Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis

• ClinicalTrials.gov Identifier: NCT01326949
• Recruitment Status: Completed
• First Posted: March 31, 2011
• Last Update Posted: May 19, 2017
• Sponsor: Air Force Military Medical University, China
• Information provided by (Responsible Party): Guohong Han, Air Force Military Medical University, China

Tracking Information

• First Submitted Date: March 29, 2011
• First Posted Date: March 31, 2011
• Last Update Posted Date: May 19, 2017
• Study Start Date: May 2011
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2011)

Number of participants with variceal rebleeding [ Time Frame: 4 years ]

Variceal rebleeding is the primary endpoint of this study. Cumulative variceal rebleeding rate is compared between the two groups.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 30, 2011)

• Number of death [ Time Frame: 4 years ]
  Death is a secondary endpoint of this study. Cumulative survival rate is compared between the two groups.
• Number of participants achieving portal vein recanalization [ Time Frame: 4 years ]
  Portal vein recanalization is a secondary endpoint of this study. Recanalization rate of thrombosed portal vein is compared between the two groups.
• Changes of degree of PVT in patients without portal vein recanalization [ Time Frame: 4 years ]
  We also observed changes of degree of portal vein thrombosis in patients without portal vein recanalization.
• Number of complications [ Time Frame: 4 years ]
  Complications include: TIPS-related complications: procedural complications, shunt dysfunction and hepatic encephalopathy. Complications related to endoscopic and drug treatment.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis
• Official Title: Transjugular Intrahepatic Portosystemic Shunt Versus Endoscopic Treatment Combined With Propranolol for Prevention of Variceal Rebleeding in Cirrhotic Patients With Portal Vein Thrombosis: A Randomized Controlled Trial

Brief Summary

Portal vein thrombosis (PVT) refers to an obstruction in the trunk of the portal vein. It can extend downstream to the portal branches, or upstream to the splenic and/or the mesenteric veins. The prevalence of PVT is 10-25% and incidence is about 16% in cirrhotic patients. Recent studies demonstrate that the presence of PVT is not only an independent predictor of failure to control active variceal bleeding and prevent variceal rebleeding, but also significantly associated with increased mortality in patients with liver cirrhosis.

However, in recent American Association of the Study of Liver Disease (AASLD) practice guidelines and Baveno V consensus, no treatment strategies in cirrhotic patients with PVT was clearly recommended due to the absence of randomized controlled trials.

Detailed Description

Usually, cirrhotic patients with PVT are submitted to variceal rebleeding prophylaxis with endoscopic band ligation combined with non-selective beta-blockers and, when necessary, the anticoagulation is started after the varices eradication.

TIPS is just regarded as the second-line therapy for the secondary prophylaxis of variceal bleeding in cirrhotic patients. However, this indication might be changed in the setting of PVT. Indeed, the risk to benefit ratio of TIPS in cirrhotic patients with PVT for the prevention of recurrent variceal bleeding has never been evaluated.

The aim of this study is to compare the efficacy and safety of TIPS and endoscopic band ligation + propranolol in decompensated cirrhosis patients with PVT and a history of variceal bleeding in the past 6 weeks.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Decompensated Cirrhosis
• Portal Vein Thrombosis
• Bleeding Varices

Intervention

• Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)
  Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS was performed in a conventional fashion or in combination of percutaneous transhepatic or transsplenic approach. Postoperatively, intravenous heparin (8,000-12,000 u/d) for five days, warfarin for six months were given.
• Procedure: ET+NSBB

  ET-Esophageal varices was treated by endoscopic variceal ligation (EVL). EVL was repeated at intervals of 1-2 weeks until the varices were obliterated or reduced to grade-I size.

  NSBB-Propranolol started at a dose of 20mg twice a day. The dose is adjusted to the maximal tolerated doses to heart rate (HR) of 55 bpm or to decrease the HR 25% from baseline.

  AT-A continuously intravenous infusion of unfractionated heparin followed by oral warfarin is employed. Initially, heparin is administered intravenously for 5 days. Subsequently, oral warfarin is prescribed at the dosage of 2.5 mg/d for 6 months or until complete portal vein recanalization and adjusted to maintain the INR at a target of 2.5 (range 2.0-3.0).

Study Arms

• Active Comparator: ET+NSBB

  Endoscopic treatment(ET)- Endoscopic variceal ligation (EVL)

  Non-selective beta blocker(NSBB)-Propranolol.

  Anticoagulation(AT)- Heparin followed by warfarin.

  Intervention: Procedure: ET+NSBB
• Active Comparator: TIPS
  Transjugular intrahepatic portosystemic shunt(TIPS)- TIPS.
  Intervention: Procedure: Transjugular intrahepatic portosystemic shunt (TIPS)

Publications *

• Han G, Qi X, He C, Yin Z, Wang J, Xia J, Yang Z, Bai M, Meng X, Niu J, Wu K, Fan D. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis. J Hepatol. 2011 Jan;54(1):78-88. doi: 10.1016/j.jhep.2010.06.029. Epub 2010 Aug 27.
• Simonetti RG, Perricone G, Robbins HL, Battula NR, Weickert MO, Sutton R, Khan S. Portosystemic shunts versus endoscopic intervention with or without medical treatment for prevention of rebleeding in people with cirrhosis. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD000553. doi: 10.1002/14651858.CD000553.pub3.
• Lv Y, Qi X, He C, Wang Z, Yin Z, Niu J, Guo W, Bai W, Zhang H, Xie H, Yao L, Wang J, Li T, Wang Q, Chen H, Liu H, Wang E, Xia D, Luo B, Li X, Yuan J, Han N, Zhu Y, Xia J, Cai H, Yang Z, Wu K, Fan D, Han G; PVT-TIPS Study Group.. Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: a randomised controlled trial. Gut. 2018 Dec;67(12):2156-2168. doi: 10.1136/gutjnl-2017-314634. Epub 2017 Sep 28.
• Qi X, He C, Yin Z, Wang Z, Zhang H, Yao L, Wang J, Xia J, Cai H, Yang Z, Bai M, Guo W, Niu J, Wu K, Fan D, Han G; PVT-TIPS Study Group. Transjugular intrahepatic portosystemic shunt for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: study protocol for a randomised controlled trial. BMJ Open. 2013 Jul 11;3(7):e003370. doi: 10.1136/bmjopen-2013-003370. Print 2013.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2015): 52
• Original Estimated Enrollment (submitted: March 30, 2011): 50
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Written informed consent
• Liver cirrhosis
• Portal vein thrombosis (degree of vessel obstruction > 50%)
• History of variceal hemorrhage in the past 6 weeks (recent variceal bleeding has been controlled for at least 120 hours)

Exclusion Criteria:

• Uncontrolled active variceal bleeding
• Fibrotic cord of the portal vein
• Prior history of TIPS placement or shunt surgery or endoscopic ban ligation +NSBB
• Concomitant renal insufficiency
• Severe cardiopulmonary diseases
• Uncontrolled systemic infection or sepsis
• Malignancy or other serious medical illness which may reduce the life expectancy
• Contraindications for propranolol, such as asthma, insulin-dependent diabetes (with episodes of hypoglycemia), and peripheral vascular disease
• Contraindications for heparin or warfarin
• Contraindications for TIPS

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01326949
• Other Study ID Numbers: 1PVT-TIPS
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Guohong Han, Air Force Military Medical University, China
• Original Responsible Party: Guohong Han, MD., Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University
• Current Study Sponsor: Air Force Military Medical University, China
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Guohong Han; Xijing Hospital of Digestive Diseases, Fourth Military Medical University

• PRS Account: Air Force Military Medical University, China
• Verification Date: May 2017