Early Postoperative Extracorporal Liver Support Therapy (ELS) as a Tool to Manage Post Hepatectomy Liver Failure (PLF)

January 2, 2019 updated by: Lars Lundell, Karolinska University Hospital

Early postoperative extracorporal liver support therapy (ELS) as a tool to manage post hepatectomy liver failure (PLF).

Post-operative liver failure (PLF) has been identified as a major risk factor leading to increased morbidity and mortality. The incidence of PLF varies largely between 0-30%, and may be accounted for the main reason of postoperative mortality related to liver surgery (reported figures ranging from 18 to 75 %).

Currently, there are only a few treatment options for PLF, mainly restricted to the treatment of complications like bile leakage, infections as well as the prevention of further liver damage caused by e.g. thrombosis or haemorrhage as well as administration of liver toxic drugs. Recently the international study group on liver surgery (ISGLS) published criteria for a new definition of PLF which will greatly facilitate the comparison of results from future studies on a variety of aspects on liver failure.

ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin. Thus, MARS can support the compromised detoxification capacity of the liver as well as improve physiological parameters. This would offer the potential for temporary support for the harmed liver after liver resection allowing for a more uneventful recovery.

For obvious reasons previous reports contain few patients, present heterogonous treatment groups and all suffer from lack of standardized treatment protocols. Few if any surviving patients, thus providing no evidence to encourage ELS as a possible treatment option for patients suffering of PLF. However, studies with defined patient populations and treatments according to a predefined standardised treatment protocol are warranted.

Primary issues to be addressed:

  1. Can ELS be applied in an early phase of PLF?
  2. Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol?

Secondary issues to be addressed:

  1. The development of predictive laboratory-chemical markers of liver failure
  2. Indirect measures of portal flow and portal pressure
  3. Indocyanine green clearance (ICG) under ELS treatment
  4. Clearance of toxic products as assessed in aliquots taken from the dialysate

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary issues to be addressed

  1. Can ELS be applied in an early phase of PLF?
  2. Is ELS safe and feasible for the treatment of PLF when practised according to a predefined protocol?

Secondary issues to be addressed

  1. The development of predictive laboratory-chemical markers of liver failure
  2. Indirect measures of portal flow and portal pressure
  3. Indocyanine green clearance (ICG) under ELS treatment
  4. Clearance of toxic products as assessed in aliquots taken from the dialysate

Design

  • Prospective phase 1 safety and feasibility study

Study Population

  • 10 consecutive patients being subjected to extended liver surgery (at least right sided or extended right/left sided hemihepatectomy)

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 14186
        • Department of Surgery Gastrocentrum Karolinska Univeristy Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 18 and 70 years
  • Patients subjected for major liver surgery (4 or more Couinaud segments, ca. 50 % or more of total liver volume)
  • Pre-operative chemotherapy and/or biological agents are allowed
  • Liver cirrhosis Child Pugh Score A is allowed

Exclusion Criteria:

  • Any contra indication for ELS such as uncontrolled active bleeding or platelet counts <20.000 /µl
  • Macroscopic liver cirrhosis (Child Pugh Score B and C)
  • Inability or unwilling to give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early Postoperative Extracorporal Liver Support Therapy (ELS)
Early Postoperative Extracorporal Liver Support Therapy (ELS) by using the Molecular Adsorbent Recirculating System (MARS)
Device: Extracorporeal liver support therapy (ELS)
ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of PLF patients who develop serious adverse events during ELS according to SOFA scores and Westhaven criteria
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars. SOFA (score 1-4).
First two weeks postoperatively after major hepatectomy
Number of PLF patients who develop serious adverse events during ELS
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars. Westhaven (criteria 1-4)
First two weeks postoperatively after major hepatectomy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The predictive value of liver enzymes and bilirubin changes as marker of liver failure
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars. Liver enzymes measured( liver transaminases microkat/L ), bilirubin (mmol/L)
First two weeks postoperatively after major hepatectomy
Portal flow (ml/minute) before and during ELS
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars
First two weeks postoperatively after major hepatectomy
To assess liver function by use of Indocyanine green clearance (ICG)(% clearance/unit time) under ELS treatment
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars
First two weeks postoperatively after major hepatectomy
Portal pressure (cmH2O) before and during ELS
Time Frame: First two weeks postoperatively after major hepatectomy
At least five sessions of Mars
First two weeks postoperatively after major hepatectomy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Investigators

  • Principal Investigator: Bengt Isaksson, Ass prof, Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

October 24, 2016

First Submitted That Met QC Criteria

January 4, 2017

First Posted (Estimate)

January 5, 2017

Study Record Updates

Last Update Posted (Actual)

January 4, 2019

Last Update Submitted That Met QC Criteria

January 2, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013/149-31/2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Publication in peer reviewed journal

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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