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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| Standard medical treatment | Active Comparator | Patients assigned to the control arm will receive standard medical treatment (SMT) as specified in the study protocol. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Molecular Adsorbent Recirculating System | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 90 day survival | Overall survival rate from time of randomization to death from any cause. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stefan Gilg, MD PhD | Contact | 0702677722 | 46 | stefan.gilg@ki.se |
| Name | Affiliation | Role |
|---|---|---|
| Stefan Gilg, MD PhD | Karolinska Institutet | Principal Investigator |
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| Standard medical treatment (SMT) | Other | Patient management and standard medical treatment (SMT) as specified in the study protocol. |
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| 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. | 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. | 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) | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | At randomization (day 0) and on days 5 and 10. |