Preemptive TIPS for Gastric Variceal Bleeding in Patients With Cirrhosis

NCT ID: NCT06122792

Last Updated: 2023-11-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2026-12-31

Brief Summary

The prevalence of gastric varices is approximately 20%. It is important to note that gastric varices tend to bleed more severely, have a higher morbidity and mortality rate, and have a 35% to 90% risk of rebleeding after the cessation of acute hemorrhage. Because of the relatively low prevalence of gastric varices, the existing clinical studies have many deficiencies, and there is much controversy in the academic community, the optimal treatment and prevention strategies for gastric varices have not yet been fully defined.

In the last few years, important advances have been made in the treatment and prevention of gastric variceal bleeding in patients with cirrhosis. Experts agree that the combination of pharmacological and endoscopic injection of tissue adhesives should be the first line of therapy in the acute bleeding episode from isolated gastric varices (IGV1) or type 2 gastroesophageal varices (GOV2) varices; whereas transjugular intrahepatic portosystemic shunt (TIPS) is considered a rescue therapy. TIPS has been shown to effectively prevent variceal rebleeding but with a potential increase in the incidence of hepatic encephalopathy and/or liver failure. In this sense, a recent randomized controlled trial (RCT) in fundal variceal bleeding showed that an early TIPS, performed during the first 5 days after patient admission resulted in a significant decrease in failure to control bleeding and early and late rebleeding. However, the study was conducted for 4 years and only included 25 patients. Due to insufficient sample size, it was unable to reflect whether priority TIPS can bring survival benefits to patients with gastric variceal bleeding. Therefore, there is an urgent need for multi-center clinical studies with large samples to provide high-quality evidence in the field of prioritizing TIPS for the treatment of acute gastric variceal bleeding.

The present study aims to compare the preemptive TIPS (performed during the first 72 hours after endoscopy) with standard second prophylaxis (endoscopic injection of tissue adhesives plus carvedilol) for patients with acute bleeding from gastric varices (IGV1 or GOV2). The primary outcome will be a 6-week mortality from inclusion.

Conditions

Portal Hypertension; Gastric Varices Bleeding; Portosystemic Shunt

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Therapy

Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic hemostasis according to the center protocol.

Standard combined endoscopic and pharmacological therapy as secondary prophylaxis (carvedilol + repeated endoscopic injection of tissue adhesives until the eradication of the gastric varices).

Group Type: ACTIVE_COMPARATOR

standard second prophylaxis

Intervention Type: PROCEDURE

Patients will receive vasoactive drugs up to 5 days; then a non-selective beta-blocker (carvedilol) will be started with an initial dose of 6.25 mg, the dose of propranolol will be increased to 12.5 mg.

The second elective session of endoscopic injection of tissue adhesives will be performed within the first 28 days after the initial endoscopic treatment. The following sessions will be performed at 28 +/- 3 days intervals until variceal eradication. Once eradication is achieved, endoscopic monitoring will be performed every 6 months. If varices reappear, new endoscopic injection of tissue adhesives will be performed.

Preemptive TIPS

Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic hemostasis according to the center protocol.

Performance of TIPS in the first 72 hours following initial endoscopic hemostasis.

Group Type: EXPERIMENTAL

preemptive TIPS

Intervention Type: PROCEDURE

The TIPS procedure should be performed within 72 hours after the initial endoscopic examination or treatment. An 8 mm Viatorr stent will be used for TIPS establishment. The aim will be to reduce the portal pressure gradient below 12 mm Hg. Embolization, either with coils or glue, can be performed, if it is felt necessary, especially in patients where portography shows the filling of large portosystemic collaterals feeding the varices. After TIPS, anticoagulation will not be used as a rule but is allowed if the attending physician thinks that it is warranted.

Interventions

preemptive TIPS

The TIPS procedure should be performed within 72 hours after the initial endoscopic examination or treatment. An 8 mm Viatorr stent will be used for TIPS establishment. The aim will be to reduce the portal pressure gradient below 12 mm Hg. Embolization, either with coils or glue, can be performed, if it is felt necessary, especially in patients where portography shows the filling of large portosystemic collaterals feeding the varices. After TIPS, anticoagulation will not be used as a rule but is allowed if the attending physician thinks that it is warranted.

Intervention Type: PROCEDURE

standard second prophylaxis

Patients will receive vasoactive drugs up to 5 days; then a non-selective beta-blocker (carvedilol) will be started with an initial dose of 6.25 mg, the dose of propranolol will be increased to 12.5 mg.

The second elective session of endoscopic injection of tissue adhesives will be performed within the first 28 days after the initial endoscopic treatment. The following sessions will be performed at 28 +/- 3 days intervals until variceal eradication. Once eradication is achieved, endoscopic monitoring will be performed every 6 months. If varices reappear, new endoscopic injection of tissue adhesives will be performed.

Intervention Type: PROCEDURE

Other Intervention Names

early TIPS; endoscopy plus drug treatment

Eligibility Criteria

Inclusion Criteria

• Cirrhosis (diagnosed by imaging, laboratory tests, clinical symptoms, or liver biopsy);
• Admission due to acute bleeding from gastric varices (IGV1 or GOV2).

Exclusion Criteria

• Prior treatment with TIPS or surgical shunt;
• Presence of contraindications to endoscopic treatment, carvedilol, or TIPS;
• Presence of hepatocellular carcinoma exceeding Milan criteria;
• Presence of other systemic malignant tumors with expected survival time not exceeding 6 months;
• Presence of uncontrollable infection or sepsis;
• Presence of cardiac, pulmonary, or renal failure;
• Pregnant or lactating women;
• Refusal to sign the informed consent form.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing YouAn Hospital

OTHER

Sponsor Role: collaborator

Renmin Hospital of Wuhan University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Guangzhou First People's Hospital

OTHER

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

luo xuefeng

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xuefeng Luo

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Central Contacts

Xiaoze Wang

Role: CONTACT

wang_xiaoze@wchscu.cn

+8615208207573

References

Escorsell A, Garcia-Pagan JC, Alvarado-Tapia E, Aracil C, Masnou H, Villanueva C, Bosch J. Pre-emptive TIPS for the treatment of bleeding from gastric fundal varices: Results of a randomised controlled trial. JHEP Rep. 2023 Mar 1;5(6):100717. doi: 10.1016/j.jhepr.2023.100717. eCollection 2023 Jun.

Reference Type: BACKGROUND

PMID: 37284139 (View on PubMed)

Other Identifiers

pTIPS-GV

Identifier Type: -

Identifier Source: org_study_id