Liver FailureRELIEFNCT00614146
Recompensation of Exacerbated Liver Insufficiency With Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure
A study testing MARS device and Standard medical therapy in people with Liver Failure, run by Vantive Health LLC at 19 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Failure
- What is being tested?
- MARS device and Standard medical therapy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 19 sitesin 9 countries
- Study dates
- Apr 2003to Apr 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
19 sites in 9 countries.
19 sites in 9 countries
Germany6 sites
Charite Berlin, Campus Mitte
Berlin, 10117
Uniklinik Bonn
Bonn, 53105
Martin Luther Universität Halle-Wittenberg
Halle, 06097
Klinikum der Universität Regensburg
Regensburg, 93053
Uniklinik Rostock
Rostock, 18057
Universitätsklinikum Tübingen
Tübingen, 72076
Spain4 sites
Hospital clinic
Barcelona, 8036
Hospital Reina Sofia
Córdoba, 14004
Hospital General Universitario
Madrid, 28007
Hospital Ramon y Cajal
Madrid, 28034
United Kingdom2 sites
King's College Hospital
London, SE 5 9RS
University College London
London, WC1E 6HX
About this study
Official title: Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease
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.
Read the 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
- Being tested
- MARS device, Standard medical therapy
- Keywords
- liver failure, albumin dialysis, liver support
- Medical subject headings
- Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MARS deviceDevice
Also called Liver support
10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each.
Standard medical therapyProcedure or surgery
Also called SMT
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol
Standard medical therapyProcedure or surgery
Also called SMT
Standard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Device: MARS device; Procedure: Standard medical therapy |
| 2 | Active comparator | Not described Receives: Procedure: Standard medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.
Measured: 28 days
Secondary outcomes (5)
Survival regardless of transplantation
Measured: 28 days
general survival
Measured: 3 months
in-hospital mortality
Measured: 3 months
time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)
Measured: 3 months
economic analysis (length of stay, ICU days, readmissions within observation period)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2008 (estimated)
- Study startApr 2003
- Primary completionJan 2008
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vantive Health LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- 2ConduCT, G.E.M. mbh Meerbusch, DatInf, Gambro Lundia AB, Baxter Healthcare Corporation
- Responsible party
- Sponsor
- Investigators
- Rafael Banarès, Dr, Study chair, Hospital Gregorio Maranon, MadridVicente Arroyo, Pf, Study chair, Clínic Barcelona, Hospital Universitari VillarroelRoger Williams, Pf, Study chair, Royal Free and University College Medical School, University College LondonSteffen Mitzner, Dr, Study chair, Dept. of Internal Medicine, University of Rostock
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00614146
- Sponsor's protocol ID
- 1438
- Other IDs
- ISRCTN67377557
- Acronym
- RELIEF
- Status last verified
- Mar 2025
- First submitted
- 31 Jan 2008
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 8268613Stange 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.
PubMed 8240075
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Impact of Albumin Dialysis With the Molecular Adsorbents Recirculating System (MARS®) in Severely Decompensated Chronic Liver Disease
- ClinicalTrials.gov ID
- NCT00614146
- Acronym / sponsor ID
- RELIEF / 1438
- Conditions
- Liver Failure
- Keywords
- liver failure, albumin dialysis, liver support
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Vantive Health LLCIndustry (pharma, biotech, devices)
- Collaborators
- 2ConduCT, G.E.M. mbh Meerbusch, DatInf, Gambro Lundia AB, Baxter Healthcare Corporation
- Study start
- Apr 2003
- Primary completion
- Jan 2008 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 13 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Device: MARS device, Procedure: Standard medical therapy |
| 2 | Active comparator | Procedure: Standard medical therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MARS deviceAlso: Liver support10 treatments with the MARS system during the first three weeks after enrollment of 5-8 hours each. | Device | 1 |
| Standard medical therapyAlso: SMTStandard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol | Procedure or surgery | 2 |
| Standard medical therapyAlso: SMTStandard medical therapy for treatment of the liver disease according to local policy with recommendations as per protocol | Procedure or surgery | 1 |
Primary outcome
Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment.
Time frame: 28 days
5 secondary outcomes
Survival regardless of transplantation
Time frame: 28 days
general survival
Time frame: 3 months
in-hospital mortality
Time frame: 3 months
time course of clinical state (number and severity of complications, vital signs, scoring systems, lab tests)
Time frame: 3 months
economic analysis (length of stay, ICU days, readmissions within observation period)
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Background: PubMed 8268613Stange 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.
- Background: PubMed 8240075Stange 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.
Related trials for Liver Failure
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Acute-on-Chronic Liver Failure (ACLF)
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Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
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Active, not recruiting
LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease
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RecruitingObservational study
Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe
End-stage Liver Disease (ESLD), Acute Liver Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafael Banarès, Dr study chair
Hospital Gregorio Maranon, Madrid
Vicente Arroyo, Pf study chair
Clínic Barcelona, Hospital Universitari Villarroel
Roger Williams, Pf study chair
Royal Free and University College Medical School, University College London
19 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MARS device and Standard medical therapy in people with Liver Failure, run by Vantive Health LLC at 19 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Germany, Spain, France, United Kingdom, Austria and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Show improvement of transplant free survival under MARS in comparison to Standard Medical Treatment. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00614146, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.