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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Failure
• Intervention / Treatment: Device: MARS device; Procedure: Standard medical therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • AKH Wien
• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuitzen
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet Copenhagen
• France
  • Lille, France, 59037
    • Hôpital Huriez
  • Villejuif, France, 94800
    • Hopital Paul Brousse
• Germany
  • Berlin, Germany, 10117
    • Charite Berlin, Campus Mitte
  • Bonn, Germany, 53105
    • Uniklinik Bonn
  • Halle, Germany, 06097
    • Martin Luther Universitat Halle-Wittenberg
  • Regensburg, Germany, 93053
    • Klinikum der Universität Regensburg
  • Rostock, Germany, 18057
    • Uniklinik Rostock
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Italy
  • Rome, Italy, 00168
    • Catholic University of Rome
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic
  • Cordoba, Spain, 14004
    • Hospital Reina Sofia
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitätshospital Zürich
• United Kingdom
  • London, United Kingdom, SE 5 9RS
    • King's College Hospital
  • London, United Kingdom, WC1E 6HX
    • University College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Device: MARS device; 10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each.; Other Names: Liver support; Procedure: Standard medical therapy; Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol; Other Names: SMT
Active Comparator: 2	Procedure: Standard medical therapy; Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol; Other Names: SMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival regardless of transplantation	28 days
general survival	3 months
in-hospital mortality	3 months
time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)	3 months
economic analysis (length of stay, ICU days, readmissions within observation period)	3 months

Collaborators and Investigators

• Sponsor: Vantive Health LLC
• Collaborators: Baxter Healthcare Corporation; Gambro Lundia AB; 2ConduCT; G.E.M. mbh Meerbusch; DatInf
• Investigators: Study Chair: Rafael Banarès, Dr, Hospital Gregorio Marañón, Madrid; Study Chair: Vicente Arroyo, Pf, Clínic Barcelona, Hospital Universitari Villarroel; Study Chair: Roger Williams, Pf, Royal Free and University College Medical School, University College London; Study Chair: Steffen Mitzner, Dr, Dept. of Internal Medicine, University of Rostock

Publications and helpful links

General Publications

• 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.
• 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. doi: 10.1111/j.1525-1594.1993.tb00635.x.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: January 31, 2008
• First Posted (Estimated): February 13, 2008

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: liver failure, albumin dialysis, liver support
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: 1438; ISRCTN67377557