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

Phase 1

Completed

Conditions: Chronic Hepatitis
Acute Hepatitis

Interventions: Other: Standard of care treatment
Biological: ELAD plus standard of care treatment

Registration Number: NCT00771446

Lead Sponsor: Vital Therapies, Inc.

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Weight >40 kilograms
Age >18 and <70 years
Acute decompensation of cirrhosis over the preceding 48-72 hour period
Up to 4 weeks from symptom onset to presentation
Presence of a precipitating event
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
SOFA score ≥9 at the initial Screening Visit

Exclusion Criteria

Platelets <50,000 or reducing to <80,000 over a 72 hour period
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
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
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
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;
Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis
Evidence of Small Bowel Perforation within 48 hours of treatment;
Evidence of brain death as determined by blood flow studies positive for herniation and/or absence of pupillary reflex
Mean Arterial Pressures (MAP) < 50 mm Hg for one hour or longer;
Requirement for escalating doses of vasopressor support of an alpha-adrenergic agent for one hour or longer and evidence of hemodynamic instability;
Clinical or radiographic evidence of a new stroke or intracerebral bleeding
Seizures uncontrolled by medication
Acute myocardial infarction based on clinical and/or electrocardiographic evidence
Lung disease defined by a PaO2 <60 mm Hg or a history of severe COPD or interstitial lung disease
Pregnancy as determined by βHCG results, or lactation
Participation in another investigational drug, biologic, or device study within one month of enrollment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care (Control)	Standard of care treatment	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)
ELAD (plus Standard of Care)	ELAD plus standard of care treatment	Treatment with ELAD in addition to standard of care therapy Standard of care therapy defines uniform treatment for ascites, esophageal varices, dietary recommendations, etc.
ELAD (plus Standard of Care)	Standard of care treatment	Treatment with ELAD in addition to standard of care therapy Standard of care therapy defines uniform treatment for ascites, esophageal varices, dietary recommendations, etc.

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (6): California Pacific Medical Center
🇺🇸
San Francisco, California, United States
University of Michigan Hospital
🇺🇸
Ann Arbor, Michigan, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Scripps Clinic
🇺🇸
La Jolla, California, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States