Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure
Condition: Acute Alcoholic Hepatitis
MeSH terms: Hepatitis; Hepatitis, Alcoholic
Intervention: ELAD treatment; Standard of care (Control)
Intervention description: ELAD treatment consists of treatment with an extracorporeal liver assist system.; Control receives standard medical treatment.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 203.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute alcoholic hepatitis; alcoholic; hepatitis; liver

Summary:

      The primary objective of the study is to evaluate safety and efficacy of ELAD® with respect
      to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver
      decompensation (AILD) up to at least Study Day 91, with follow-up Protocol VTI-208E providing
      additional survival data up to a maximum of 5 years that will be included, as available,
      through VTI-208 study termination (after the last surviving enrolled subject completes Study
      Day 91).

      Secondary objectives are to determine the proportion of survivors at Study Days 28 and 91.

      Exploratory objectives are to evaluate the ability of ELAD to stabilize liver function,
      measured using the Model for End Stage Liver Disease (MELD)-based time to progression (TTP)
      up to Study Day 91, and the proportion of progression-free survivors (PFS) up to Study Days
      28 and 91. Progression is defined as death or the first observed increase of at least 5
      points from End of Study Day 1 MELD score (for both the ELAD and Control groups) until at
      least 24 hours after the ELAD Treatment Period is ended (end of Day 7 for Controls) and up to
      both End of Study Days 28 and 91 following Randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years;

          -  Total bilirubin ≥ 8 mg/dL;

          -  A clinical diagnosis of alcohol-induced liver decompensation (AILD), based upon
             evidence (by lab test, medical history, or family interview) of a clinical judgment of
             a temporal (6 weeks or less) and causal relationship between use of alcohol and this
             onset of symptoms;

          -  Subjects meeting inclusion criteria 1 through 3 will be classified as having either:

             a. Severe acute alcoholic hepatitis (AAH), with: i. Medical history of alcohol abuse;
             AND ii. Maddrey score of ≥ 32; AND iii. AAH documented by either:

             1. Confirmatory liver biopsy; OR 2. Two or more of the following:

               1. Hepatomegaly,

               2. AST > ALT,

               3. Ascites,

               4. Leukocytosis (WBC count above lab normal at site), OR

             b. Alcohol-induced decompensation of chronic liver disease that is not acute alcoholic
             hepatitis (as defined above), with: i. MELD score of 18-35; AND ii. Underlying chronic
             liver disease documented by:

               1. Liver biopsy, AND/OR

               2. Laboratory findings, AND/OR

               3. Medical history;

          -  Not eligible for liver transplant during this hospitalization;

          -  Subject or legally authorized representative must provide Informed Consent;

          -  Subject must be eligible for Standard of Care treatment as defined in the protocol.

        Exclusion Criteria:

          -  Platelet count < 40,000/mm3;

          -  International Normalization Ratio (INR) > 3.5;

          -  MELD Score > 35;

          -  AST > 500 IU/L;

          -  Evidence of infection unresponsive to antibiotics;

          -  Evidence of reduction in total bilirubin of 20% or more in the previous 72 hours, if
             available. Bilirubin measurements must be taken at least 12 hours after any procedure
             known to artificially alter serum bilirubin (e.g., administration of packed red blood
             cells, plasma exchange);

          -  Evidence of hemodynamic instability as defined by the following:

               1. Systolic blood pressure < 90 mmHg with evidence of diminished perfusion
                  unresponsive to fluid resuscitation and/or low-dose pressor support; OR

               2. Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion
                  unresponsive to fluid resuscitation and/or low-dose pressor support; OR

               3. Requirement for escalating doses of vasopressor support prior to Screening; OR

               4. Subject at maximum vasopressor dose at Screening;

          -  Evidence of active bleeding or of major hemorrhage defined as requiring ≥ 2 units
             packed red blood cells to maintain stable hemoglobin occurring within 48 hours of
             Screening;

          -  Clinical evidence of liver size reduction due to cirrhosis (liver size of the
             craniocaudal diameter (sagittal view) < 10 cm when measured on the mid clavicular line
             (or equivalent measurement) by ultrasound, or liver volume < 750 cc as determined by
             CT), unless Investigator interpretation of the clinical evidence indicates liver size
             of < 10 cm or volume < 750 cc is not considered reduced for the individual subject;

          -  Occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct
             obstruction;

          -  Evidence by physical exam, history, or laboratory evaluation, of significant
             concomitant disease with expected life expectancy of less than 3 months, including,
             but not limited to:

               1. Severe acute or chronic cardiovascular, central nervous system, or pulmonary
                  disease;

               2. Cancer that has metastasized or has not yet been treated;

          -  Subject has chronic end-stage renal disease requiring chronic hemodialysis for more
             than 8 weeks (not classified as hepatorenal syndrome);

          -  Subject has liver disease related to homozygous hemachromatosis, Wilson's Disease, has
             non-alcoholic fatty liver disease, or Budd-Chiari Syndrome;

          -  Pregnancy as determined by β-human chorionic gonadotropin (HCG) results, or lactation;

          -  Participation in another investigational drug, biologic, or device study within one
             month of enrollment, except for observational studies (the observational study setting
             should not affect safety and/or efficacy of the VTI-208 clinical trial);

          -  Previous liver transplant;

          -  Previous enrollment in the treatment phase of another ELAD trial (e.g. a subject is
             not disqualified from enrollment in VTI-208 if they were screened for VTI-210 but did
             not qualify for enrollment in the treatment phase of the study and therefore did not
             receive ELAD or Control treatment;

          -  Have a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or such local
             equivalent) or any other Advanced Directive limiting Standard of Care in place (the
             DNR/DNI criterion is not applicable in the UK);

          -  Refusal to participate in the VTI-208E follow-up study;

          -  Inability to provide an address for home visits.