Alfapump System Versus Transjugular Intrahepatic Portosystemic Shunt and Paracentesis in the Treatment of Ascites

Alfapump System Versus Transjugular Intrahepatic Portosystemic Shunt and Paracentesis in the Treatment of Ascites. A Multicentre Randomised Controlled Study

Multicentre, open, randomised, and controlled trial conducted in patients diagnosed with recurrent/refractory ascites who meet inclusion/exclusion criteria. The efficacy of the Alfapump, TIPS and paracentesis with regard to the treatment of ascites will be compared. All patients will receive medical care for cirrhosis and ascites according to the institution's standards of care. Standard of care may include, but is not limited to the administration of diuretics, paracentesis and consideration for orthotopic liver transplantation.

The study will include patients with decompensated liver cirrhosis and recurrent or refractory, with regular requirements for large volume paracentesis (see subject inclusion criteria). With respect to TIPS-contraindications patients will be assigned to two substudies. If no TIPS-contraindications exists (sub-study 1) patients will be randomized to Alfapump or TIPS. The presence of at least one TIPS-contraindication (sub-study 2) is leading to a randomization to Alfapump or standard of care. All patients will receive medical care for cirrhosis and ascites according to the institution's standards medical care. Standard of care may include, but is not limited to, administration of diuretics, paracentesis and consideration for orthotopic liver transplantation.

Inclusion Criteria:

1. Cirrhosis of the liver
2. Recurrent or refractory ascites
3. Age ≥ 18 years (at informed consent)
4. Written informed consent
5. Expected ability to operate the Alfapump device
6. Alcohol abstinence ≥ 3 months at date of inclusion

Exclusion Criteria:

1. General contraindications indicating an advanced stage of liver cirrhosis:

   • Bilirubin > 5 mg/dl and/or
   • INR > 1.5 (without oral anticoagulant such as Vitamin K antagonists or new oral anticoagulants (NOAKs), which inhibit the determination of INR. Therefore patients must be switched to alternative anticoagulants such as heparin or low molecular heparin or fondaparinux that do not interfere with INR measurements) and/or
   • Serum-Sodium < 130 mmol/l and/or
   • ECOG > 2 (Performance status)

2. Gastrointestinal haemorrhage during the last 7 days before inclusion

3. Renal failure defined as serum creatinine higher than or equal to 1,5 mg/dl at time of inclusion

4. Clinical evidence of recurring bacterial peritonitis, defined as 2 or more episodes over the last 6 months or a single episode within the last 2 weeks before inclusion.

5. Clinical evidence of recurring urinary infections, defined as 2 or more episodes over the last 6 months or a single episode within the last 2 weeks before inclusion.

6. Clinical evidence of loculated ascites.

7. Residual urinary volume exceeding 100 ml if obstructive uropathy is known or suspected

8. Known bladder anomaly which might contraindicate implantation of the device.

9. Known or suspected hepatic or extra hepatic malignancy, unless adequately treated and in complete remission for ≥ 3 years

10. Known active chronic hepatitis C (unless adequately treated, i.e no Virus-RNA detectable after cessation of antiviral treatment)

11. Acute peritonitis

12. Pregnant or nursing women. (A serum pregnancy test is required for fertile women within two years of their last menstruation.)

13. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implantation, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial

14. Suspected lack of compliance

15. Patients enrolled in another interventional clinical study