Clinical trial NCT01528410: ALFApump System Versus Standard of Care in Ascites Treatment
Official title: ALFApump® System Versus Large Volume Paracentesis in the Treatment of Refractory Ascites. A Multicentre Randomised Controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Refractory or Recurrent Ascites
Lead sponsor: Sequana Medical N.V.
Sponsor class: INDUSTRY
First posted: 2012-02-08
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will be a single center, open-label trial.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Paracentesis free survival
timeFrame: 6 months
Secondary outcomes:
measure: Non-inferiority of cirrhosis related complication in the patient group treated with the ALFApump system
timeFrame: 6 months
measure: Quality of Life
timeFrame: 6 months
measure: Body weight
timeFrame: 6 months
measure: Nutritional profile
timeFrame: 6 months
measure: Resource utilisation
timeFrame: 6 months
measure: Survival
timeFrame: 6 months
measure: Assess the need for repeat evacuation paracentesis
timeFrame: 6 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Vienna General Hospital and Medical School, AKH
city: Clichy, Paris
country: France
facility: Hopital Beaujon
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: UCL Institute of Hepatology, Royal Free Hospital, London
name: Rajiv Jalan, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.