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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease

Conditions
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Liver Failure

Intervention / Treatment
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* Device: MARS device
* Procedure: Standard medical therapy
* Procedure: Standard medical therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Device: MARS device<br>* 10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each.<br>* Other names: Liver support;Procedure: Standard medical therapy<br>* Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol<br>* Other names: SMT;|
| Active Comparator: 2<br> | Procedure: Standard medical therapy<br>* Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol<br>* Other names: SMT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment. |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival regardless of transplantation |  | 28 days | 
| general survival |  | 3 months | 
| in-hospital mortality |  | 3 months | 
| time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests) |  | 3 months | 
| economic analysis (length of stay, ICU days, readmissions within observation period) |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver failure, albumin dialysis, liver support