Alfapump-albumin Replacement Therapy

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02448160
• Other study ID #: 2015-AAR-009
• Status: Terminated
• Phase: N/A
• First received: April 30, 2015
• Last updated: April 5, 2018
• Start date: January 2016
• Est. completion date: December 2017

Study information

• Verified date: April 2018
• Source: Sequana Medical AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Liver Cirrhosis

Intervention

Device:
• alfapump
Implantation of alfapump

Drug:
• salt-poor Human Albumin solution
Patients implanted with an alfapump will receive intermittent salt-poor human albumin solution

Locations

Country	Name	City	State
United Kingdom	Royal Free Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Sequana Medical AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

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