Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)

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 Read More

Inclusion Criteria:

1. Weight ≥ 40 kg;
2. Age ≥ 18;

3. Diagnosis of ALF attributed to one of the following:

   1. FHF (acute liver failure with no preexisting liver disease, see below);
   2. Primary Graft Non-Function (PNF);
   3. 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);
4. 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;

5. 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:

6. Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:

   1. Prothrombin time (PT) > 100 seconds [International Normalized Ratio (INR) > 6.5], OR
   2. 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

7. Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia >100 umol/liter, and at least two of the following:

   1. Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF
   2. Serum bilirubin > 17 mg/dL
   3. Subject > 40 years old
   4. PT > 50 seconds (INR > 3.5)
   5. Jaundice to encephalopathy time ≥ 7 days

Exclusion Criteria:

1. 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);
2. 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);
3. Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;

4. 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:

   1. Presence of sepsis or septic shock; OR
   2. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Enrollment; OR
   3. Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR
   4. Clinical and radiological signs of pneumonia.
5. 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);
6. Portal hypertension;
7. Liver dysfunction due to trauma;
8. Irreversible brain death;
9. 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]
10. Cardiovascular sepsis-related organ failure assessment score (SOFA score) >3;
11. Stroke or intracranial hemorrhage;
12. Seizures uncontrolled by medication;
13. Acute myocardial infarction;
14. 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;
15. Acute Respiratory Distress Syndrome;
16. Pregnancy as determined by beta-human chorionic gonadotropin (β-hCG) results;
17. ≤ 2 weeks postpartum;
18. 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);
19. Prior ELAD therapy;
20. 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).