Preemptive TIPS for Variceal Bleeding in Cirrhotic Patients With Occlusive Portal Vein Thrombosis

NCT ID: NCT06122753

Last Updated: 2023-11-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2026-12-31

Brief Summary

Portal vein thrombosis (PVT) can lead to a further increase in portal venous pressure and increase the risk of rebleeding. Whether patients with acute esophagogastric variceal bleeding with occlusive PVT benefit from preemptive TIPS is still controversial. The present study is directed at comparing the outcome of patients with acute variceal bleeding with occlusive PVT treated by standard therapy (vasoactive drugs + endoscopic variceal ligation) with or without preemptive TIPS (performed during the first 1-3 days after endoscopic procedure). The primary outcome is survival free of variceal rebleeding at 6 weeks from inclusion.

Detailed Description

Portal vein thrombosis (PVT) is a common complication in patients with cirrhosis, and the cumulative incidence of PVT is 4.6%, 8.2%, and 10.7% at 1 year, 3 years, and 5 years, respectively. PVT can lead to a further increase in portal venous pressure and increase the risk of rebleeding. According to Baveno VII, PVT can be classified according to the degree of occlusion of the portal trunk as complete occlusion (no continuous luminal structure), partial occlusion (≥50% thrombus obstruction of the lumen), mild occlusion (<50% thrombus obstruction of the lumen), or spongiotic degeneration (a large number of collateral vessels of the portal vein, with no visualization of the main portal vein). The results of a recent observational study suggested that patients with severe PVT with ≥50% thrombotic luminal obstruction had higher 6-week rebleeding rates (8.8% vs. 3.8%) and 1-year rebleeding rates (29.4% vs. 21.4%) after acute variceal bleeding. Our previous clinical study showed that patients with cirrhotic PVT treated with TIPS had lower rebleeding rates and significantly higher rates of portal vein recanalization, and it was inferred that patients with acute esophagogastric variceal bleeding with severe PVT might benefit from preemptive TIPS. Therefore, we propose to conduct a multicentre randomized controlled trial to enroll patients with acute esophagogastric variceal bleeding with occlusive PVT to compare the preemptive TIPS with the standardized therapy. The outcomes are rates of mortality, rebleeding, and complications.

Conditions

Portal Hypertension; Portal Vein Thrombosis; Esophageal Varix 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 variceal ligation until the eradication of the esophageal 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 band ligation 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 band ligation 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 band ligation 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 band ligation 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 esophagogastric varices;
• Thrombus in the main trunk of the portal vein occupying ≥50% of the lumen.

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

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: collaborator

Beijing YouAn Hospital

OTHER

Sponsor Role: collaborator

Beijing Friendship Hospital

OTHER

Sponsor Role: collaborator

Beijing 302 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, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Countries

China

Central Contacts

Xiazoe Wang, M.D.

Role: CONTACT

wang_xiaoze@wchscu.cn

+8615208207573

References

Wang X, Liu G, Wu J, Xiao X, Yan Y, Guo Y, Yang J, Li X, He Y, Yang L, Luo X. Small-Diameter Transjugular Intrahepatic Portosystemic Shunt versus Endoscopic Variceal Ligation Plus Propranolol for Variceal Rebleeding in Advanced Cirrhosis. Radiology. 2023 Aug;308(2):e223201. doi: 10.1148/radiol.223201.

Reference Type: BACKGROUND

PMID: 37606572 (View on PubMed)

Luo X, Wang Z, Tsauo J, Zhou B, Zhang H, Li X. Advanced Cirrhosis Combined with Portal Vein Thrombosis: A Randomized Trial of TIPS versus Endoscopic Band Ligation Plus Propranolol for the Prevention of Recurrent Esophageal Variceal Bleeding. Radiology. 2015 Jul;276(1):286-93. doi: 10.1148/radiol.15141252. Epub 2015 Mar 10.

Reference Type: RESULT

PMID: 25759969 (View on PubMed)

Other Identifiers

pTIPS-PVT

Identifier Type: -

Identifier Source: org_study_id