Early Liver Support With MARS in Post-hepatectomy Liver Failure

Stefan Gilg, MD, PhD44 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Failure as A Complication of Care

Interventions

Molecular Adsorbent Recirculating SystemDEVICE

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.

Standard medical treatment (SMT)OTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

60 day survival

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 Outcomes

28 day survival

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

90 day survival

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

6 month survival

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

1 year survival

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.

Impact of MARS therapy on liver function

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.

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).

Central Contacts

Stefan Gilg, MD PhD

CONTACT

0702677722 stefan.gilg@ki.se

Data from ClinicalTrials.gov

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Time frame: From randomization up to 1 year.

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).

Time frame: From randomization up to 1 year.

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).

Time frame: From randomization up to 1 year.

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).

Time frame: From randomization up to 1 year.

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).

Time frame: At randomization (day 0) and on day 10.

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).

Time frame: At randomization (day 0) and on day 10.

Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.

Time frame: At randomization (day 0) and on day 10.

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 .

Impact of MARS therapy on liver regeneration assessed by serum levels of phosphate.