Recompensation of Exacerbated Liver Insufficiency With Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure - Full Text View

Sponsors and Collaborators:	Gambro Lundia AB 2ConduCT G.E.M. mbh Meerbusch DatInf
Information provided by:	Gambro Lundia AB
ClinicalTrials.gov Identifier:	NCT00614146

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

MedlinePlus related topics: Jaundice Kidney Failure Liver Diseases

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease

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
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	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
2: Active Comparator	Procedure: Standard medical therapy Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol

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

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

Contacts

Contact: Rafael Banarès, Dr	00 34 606 652 687	rbanares@telephonica.net
Contact: Ludger Thiele	00 49 40 18 044 507	thiele@2conduct.de

Locations

Austria
AKH Wien	Recruiting
Wien, Austria, 1090
Principal Investigator: Ludwig Kramer, Prof. Dr
Belgium
Universitaire Ziekenhuitzen	Recruiting
Leuven, Belgium, 3000
Principal Investigator: Frederik Nevens, Dr
Denmark
Rigshospitalet Copenhagen	Recruiting
Copenhagen, Denmark, 2100
Principal Investigator: Fin Stolze Larsen, Prof. Dr
France
Hôpital Paul Brousse	Recruiting
Villejuif, France, 94800
Principal Investigator: Faouzi Saliba, Prof. Dr
Hôpital Huriez	Recruiting
Lille, France, 59037
Principal Investigator: Philippe Mathurin, Prof.
Germany
Uniklinik Rostock	Recruiting
Rostock, Germany, 18057
Principal Investigator: Reinhard Schmidt, Prof. Dr
Charite Berlin, Campus Mitte	Active, not recruiting
Berlin, Germany, 10117
Uniklinik Bonn	Recruiting
Bonn, Germany, 53105
Principal Investigator: Tilman Sauerbruch, Prof. Dr
Klinikum der Universität Regensburg	Recruiting
Regensburg, Germany, 93053
Principal Investigator: Jürgen Schölmerich, Prof. Dr
Universitätsklinikum Tübingen	Active, not recruiting
Tübingen, Germany, 72076
Martin Luther Universität Halle-Wittenberg	Recruiting
Halle, Germany, 06097
Principal Investigator: Matthias Dollinger, Dr
Italy
Catholic University of Rome	Active, not recruiting
Rome, Italy, 00168
Spain
Hospital clinic	Recruiting
Barcelona, Spain, 8036
Principal Investigator: Albert Pares, Dr
Hospital General Universitario	Recruiting
Madrid, Spain, 28007
Principal Investigator: Rafael Banares, Dr
Hospital Reina Sofia	Recruiting
Cordoba, Spain, 14004
Principal Investigator: Manuel De La Mata Garcia, Dr
Hospital Ramon y Cajal	Recruiting
Madrid, Spain, 28034
Principal Investigator: Agustin Albillos, Prof. Dr
Switzerland
Universitätshospital Zürich	Active, not recruiting
Zürich, Switzerland, 8091
United Kingdom
King's College Hospital	Suspended
London, United Kingdom, SE 5 9RS
University College London	Recruiting
London, United Kingdom, WC1E 6HX
Principal Investigator: Rajiv Jalan, Dr

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:

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.

Responsible Party:	Gambro Lundia AB ( Clinical Affairs Manager )
Study ID Numbers:	1438, ISRCTN67377557
Study First Received:	January 31, 2008
Last Updated:	October 28, 2008
ClinicalTrials.gov Identifier:	NCT00614146
Health Authority:	Austria: Agency for Health and Food Safety; Austria: Ethikkommission; Belgium: Directorate general for the protection of Public health: Medicines; Belgium: Institutional Review Board; Denmark: Danish Dataprotection Agency; Denmark: Danish Medicines Agency; Denmark: Ethics Committee; France: Afssaps - French Health Products Safety Agency; 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

Study placed in the following topic categories:

Liver Failure
Liver Diseases
Digestive System Diseases

Hyperbilirubinemia
Kidney Failure
Hepatic Insufficiency

ClinicalTrials.gov processed this record on January 14, 2009