Early Liver Support With MARS in Post-hepatectomy Liver Failure

Liver Failure as A Complication of Care Clinical Trial

— ELISH  

Official title:

Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03761238
• Other study ID #: ELISH
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 15, 2019
• Est. completion date: September 15, 2022

Study information

• Verified date: November 2018
• Source: Karolinska University Hospital
• Contact: Stefan Gilg, MD PhD
• Phone: 0702677722
• Email: stefan.gilg[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 44
• Est. completion date: September 15, 2022
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Liver Failure
• Liver Failure as A Complication of Care

Intervention

Device:
• Molecular Adsorbent Recirculating System
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.

Other:
• Standard medical treatment (SMT)
Patient management and standard medical treatment (SMT) as specified in the study protocol.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Stefan Gilg, MD, PhD

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	60 day survival	Overall survival rate from time of randomization to death from any cause	From randomization to death from any cause, assessed up to 60 days postop
Secondary	28 day survival	Overall survival rate from time of randomization to death from any cause.	From randomization to death from any cause, assessed up to 28 days post-op
Secondary	90 day survival	Overall survival rate from time of randomization to death from any cause.	From randomization to death from any cause, assessed up to 90 days postop
Secondary	6 month survival	Overall survival rate from time of randomization to death from any cause.	From randomization to death from any cause, assessed up to 6 months postop
Secondary	1 year survival	Overall survival rate from time of randomization to death from any cause.	From randomization to death from any cause, assessed up to 1 year.
Secondary	Impact of MARS therapy on liver function	Impact of MARS therapy on liver function according to Child Pugh score (grade A, B and C)	From randomization up to 1 year.
Secondary	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).	From randomization up to 1 year.
Secondary	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).	From randomization up to 1 year.
Secondary	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).	From randomization up to 1 year.
Secondary	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).	From randomization up to 1 year.
Secondary	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).	At randomization (day 0) and on day 10.
Secondary	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).	At randomization (day 0) and on day 10.
Secondary	Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.	Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.	At randomization (day 0) and on day 10.
Secondary	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).	At randomization (day 0) and on days 5, 10 and 30 .
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	Impact of MARS therapy on liver performance status.	Impact of MARS therapy on liver performance status estimated using indocyanine green (ICG) clearance.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.
Secondary	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.	At randomization (day 0) and on days 5 and 10.