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

NCT ID: NCT04207398

Last Updated: 2020-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-01

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Variceal Hemorrhage TIPS NSBB Liver Cirrhosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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TIPS

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver.

Group Type EXPERIMENTAL

Transjugular intrahepatic portosystemic shunts

Intervention Type PROCEDURE

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).

NSBB+EBL

Participants randomized to this group will receive the combination therapy of non-selective beta-blocker (NSBB) and endoscopic band ligation (EBL) . NSBB, including propranolol and carvidilol, will be started at day 5 after the index bleeding and elective EBL sessions started 2 weeks after the index bleeding.

Group Type ACTIVE_COMPARATOR

Nonselective β-blocker (NSBB)+ endoscopic band ligation (EBL)

Intervention Type OTHER

Combination therapy of nonselective β-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.

Interventions

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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).

Intervention Type PROCEDURE

Nonselective β-blocker (NSBB)+ endoscopic band ligation (EBL)

Combination therapy of nonselective β-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.

Intervention Type OTHER

Other Intervention Names

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Combination therapy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Air Force Military Medical University, China

OTHER

Sponsor Role lead

Responsible Party

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Tie Jun

Director of clinical research

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Jun Tie, Professor

Role: CONTACT

+862984771537

Hui Chen, M.D.,Ph.D.

Role: CONTACT

+862984771537

References

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de Souza AR, La Mura V, Reverter E, Seijo S, Berzigotti A, Ashkenazi E, Garcia-Pagan JC, Abraldes JG, Bosch J. Patients whose first episode of bleeding occurs while taking a beta-blocker have high long-term risks of rebleeding and death. Clin Gastroenterol Hepatol. 2012 Jun;10(6):670-6; quiz e58. doi: 10.1016/j.cgh.2012.02.011. Epub 2012 Feb 22.

Reference Type RESULT
PMID: 22366180 (View on PubMed)

Other Identifiers

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KY20192149-C-1

Identifier Type: -

Identifier Source: org_study_id

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