Recompensation of Exacerbated Liver Insufficiency With Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure

Liver Failure Clinical Trial

— RELIEF  

Official title:

Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00614146
• Other study ID #: 1438
• Secondary ID: ISRCTN67377557
• Status: Completed
• Phase: N/A
• First received: January 31, 2008
• Last updated: May 5, 2017
• Start date: April 2003
• Est. completion date: April 2009

Study information

• Verified date: April 2017
• Source: Baxter Healthcare Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this trial is to evaluate the impact of elimination of albumin bound substances during albumin dialysis (MARS®) on mortality and the clinical time course in patients with a recent severe clinical deterioration of chronic liver disease caused by a precipitating (trigger) event within 4 weeks manifested by jaundice, encephalopathy and/or renal failure.

Description:

Current medical therapy for end stage liver disease is focused on substitution of blood or plasma products, volume expansion or antibiotic treatment. The only specific treatment is liver transplantation, which is limited by available organs and may be a therapeutic option only for a very minority of patients with recently deteriorated end stage liver disease. The clinical management of defect hepatic synthesis and metabolic regulation has been improved dramatically within the past decades by the development of transfusion and intensive care medicine, but the replacement of detoxification has been more difficult, as the majority of endogenous toxins accumulating in liver failure is bound to albumin. Therefore, conventional dialysis and hemofiltration have been shown to be ineffective for their removal. The present study is based on the theory, that supporting the failing liver by the removal of toxic substances with a biocompatible method (the MARS system) may improve the capacity for recovery of the patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: April 2009
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written informed consent by patient or next of kin

• Age greater than 18 years

• Patients with a recent clinical severe decompensation of a presumed cirrhosis (based on clinical evaluation or radiological imaging) related to a precipitating (trigger) event (e.g. infection, bleeding, alcohol abuse)

• Intrahepatic cholestasis (bilirubin greater than 5 mg/dl or greater than 85 µmol/l, respectively) without evidence of extrahepatic origin

• and at least one of the following three:

• Hepatorenal syndrome (impaired renal function with creatinine greater than 1.5 mg/dl or greater than 133µmol/l without evidence of reduced vascular volume [e.g. central venous pressure {CVP} greater than 8 cm H2O] and no evidence of pre-existing renal failure)

• Hepatic Encephalopathy greater than or equal to II°

• Progressive Hyperbilirubinaemia: defined as a more than 50% increase of bilirubin before enrolment, whether in referral or currently in hospital up to a level of greater than 20 mg/dl (or greater than 340 µmol/l)

Exclusion Criteria:

• Progressive jaundice and deterioration as a natural course of a chronic liver disease without precipitating (trigger) event

• Severe thrombocytopenia (platelet count less than or equal to 50 Glutamic Pyruvic Transaminase [GPT]/l)

• Severe coagulopathy (International Normalised Ratio [INR] greater than 2.3)

• Need for renal replacement therapy within three days prior to enrolment

• Severe infection without antibiotic treatment for at least 24 hours. Uncontrolled bacterial infection

• Active bleeding within 48 hours prior to enrolment

• Proven hepatocellular carcinoma (HCC) greater than 4 cm or infiltration of portal vein or acute portal vein thrombosis

• Severe cardiopulmonary disease (New York Heart Association [NYHA] greater than or equal to 2)

• Pregnancy/lactation

• Mean arterial pressure (MAP) less than 60 mmHg despite vasopressor agents (norepinephrine greater than 1 µg/kg/min) for blood pressure support

• Overt clinical evidence for Disseminated Intravascular Coagulation (DIC)

• Clinical evidence for coma of non-hepatic origin

• Extra-hepatic cholestasis

• Severe intrinsic renal disease

• Extended surgical procedure within the last four weeks or unsolved surgical problems

• Known human immunodeficiency virus (HIV) infection

Related Conditions & MeSH terms

• Liver Failure

Intervention

Device:
• MARS device
10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each.

Procedure:
• Standard medical therapy
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol
• Standard medical therapy
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol

Locations

Country	Name	City	State
Austria	AKH Wien	Wien
Belgium	Universitaire Ziekenhuitzen	Leuven
Denmark	Rigshospitalet Copenhagen	Copenhagen
France	Hôpital Huriez	Lille
France	Hôpital Paul Brousse	Villejuif
Germany	Charite Berlin, Campus Mitte	Berlin
Germany	Uniklinik Bonn	Bonn
Germany	Martin Luther Universität Halle-Wittenberg	Halle
Germany	Klinikum der Universität Regensburg	Regensburg
Germany	Uniklinik Rostock	Rostock
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	Catholic University of Rome	Rome
Spain	Hospital clinic	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital General Universitario	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Switzerland	Universitätshospital Zürich	Zürich
United Kingdom	King's College Hospital	London
United Kingdom	University College London	London

Sponsors (5)

Lead Sponsor	Collaborator
Baxter Healthcare Corporation	2ConduCT, DatInf, G.E.M. mbh Meerbusch, Gambro Lundia AB

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Germany,  Italy,  Spain,  Switzerland,  United Kingdom, 

References & Publications (2)

Stange J, Mitzner S, Ramlow W, Gliesche T, Hickstein H, Schmidt R. A new procedure for the removal of protein bound drugs and toxins. ASAIO J. 1993 Jul-Sep;39(3):M621-5. — View Citation

Stange J, Ramlow W, Mitzner S, Schmidt R, Klinkmann H. Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. Artif Organs. 1993 Sep;17(9):809-13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.		28 days
Secondary	Survival regardless of transplantation		28 days
Secondary	general survival		3 months
Secondary	in-hospital mortality		3 months
Secondary	time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)		3 months
Secondary	economic analysis (length of stay, ICU days, readmissions within observation period)		3 months