Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy
Primary Purpose
Liver Cirrhosis
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
TIPS
SPSS embolization
Sponsored by
About this trial
This is an interventional prevention trial for Liver Cirrhosis focused on measuring hepatic encephalopathy (HE), vericeal bleeding, spontaneous portosystemic shunts (SPSS), transjugular intrahepatic portosystemic shunt (TIPS), embolization
Eligibility Criteria
Inclusion Criteria:
- Signed written informed consent
- Dignosis of liver cirrhosis (clinical or by liver biopsy)
- Admission due to variceal bleeding occurred 5 to 42 days prior and standard treatment for secondary prophylaxis failed
- Confirmed spontaneous portosystemic shunts in abdominal imagings
- Sum of targeted spontaneous portosystemic shunts diameters greater than half the diameter of portal vein
Exclusion Criteria:
- Hepatic carcinoma and/or other malignancy diseases
- Portal vein thrombosis (≥50% of the lumen)
- Budd-Chiari syndrome
- Child-Pugh score>13 points
- Sepsis
- Spontaneous bacterial peritonitis
- Uncontrollable hypertension
- Serious cardiac or pulmonary dysfunction
- Renal failure
- With TIPS contraindications
- Spontaneous recurrent hepatic encephalopathy
- Previous TIPS or collateral embolization
- Pregnancy or breast-feeding
- History of liver transplantation
Sites / Locations
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
TIPS, SPSS Emboliaztion
TIPS alone
Arm Description
The covered stents wil be used for TIPS The SPSS will be embolized during the procedure of TIPS
The covered stents will be used for TIPS No embolization of SPSS will be performed during TIPS
Outcomes
Primary Outcome Measures
Number and severiy of participants with overt hepatic encephalopathy
Secondary Outcome Measures
Number of participants with variceal rebleeding
Number of participants with shunt dysfunction
Change of liver function
All-cause mortality
Adverse events
Full Information
NCT ID
NCT02156232
First Posted
June 3, 2014
Last Updated
October 22, 2022
Sponsor
Air Force Military Medical University, China
1. Study Identification
Unique Protocol Identification Number
NCT02156232
Brief Title
Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy
Official Title
Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy: a Prospective、Open-labeled、Randomized、Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2014 (undefined)
Primary Completion Date
March 5, 2021 (Actual)
Study Completion Date
March 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Air Force Military Medical University, China
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether transjugular intrahepatic portosystemic shunt (TIPS) combined with large spontaneous portosystemic shunts embolization are effective in the prevention of hepatic encephalopathy (HE).
Detailed Description
Transjugular intrahepatic portosystemic shunt (TIPS) has been used for more than 20 years since 1988 to treat some of the complications of portal hypertension, especially variceal bleeding and ascites refractory to conventional therapy. However, this procedure has two major disadvantages: shunt dysfunction and hepatic encephalopathy (HE). Notabley, the use of expanded polytetrafluoroethylene (ePTFE)-covered stent has significantly reduced the risk of shunt dysfunction, but the post-TIPS HE remains a problem even with these new stents.
The incidence of post-TIPS HE ranges between 5% and 35% HE during the first year and tends to be particularly frequent during the first months after TIPS and less common with time. Meta-analysis has that increased age, prior HE and higher Child-Pugh class/score were the most robust predictors for post-TIPS HE.
There is no consensus on the management of post-TIPS HE. Episodic HE after TIPS can be treated traditionally. The cornerstones of the treatment of this type of HE are the identification and treatment of the precipitating event and the general support of the patients. Refractory HE not responding to standard treatment is, in our opinion, the most important problem faced when a patients has to be treated with TIPS. In some cases, the occurrence of this complication may deeply reduce the patient's quality of life and the cure may be worse than the disease. Refractory HE can be treated by reducing the diameter of the stent or by occluding the shunt. However, the procedure is not without dangers and may not solve the problem in all patients, and the complications of portal hypertension, such as varices or refractory ascites, which were supposed to be managed by the TIPS, may recur as a consequence of shunt reduction or occlusion.
Besides, there are no established methods or drugs to effectively prevent the occurrence of HE after TIPS. One possibility is the use of stents with a small diameter, since post-TIPS HE was related to the amount of blood shunted. Riggio et al. compared the incidence of HE after TIPS created with 8-or 10-mm PTFE-covered stents and the study was stopped because of higher complications due to portal hypertension after TIPS in the 8-mm group. Our center performed a RCT to evaluate the effectiveness of L-ornithine-L-aspartate (LOLA) on plasma ammonia in cirrhotic patients after TIPS. Another RCT reevaluateing the effect of TIPS with 8- or 10-mm covered stent for the prevention of variceal rebleeding in cirrhotic patients was also undergoing.
But for those with large spontaneous portosystemic shunts(SPSS), embolization might also represent a therapeutic target.SPSS is, as the name implies, potential communications between the portal venous circulation and the systemic venous circulation that can open, develop, and potentially grow to enable flow within them when one of these circulations (portal or venous) has high pressure or is obstructed or both in an effort to reduce pressure or bypass an obstruction or both. SPSS mainly include splenorenal shunt, gastrorenal shunt, paraesophageal vein, paraumbilical vein, et al. For patients with decompensated cirrhosis, the portal vein pressure increased significantly and some blood were diverted to the systemic circulation by collateral vessels between the splenorenal vein, short gastric veins, posterior gastric vein, and so on, namely SPSS. The nature history of SPSS in patients with liver cirrhosis is still unclear. Most patients were diagnosed by chance.
Previous reports have suggested that the incidence of SPSS was 16% in patients with liver cirrhosis and portal hypertension and the incidence of refractory HE was about 46%. A study published in 2005 revealed that about 71% of the patients with cirrhosis with refractory HE have large SPSS. Therefore, the presence of a SPSS not only provides an explanation for the persistence or recurrence of HE despite an acceptable liver function, it might also represent a therapeutic target. Nowadays, several series have reported embolization of large SPSSs for the treatment of chronic therapy-refractory HE.To date, no data was about the safety and efficacy of embolization of large SPSS in the prevention of post-TIPS HE.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
Keywords
hepatic encephalopathy (HE), vericeal bleeding, spontaneous portosystemic shunts (SPSS), transjugular intrahepatic portosystemic shunt (TIPS), embolization
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TIPS, SPSS Emboliaztion
Arm Type
Active Comparator
Arm Description
The covered stents wil be used for TIPS The SPSS will be embolized during the procedure of TIPS
Arm Title
TIPS alone
Arm Type
Active Comparator
Arm Description
The covered stents will be used for TIPS No embolization of SPSS will be performed during TIPS
Intervention Type
Procedure
Intervention Name(s)
TIPS
Intervention Description
TIPS is performed with a standard technique. TIPS revision will be planned if any evidence of shunt dysfunction is observed.
Intervention Type
Procedure
Intervention Name(s)
SPSS embolization
Intervention Description
Embolization of SPSS will be conducted via the same jugular vein before TIPS implantation. The major procedures included (a) angiography of SPSS after successful intrahepatic puncture of a branch of the portal vein and (b) embolization of SPSS with coils of varying diameters or Amplatzer Vascular Plug, which resulted in the SPSS disappearing at postembolization angiography.
Primary Outcome Measure Information:
Title
Number and severiy of participants with overt hepatic encephalopathy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of participants with variceal rebleeding
Time Frame
2 years
Title
Number of participants with shunt dysfunction
Time Frame
2 years
Title
Change of liver function
Time Frame
2 years
Title
All-cause mortality
Time Frame
2 years
Title
Adverse events
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed written informed consent
Dignosis of liver cirrhosis (clinical or by liver biopsy)
Admission due to variceal bleeding occurred 5 to 42 days prior and standard treatment for secondary prophylaxis failed
Confirmed spontaneous portosystemic shunts in abdominal imagings
Sum of targeted spontaneous portosystemic shunts diameters greater than half the diameter of portal vein
Exclusion Criteria:
Hepatic carcinoma and/or other malignancy diseases
Portal vein thrombosis (≥50% of the lumen)
Budd-Chiari syndrome
Child-Pugh score>13 points
Sepsis
Spontaneous bacterial peritonitis
Uncontrollable hypertension
Serious cardiac or pulmonary dysfunction
Renal failure
With TIPS contraindications
Spontaneous recurrent hepatic encephalopathy
Previous TIPS or collateral embolization
Pregnancy or breast-feeding
History of liver transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guohong Han, PhD,MD
Organizational Affiliation
Xijing Hospital of Digestive Diseases, Fourth Military Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xijing Hospital of Digestive Diseases, Fourth Military Medical University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710032
Country
China
12. IPD Sharing Statement
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Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy
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