Comparison of Two Liver Dialysis Systems : MARS Versus SPAD in Severe Liver Failure

Study Overview
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Brief Summary
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A critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, albumin dialysis is used to remove those substances. Albumin dialysis with recirculation (MARS) is the most used system but required specific system and expert environment. Alternative system without recirculation (SPAD) is less expensive and can be realised in critical care services trained to extrarenal epuration. The primary objective of this study is to compare biological and clinical efficacy, pulsatility index of middle cerebral artery modification and tolerance of both systems. This is a prospective, open, cross-over comparative study of two albumin dialysis system. Each patient will receive the two systems in an randomly assessed order. Patients are divided up according to bilirubin plasmatic level. (250µmol/L to 400 µmol/L and >400µmol/L).

Official Title
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Comparison of Two Extracorporeal Liver Support System (With or Without Recirculation) : MARS (Molecular Adsorbents Recirculating System) Versus SPAD (Single Pass Albumin Dialysis) in Severe Liver Failure.

Conditions
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Liver Failure, Acute, Chronic Hepatic Failure

Intervention / Treatment
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* Device: MARS albumin dialysis system
* Device: SPAD albumin dialysis system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: severe hepatic failure on acute liver failure or acute on chronic liver failure hyperbilirubinemia (total plasmatic bilirubin level above 250µmol/L) hepatic encephalopathy or pruritus or hepatorenal syndrome. waiting for liver function recovery or liver transplantation Signed written informed consent by patient or patient's legally appointed representative or reliable person affiliation to social security Exclusion Criteria: contraindication to extra-renal epuration hypersensibility to albumin or excipients patients for whom 2 albumin dialysis treatment cannot be considered

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MARS-SPAD<br>Patients will receive first the MARS albumin dialysis system and then, in a second time, the SPAD albumin dialysis system. | Device: MARS albumin dialysis system<br> <br> Device: SPAD albumin dialysis system<br> <br> |
| Experimental: SPAD-MARS<br>Patients will receive first the SPAD albumin dialysis system and then, in a second time, the MARS albumin dialysis system. | Device: MARS albumin dialysis system<br> <br> Device: SPAD albumin dialysis system<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of total plasmatic bilirubin level before and after two albumin dialysis systems : with recirculation (MARS™ system) and without recirculation (SPAD™ system) | Determination of total plasmatic bilirubin level will be performed by arterial sample and expressed in µmol/liter. Total plasmatic bilirubin purification will be compared between the two dialysis systems: total plasmatic bilirubin level will be measured before and at the end of MARS™ dialysis (8 hours) and before and at the end of SPAD™ dialysis (10 hours) ; the two variations will be compared. Each patient will receive the two dialysis systems separated by a free interval that will last between 12 and 48 hours. | Before and at the end of a MARS™ dialysis (8h) and before and at the end of a SPAD™ system dialysis (10h). Participants will be followed for the duration of critical care stay, an expected average of 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of bile acids and conjugated bilirubin levels before and after two albumin dialysis systems: with recirculation (MARS™ system) and without recirculation (SPAD™ system). | Determination of bile acids and conjugated bilirubin levels will be performed by arterial sample and expressed in µmol/liter. Bile acids and conjugated bilirubin purifications will be compared between the two dialysis systems: Bile acids and conjugated bilirubin levels will be measured before and at the end of MARS™ dialysis (8 hours) and before and at the end of SPAD™ dialysis (10 hours) ; the two variations will be compared. Each patient will receive the two dialysis systems separated by a free interval that will last between 12 and 48 hours. | Before and at the end of a MARS™ system dialysis (8h) and before and at the end of a SPAD™ dialysis (10h) . Participants will be followed for the duration of critical care stay, an expected average of 1 week. | 
| Comparison of hepatic encephalopathy score before and after two albumin dialysis systems : with recirculation (MARS™ system) and without recirculation (SPAD™ system) | Determination of hepatic encephalopathy score will be performed by clinical evaluation. Hepatic encephalopathy score will be compared between the two dialysis systems: hepatic encephalopathy score will be measured before and at the end of MARS™ dialysis (8 hours) and before and at the end of SPAD™ dialysis (10 hours) ; the two variations will be compared. Each patient will receive the two dialysis systems separated by a free interval that will last between 12 and 48 hours. | Before and at the end of a MARS™ system dialysis (8h) and before and at the end of a SPAD™ system dialysis (10h) . Participants will be followed for the duration of critical care stay, an expected average of 1 week. | 
| Comparison of pulsatility index of middle cerebral artery recorded by transcranial doppler before and after two albumin dialysis system : with recirculation (MARS™ system) and without recirculation (SPAD™ system) | Pulsatility index of middle cerebral artery will be recorded by transcranial doppler. Pulsatility index of middle cerebral artery will be compared between the two dialysis systems: Pulsatility index of middle cerebral artery will be measured before and at the end of MARS™ dialysis (8 hours) and before and at the end of SPAD™ dialysis (10 hours) ; the two variations will be compared. Each patient will receive the two dialysis systems separated by a free interval that will last between 12 and 48 hours. | Before and at the end of a MARS™ dialysis (8h) and before and at the end of a SPAD™ system dialysis (10h). Participants will be followed for the duration of critical care stay, an expected average of 1 week | 
| Comparison of tolerance of two albumin dialysis sytems : with recirculation (MARS™ system) and without recirculation (SPAD™ system) | Tolerance will be evaluated by effect of albumin dialysis on coagulation indices : prothrombin time (seconds) and international normalized ratio, activated partial thromboplastin time ratio, fibrinogen level (g/L), factor V level (%), platelet count (×10(9) /L), hemoglobin level (g/L), red cell count (10(12)/L), hematocrit level (%). Coagulation indices will be measured by an arterial sample before and at the end of MARS™ dialysis (8 hours) and before and at the end of SPAD™ dialysis (10 hours) ; the two variations will be compared. Each patient will receive the two dialysis systems separated by a free interval that will last between 12 and 48 hours. | During MARS™ system dialysis (8h) and during SPAD™ system dialysis (10h) . Participants will be followed for the duration of critical care stay, an expected average of 1 week. |