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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00614146
Recruitment Status : Completed
First Posted : February 13, 2008
Last Update Posted : May 8, 2017
G.E.M. mbh Meerbusch
Gambro Lundia AB
Information provided by (Responsible Party):
Baxter Healthcare Corporation

Brief 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.

Condition or disease Intervention/treatment Phase
Liver Failure Device: MARS device Procedure: Standard medical therapy Not Applicable

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  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease
Study Start Date : April 2003
Actual Primary Completion Date : January 2008
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

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 Name: 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 Name: 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 Name: SMT

Primary Outcome Measures :
  1. Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment. [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Survival regardless of transplantation [ Time Frame: 28 days ]
  2. general survival [ Time Frame: 3 months ]
  3. in-hospital mortality [ Time Frame: 3 months ]
  4. time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests) [ Time Frame: 3 months ]
  5. economic analysis (length of stay, ICU days, readmissions within observation period) [ Time Frame: 3 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00614146

AKH Wien
Wien, Austria, 1090
Universitaire Ziekenhuitzen
Leuven, Belgium, 3000
Rigshospitalet Copenhagen
Copenhagen, Denmark, 2100
Hôpital Huriez
Lille, France, 59037
Hôpital Paul Brousse
Villejuif, France, 94800
Charite Berlin, Campus Mitte
Berlin, Germany, 10117
Uniklinik Bonn
Bonn, Germany, 53105
Martin Luther Universität Halle-Wittenberg
Halle, Germany, 06097
Klinikum der Universität Regensburg
Regensburg, Germany, 93053
Uniklinik Rostock
Rostock, Germany, 18057
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
Catholic University of Rome
Rome, Italy, 00168
Hospital clinic
Barcelona, Spain, 8036
Hospital Reina Sofia
Cordoba, Spain, 14004
Hospital General Universitario
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Universitätshospital Zürich
Zürich, Switzerland, 8091
United Kingdom
King's College Hospital
London, United Kingdom, SE 5 9RS
University College London
London, United Kingdom, WC1E 6HX
Sponsors and Collaborators
Baxter Healthcare Corporation
G.E.M. mbh Meerbusch
Gambro Lundia AB
Study Chair: Rafael Banarès, Dr Hospital Gregorio Maranon, 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

Responsible Party: Baxter Healthcare Corporation Identifier: NCT00614146     History of Changes
Other Study ID Numbers: 1438
First Posted: February 13, 2008    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: April 2017

Keywords provided by Baxter Healthcare Corporation:
liver failure, albumin dialysis, liver support

Additional relevant MeSH terms:
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Liver Extracts