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

Vantive Health LLC

Status

Completed

Conditions

Liver Failure

Treatments

Procedure: Standard medical therapy

Device: MARS device

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00614146

1438

ISRCTN67377557

Details and patient eligibility

About

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.

Full 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.

Enrollment

59 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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