Liver CirrhosisNCT02156232
Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy
A study testing TIPS and SPSS embolization in people with Liver Cirrhosis, run by Air Force Military Medical University, China at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- TIPS and SPSS embolization
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteChina
- Study dates
- 15 Jun 2014to 5 Mar 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Xijing Hospital of Digestive Diseases, Fourth Military Medical University
Xi'an, Shaanxi, 710032
About this study
Official title: Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy: a Prospective、Open-labeled、Randomized、Controlled Trial
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).
Read the 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.
- Conditions
- Liver Cirrhosis
- Being tested
- TIPS, SPSS embolization
- Keywords
- hepatic encephalopathy (HE), vericeal bleeding, spontaneous portosystemic shunts (SPSS), transjugular intrahepatic portosystemic shunt (TIPS), embolization
- Medical subject headings
- Liver Cirrhosis, Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TIPSProcedure or surgery
TIPS is performed with a standard technique. TIPS revision will be planned if any evidence of shunt dysfunction is observed.
SPSS embolizationProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| TIPS, SPSS Emboliaztion | Active comparator | The covered stents wil be used for TIPS The SPSS will be embolized during the procedure of TIPS Receives: Procedure: TIPS; Procedure: SPSS embolization |
| TIPS alone | Active comparator | The covered stents will be used for TIPS No embolization of SPSS will be performed during TIPS Receives: Procedure: TIPS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severiy of participants with overt hepatic encephalopathy
Measured: 2 years
Secondary outcomes (5)
Number of participants with variceal rebleeding
Measured: 2 years
Number of participants with shunt dysfunction
Measured: 2 years
Change of liver function
Measured: 2 years
All-cause mortality
Measured: 2 years
Adverse events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2014 (estimated)
- Study start15 Jun 2014
- Primary completion5 Mar 2021
- Study completion5 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Air Force Military Medical University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guohong Han, Air Force Military Medical University, China
- Investigators
- Guohong Han, PhD,MD, Principal investigator, Xijing Hospital of Digestive Diseases, Fourth Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02156232
- Sponsor's protocol ID
- TIPS-SPSS
- Status last verified
- Oct 2022
- First submitted
- 3 Jun 2014
- Last updated
- 25 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Embolization of Large Spontaneous Portosystemic Shunts for the Prevention of Post-TIPS Hepatic Encephalopathy: a Prospective、Open-labeled、Randomized、Controlled Trial
- ClinicalTrials.gov ID
- NCT02156232
- Acronym / sponsor ID
- TIPS-SPSS
- Conditions
- Liver Cirrhosis
- Keywords
- hepatic encephalopathy (HE), vericeal bleeding, spontaneous portosystemic shunts (SPSS), transjugular intrahepatic portosystemic shunt (TIPS), embolization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 15 Jun 2014
- Primary completion
- 5 Mar 2021 (actual)
- Study completion
- 5 Mar 2021 (actual)
- First posted
- 5 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TIPS, SPSS Emboliaztion | Active comparator | Procedure: TIPS, Procedure: SPSS embolizationThe covered stents wil be used for TIPS The SPSS will be embolized during the procedure of TIPS |
| TIPS alone | Active comparator | Procedure: TIPSThe covered stents will be used for TIPS No embolization of SPSS will be performed during TIPS |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- Hepatic carcinoma and/or other malignancy diseases
- Portal vein thrombosis (≥50% of the lumen)
- Budd-Chiari syndrome
- Child-Pugh score>13 points
- Sepsis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TIPSTIPS is performed with a standard technique. TIPS revision will be planned if any evidence of shunt dysfunction is observed. | Procedure or surgery | TIPS alone, TIPS, SPSS Emboliaztion |
| SPSS embolizationEmbolization 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. | Procedure or surgery | TIPS, SPSS Emboliaztion |
Primary outcome
Number and severiy of participants with overt hepatic encephalopathy
Time frame: 2 years
5 secondary outcomes
Number of participants with variceal rebleeding
Time frame: 2 years
Number of participants with shunt dysfunction
Time frame: 2 years
Change of liver function
Time frame: 2 years
All-cause mortality
Time frame: 2 years
Adverse events
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guohong Han, PhD,MD principal investigator
Xijing Hospital of Digestive Diseases, Fourth Military Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TIPS and SPSS embolization in people with Liver Cirrhosis, run by Air Force Military Medical University, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and severiy of participants with overt hepatic encephalopathy (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.