Clinical trial NCT00771446: Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) System in Patients With Hepatic Insufficiency
Official title: Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) in Patients With Acute on Chronic Hepatitis (AOCH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Hepatitis
Chronic Hepatitis
Keywords: Hepatitis, acute
Acute Hepatitis OR Chronic Hepatitis
Lead sponsor: Vital Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2008-10-13
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: California Pacific Medical Center
name: Todd Frederick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Scripps Green Hospital
name: Donald Hillebrand, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Helen Te, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Robert Brown, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan Hospital
name: Lena Napolitano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Winfred Williams, MD
role: PRINCIPAL_INVESTIGATOR
References: