Back to resultsEarly Liver Support With MARS in Post-hepatectomy Liver Failure (ELISH)
Primary Purpose
Liver Failure as A Complication of Care
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Molecular Adsorbent Recirculating System
Standard medical treatment (SMT)
Sponsored by
About this trial
This is an interventional treatment trial for Liver Failure as A Complication of Care focused on measuring Molecular Adsorbent Recirculating System, post-hepatectomy liver failure, liver dialysis, post-hepatectomy liver dysfunction
Eligibility Criteria
Inclusion Criteria:
- Patients subjected for major liver surgery (4 or more Couinaud segments) or patients undergoing a 2nd, 3rd or 4th hepatic resection. Pre-operative chemotherapy and/or biological agents are allowed.
- Primary PHLF occurring early after surgery defined by the 50:50 criteria (from PO day 5 to day 14) or by the presence of hepatic encephalopathy grade 2 or more and the 50:50 criteria (from PO day 3 to 4).
- Written informed consent.
Exclusion Criteria:
- ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) procedure.
- In patients with chronic liver disease presence of significant portal hypertension (hepatic venous pressure gradient ≥ 10 mmHg and/or Fibroscan ≥ 21kPa) prior to surgical intervention.
- Any contraindication for MARS therapy such as uncontrolled active bleeding, platelet counts <20.000 /µl or uncontrolled infection (presence of fever or adequate antibiotic therapy for less than 48h), septic shock, haemodynamic instability requiring inotropic support (noradrenaline > 1mg/h).
- PHLF occurring after post operative day 14.
- Secondary PHLF: post-operative liver failure secondary to vascular (outflow or inflow thrombosis) or septic problems.
- Persistant biliary complications (infected biloma, main biliary tree damage).
- Inability or unwilling of the patient or family to give informed consent.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Standard medical treatment + MARS
Standard medical treatment
Arm Description
Patients assigned to the control arm will receive standard medical treatment (SMT) and liver dialysis using Molecular Adsorbent Recirculating System (MARS).
Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol.
Outcomes
Primary Outcome Measures
60 day survival
Overall survival rate from time of randomization to death from any cause
Secondary Outcome Measures
28 day survival
Overall survival rate from time of randomization to death from any cause.
90 day survival
Overall survival rate from time of randomization to death from any cause.
6 month survival
Overall survival rate from time of randomization to death from any cause.
1 year survival
Overall survival rate from time of randomization to death from any cause.
Impact of MARS therapy on liver function
Impact of MARS therapy on liver function according to Child Pugh score (grade A, B and C)
Impact of MARS therapy on liver function
Impact of MARS therapy on liver function according to the Model for End-stage Liver Disease (MELD) score (5 groups: < 9, 10-19, 20-29, 30-39 and >40 points, lower points indicate improvement of liver function).
Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)
Impact of MARS therapy on extra-hepatic function assessed by the Acute Physiology And Chronic Health Evaluation II (APACHE II) scoring system (range 0-71 points, lower points indicate less severe disease).
Impact of MARS therapy on extra-hepatic function (SOFA scoring)
Impact of MARS therapy on extra-hepatic function assessed by the Sequential Organ Failure Assessment (SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)
Impact of MARS therapy on extra-hepatic function assessed by the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow (ml/min).
Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography.
Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography (ml/min).
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
Impact of MARS therapy on liver performance status.
Impact of MARS therapy on liver performance status estimated using indocyanine green (ICG) clearance.
Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.
impact of MARS therapy on liver toxins (ammonia, bile acids and cytokines (IL-6 and TNF-alpha)). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.
impact of MARS therapy on liver toxins (ammonia). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.
impact of MARS therapy on liver toxins (IL-6). Determinations in serum and in the dialysate.
Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.
impact of MARS therapy on liver toxins (TNF-alpha). Determinations in serum and in the dialysate.
Full Information
NCT ID
NCT03761238
First Posted
November 20, 2018
Last Updated
November 29, 2018
Sponsor
Stefan Gilg, MD, PhD
1. Study Identification
Unique Protocol Identification Number
NCT03761238
Brief Title
Early Liver Support With MARS in Post-hepatectomy Liver Failure
Acronym
ELISH
Official Title
Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 15, 2019 (Anticipated)
Primary Completion Date
September 15, 2021 (Anticipated)
Study Completion Date
September 15, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stefan Gilg, MD, PhD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a prospective, randomized, open-label, multicentre study involving European centers with experience in the management of PHLF to assess the impact of early liver support with MARS on survival in patients with post-hepatectomy liver failure (PHLF).
Detailed Description
PHLF is a major risk factor for mortality in patients who underwent major hepatectomy. A specific treatment is yet not available. In a primary proof-of-concept study, it was shown that it is safe and feasible to use MARS in patients with PHLF early after hepatectomy. Survival was superior to a historical control group.
This study will include patients with early, primary PHLF (based on the 50:50 criteria) after major liver surgery. Patients will be randomized 1:1 to receive standard treatment alone or standard treatment + liver dialysis using the Molecular Adsorbent Recirculating System (MARS). Relevant outcome along with several physiological parameters will be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Failure as A Complication of Care
Keywords
Molecular Adsorbent Recirculating System, post-hepatectomy liver failure, liver dialysis, post-hepatectomy liver dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard medical treatment + MARS
Arm Type
Experimental
Arm Description
Patients assigned to the control arm will receive standard medical treatment (SMT) and liver dialysis using Molecular Adsorbent Recirculating System (MARS).
Arm Title
Standard medical treatment
Arm Type
Active Comparator
Arm Description
Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol.
Intervention Type
Device
Intervention Name(s)
Molecular Adsorbent Recirculating System
Other Intervention Name(s)
MARS 1116/1 - X-MARS
Intervention Description
MARS therapy will start within 24-48 h after randomization and be given on 3 consecutive days in sessions of 8-12 h. The patients are observed for 2 days following the last session, with focus on bilirubin INR and signs of encephalopathy, and can thereafter receive 3 additional sessions in case of no or partial response to treatment.
Intervention Type
Other
Intervention Name(s)
Standard medical treatment (SMT)
Intervention Description
Patient management and standard medical treatment (SMT) as specified in the study protocol.
Primary Outcome Measure Information:
Title
60 day survival
Description
Overall survival rate from time of randomization to death from any cause
Time Frame
From randomization to death from any cause, assessed up to 60 days postop
Secondary Outcome Measure Information:
Title
28 day survival
Description
Overall survival rate from time of randomization to death from any cause.
Time Frame
From randomization to death from any cause, assessed up to 28 days post-op
Title
90 day survival
Description
Overall survival rate from time of randomization to death from any cause.
Time Frame
From randomization to death from any cause, assessed up to 90 days postop
Title
6 month survival
Description
Overall survival rate from time of randomization to death from any cause.
Time Frame
From randomization to death from any cause, assessed up to 6 months postop
Title
1 year survival
Description
Overall survival rate from time of randomization to death from any cause.
Time Frame
From randomization to death from any cause, assessed up to 1 year.
Title
Impact of MARS therapy on liver function
Description
Impact of MARS therapy on liver function according to Child Pugh score (grade A, B and C)
Time Frame
From randomization up to 1 year.
Title
Impact of MARS therapy on liver function
Description
Impact of MARS therapy on liver function according to the Model for End-stage Liver Disease (MELD) score (5 groups: < 9, 10-19, 20-29, 30-39 and >40 points, lower points indicate improvement of liver function).
Time Frame
From randomization up to 1 year.
Title
Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)
Description
Impact of MARS therapy on extra-hepatic function assessed by the Acute Physiology And Chronic Health Evaluation II (APACHE II) scoring system (range 0-71 points, lower points indicate less severe disease).
Time Frame
From randomization up to 1 year.
Title
Impact of MARS therapy on extra-hepatic function (SOFA scoring)
Description
Impact of MARS therapy on extra-hepatic function assessed by the Sequential Organ Failure Assessment (SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Time Frame
From randomization up to 1 year.
Title
Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)
Description
Impact of MARS therapy on extra-hepatic function assessed by the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scoring system (0-24 points, higher points indicate more severe disease).
Time Frame
From randomization up to 1 year.
Title
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.
Description
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow (ml/min).
Time Frame
At randomization (day 0) and on day 10.
Title
Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography.
Description
Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography (ml/min).
Time Frame
At randomization (day 0) and on day 10.
Title
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Description
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Time Frame
At randomization (day 0) and on day 10.
Title
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Description
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Time Frame
At randomization (day 0) and on days 5, 10 and 30 .
Title
Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
Description
Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
Description
Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
Description
Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver performance status.
Description
Impact of MARS therapy on liver performance status estimated using indocyanine green (ICG) clearance.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.
Description
impact of MARS therapy on liver toxins (ammonia, bile acids and cytokines (IL-6 and TNF-alpha)). Determinations in serum and in the dialysate.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.
Description
impact of MARS therapy on liver toxins (ammonia). Determinations in serum and in the dialysate.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.
Description
impact of MARS therapy on liver toxins (IL-6). Determinations in serum and in the dialysate.
Time Frame
At randomization (day 0) and on days 5 and 10.
Title
Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.
Description
impact of MARS therapy on liver toxins (TNF-alpha). Determinations in serum and in the dialysate.
Time Frame
At randomization (day 0) and on days 5 and 10.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients subjected for major liver surgery (4 or more Couinaud segments) or patients undergoing a 2nd, 3rd or 4th hepatic resection. Pre-operative chemotherapy and/or biological agents are allowed.
Primary PHLF occurring early after surgery defined by the 50:50 criteria (from PO day 5 to day 14) or by the presence of hepatic encephalopathy grade 2 or more and the 50:50 criteria (from PO day 3 to 4).
Written informed consent.
Exclusion Criteria:
ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) procedure.
In patients with chronic liver disease presence of significant portal hypertension (hepatic venous pressure gradient ≥ 10 mmHg and/or Fibroscan ≥ 21kPa) prior to surgical intervention.
Any contraindication for MARS therapy such as uncontrolled active bleeding, platelet counts <20.000 /µl or uncontrolled infection (presence of fever or adequate antibiotic therapy for less than 48h), septic shock, haemodynamic instability requiring inotropic support (noradrenaline > 1mg/h).
PHLF occurring after post operative day 14.
Secondary PHLF: post-operative liver failure secondary to vascular (outflow or inflow thrombosis) or septic problems.
Persistant biliary complications (infected biloma, main biliary tree damage).
Inability or unwilling of the patient or family to give informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stefan Gilg, MD PhD
Phone
0702677722
Ext
46
Email
stefan.gilg@ki.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Gilg, MD PhD
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Early Liver Support With MARS in Post-hepatectomy Liver Failure
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