Liver Failure as A Complication of CareELISHNCT03761238
Early Liver Support With MARS in Post-hepatectomy Liver Failure
A study testing Molecular Adsorbent Recirculating System and Standard medical treatment (SMT) in people with Liver Failure as A Complication of Care, run by Stefan Gilg, MD, PhD.
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Liver Failure as A Complication of Care
- What is being tested?
- Molecular Adsorbent Recirculating System and Standard medical treatment (SMT)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- 15 Mar 2019to 15 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial
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).
Read the 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.
- Conditions
- Liver Failure as A Complication of Care
- Being tested
- Molecular Adsorbent Recirculating System, Standard medical treatment (SMT)
- Keywords
- Molecular Adsorbent Recirculating System, post-hepatectomy liver failure, liver dialysis, post-hepatectomy liver dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Molecular Adsorbent Recirculating SystemDevice
Also called MARS 1116/1 - X-MARS
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard medical treatment + MARS | Experimental | Patients assigned to the control arm will receive standard medical treatment (SMT) and liver dialysis using Molecular Adsorbent Recirculating System (MARS). Receives: Device: Molecular Adsorbent Recirculating System |
| Standard medical treatment | Active comparator | Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol. Receives: Other: Standard medical treatment (SMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
60 day survival
Overall survival rate from time of randomization to death from any cause
Measured: From randomization to death from any cause, assessed up to 60 days postop
Secondary outcomes (21)
28 day survival
Overall survival rate from time of randomization to death from any cause.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: At randomization (day 0) and on day 10.
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Impact of MARS therapy on splanchnic hemodynamics assessed by portal pressure measuring.
Measured: 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).
Impact of MARS therapy on liver regeneration assessed by volumetric liver analysis using combined Computed Tomography (CT) and Magnetic Resonance Imaging (MR).
Measured: At randomization (day 0) and on days 5, 10 and 30 .
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.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
Impact of MARS therapy on liver performance status.
Impact of MARS therapy on liver performance status estimated using indocyanine green (ICG) clearance.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
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.
Measured: At randomization (day 0) and on days 5 and 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2018
- Study start15 Mar 2019 (estimated)
- Primary completion15 Sep 2021 (estimated)
- Study completion15 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Failure as A Complication of CareStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stefan Gilg, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stefan Gilg, MD, PhD, Karolinska University Hospital
- Investigators
- Stefan Gilg, MD PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03761238
- Sponsor's protocol ID
- ELISH
- Acronym
- ELISH
- Status last verified
- Nov 2018
- First submitted
- 20 Nov 2018
- Last updated
- 3 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Liver Support With MARS in Post-hepatectomy Liver Failure: a Randomized, Multicentre Trial
- ClinicalTrials.gov ID
- NCT03761238
- Acronym / sponsor ID
- ELISH / ELISH
- Conditions
- Liver Failure as A Complication of Care
- Keywords
- Molecular Adsorbent Recirculating System, post-hepatectomy liver failure, liver dialysis, post-hepatectomy liver dysfunction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Stefan Gilg, MD, PhDUniversity, hospital or other
- Study start
- 15 Mar 2019 (estimated)
- Primary completion
- 15 Sep 2021 (estimated)
- Study completion
- 15 Sep 2022 (estimated)
- First posted
- 3 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard medical treatment + MARS | Experimental | Device: Molecular Adsorbent Recirculating SystemPatients assigned to the control arm will receive standard medical treatment (SMT) and liver dialysis using Molecular Adsorbent Recirculating System (MARS). |
| Standard medical treatment | Active comparator | Other: Standard medical treatment (SMT)Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Molecular Adsorbent Recirculating SystemAlso: MARS 1116/1 - X-MARSMARS 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. | Device | Standard medical treatment + MARS |
| Standard medical treatment (SMT)Patient management and standard medical treatment (SMT) as specified in the study protocol. | Other | Standard medical treatment |
Primary outcome
60 day survival
Time frame: From randomization to death from any cause, assessed up to 60 days postop
Overall survival rate from time of randomization to death from any cause
21 secondary outcomes
28 day survival
Time frame: From randomization to death from any cause, assessed up to 28 days post-op
90 day survival
Time frame: From randomization to death from any cause, assessed up to 90 days postop
6 month survival
Time frame: From randomization to death from any cause, assessed up to 6 months postop
1 year survival
Time frame: From randomization to death from any cause, assessed up to 1 year.
Impact of MARS therapy on liver function
Time frame: From randomization up to 1 year.
Impact of MARS therapy on liver function
Time frame: From randomization up to 1 year.
Impact of MARS therapy on extra-hepatic function (APACHE-II scoring)
Time frame: From randomization up to 1 year.
Impact of MARS therapy on extra-hepatic function (SOFA scoring)
Time frame: From randomization up to 1 year.
Impact of MARS therapy on extra-hepatic function (CLIF-SOFA scoring)
Time frame: From randomization up to 1 year.
Impact of MARS therapy on splanchnic hemodynamics assessed by direct estimation of portal blood flow.
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.
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.
Time frame: At randomization (day 0) and on days 5 and 10.
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.
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.
Impact of MARS therapy on liver performance status.
Time frame: At randomization (day 0) and on days 5 and 10.
Impact of MARS therapy on liver toxins (bile acids) in serum and dialysate.
Time frame: At randomization (day 0) and on days 5 and 10.
Impact of MARS therapy on liver toxins (ammonia) in serum and dialysate.
Time frame: At randomization (day 0) and on days 5 and 10.
Impact of MARS therapy on liver toxins (IL-6) in serum and dialysate.
Time frame: At randomization (day 0) and on days 5 and 10.
Impact of MARS therapy on liver toxins (TNF-alpha) in serum and dialysate.
Time frame: At randomization (day 0) and on days 5 and 10.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Gilg, MD PhD principal investigator
Karolinska Institutet
Questions about this trial
What is this clinical trial studying?
A study testing Molecular Adsorbent Recirculating System and Standard medical treatment (SMT) in people with Liver Failure as A Complication of Care, run by Stefan Gilg, MD, PhD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stefan Gilg, MD PhD (0702677722 ext. 46, stefan.gilg@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
60 day survival (time frame: From randomization to death from any cause, assessed up to 60 days postop). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2018.