TIPS vs. NSBB Plus Endotherapy for the Prevention of Variceal Rebleeding in NSBB Non-responders of Primary Prophylaxis
1 other identifier
interventional
114
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Jun 2020
Typical duration for not_applicable
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 27, 2019
CompletedFirst Posted
Study publicly available on registry
December 20, 2019
CompletedStudy Start
First participant enrolled
June 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2022
CompletedFebruary 5, 2020
February 1, 2020
2.6 years
November 27, 2019
February 2, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (4)
Cumulative incidence of variceal bleeding related mortality
12 months
Cumulative incidence of all cause mortality
12 months
Cumulative incidence of hepatic encephalopathy (HE)
12 months
Cumulative incidence of adverse events (AE)
12 months
Study Arms (2)
TIPS
EXPERIMENTALTransjugular intrahepatic portosystemic shunt (TIPS) is a procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver.
NSBB+EBL
ACTIVE COMPARATORParticipants 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.
Interventions
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).
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (1)
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.
PMID: 22366180RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director of clinical research
Study Record Dates
First Submitted
November 27, 2019
First Posted
December 20, 2019
Study Start
June 1, 2020
Primary Completion
December 31, 2022
Study Completion
December 31, 2022
Last Updated
February 5, 2020
Record last verified: 2020-02