TIPS With Coated Stents for Refractory Ascites in Patients With Cirrhosis

Cirrhosis Clinical Trial

Official title:

TIPS (With Coated Stents) OR PARACENTESIS + ALBUMIN ADMINISTRATION FOR THE TREATMENT OF REFRACTORY ASCITES IN PATIENTS WITH CIRRHOSIS : A RANDOMIZED TRIAL COMPARING SURVIVAL, QUALITY OF LIFE AND NUTRITIONAL STATUS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00222014
• Other study ID #: 0402308
• Secondary ID: PHRC
• Status: Completed
• Phase: N/A
• First received: September 13, 2005
• Last updated: January 22, 2013
• Start date: May 2005
• Est. completion date: January 2013

Study information

• Verified date: January 2013
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The main end point of the study is to assess survival in cirrhotic patients with refractory ascites treated by TIPS (using PTFE covered stents) vs patients treated by paracentesis + albumin infusion.

Description:

Diagnostic evaluation before randomisation includes assessment of clinical hepatic encephalopathy, usual blood tests, and Doppler-ultrasonography of the abdomen. Inclusion and exclusion criteria will be checked during the inclusion visit. Informations concerning the trial will also be given. After the investigator receives written informed consent, randomisation will be performed online. Randomisation will be centralized, equilibrated for each center, stratified according to whether cirrhosis is alcoholic or not and adjusted every ten patients.

I Treatments

1. TIPS :

TIPS will be performed under sedation or general anesthesia with tracheal intubation according to the usual policy of participating centers. Pre-tips portosystemic pressure gradient and diameter of the shunt must be notified.

However, for homogeneity reasons the following will be adhered:

A 10 mm Viator stent will be used, that will be dilated to 8 or 10 mm according to the hemodynamic response. The aim will be to reduce portal pressure gradient (PPG) below 12 mmHg. Ideal PPG should be 7-8 mmHg.

2. Paracentesis + albumin infusion :

After a paracentesis > 3 liters, 8 g of Albumin per liter of extracted ascites must be infused.

If possible, analysis of ascitic fluid will be performed after each paracentesis for biochemical, cytological and bacterial analyses.

II Follow up

1. In all patients:

Low salt diet (2 - 4 g/j). Follow up of the patient is as usual. Patients will have a clinical examination at 1 month and then every 3 months up to 1 year. At each visit, clinical and biochemical variables needed to calculate Child-Pugh score will be recorded.

Doppler ultrasonography will be performed at the beginning, 6 and 12 months. Patients will be followed 1 year or until liver transplantation or death.

1. Nutritional status evaluation:

• Weight: M0, M3, M6, M9, M12

• Anthropometrics measurements: M0, M3, M6, M12: they will include : triceps skinfold thickness, biceps skinfold thickness, brachial circumference.

• Biochemical parameters: M0, M3, M6, M12: they will include : albumin, pre-albumin, orosomucoïde, C-reactive protein, haptoglobin, natriuresis, 24 hour urinary excretion of creatinine. Four blood samples will be collected and conserved for a posteriori analysis if required (transferrin, retinol binding protein, leptin, hormonal dosages). These analyses will be centralized in Toulouse (Toulouse center will be charged for the shipment of those blood samples).

• Physical parameters: dual energy x-ray absorptiometry M0, M12

• Grip test M0, M6, M12 [16, 17].

2. Quality of Life :

SF-36 (Short Form 36 (SF-36) Health Survey Questionnaire) at inclusion and then every three months [18, 19].

2. Paracentesis + albumin infusion group:

Patients included in this group will be treated by paracentesis whenever required. Eight grams of albumin per liter of ascites extracted will be infused when more than 3 liters of ascitic fluid will be removed.

3. TIPS group :

When shunt dysfunction will be suspected because of relapse of ascites or incomplete response 2 months after the procedure, an angiography and PPG measurement will be performed. If shunt dysfunction is confirmed, angioplasty or PTFE re-stenting will aim at reducing PPG below 12 mmHg.

III Definition of treatment failure:

After TIPS: relapse of ascites requiring at least 2 paracenteses or persistence after 2 months will be considered as treatment failure. A hemodynamic and angiographic control will be performed. Patients will be treated by refection of the shunt. If severe encephalopathy occurs and persists despite treatment, the diameter of the shunt should be decreased or the TIPS occluded. Total occlusion of the shunt or relapse of ascites after the reduction of its diameter will be also considered treatment failures.

In the group treated by paracentesis + albumin infusion, patients having more than 6 paracenteses within 3 months will be considered for alternative treatment (TIPS, transplantation). Technical impossibility or refusal of the patient to proceed with paracenteses will be also considered treatment failure. In these cases, a TIPS could also be proposed.

All these patients with treatment failure must be followed up to one year after inclusion

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• patients of both sexes, with cirrhosis, as documented by previous liver-biopsy or usual clinical and biochemical stigmata

• with refractory or recurrent ascites as defined in chapter IV

• who signed the informed consent form

Exclusion Criteria:

• patients not fulfilling inclusion criteria

• patients having needed more than 6 paracenteses within the last 3 months

• patients expected to be transplanted within the next 6 months

• usual contra-indication for TIPS : congestive heart failure NYHA>III or medical history of pulmonary hypertension, portal vein thrombosis, hepatic polycystosis, intra-hepatic bile ducts dilatation, spontaneous clinical recurrent hepatic encephalopathy

• hepatocarcinoma on the expected tract of the shunt

• severe liver failure as defined by : Prothrombin index < 35 % or total bilirubin > 100 micromol/l or Child Pugh Score >12

• serum creatinine > 250 micromol/l

• uncontrolled sepsis

• known allergy to albumin

• pregnant or breast feeding women

• refusal to participate or patient unable to receive informations or to sign written informed consent

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Liver Cirrhosis

Intervention

Procedure:
• TIPS
Transjugular intrahepatic portosystemic shunt with covered PTFE
• Paracenthese
Paracenthese

Locations

Country	Name	City	State
France	University Hospital	Angers
France	University Hospital	Lille
France	Hôpital de la Pitié-Salpétrière	Paris
France	Service d'Hépato-Gastro-Entérologie, Hôpital Purpan	Toulouse

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Toulouse	GORE Laboratory, Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Bureau C, Garcia-Pagan JC, Otal P, Pomier-Layrargues G, Chabbert V, Cortez C, Perreault P, Péron JM, Abraldes JG, Bouchard L, Bilbao JI, Bosch J, Rousseau H, Vinel JP. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology. 2004 Feb;126(2):469-75. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at one year		one year	Yes
Secondary	Quality of life, nutritional status, occurrence of complications (other than ascites) secondary to portal hypertension.		one year	Yes