Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure
Acute Alcoholic Hepatitis
About this trial
This is an interventional treatment trial for Acute Alcoholic Hepatitis focused on measuring Acute alcoholic hepatitis, alcoholic, hepatitis, liver
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:
- Hepatomegaly,
- AST > ALT,
- Ascites,
- 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:
- Liver biopsy, AND/OR
- Laboratory findings, AND/OR
- 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:
- Systolic blood pressure < 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
- Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
- Requirement for escalating doses of vasopressor support prior to Screening; OR
- 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:
- Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
- 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.
Sites / Locations
- Maricopa Integrated Health System (MIHS)
- University of Arizona Medical Center
- University of Arkansas for Medical Sciences
- Sharp Coronado Hospital
- Keck Hospital of University of Southern California
- Cedars-Sinai Medical Center
- Stanford School of Medicine/Stanford University Medical Center
- University of California San Diego Medical Center - Hillcrest
- Georgetown University Hospital
- University of Miami Hospital
- Tampa General Hospital
- Cleveland Clinic Florida
- Piedmont Atlanta Hospital
- Emory University Hospital
- Rush University Medical Center
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- University of Minnesota - Twin Cities Campus
- University of Mississippi Medical Center
- Rutgers University Hospital
- Montefiore Medical Center
- North Shore University Hospital
- New York University Langone Medical Center
- Columbia University Medical Center
- Westchester Medical Center
- Cleveland Clinic Foundation
- Drexel University College of Medicine
- Albert Einstein Medical Center
- University of Pittsburgh Medical Center
- Methodist Dallas Medical Center
- Baylor University Medical Center
- The University of Texas Health Science Center - Texas Liver Institute
- University of Utah Hospital
- Swedish Medical Center - Transplant Program
- University of Washington - Harborview Medical Center
- Royal Prince Alfred Hospital
- Flinders Medical Centre
- Sir Charles Gairdner Hospital
- Hospital Ramón y Cajal
- King's College Hospital
- Royal Free Hospital
- University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
- United Hospitals Bristol NHS Foundation Trust
- Cambridge University Hospitals NHS Foundation Trust
- Royal Infirmary of Edinburgh
Arms of the Study
Arm 1
Arm 2
Experimental
Other
ELAD Treatment
Standard of care (Control)
This group will receive treatment with ELAD plus standard of care treatment.
This group will receive standard of care treatment as defined in the protocol.