procedure.

Tranexamic acid (TXA) is a synthetic derivative of lysine that exerts antifibrinolytic effects by inhibition of lysine binding sites on plasminogen molecules and therefore stabilizes the fibrin meshwork produced by secondary hemostasis. TXA was patented by Dr. S. Okamoto in 1957, and it was found to be significantly more potent than a precursor molecule known as epsilon-amino-caproic acid.

During the past few years, TXA has been 'rediscovered' and is currently used in many conditions that are associated with either overt or occult hemorrhage. It is one of the most frequently cited drugs in recent surgical publications involving nearly all surgical specialties.

After the CRASH-2 study which showed that administration of TXA to bleeding trauma patients within 3 hours of injury significantly reduced the risk of death due to bleeding and all-cause mortality without increasing the risk of vascular occlusive events, it has become an important part of trauma management.

It is also widely used in gynecological practice. Early treatment with TXA reduces death due to bleeding in women with post-partum hemorrhage, as well as total blood loss and transfusion requirements in hemorrhage after caesarean delivery. Therefore, TXA has been recommended by the WHO as part of postpartum hemorrhage management.

TXA is also commonly used in orthopedic surgery, either systemically or topically, to reduce excessive bleeding and transfusion requirements.

Other hemorrhagic conditions in which TXA has been shown effective are epistaxis, hemoptysis , endoscopic ear surgery , mastectomy, and hereditary hemorrhagic telangiectasia with bleeding.

Topical use of TXA may be more beneficial than systemic use as it may provide a higher drug concentration on the wound surface with negligible systemic concentrations. Most publications concerning topically administered TXA come from orthopedic literature where instilling TXA as a bolus into the joint reduces bleeding. Recently, a study revealed that intradermal injections of TXA in dermatological surgery reduces bleeding, especially in those on anticoagulant medications.

While TXA is an inhibitor of fibrinolysis, and therefore might theoretically increase the risk of thrombotic vascular events, most studies show no increased risk of thromboembolism. This finding has been consistent with all routes of TXA administration including IV, topical/intra-articular, and other routes.

The most frequently described contraindications to TXA administration include patients with histories of allergic reactions to TXA, seizures, and patients with acute renal failure or chronic kidney disease.

The investigators propose that the use of TXA in the injection gel during ER procedures will be as effective as epinephrine usage in reducing intraprocedural and postprocedural bleeding, while also decreasing the incidence of side effects including abdominal pain.

Conditions

Gastric Polyp; Gastric Neoplasm; Duodenal Neoplasms; Esophageal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Tranexamic acid

During the ER procedure, de-identified injectate solution will be introduced. Study group: 9 ml of standart solution for injection \[Consisit of: 6 ml indigo carmine + 500 ml succinylated gelatin 4% (Gelofusine; B. Braun, Crissier, Switzerland)\] + 1 ml (100mg) of TXA (tranexamic acid).

Group Type: EXPERIMENTAL

Tranexamic acid

Intervention Type: DRUG

Tranexamic acid will be injected as part of the injectate during endoscopic resection.

Epinephrine

During the ER procedure, de-identified injectate solution will be introduced. 9 ml of standart solution for injection \[Consisit of: 6 ml indigo carmine + 500 ml succinylated gelatin 4% (Gelofusine; B. Braun, Crissier, Switzerland)\] + 1 ml epinephrine 1:100,000 + 1 ml saline 0.9%.

Group Type: ACTIVE_COMPARATOR

Epinephrine injection

Intervention Type: DRUG

Epinephrine will be injected as part of the standard injectate used during endoscopic resection.

Interventions

Tranexamic acid

Tranexamic acid will be injected as part of the injectate during endoscopic resection.

Intervention Type: DRUG

Epinephrine injection

Epinephrine will be injected as part of the standard injectate used during endoscopic resection.

Intervention Type: DRUG

Other Intervention Names

Hexakapron; Adrenaline

Eligibility Criteria

Inclusion Criteria

• Patients referred for endoscopic resection of a non-neoplastic and neoplastic lesions in the upper GI presenting to our tertiary academic center.
• Age > 18 years

Exclusion Criteria

• patients with histories of allergic reactions to TXA
• history of seizures
• pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anton Bermont, MD

Role: PRINCIPAL_INVESTIGATOR

Assaf-Harofeh Medical Center

Locations

Shamir Medical Center

Be’er Ya‘aqov, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Anton Bermont, MD

Role: CONTACT

bermont@doctor.com

972-52-6944145

Sergei Vosko, MD

Role: CONTACT

sergeivosko@gmail.com

Facility Contacts

Anton Bermont, MD

Role: primary

References

ASGE Technology Committee; Hwang JH, Konda V, Abu Dayyeh BK, Chauhan SS, Enestvedt BK, Fujii-Lau LL, Komanduri S, Maple JT, Murad FM, Pannala R, Thosani NC, Banerjee S. Endoscopic mucosal resection. Gastrointest Endosc. 2015 Aug;82(2):215-26. doi: 10.1016/j.gie.2015.05.001. Epub 2015 Jun 12.

Reference Type: BACKGROUND

PMID: 26077453 (View on PubMed)

Park CH, Lee SK. Preventing and controlling bleeding in gastric endoscopic submucosal dissection. Clin Endosc. 2013 Sep;46(5):456-62. doi: 10.5946/ce.2013.46.5.456. Epub 2013 Sep 30.

Reference Type: BACKGROUND

PMID: 24143302 (View on PubMed)

Libanio D, Pimentel-Nunes P, Dinis-Ribeiro M. Complications of endoscopic resection techniques for upper GI tract lesions. Best Pract Res Clin Gastroenterol. 2016 Oct;30(5):735-748. doi: 10.1016/j.bpg.2016.09.010. Epub 2016 Sep 14.

Reference Type: BACKGROUND

PMID: 27931633 (View on PubMed)

Yang Z, Wu Q, Liu Z, Wu K, Fan D. Proton pump inhibitors versus histamine-2-receptor antagonists for the management of iatrogenic gastric ulcer after endoscopic mucosal resection or endoscopic submucosal dissection: a meta-analysis of randomized trials. Digestion. 2011;84(4):315-20. doi: 10.1159/000331138. Epub 2011 Nov 9.

Reference Type: BACKGROUND

PMID: 22075541 (View on PubMed)

Castro R, Libanio D, Pita I, Dinis-Ribeiro M. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb 21;25(7):777-788. doi: 10.3748/wjg.v25.i7.777.

Reference Type: BACKGROUND

PMID: 30809079 (View on PubMed)

Watts G. Utako Okamoto. Lancet. 2016 Jun 4;387(10035):2286. doi: 10.1016/s0140-6736(16)30697-3. No abstract available.

Reference Type: BACKGROUND

PMID: 27308678 (View on PubMed)

Montroy J, Hutton B, Moodley P, Fergusson NA, Cheng W, Tinmouth A, Lavallee LT, Fergusson DA, Breau RH. The efficacy and safety of topical tranexamic acid: A systematic review and meta-analysis. Transfus Med Rev. 2018 Feb 19:S0887-7963(17)30151-7. doi: 10.1016/j.tmrv.2018.02.003. Online ahead of print.

Reference Type: BACKGROUND

PMID: 29567052 (View on PubMed)

Other Identifiers

0118-22-ASF

Identifier Type: -

Identifier Source: org_study_id