Alfapump-albumin Replacement Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Device: alfapump
* Drug: salt-poor Human Albumin solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Cirrhosis of the liver defined by histological and/or clinical, and/or radiological criteria 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). Capable of giving written informed consent, willing to comply with study procedures and ability to operate the device Exclusion Criteria: Gastrointestinal haemorrhage over the last 7 days Renal failure defined as serum creatinine higher than or equal to 2 mg/dl Severe coagulopathy defined as prothrombin time greater than 40% more than Upper Limit of Normal Platelet count of less than 40,000 / μL unless platelet therapy is given at the time of surgery 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 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 Clinical evidence of loculated ascites Advanced hepatocellular carcinoma, defined as exceeding Milan criteria Obstructive uropathy, residual urinary volume exceeding 100ml, or any bladder anomaly which might contraindicate implantation of the device Concurrently implanted with any other Active Implantable Medical Device, including, but not limited to cardiac pacemaker or cardiovertering defibrillator Pregnant females or females anticipating pregnancy during study period Patients currently enrolled in another interventional clinical study Other concomitant disease or condition likely to significantly decrease life expectancy or present anaesthetic risk (e.g., moderate to severe congestive heart failure) Known presence of human immunodeficiency virus (HIV) Immuno-modulatory treatment (including azathioprine, methotrexate, anti-TNF therapies) used within last 4 months Known or suspected hepatic or extra hepatic malignancy, unless adequately treated or in complete remission for ≥ 3 years BMI>40 presenting a risk for surgery and tunnelled lines Patients with contraindications for general anesthesia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |