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

Primary Purpose

Liver Failure

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
MARS device
Standard medical therapy
Standard medical therapy
Sponsored by
Baxter Healthcare Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Failure focused on measuring liver failure, albumin dialysis, liver support

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • AKH Wien
  • Universitaire Ziekenhuitzen
  • Rigshospitalet Copenhagen
  • Hôpital Huriez
  • Hôpital Paul Brousse
  • Charite Berlin, Campus Mitte
  • Uniklinik Bonn
  • Martin Luther Universität Halle-Wittenberg
  • Klinikum der Universität Regensburg
  • Uniklinik Rostock
  • Universitätsklinikum Tübingen
  • Catholic University of Rome
  • Hospital clinic
  • Hospital Reina Sofia
  • Hospital General Universitario
  • Hospital Ramon y Cajal
  • Universitätshospital Zürich
  • King's College Hospital
  • University College London

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.

Secondary Outcome Measures

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

Full Information

First Posted
January 31, 2008
Last Updated
May 5, 2017
Sponsor
Baxter Healthcare Corporation
Collaborators
2ConduCT, G.E.M. mbh Meerbusch, DatInf, Gambro Lundia AB
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1. Study Identification

Unique Protocol Identification Number
NCT00614146
Brief Title
Recompensation of Exacerbated Liver Insufficiency With Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure
Acronym
RELIEF
Official Title
Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxter Healthcare Corporation
Collaborators
2ConduCT, G.E.M. mbh Meerbusch, DatInf, Gambro Lundia AB

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Failure
Keywords
liver failure, albumin dialysis, liver support

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
MARS device
Other Intervention Name(s)
Liver support
Intervention Description
10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each.
Intervention Type
Procedure
Intervention Name(s)
Standard medical therapy
Other Intervention Name(s)
SMT
Intervention Description
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol
Intervention Type
Procedure
Intervention Name(s)
Standard medical therapy
Other Intervention Name(s)
SMT
Intervention Description
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol
Primary Outcome Measure Information:
Title
Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Survival regardless of transplantation
Time Frame
28 days
Title
general survival
Time Frame
3 months
Title
in-hospital mortality
Time Frame
3 months
Title
time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)
Time Frame
3 months
Title
economic analysis (length of stay, ICU days, readmissions within observation period)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rafael Banarès, Dr
Organizational Affiliation
Hospital Gregorio Maranon, Madrid
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Vicente Arroyo, Pf
Organizational Affiliation
Clínic Barcelona, Hospital Universitari Villarroel
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Roger Williams, Pf
Organizational Affiliation
Royal Free and University College Medical School, University College London
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Steffen Mitzner, Dr
Organizational Affiliation
Dept. of Internal Medicine, University of Rostock
Official's Role
Study Chair
Facility Information:
Facility Name
AKH Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universitaire Ziekenhuitzen
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Rigshospitalet Copenhagen
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Hôpital Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Paul Brousse
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Charite Berlin, Campus Mitte
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Uniklinik Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Martin Luther Universität Halle-Wittenberg
City
Halle
ZIP/Postal Code
06097
Country
Germany
Facility Name
Klinikum der Universität Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Uniklinik Rostock
City
Rostock
ZIP/Postal Code
18057
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Catholic University of Rome
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
Hospital clinic
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital General Universitario
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Universitätshospital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE 5 9RS
Country
United Kingdom
Facility Name
University College London
City
London
ZIP/Postal Code
WC1E 6HX
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
8268613
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.
Results Reference
background
PubMed Identifier
8240075
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.
Results Reference
background

Learn more about this trial

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

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