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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT00771446
First received: October 9, 2008
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Acute Hepatitis
Chronic Hepatitis
Biological: ELAD plus standard of care treatment
Other: Standard of care treatment
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) in Patients With Acute on Chronic Hepatitis (AOCH)

Resource links provided by NLM:


Further study details as provided by Vital Therapies, Inc.:

Primary Outcome Measures:
  • 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. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: October 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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)

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

Ages Eligible for Study:   19 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771446

Locations
United States, California
Scripps Clinic
La Jolla, California, United States, 92037
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Principal Investigator: Todd Frederick, MD California Pacific Medical Center
Principal Investigator: Donald Hillebrand, MD Scripps Green Hospital
Principal Investigator: Helen Te, MD University of Chicago
Principal Investigator: Robert Brown, MD Columbia University
Principal Investigator: Lena Napolitano, MD University of Michigan Hospital
Principal Investigator: Winfred Williams, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT00771446     History of Changes
Other Study ID Numbers: VTI-201
Study First Received: October 9, 2008
Last Updated: April 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vital Therapies, Inc.:
Hepatitis, acute
Acute Hepatitis OR Chronic Hepatitis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Pentoxifylline
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on September 18, 2014