Status:

TERMINATED

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

Lead Sponsor:

Vital Therapies, Inc.

Conditions:

Acute Liver Failure

Fulminant Hepatic Failure

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls.

Detailed Description

The VTI-212 study (VTI-212) is an open-label, multicenter, historically-controlled study of subjects with acute liver failure (ALF). Approximately 40 subjects who meet the eligibility requirements of ...

Eligibility Criteria

Inclusion

  • 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

  • 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).

Key Trial Info

Start Date :

October 1 2014

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2018

Estimated Enrollment :

8 Patients enrolled

Trial Details

Trial ID

NCT01875874

Start Date

October 1 2014

End Date

September 1 2018

Last Update

February 12 2019

Active Locations (18)

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Page 1 of 5 (18 locations)

1

Keck Hospital of USC

Los Angeles, California, United States, 90033

2

Georgetown University Hospital

Washington D.C., District of Columbia, United States, 20007

3

University of Miami Hospital

Miami, Florida, United States, 33136

4

Tampa General Hospital

Tampa, Florida, United States, 33606