Cyanoacrylate Glue Versus Absorbable Gelatin Sponge for Gastric Varices

Official title

Cyanoacrylate Glue Versus Absorbable Gelatin Sponge for Endoscopic Treatment of Gastric Varices (CoAGS-GV): A Randomized, Patient- and Assessor-Blinded, Non-Inferiority Trial

Overview

This study compares two endoscopic ultrasound-guided treatments for gastric varices, which are enlarged veins in the stomach that can bleed. Both treatments use small coils placed into the varix. One group will receive coils with cyanoacrylate medical glue, and the other group will receive coils with absorbable gelatin sponge. The purpose of the study is to determine whether absorbable gelatin sponge with coils is not worse than cyanoacrylate glue with coils for closing off gastric varices, and to compare safety outcomes. Participants will be randomly assigned to one of the two treatment groups. Participants and outcome assessors will not know which treatment was used, but the doctor performing the procedure will know. After the procedure, participants will be followed for up to 12 months. Follow-up may include clinical assessments, questionnaires about health and quality of life, CT imaging shortly after the procedure, and repeat endoscopic ultrasound assessments to evaluate whether the gastric varix has been successfully treated.

Detailed description

Gastric varices are enlarged veins in the stomach that occur in patients with portal hypertension and can cause serious bleeding. Endoscopic ultrasound-guided therapy allows direct visualization of the target varix, placement of embolization coils, delivery of an embolic material, and Doppler assessment of blood flow after treatment.

Cyanoacrylate glue combined with coils is an established treatment approach for gastric varices. However, glue injection can be technically challenging and may be associated with complications such as embolization or equipment-related issues. Absorbable gelatin sponge, delivered as a slurry with coils, is an alternative approach that is used in clinical care and may avoid some of the practical limitations of glue. Comparative randomized data between these approaches are limited.

This is a randomized, patient- and assessor-blinded, non-inferiority trial comparing endoscopic ultrasound-guided coil embolization with cyanoacrylate glue versus endoscopic ultrasound-guided coil embolization with absorbable gelatin sponge for the treatment of gastric varices. Eligible participants will be randomized in a 1:1 ratio after confirmation of eligibility and informed consent. Randomization will occur intra-procedurally before treatment.

Participants assigned to the cyanoacrylate group will undergo endoscopic ultrasound-guided coil deployment followed by injection of cyanoacrylate glue mixed with Lipiodol. Participants assigned to the absorbable gelatin sponge group will undergo endoscopic ultrasound-guided coil deployment followed by injection of absorbable gelatin sponge slurry. In both groups, Doppler assessment will be used to evaluate blood flow in the target varix after treatment. Repeat coil and/or embolic material injection may be performed at the discretion of the treating endoscopist.

Participants will be monitored after the procedure for complications, including bleeding and embolization. Follow-up includes CT imaging approximately 48 hours after the procedure, clinical and questionnaire-based follow-up at 1, 3, 6, and 12 months, and repeat endoscopic assessment with endoscopic ultrasound at approximately 3 months and 12 months. The primary endpoint is complete obliteration of the target gastric varix, assessed by absence of Doppler flow on follow-up endoscopic ultrasound at 3 months. Secondary and tertiary outcomes include immediate technical success, clinical success, rebleeding, adverse events, hospital admission, ICU admission, transfusion requirements, reintervention, length of stay, procedural technical difficulty, costs, and health-related quality of life.

Interventions

• Procedure EUS-Guided Coil Embolization With Cyanoacrylate Glue and Lipiodol
  Endoscopic ultrasound-guided treatment of a gastric varix using coil deployment followed by injection of cyanoacrylate glue mixed with Lipiodol under direct visualization. The injection is flushed with sterile water. Repeat coil and/or glue injection may be performed at the discretion of the treating endoscopist. Doppler assessment is performed to assess eradication of flow in the treated gastric varix.
• Procedure EUS-Guided Coil Embolization With Absorbable Gelatin Sponge
  Endoscopic ultrasound-guided treatment of a gastric varix using coil deployment followed by injection of absorbable gelatin sponge slurry under direct visualization. The slurry is flushed with sterile water. Repeat coil and/or absorbable gelatin sponge injection may be performed at the discretion of the treating endoscopist. Doppler assessment is performed to assess eradication of flow in the treated gastric varix.

Primary outcome measures

• Complete Obliteration of the Target Gastric Varix on EUS [Time frame: 3 months post-intervention]

Secondary outcome measures (5)

• Immediate Technical Success [Time frame: During index procedure]
• Short-Term Clinical Success [Time frame: Up to 3 months post-intervention]
• Procedure-Related Adverse Events [Time frame: From index procedure through 12 months]
• Long-Term Technical Success [Time frame: 12 months post-intervention]
• Long-Term Clinical Success [Time frame: Up to 12 months post-intervention]

Eligibility criteria

Inclusion criteria

• Adults aged 18 years or older.
• Gastric varices deemed suitable for EUS-guided endoscopic treatment.
• History of suspected gastric variceal bleeding or active gastric variceal bleeding, with treatment intended for secondary prophylaxis.
• Ability to provide informed consent directly or through a substitute decision maker.
• Willingness and ability to undergo clinical follow-up, EUS assessment, and CT imaging.

Exclusion criteria

• Inability or unwillingness to provide informed consent directly or through a substitute decision maker.
• No gastric varix present, or gastric varix too small or not amenable to combination therapy.
• Contraindication to therapeutic EUS or endoscopy.
• Contraindication to any study material used in the assigned treatment arm.
• Contraindication to contrast-enhanced CT, if not clinically manageable.
• Inability to complete planned follow-up.
• Pregnancy.
• Any clinical situation in which the treating endoscopist determines that randomization would be unsafe or inappropriate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• St. Michael's Hospital - Unity Health Toronto — Toronto

Publications

• Saracco G, Giordanino C, Roberto N, Ezio D, Luca T, Caronna S, Carucci P, De Bernardi Venon W, Barletti C, Bruno M, De Angelis C, Musso A, Repici A, Suriani R, Rizzetto M. Fatal multiple systemic embolisms after injection of cyanoacrylate in bleeding gastric varices of a patient who was noncirrhotic but with idiopathic portal hypertension. Gastrointest Endosc. 2007 Feb;65(2):345-7. doi: 10.1016/j. PMID 17141231
• McCarty TR, Bazarbashi AN, Hathorn KE, Thompson CC, Ryou M. Combination therapy versus monotherapy for EUS-guided management of gastric varices: A systematic review and meta-analysis. Endosc Ultrasound. 2020 Jan-Feb;9(1):6-15. doi: 10.4103/eus.eus_37_19. PMID 31417066
• Bazarbashi AN, Wang TJ, Thompson CC, Ryou M. Endoscopic ultrasound-guided treatment of gastric varices with coil embolization and absorbable hemostatic gelatin sponge: a novel alternative to cyanoacrylate. Endosc Int Open. 2020 Feb;8(2):E221-E227. doi: 10.1055/a-1027-6708. Epub 2020 Jan 28. PMID 32010757
• Bazarbashi AN, Wang TJ, Jirapinyo P, Thompson CC, Ryou M. Endoscopic Ultrasound-Guided Coil Embolization With Absorbable Gelatin Sponge Appears Superior to Traditional Cyanoacrylate Injection for the Treatment of Gastric Varices. Clin Transl Gastroenterol. 2020 May;11(5):e00175. doi: 10.14309/ctg.0000000000000175. PMID 32677809
• Florencio de Mesquita C, Antunes VLJ, Milioli NJ, Fernandes MV, Correa TL, Martins OC, Chavan R, Baraldo S. EUS-guided coiling plus glue injection compared with endoscopic glue injection alone in endoscopic treatment for gastric varices: a systematic review and meta-analysis. Gastrointest Endosc. 2025 Feb;101(2):331-340.e8. doi: 10.1016/j.gie.2024.10.005. Epub 2024 Oct 9. PMID 39389435
• Bhat YM, Weilert F, Fredrick RT, Kane SD, Shah JN, Hamerski CM, Binmoeller KF. EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years (with video). Gastrointest Endosc. 2016 Jun;83(6):1164-72. doi: 10.1016/j.gie.2015.09.040. Epub 2015 Oct 9. PMID 26452992
• Kaplan DE, Ripoll C, Thiele M, Fortune BE, Simonetto DA, Garcia-Tsao G, Bosch J. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024 May 1;79(5):1180-1211. doi: 10.1097/HEP.0000000000000647. Epub 2023 Oct 23. No abstract available. PMID 37870298

Identifiers

NCT: NCT07699354 · CoAGS-GV-UHT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗