TIPS with PTFE covered stents vs paracentesis + albumin infusion for the treatment of refractory ascites in patients with cirrhosis: a randomized trial comparing survival, quality of life and nutritional status.

For patients with liver cirrhosis, complicated by ascites, which is not well
controlled by paracentesis (surgical puncture of the abdominal cavity for the
aspiration of peritoneal fluid), because ascites returns quickly, there is an
alternative, TIPS-procedure. For this procedure, a small tube (a stent) is
placed between two veins in the liver to decompress the veins of the liver.
When this is successful, ascites will decrease as well. However, the main
drawback of TIPS, which, until recently, occurred in most cases (80%) was the
closure of the tube. Because of this the pressure in the veins of the liver
increased again, and the ascites returned as well.
This problem of TIPS, however, now seems solved, because of recent improvements
in stent-technology. TIPS procedures are nowadays being carried out using
covered stent-grafts instead of open bare metal stents, and this has
dramatically improved the patency of the stents, and thus decreases the
possibility of the development of ascites. The absence of ascites might improve
nutritional status, because there is no fluid in the abdomen, which could
bother the appetite and quality of life.
When ascites could be treated earlier, this could lead to better nutritional
pattern and hence decreases the possibility of complications and thus improves
survival. This has never been investigated with the current stents.

The aim of this study is to compare the new covered TIPS-stent with
paracentesis with albumin infusion with regard to nutritional status, quality
of life and survival.
The theory is that when ascites is treated in an earlier stage of liver
cirrhosis, patients will keep a better nutritional status. Hence, the risk of
complications because of weakness could be decreased and thus quality of life
and survival improved.

In total 136 patients, divided over 7 hospitals in Europe, will take part in
this study. The study was started from a hospital in Toulouse, France and the
Erasmus medical center is the only Dutch center participating.
To determine whether one treatment option is better than the other, the
participants will be randomized into two groups. Whether TIPS is more effective
than the common used therapy, paracentesis with albumin infusion, can be
discovered by comparing the groups. The participants will be controlled every
three months for one year, from the moment the TIPS-stent is placed, or the
first paracentesis has taken place. Several measurements will be done. After
the last measurement after 12 months the study will end.
The study will continue for 3 years, 2 years in which patients will be asked to
participate, and one year to follow the last participants.

TIPS (Transjugular Intrahepatic Portosystemic Shunt) procedure.

Through a vein in the neck, a small tube (a stent) is placed between two veins
in the liver to decompress the veins of the liver.

TIPS-procedure:

TIPS will be performed under general anesthesia. Nausea and vomiting after
waking are less frequent with the current medication techniques, but might
occur. During the first hours after anesthesia some problems concerning memory
or concentration might arise.
Because of intubating ( to ensure the respiration during the
intervention)dental damage by the tube could arise. Unforeseen complications,
which are life threatening, like a grave allergy, cardiac arrest, or
respiration arrest are very rare, and they occur in less than 3 out of 10.000
anesthesia*s. The stent will be placed between the veins in the liver through a
vein in the neck. The place in the neck where this is done might get a bruise
after the intervention. Some days after the intervention pain from the veins
may be perceived. This will disappear spontaneously. Other complications that
might occur after the TIPS-procedure, are temporal cardiac arrhythmias,
jaundice and fever. In rare cases puncture of the liver capsule with the needle
can occur and blood might flow into the abdominal cavity, but usely this has no
major consequences.
TIPS increases the risk of hepatic encephalopathy. This is confusion and
dullness related to the liver disease. When this happens it might be neccesary
to close the stent, to decline the disturbances. Patients who will be treated
with TIPS will be hospitalized to place the stent; this will take some days.
When the patient does not get better after the TIPS-procedure, he will be
treated further by the conventional therapy, paracentesis with albumin infusion.

Participation in the study means that the patient will be controlled 5 times
during 1 year in view of the study. In many cases this will go together with
the usual control in the policlinic. During these controls several measurements
will be done. Twice abdominal ultrasonography will be done, twice radiological
examination will be done to determine nutritional status and every control a
questionnaire should be filled in and blood will be taken.

Burden and risks of conventional therapy (paracentesis with albumin infusion):
During the year patient will undergo this treatment, every time there is a big
amount of ascites.

Both treatment groups get a low-salt diet and will be controlled in the
policlinic every three months. In all controls participants will be weighed,
particular measurements will be done, a questionnaire should be filled in and
blood and urine is taken for specific measurings. In the first and in the last
visit nutritional status will be observed by x-ray on the radiology-department
(by measuring the fat content of the body). After 6 months and 1 year an
abdominal ultrasonography will be done.

Within the framework of the study the patient has to visit the hospital 5 times
extra. These controls will as much as possible be subsequent to the controls of
the treating doctor, but will take approximately 30 minutes extra each visit.
When ultrasonography or nutritional-status-examination at the
radiology-department is done the visit will take a couple of hours longer.