Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) System in Patients With Hepatic Insufficiency (ELAD)

Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) in Patients With Acute on Chronic Hepatitis (AOCH)

Evaluate on how well the ELAD system works in treating people with liver failure.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis; Acute Hepatitis
• Intervention / Treatment: Biological: ELAD plus standard of care treatment; Other: Standard of care treatment

Detailed Description

This is a multicenter, open-label, randomized, concurrent control study of subjects with acute on chronic hepatitis. Subjects meeting the eligibility requirements of the study will be randomly assigned in a 2:1 ratio to receive either standard medical therapy for acute liver failure plus the ELAD system, or standard medical therapy alone, with the latter defined as conventional therapy for acute on chronic hepatitis determined to be clinically appropriate by the treating physician.

Immediately prior to treatment initiation, subject eligibility will be confirmed. Treatment with ELAD will continue for a minimum of 3 days and up to a maximum of 10 days or until clinical status improves relative to study entry. Subjects will be followed until 30 days has elapsed since study enrollment (control) or 30 days has elapsed since cessation of ELAD therapy (ELAD group), whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Weight >40 kilograms
2. Age >18 and <70 years
3. Acute decompensation of cirrhosis over the preceding 48-72 hour period
4. Up to 4 weeks from symptom onset to presentation
5. Presence of a precipitating event

6. Either a MELD score of ≥32, or ≥24 with one or more of the following

   • Severe encephalopathy of grade 3 or 4 on the Westhaven scale
   • Renal dysfunction typical of type-1 hepato-renal syndrome, i.e. acute renal failure without evidence of elevated serum creatinine (>2.5mg/dL) during the 1 to 6 months prior to study entry. Serum creatinine at study entry >2.5mg/dL does not exclude the subject from enrolment
7. SOFA score ≥9 at the initial Screening Visit

Exclusion Criteria:

1. Platelets <50,000 or reducing to <80,000 over a 72 hour period
2. Renal failure: Serum creatinine ≥2.5 mg/dL as measured during the 1 - 6 month period prior to study entry. If a subject has a contraindication to renal replacement therapy (hemodialysis or hemofiltration), then the subject should be excluded from entry into the study
3. Active sepsis. Sepsis will be defined as positive microbiological culture, ascitic white cell count >450 cells/mm³ (or ascitic neutrophil count >250 cells/mm³), or clinical signs and chest x-ray appearances for at least 48 hours without clinical improvement prior to randomization, or other evidence of infection not under control
4. Evidence of major hemorrhage indicated by requiring ≥ 4 unit blood transfusion within a 24 hour period, or hemodynamic instability (sustained pulse >120 beats/min and systolic blood pressure <100 mmHg over one hour). Subjects with a recent history of gastrointestinal hemorrhage who have been successfully treated and remain hemodynamically stable for a period of 48 hours will then be eligible for the study
5. Evidence (by physical exam, history, or laboratory evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, fatty-liver disease of non-alcoholic origin, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome;
6. Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis
7. Evidence of Small Bowel Perforation within 48 hours of treatment;
8. Evidence of brain death as determined by blood flow studies positive for herniation and/or absence of pupillary reflex
9. Mean Arterial Pressures (MAP) < 50 mm Hg for one hour or longer;
10. Requirement for escalating doses of vasopressor support of an alpha-adrenergic agent for one hour or longer and evidence of hemodynamic instability;
11. Clinical or radiographic evidence of a new stroke or intracerebral bleeding
12. Seizures uncontrolled by medication
13. Acute myocardial infarction based on clinical and/or electrocardiographic evidence
14. Lung disease defined by a PaO2 <60 mm Hg or a history of severe COPD or interstitial lung disease
15. Pregnancy as determined by βHCG results, or lactation
16. Participation in another investigational drug, biologic, or device study within one month of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ELAD (plus Standard of Care); Treatment with ELAD in addition to standard of care therapy Standard of care therapy defines uniform treatment for ascites, esophageal varices, dietary recommendations, etc.	Biological: ELAD plus standard of care treatment; ELAD is a liver assist system - Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated); Other: Standard of care treatment; Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)
OTHER: Standard of Care (Control); Standard of care treatment Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)	Other: Standard of care treatment; Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To provide evidence that (1) subjects treated with ELAD have a higher 30-day transplant-free survival in subjects with AOCH than those not treated with ELAD, and (2) it is safe when used for 3 to 10 days of treatment.	12 months

Collaborators and Investigators

• Sponsor: Vital Therapies, Inc.
• Investigators: Principal Investigator: Todd Frederick, MD, California Pacific Medical Center; Principal Investigator: Donald Hillebrand, MD, Scripps Green Hospital; Principal Investigator: Robert Brown, MD, Columbia University; Principal Investigator: Lena Napolitano, MD, University of Michigan Hospital; Principal Investigator: Winfred Williams, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): April 1, 2009

Study Registration Dates

• First Submitted: October 9, 2008
• First Submitted That Met QC Criteria: October 10, 2008
• First Posted (ESTIMATE): October 13, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 5, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Hepatitis, acute; Acute Hepatitis OR Chronic Hepatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis, Chronic
• Other Study ID Numbers: VTI-201