ALFApump System Versus Standard of Care in Ascites Treatment

ALFApump® System Versus Large Volume Paracentesis in the Treatment of Refractory Ascites. A Multicentre Randomised Controlled Study.

This is a multicentre, open, randomised, and controlled trial conducted in sixty (60) patients diagnosed with refractory or recurrent ascites. Patients will be randomised (enrolled) to either treatment arm A- implanted with the ALFApump System or treatment arm B-standard of care with evacuation large volume paracentesis. The main aims of the study are to determine the paracentesis free survival, defined as the time to the first large volume therapeutic paracentesis > 5 litres. The secondary aims are to assess non-inferiority of cirrhosis-related complications in the group of patients randomized to the ALFApump system group, as well as nutritional effects, resource utilisation, patient quality of life and survival non-inferiority.

Study Overview

• Status: Completed
• Conditions: Refractory or Recurrent Ascites
• Intervention / Treatment: Device: ALFApump removal of ascites; Procedure: Large volume paracentesis for removal of ascites

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Vienna General Hospital and Medical School, AKH
• France
  • Clichy, Paris, France
    • Hopital Beaujon
  • Toulouse, France
    • Centre Hospitalier Universitaire de Toulouse
• Italy
  • Padova, Italy
    • Azienda Ospedaliera di Padova
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
• United Kingdom
  • Bristol, United Kingdom
    • Bristol Royal Infirmary
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital

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. Males and non-pregnant females (determined by serum pregnancy test) ≥ 18 years of age. Women of childbearing age must be prepared to use at least 1 effective (≤ 1% failure rate) method of contraception during the course of the study
2. Cirrhosis of the liver defined by histological and/or clinical, and/or radiological criteria
3. Presenting refractory or recurrent ascites and requiring periodic large volume paracentesis (large volume defined as > 5 L to accord with teh clinical guidance of EASL, European Association for the Study of the Liver, which recommends withdrawal of 5 L should precipitate administration of albumin).
4. Capable of giving written informed consent, willing to comply with study procedures and ability to operate the device

Exclusion Criteria:

1. Gastrointestinal haemorrhage over the last 7 days
2. Renal failure defined as serum creatinine higher than or equal to 2 mg/dl
3. Severe coagulopathy defined as prothrombin time greater than 40% more than upper limit of Normal (as determined locally).
4. Platelet count of less than 40000 /uL unless platelet therapy is given at the time of surgery
5. 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.
6. 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.
7. Clinical evidence of loculated ascites.
8. Advanced hepatocarcinoma, defined as one which exceeds Milan criteria.
9. Obstructive uropathy, residual urinary volume exceeding 100 ml, or any bladder anomaly which might contraindicate implantation of the device.
10. Concurrently implanted with any other Active Implantable Medical Device, including, but not limited to, cardiac pacemaker or cardioverter defibrillator.
11. Pregnant females or females anticipating pregnancy during study period
12. Patients currently enrolled in another interventional clinical study
13. Other concomitant disease or condition likely to significantly decrease life expectancy or present anaesthetic risk (e.g., moderate to severe congestive heart failure)
14. Known presence of human immunodeficiency virus (HIV)
15. Immuno-modulatory treatment (including azothioprine, methotrexate, anti-TNF therapies) used within last 4 months
16. Known or suspected hepatic or extra hepatic malignancy, unless adequately treated or in complete remission for ≥ 3 years
17. BMI > 40 presenting a risk for surgery and tunneled lines
18. Patients with contraindications for general anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ALFApump removal of ascites; Removal of ascites	Device: ALFApump removal of ascites; Implanted ALFApump, removing produced ascites according to programmed schedule; Other Names: ALFApump (Automated Low Flow Ascites pump)
ACTIVE_COMPARATOR: Large volume paracentesis for removal of ascites; Removal of ascites	Procedure: Large volume paracentesis for removal of ascites; Large volume paracentesis - standard of care, removing ascites according to patient need; Other Names: Extraction of fluid from the abdominal cavity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paracentesis free survival	Paracentesis-free survival, defined as time to first large volume therapeutic paracentesis > 5 litres	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival		6 months
Quality of Life		6 months
Body weight		6 months
Non-inferiority of cirrhosis related complication in the patient group treated with the ALFApump system	Cirrhosis-related complications	6 months
Nutritional profile		6 months
Resource utilisation		6 months
Assess the need for repeat evacuation paracentesis		6 months

Collaborators and Investigators

• Sponsor: Sequana Medical N.V.
• Investigators: Principal Investigator: Rajiv Jalan, Professor, UCL Institute of Hepatology, Royal Free Hospital, London

Publications and helpful links

General Publications

• Stepanova M, Nader F, Bureau C, Adebayo D, Elkrief L, Valla D, Peck-Radosavljevic M, McCune A, Vargas V, Simon-Talero M, Cordoba J, Angeli P, Rossi S, MacDonald S, Capel J, Jalan R, Younossi ZM. Patients with refractory ascites treated with alfapump(R) system have better health-related quality of life as compared to those treated with large volume paracentesis: the results of a multicenter randomized controlled study. Qual Life Res. 2018 Jun;27(6):1513-1520. doi: 10.1007/s11136-018-1813-8. Epub 2018 Feb 19.
• Bureau C, Adebayo D, Chalret de Rieu M, Elkrief L, Valla D, Peck-Radosavljevic M, McCune A, Vargas V, Simon-Talero M, Cordoba J, Angeli P, Rosi S, MacDonald S, Malago M, Stepanova M, Younossi ZM, Trepte C, Watson R, Borisenko O, Sun S, Inhaber N, Jalan R. Alfapump(R) system vs. large volume paracentesis for refractory ascites: A multicenter randomized controlled study. J Hepatol. 2017 Nov;67(5):940-949. doi: 10.1016/j.jhep.2017.06.010. Epub 2017 Jun 21. Erratum In: J Hepatol. 2018 Jan 29;: J Hepatol. 2020 Mar;72(3):595-596.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 17, 2012
• Primary Completion (ACTUAL): September 21, 2016
• Study Completion (ACTUAL): September 21, 2016

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (ESTIMATE): February 8, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 12, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: 2012-AAR-005