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

This study has been completed.
Sponsor:
Collaborators:
2ConduCT
G.E.M. mbh Meerbusch
DatInf
Information provided by:
Gambro Lundia AB
ClinicalTrials.gov Identifier:
NCT00614146
First received: January 31, 2008
Last updated: June 15, 2009
Last verified: June 2009
  Purpose

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 Intervention
Liver Failure
Device: MARS device
Procedure: Standard medical therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Gambro Lundia AB:

Primary Outcome Measures:
  • Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment. [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival regardless of transplantation [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • general survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • in-hospital mortality [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • economic analysis (length of stay, ICU days, readmissions within observation period) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 172
Study Start Date: April 2003
Study Completion Date: April 2009
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614146

Locations
Austria
AKH Wien
Wien, Austria, 1090
Belgium
Universitaire Ziekenhuitzen
Leuven, Belgium, 3000
Denmark
Rigshospitalet Copenhagen
Copenhagen, Denmark, 2100
France
Hôpital Huriez
Lille, France, 59037
Hôpital Paul Brousse
Villejuif, France, 94800
Germany
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
Italy
Catholic University of Rome
Rome, Italy, 00168
Spain
Hospital clinic
Barcelona, Spain, 8036
Hospital Reina Sofia
Cordoba, Spain, 14004
Hospital General Universitario
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Switzerland
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
Gambro Lundia AB
2ConduCT
G.E.M. mbh Meerbusch
DatInf
Investigators
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
  More Information

Publications:
Responsible Party: Clinical Affairs Manager, Gambro Lundia AB
ClinicalTrials.gov Identifier: NCT00614146     History of Changes
Other Study ID Numbers: 1438, ISRCTN67377557
Study First Received: January 31, 2008
Last Updated: June 15, 2009
Health Authority: Austria: Agency for Health and Food Safety
Austria: Ethikkommission
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Institutional Review Board
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by Gambro Lundia AB:
liver failure, albumin dialysis, liver support

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

ClinicalTrials.gov processed this record on September 16, 2014