TIPS vs. NSBB Plus Endotherapy for the Prevention of Variceal Rebleeding in NSBB Non-responders of Primary Prophylaxis

Liver Cirrhosis Clinical Trial

Official title:

TIPS vs. NSBB Plus Endotherapy for the Prevention of Variceal Rebleeding in NSBB Non-responders of Primary Prophylaxis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04207398
• Other study ID #: KY20192149-C-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2020
• Source: Fourth Military Medical University
• Contact: Jun Tie, Professor
• Phone: +862984771537
• Email: tiejun7776[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Variceal bleeding (VB) is a life-threatening complication of cirrhosis with a 6-week mortality of approximately 15%-20%. The 1-year rate of recurrent VB is approximately 60% in patients without prophylaxis treatment. Therefore, all patients who survive VB must receive active treatments to prevent rebleeding. Usually, these patients are submitted to rebleeding prophylaxis with endoscopic band ligation (EBL) combined with non-selective beta-blockers (NSBB). Transjugular intrahepatic portosystemic shunts (TIPS) are reserved for those who failed endoscopic plus medical treatment.

A recent meta-analysis comparing combination therapy to monotherapy with EBL or drug therapy has demonstrated that combination therapy is only marginally more effective than NSBB alone. This suggests that NSBB is the cornerstone of combination therapy. The lowest rebleeding rates are observed in patients on secondary prophylaxis who are hepatic venous pressure gradient (HVPG) responders (defined as a reduction in HVPG below 12 mm Hg or > 20% from baseline). A recent study demonstrated that patients who have their first episode of variceal bleeding while on primary prophylaxis with NSBB have an increased risk of further bleeding and death, despite adding EBL. These patients possibly require alternative treatment approaches, such as TIPS.

The aim of the present study was to compare the effect of TIPS vs. EBL + NSBB for the prevention of rebleeding in NSBB non-responder for primary prophylaxis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 114
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of liver cirrhosis

• Standard NSBB therapy was used for primary prophylaxis

• At least 5 days after index variceal bleeding

• Child-Pugh score <13, Model for end-stage liver disease score < 19

Exclusion Criteria:

• Gastric variceal bleeding (GOV2,IGV1,IGV2)

• History of shunt surgery

• Degree of portal vein thrombosis > 50%

• Refractory ascites

• Budd-Chiari syndrome

• Hepatocellular carcinoma or other malignant tumors

• Uncontrolled infection

• HIV

• Pregnant or breast-feeding woman

• Poor compliance

Related Conditions & MeSH terms

• Hemorrhage
• Liver Cirrhosis
• NSBB
• TIPS
• Variceal Hemorrhage

Intervention

Procedure:
• Transjugular intrahepatic portosystemic shunts
Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver. A small metal device called a stent is placed to keep the connection open and allow it to bring blood draining from the bowel back to the heart. TIPS may successfully reduce internal bleeding in the stomach and esophagus in patients with cirrhosis and may also reduce the accumulation of fluid in the abdomen (ascites).

Other:
• Nonselective ß-blocker (NSBB)+ endoscopic band ligation (EBL)
Combination therapy of nonselective ß-blocker (NSBB) and endoscopic variceal ligation (EBL) will be used for participants in this group. NSBB, which will be titrated to the maximum tolerated dose aiming to decrease the heart rate by 25%, with a lower limit of 50 beats per minute, was started at day 5 after the index bleeding, unless a contraindication was present (severe arrhythmia, severe obstructive chronic obstructive pulmonary disease, or known intolerance). Endoscopic variceal ligation sessions started 2 weeks after the index bleeding and were performed every 2-4 weeks thereafter until eradication of varices, followed by endoscopic surveillance and retreatment, if indicated, every 6-12 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fourth Military Medical University

References & Publications (1)

de Souza AR, La Mura V, Reverter E, Seijo S, Berzigotti A, Ashkenazi E, García-Pagán JC, Abraldes JG, Bosch J. Patients whose first episode of bleeding occurs while taking a ß-blocker have high long-term risks of rebleeding and death. Clin Gastroenterol H — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of clinically significant variceal rebleeding	Recurrent melena or hematemesis resulting in either hospital admission, blood transfusion, drop in hemoglobin of at least 3 g/L, or death within 6 weeks after rebleeding.	12 months
Secondary	Cumulative incidence of variceal bleeding related mortality	Death due to variceal bleeding	12 months
Secondary	Cumulative incidence of all cause mortality	Including liver related and non-liver related death	12 months
Secondary	Cumulative incidence of hepatic encephalopathy (HE)	HE was evaluated and classified according to West-Haven criteria	12 months
Secondary	Cumulative incidence of adverse events (AE)	All kinds of adverse events	12 months