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

Portal Hypertension Clinical Trial

Official title:

Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Variceal Bleeding in Cirrhotic Patients With Occlusive Portal Vein Thrombosis (PVT): A Multicenter Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06122753
• Other study ID #: pTIPS-PVT
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: West China Hospital
• Contact: Xiazoe Wang, M.D.
• Phone: +8615208207573
• Email: wang_xiaoze[@]wchscu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Esophageal and Gastric Varices
• Hemorrhage
• Hypertension, Portal
• Portal Hypertension
• Portal Vein Thrombosis
• Portosystemic Shunt
• Thrombosis
• Venous Thrombosis

Intervention

Procedure:
• 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.
• 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.

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University	Chengdu	Sichuan

Sponsors (5)

Lead Sponsor	Collaborator
West China Hospital	Beijing 302 Hospital, Beijing Friendship Hospital, Beijing YouAn Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

References & Publications (2)

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. 20 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-week mortality	The rate of mortality during the first 6 weeks after inclusion in the study.	6 weeks
Secondary	5-day treatment failure	Incidence of cases requiring adjustment of treatment strategy within 5 days of initial standardised treatment: vomiting of blood or drainage of =100 ml of fresh blood from a gastric tube after 2 hours of treatment, hypovolemic shock, drop in haemoglobin of 30 g/L or more within 24 hours without transfusion.	5 days
Secondary	1-year mortality	The rate of mortality during the first 1 year after inclusion in the study.	1 year
Secondary	decompensation events	Rates with rebleeding, new overt ascites (moderate-heavy) or increased degree of ascites, overt hepatic encephalopathy (West-Heaven grades 2-4), or jaundice (total bilirubin >51 mmol/L) from 5 days after initial standardised treatment up to 1 year.	1 year
Secondary	adverse events	Events of various complications such as infections, new tumours, organ failure, peptic ulcers, etc., occurring after randomisation up to the follow-up period.	1 year