Early Implantation of a Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Patients With Liver Cirrhosis and Ascites: a Multicentre, Randomised Controlled Trial
Overview
- Phase
- Not Applicable
- Intervention
- Transjugular intrahepatic portosystemic shunt (TIPS)
- Conditions
- Liver Cirrhosis
- Sponsor
- University Hospital Freiburg
- Enrollment
- 134
- Locations
- 2
- Primary Endpoint
- Transplantation-free survival (TFS)
- Status
- Recruiting
- Last Updated
- yesterday
Overview
Brief Summary
The aim of this clinical trial is to compare the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) implantation with standard treatment (diuretic medications, and if necessary, paracenteses) in patients with liver cirrhosis and development of ascites as the first decompensating event.
By creating a shunt between the liver vein and the portal vein, blood is diverted from the portal vein directly into the hepatic vein, which results in a reduction of pressure in the portal vein so that development of ascites is reduced.
Detailed Description
Complications in patients with liver cirrhosis are mainly due to the development of clinical significant portal hypertension. These complications include development of varices and ascites. Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has emerged as a safe and effective interventional treatment of portal hypertension. TIPS implantation is recommended for secondary prophylaxis of variceal bleeding. Further, in patients with acute variceal bleeding, early TIPS implantation within 72 hours after the bleeding episode is associated with a lower re-bleeding rate and also improved survival in high risk patients. In patients with ascites, TIPS implantation is recommend in more advanced stages when conservative treatment has failed to control ascites. Importantly, ascites clearance can be achieved in only 51% in these patients. Recently, it has been shown that patients with a lower paracenteses frequency have a higher chance of ascites control compared to patients with long-term paracenteses. These data suggest that TIPS implantation in patients with ascites should not be delayed comparable to patients with acute variceal bleeding. The presented study aims to analyse the concept of early TIPS implantation in patients with liver cirrhosis and ascites.
Investigators
Prof. Dr. Dominik Bettinger
Principal Investigator
University Hospital Freiburg
Eligibility Criteria
Inclusion Criteria
- •Patients eligible for inclusion in this trial must meet all of the following criteria:
- •Patients ≥ 18 years and \< 80 years
- •Liver cirrhosis as documented by previous liver biopsy or by a combination of typical clinical, biochemical and sonographic features
- •Ascites as the first single decompensating event with grade 2 ascites and MELD ≥ 15 OR grade 3 ascites
- •Ability to understand the nature of the trial and the trial related procedures and to comply with them
Exclusion Criteria
- •Patients eligible for this trial must not meet any of the following criteria:
- •Treatment refractory or recurrent ascites at the time of study inclusion
- •Patients with concomitant variceal bleeding fulfilling the criteria for pre-emptive TIPS implantation (Child-Pugh class C \< 14 points or Child-Pugh class B \>7 with active bleeding at initial endoscopy or hepatic venous pressure gradient \[HVPG\] \> 20 mmHg at the time of bleeding)
- •Budd-Chiari syndrome
- •Portal vein thrombosis (PVT)
- •Spontaneous bacterial peritonitis (SBP)
- •Uncontrolled systemic infection (defined as an increase of \> 20% if inflammatory parameters \[C-reactive protein, procalcitonin, leukocytes\] and/or sepsis as a reason for development of ascites
- •Cardiac cirrhosis (defined as the development of liver cirrhosis in a patient with cardiac heart failure due to primary cardiac disease)
- •Clinical significant cardiac disease (NYHA ≥II)
- •Untreated valvular heart disease: middle to high-grade valve stenosis or insufficiency (applies to mitral, tricuspid, aortic and pulmonary valves)
Arms & Interventions
Transjugular intrahepatic portosystemic shunt (TIPS)
Patients will receive TIPS implantation if ascites as the first single decompensating event with grade 2 ascites and MELD ≥ 15 OR grade 3 ascites occurs.
Intervention: Transjugular intrahepatic portosystemic shunt (TIPS)
Standard medical treatment
Patients in this group will receive standard medical treatment according to the current EASL guidelines (salt restriction, diuretic treatment, carvedilol, large-volume paracentesis if necessary, albumin substitution if more than 5 litre of ascites is removed)
Outcomes
Primary Outcomes
Transplantation-free survival (TFS)
Time Frame: Through study completion, an average of 12 months
The primary objective of this study is to assess a survival benefit in patients with early allocation to TIPS implantation in comparison to patients with standard medical treatment (SMT).
Secondary Outcomes
- Rate of TIPS implantation in the standard medical treatment group(Through study completion, an average of 12 months)
- Rate of TIPS dysfunction(Through study completion, an average of 12 months)
- Assessment of quality of life(Through study completion, an average of 1 year: at study inclusion, at 6 and 12 months after randomisation)
- Time to ascites with need for paracenteses(Through study completion, an average of 12 months)