Clinical trial NCT02156232: 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
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Keywords: hepatic encephalopathy (HE)
vericeal bleeding
spontaneous portosystemic shunts (SPSS)
transjugular intrahepatic portosystemic shunt (TIPS)
embolization
Lead sponsor: Air Force Military Medical University, China
Sponsor class: OTHER
First posted: 2014-06-05
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number and severiy of participants with overt hepatic encephalopathy
timeFrame: 2 years
Secondary outcomes:
measure: Number of participants with variceal rebleeding
timeFrame: 2 years
measure: Number of participants with shunt dysfunction
timeFrame: 2 years
measure: Change of liver function
timeFrame: 2 years
measure: All-cause mortality
timeFrame: 2 years
measure: Adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Hospital of Digestive Diseases, Fourth Military Medical University
state: Shaanxi
Study officials:
affiliation: Xijing Hospital of Digestive Diseases, Fourth Military Medical University
name: Guohong Han, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: