Clinical trial NCT00614146: Recompensation of Exacerbated Liver Insufficiency With Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure
Official title: Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Failure
Keywords: liver failure, albumin dialysis, liver support
Lead sponsor: Vantive Health LLC
Sponsor class: INDUSTRY
Collaborators: name: 2ConduCT
name: G.E.M. mbh Meerbusch
name: DatInf
name: Gambro Lundia AB
name: Baxter Healthcare Corporation
First posted: 2008-02-13
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.
timeFrame: 28 days
Secondary outcomes:
measure: Survival regardless of transplantation
timeFrame: 28 days
measure: general survival
timeFrame: 3 months
measure: in-hospital mortality
timeFrame: 3 months
measure: time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)
timeFrame: 3 months
measure: economic analysis (length of stay, ICU days, readmissions within observation period)
timeFrame: 3 months
Other outcomes:
Locations:
city: Wien
country: Austria
facility: AKH Wien
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuitzen
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen
city: Lille
country: France
facility: Hôpital Huriez
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Berlin
country: Germany
facility: Charite Berlin, Campus Mitte
city: Bonn
country: Germany
facility: Uniklinik Bonn
city: Halle
country: Germany
facility: Martin Luther Universität Halle-Wittenberg
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
city: Rostock
country: Germany
facility: Uniklinik Rostock
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Rome
country: Italy
facility: Catholic University of Rome
city: Barcelona
country: Spain
facility: Hospital clinic
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Zürich
country: Switzerland
facility: Universitätshospital Zürich
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: Hospital Gregorio Maranon, Madrid
name: Rafael Banarès, Dr
role: STUDY_CHAIR
affiliation: Clínic Barcelona, Hospital Universitari Villarroel
name: Vicente Arroyo, Pf
role: STUDY_CHAIR
affiliation: Royal Free and University College Medical School, University College London
name: Roger Williams, Pf
role: STUDY_CHAIR
affiliation: Dept. of Internal Medicine, University of Rostock
name: Steffen Mitzner, Dr
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.