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.

Study Overview

• Status: Terminated
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Device: Alfapump; Device: TIPS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Medizische Klinik III
  • Dresden, Germany, 01307
    • Medizinische Klinik und Poliklinik 1 - Gastroenterologie
  • Leipzig, Germany, 04103
    • Uniklinik Leipzig

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alfapump - Substudy 1; Alfapump implantation	Device: Alfapump; Implantation of Alfapump
Active Comparator: TIPS - Substudy 1; TIPS implantation	Device: TIPS; Implantation of TIPS
Experimental: Alfapump - Substudy 2; Alfapump implantation	Device: Alfapump; Implantation of Alfapump
No Intervention: Standard - Substudy 2; Standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is the (average) number of paracenteses per quarter during time without device abandonment, transplant, or death documented on a time horizon of 4 quarters (i.e.1 year).	Starts with randomisation and ends after 12 months or when a device abandonment, transplant, or death occurs before.

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of paracenteses per quarter during time without device abandonment, transplant, or death documented on a time horizon of 24 months.	Starts with randomisation and ends after 24 months or when a device abandonment, transplant, or death occurs before.
Number of paracenteses per quarter during time without transplant or death documented on a time horizon of 24 months.	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Transplant-free survival	From randomisation to 24 months or to death, censoring patients alive at the date of last information or at the date of orthotopic liver transplantation.
Cumulative Incidence of device abandonment	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Volume of ascites removed	Starting four weeks after study inclusion and ending after 24 months or when transplant or death occurs before.
Patients Quality of Life (EQ-5D Questionnaire)	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Frequency and duration of hospital stays	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Nutrition status, assessed by time course of upper arm girth [cm]	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Albumin substitution, assessed as total amount per quarter [g].	Starts with randomisation and ends after 24 months or when transplant or death occurs before.
Cumulative incidence of first occurrence of hepatic encephalopathy Stage 2 or higher	Starts with randomisation and ends after 12 months months or when a device abandonment, transplant, or death occurs before.

Collaborators and Investigators

• Sponsor: University of Leipzig
• Investigators: Principal Investigator: Thomas Berg, Prof. Dr., Uniklinik Leipzig Sektion Hepatologie

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: November 11, 2015
• First Submitted That Met QC Criteria: November 20, 2015
• First Posted (Estimate): November 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites
• Other Study ID Numbers: Agua-Trial