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

NCT ID: NCT00614146

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2009-04-30

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.

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.

Conditions

Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

MARS device

Intervention Type: DEVICE

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

Standard medical therapy

Intervention Type: PROCEDURE

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

2

Group Type: ACTIVE_COMPARATOR

Standard medical therapy

Intervention Type: PROCEDURE

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

Interventions

MARS device

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

Intervention Type: DEVICE

Standard medical therapy

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

Intervention Type: PROCEDURE

Standard medical therapy

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

Intervention Type: PROCEDURE

Other Intervention Names

Liver support; SMT; SMT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

2ConduCT

INDUSTRY

Sponsor Role: collaborator

G.E.M. mbh Meerbusch

OTHER

Sponsor Role: collaborator

DatInf

UNKNOWN

Sponsor Role: collaborator

Gambro Lundia AB

INDUSTRY

Sponsor Role: collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

Vantive Health LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafael Banarès, Dr

Role: STUDY_CHAIR

Hospital Gregorio Maranon, Madrid

Vicente Arroyo, Pf

Role: STUDY_CHAIR

Clínic Barcelona, Hospital Universitari Villarroel

Roger Williams, Pf

Role: STUDY_CHAIR

Royal Free and University College Medical School, University College London

Steffen Mitzner, Dr

Role: STUDY_CHAIR

Dept. of Internal Medicine, University of Rostock

Locations

AKH Wien

Vienna, , Austria

Universitaire Ziekenhuitzen

Leuven, , Belgium

Rigshospitalet Copenhagen

Copenhagen, , Denmark

Hôpital Huriez

Lille, , France

Hôpital Paul Brousse

Villejuif, , France

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, , Germany

Catholic University of Rome

Rome, , Italy

Hospital clinic

Barcelona, , Spain

Hospital Reina Sofia

Córdoba, , Spain

Hospital General Universitario

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Universitätshospital Zürich

Zurich, , Switzerland

King's College Hospital

London, , United Kingdom

University College London

London, , United Kingdom

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 8268613 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8240075 (View on PubMed)

Other Identifiers

ISRCTN67377557

Identifier Type: -

Identifier Source: secondary_id

1438

Identifier Type: -

Identifier Source: org_study_id