Alfapump-albumin Replacement Therapy

Study Into the Effects of Albumin Replacement Therapy on Renal and Circulatory Function in Patients Implanted With the Alfapump

The study will be a single centre, open-label trial. The patients will have a diagnosis of refractory ascites and will meet specified inclusion/exclusion criteria Informed consent will be obtained from all patients. All patients will have an alfapump surgically inserted and in addition will receive 8g of salt-poor Human Albumin Solution (20%) per 1 litre of Ascites drained. This Intravenous administration will be intermittent (every month) and will take place as a day patient. Patients will also receive standard of care, which may include, but is not limited to, administration of diuretics, paracentesis and consideration for orthotopic liver transplantation.

Study Overview

• Status: Terminated
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Device: alfapump; Drug: salt-poor Human Albumin solution

Detailed Description

The study will be a single centre, open-label trial. The patients will have a diagnosis of refractory ascites and will meet specified inclusion/exclusion criteria Informed consent will be obtained from all patients. All patients will have an alfapump surgically inserted and in addition will receive 8g of salt-poor Human Albumin Solution (20%) per 1 litre of Ascites drained. This Intravenous administration will be intermittent (every 2 weeks) and will take place as a day patient. Patients will also receive standard of care, which may include, but is not limited to, administration of diuretics, paracentesis and consideration for orthotopic liver transplantation.

The primary objective of the study is to assess whether intermittent human albumin replacement in accordance with large volume paracentesis guidelines (8g/L ascites drained) can prevent the development of renal dysfunction at the 3-month assessment. This would potentially guide the clinical use of the alfapump system.

The secondary objectives of the study are to address the objectives of a previous alfa pump study /sub study, to allow comparison of the proposed study data to that generated in the previous studies. These will be measured at the 1-month and 3-month time points.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • 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 with refractory ascites* and requiring periodic large volume paracentesis (large volume defined as ≥ 5 L to accord with the 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
4. Platelet count of less than 40,000 / μL unless platelet therapy is given at the time of surgery
5. Clinical Evidence of recurrent 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 recurrent 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 hepatocellular carcinoma, defined as exceeding Milan criteria
9. Obstructive uropathy, residual urinary volume exceeding 100ml, 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 cardiovertering 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 azathioprine, 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 tunnelled lines
18. Patients with contraindications for general anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alfapump with albumin treatment; patients implanted with an alfapump, receiving intermittent salt-poor Human Albumin solution treatment	Device: alfapump; Implantation of alfapump; Other Names: automated low flow ascites pump; Drug: salt-poor Human Albumin solution; Patients implanted with an alfapump will receive intermittent salt-poor human albumin solution; Other Names: Human albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess whether intermittent human albumin replacement in accordance with large volume paracentesis guidelines (8g/L ascites drained) can prevent the development of renal dysfunction, measured by serum creatinine	Measured by serum creatinine.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of circulatory haemodynamics, measured by non-invasive cardiac haemodynamics	Measured by non-invasive cardiac haemodynamics	3 months
Assessment of cirrhosis- related complications, measured by Incidence of specific cirrhosis-related complications	Measured by Incidence of specific cirrhosis-related complications	3 months
Assessment of the Overall Survival at 3 months, measured by survival	Measured by overall survival at 3 months	3 months
Assessment of impact on nutrition, measured by changes in body weight	Measured by changes in the nutritional status of the patient	3 months
Assessment of impact on nutrition, measured by changes in circumference of arm	Measured by changes in the nutritional status of the patient	3 months
Assessment of impact on nutrition, measured by changes in tricipital skinfold	Measured by changes in the nutritional status of the patient	3 months
Assessment of impact on nutrition, measured by changes in handgrip	Measured by changes in the nutritional status of the patient	3 months
Assessment of the need for large volume paracentesis, measured by the overall requirements of paracentesis	Measured by the overall requirement for paracentesis	3 months
Assessment of impact on Systemic Inflammatory Response, measured by CRP	Measured by Inflammatory markers	3 months
Assessment of impact on Systemic Inflammatory Response, measured by cytokines	Measured by Inflammatory markers	3 months
Assessment of impact on Systemic Inflammatory Response, measured by function of the peripheral blood mononuclear cells	Measured by Inflammatory markers	3 months
Assessment of levels of bacterial DNA in serum, measured by presence of bacterial DNA in blood	Measured by the presence of bacterial DNA in blood.	3 months

Collaborators and Investigators

• Sponsor: Sequana Medical N.V.
• Investigators: Principal Investigator: Rajiv Jalan, Professor, Royal Free Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: April 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 2015-AAR-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED