To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
Condition: Severe Acute Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Intervention: ELAD; Standard of Care treatment
Intervention description: ELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2.; Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: liver failure; acute alcoholic hepatitis; patients failing steroid therapy; alcoholic hepatitis; steroid failure; Lille criteria; ELAD

Summary:

      The purpose of this study is to determine if treatment with the ELAD System is safe and
      effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille
      score >0.45).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 ;

          -  Total bilirubin ≥8 mg/dL;

          -  Medical history of alcohol abuse with evidence of a causal and temporal (<6 weeks)
             relationship to the use of alcohol and hospital admission for this episode of sAAH;

          -  Maddrey score ≥32

          -  A clinical diagnosis of severe acute alcoholic hepatitis (sAAH);

          -  Subject must have liver biopsy or in investigator's opinion, if risk is too great to
             perform liver biopsy, then clinical diagnosis is sufficient;

          -  Subject must be a Lille score failure (Lille score >0.45) as defined in this study.

        Exclusion Criteria:

          -  Platelet count <50,000/mm3;

          -  International Normalization Ratio (INR) >3.0;

          -  MELD score >35;

          -  Evidence of infection unresponsive to antibiotics;

          -  Evidence of jaundice for >3 months;

          -  Hospital admission for any episodes of liver decompensation not related to sAAH,
             (other than this episode of sAAH) within the past 2 months;

          -  Evidence of hemodynamic instability;

          -  Evidence of active bleeding or of major hemorrhage defined as requiring ≥2 units of
             packed red blood cells to maintain a stable hemoglobin occurring within 48 hours of
             Screening;

          -  Evidence of 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;

          -  Clinical evidence of liver size reduction due to cirrhosis, unless Investigator
             interpretation of the clinical evidence indicates liver size of <10 cm or volume of
             <750 cc is not considered reduced for the individual subject;

          -  Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks
             (not classified as hepatorenal syndrome);

          -  Uncontrolled seizures;

          -  Positive serologies for viral hepatitis B or C;

          -  Pregnancy as determined by β-human chorionic gonadotropin (HCG) results;

          -  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 the safety and/or efficacy of the VTI-210 clinical trial);

          -  Currently listed or scheduled for liver transplant during the 90-day study period;

          -  Previous liver transplant;

          -  Previous participation in a clinical trial involving ELAD;

          -  Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or 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-210E follow-up study;

          -  Is unable to provide an address for follow-up home visits.

        And other inclusion/exclusion criteria