Clinical trial NCT03761238: Early Liver Support With MARS in Post-hepatectomy Liver Failure
Official title: Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Failure as A Complication of Care
Keywords: Molecular Adsorbent Recirculating System
post-hepatectomy liver failure
liver dialysis
post-hepatectomy liver dysfunction
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2018-12-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 60 day survival
timeFrame: From randomization to death from any cause, assessed up to 60 days postop
Secondary outcomes:
measure: 28 day survival
timeFrame: From randomization to death from any cause, assessed up to 28 days post-op
measure: 90 day survival
timeFrame: From randomization to death from any cause, assessed up to 90 days postop
measure: 6 month survival
timeFrame: From randomization to death from any cause, assessed up to 6 months postop
measure: 1 year survival
timeFrame: From randomization to death from any cause, assessed up to 1 year.
measure: Impact of MARS therapy on liver function
timeFrame: From randomization up to 1 year.
measure: Impact of MARS therapy on liver function
timeFrame: From randomization up to 1 year.
measure: Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)
timeFrame: From randomization up to 1 year.
measure: Impact of MARS therapy on extra-hepatic function (SOFA scoring)
timeFrame: From randomization up to 1 year.
measure: Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)
timeFrame: From randomization up to 1 year.
measure: Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.
timeFrame: At randomization (day 0) and on day 10.
measure: Impact of MARS therapy on splanchnic hemodynamics assessed by indirect estimation of portal blood flow using ultrasonography.
timeFrame: At randomization (day 0) and on day 10.
measure: Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
timeFrame: At randomization (day 0) and on day 10.
measure: Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
timeFrame: At randomization (day 0) and on days 5, 10 and 30 .
measure: Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver regeneration assessed by serum levels of alphafetoprotein.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver regeneration assessed by serum levels of hepatocyte growth factor.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver performance status.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.
timeFrame: At randomization (day 0) and on days 5 and 10.
measure: Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.
timeFrame: At randomization (day 0) and on days 5 and 10.
Other outcomes:
Locations:
Study officials:
affiliation: Karolinska Institutet
name: Stefan Gilg, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: