Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)
Acute Liver Failure, Fulminant Hepatic Failure, Primary Graft Non-Function
About this trial
This is an interventional treatment trial for Acute Liver Failure focused on measuring liver failure, acute liver failure, fulminant hepatic failure, primary graft non-function, surgically-induced liver failure, ELAD, ALF, FHF, PNF
Eligibility Criteria
Inclusion Criteria:
- Weight ≥ 40 kg;
- Age ≥ 18;
Diagnosis of ALF attributed to one of the following:
- FHF (acute liver failure with no preexisting liver disease, see below);
- Primary Graft Non-Function (PNF);
- Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery);
- Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours;
Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E.
Subjects with FHF must meet one of the following criteria:
Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:
- Prothrombin time (PT) > 100 seconds [International Normalized Ratio (INR) > 6.5], OR
- Encephalopathy Grade 3 or 4 AND ARTERIAL AMMONIA >100 umol/liter and at least one of the following:
i. Arterial pH < 7.30 at ≥ 24 hours after drug ingestion or volume resuscitation; ii. Renal failure documented by urine output < 0.5 mL/kg/hr over the preceding 12 hours; iii. Creatinine > 2.5 mg/dL; OR
Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia >100 umol/liter, and at least two of the following:
- Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF
- Serum bilirubin > 17 mg/dL
- Subject > 40 years old
- PT > 50 seconds (INR > 3.5)
- Jaundice to encephalopathy time ≥ 7 days
Exclusion Criteria:
- Cerebral Perfusion Pressure ≤40 mm Hg for 1 hour or longer as measured by an intracranial pressure (ICP) monitor. (NOTE: In those cases where ICP monitor placement cannot be performed prior to study enrollment, this exclusion criterion will not apply);
- Chronic liver disease (e.g., compensated cirrhosis of any etiology, chronic hepatitis, nonalcoholic steatohepatitis, cholestatic liver disease, or metabolic liver disease) (NOTE: steatosis is not an exclusion criterion);
- Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;
Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) indicated by any of the following:
- Presence of sepsis or septic shock; OR
- Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Enrollment; OR
- Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR
- Clinical and radiological signs of pneumonia.
- Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer (except non-melanoma skin cancer), acute fatty-liver disease, hepatitis due to herpes virus or Budd-Chiari syndrome. (NOTE: in the case of subjects enrolled due to surgery-induced liver failure (SILF) then the original cause for the surgery will not be a criterion for exclusion);
- Portal hypertension;
- Liver dysfunction due to trauma;
- Irreversible brain death;
- Platelet count < 30,000/mm3 [NOTE: Subject may be included at the physician's discretion if platelet count exceeds 30,000/mm3 at time of initiation of therapy (even if the value is following platelet transfusion) and can be managed through the administration of blood products]
- Cardiovascular sepsis-related organ failure assessment score (SOFA score) >3;
- Stroke or intracranial hemorrhage;
- Seizures uncontrolled by medication;
- Acute myocardial infarction;
- Lung disease defined by a partial pressure of oxygen measurement (PaO2) ≤60 mmHg or a fraction of inspired oxygen (FiO2) ≥0.6, not corrected by medical management [including continuous venovenous hemofiltration (CVVH) if indicated] and ventilation with a Positive End Expiratory Pressure (PEEP) of >8cm H2O;
- Acute Respiratory Distress Syndrome;
- Pregnancy as determined by beta-human chorionic gonadotropin (β-hCG) results;
- ≤ 2 weeks postpartum;
- 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-212 clinical trial);
- Prior ELAD therapy;
- 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).
Sites / Locations
- Keck Hospital of USC
- Georgetown University Hospital
- University of Miami Hospital
- Tampa General Hospital
- Cleveland Clinic Floriday
- Piedmont Atlanta Hospital
- Emory University Hospital
- Rush University Medical Center
- Massachusetts General Hospital
- University of Minnesota Medical Center - Twin Cities Campus
- Rutgers University Hospital
- Montefiore Medical Center
- New York University Medical Center
- Cleveland Clinic Foundation
- Drexel University College of Medicine
- Methodist Dallas Medical Center - The Liver Institute
- University of Utah
- Swedish Medical Center
Arms of the Study
Arm 1
Experimental
ELAD plus standard of care
Continuous ELAD treatment for a minimum of 3 days to a maximum of 10 days in addition to a standard of care for subjects with acute liver failure.