Safety and Efficacy of the Extracorporeal Liver Assist Device (ELAD®) In Patients With Fulminant Hepatic Failure (FHF)

This study has been withdrawn prior to enrollment.
(To focus on another clinical indication.)
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT00832728
First received: January 29, 2009
Last updated: July 24, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Fulminant Hepatic Failure
Other: Standard of Care
Device: ELAD®
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 and Efficacy of the Extracorporeal Liver Assist Device (ELAD®) In Patients With Fulminant Hepatic Failure (FHF)

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

Primary Outcome Measures:
  • The effect of ELAD® therapy: 1) as a bridge-to-transplant/recovery and 2) on 30-day transplant-free survival in subjects with FHF [ Time Frame: 30 day ] [ Designated as safety issue: No ]
  • To assess its safety when used for a minimum of 3 days or up to a maximum of 30 days of treatment [ Time Frame: 30 day ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: March 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ELAD
ELAD Therapy + Standard of Care
Other: Standard of Care
Standard hospital protocol for the treatment of acute liver failure
Device: ELAD®
ELAD therapy
Standard of Care
Hospital based standard of care for acute liver failure
Other: Standard of Care
Standard hospital protocol for the treatment of acute liver failure

Detailed Description:

Therapy will generally include treatment of hepatic encephalopathy using lactulose with or without oral antibiotics, antibiotics as indicated to treat infection, volume resuscitation and vasopressors as indicated to treat hypotension. In addition general medical treatment such as glucose control and renal replacement therapy will be used as necessary. Subjects with a clinical diagnosis of hepato-renal syndrome may be treated with midodrine and octreotide or terlipressin, if considered appropriate therapy.

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 30 days, until, in the Investigator's opinion, clinical status improves relative to entry; until the subject undergoes OLT; or until the continued use of ELAD® is contraindicated, as described in Section 5.5. Subjects will be followed until discontinuation or 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:   10 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Weight ≥15 kilograms;
  2. Age ≥10 ≤65 years;
  3. Diagnosis of FHF;
  4. Patients must have been treated with a standard regimen of N-acetyl cysteine (NAC) involving a loading dose of 150mg/kg/hr over 1 hour followed by 12.5 mg/kg/hour x 4 hours then continuous infusion of 6.25 mg/kg for the remaining 67 hrs.
  5. Subject or designated representative must be willing to sign an Informed Consent Form specific to this study and comply with study requirements AND EITHER
  6. Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:

    a. prothrombin time (PT) >30 seconds (International Normalized Ratio (INR) >6.5, OR; b. Encephalopathy Grade II, III or IV and at least one of the following: i. Arterial pH <7.30 at ≥2 hours after initial diagnosis, OR; ii. renal failure documented by urine output less than 2 mL/kg/hr over 12 hours, OR; iii. creatinine >2.5 mg/dL; OR

  7. Patients with Non-Acetaminophen-Induced FHF:

    a. Stage II, III or IV encephalopathy, and the presence of at least two of the following five criteria: i. Non-A/Non-B hepatitis or drug (non-acetaminophen) induced FHF; ii. Serum bilirubin >17 mg/dL; iii. Patient ≥10 or <40 years old; iv. Prothrombin time >25 seconds (INR > 3.5), AND/OR; v. Jaundice to encephalopathy time ≥7 days; OR

  8. Liver transplantation within 10 days of the screening procedures, but meeting inclusion criteria due to primary graft non-function, and not receiving ELAD® therapy prior to the first graft

Exclusion Criteria:

  1. Cerebral Perfusion Pressure 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):

    1. Patients > 18 yrs of age with Cerebral Perfusion Pressures (CPP) ≤40 mm Hg for one hour or longer.
    2. Patients ≤18 yrs with CPP ≤35 mm Hg for one hour or longer.
  2. Chronic liver disease;
  3. Concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, cancer, acute fatty-liver disease, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome;
  4. Portal hypertension (e.g., variceal bleed, caput Medusae, and clinically obvious ascites);
  5. Liver dysfunction due to trauma;
  6. Hemorrhage or irreversible brain death ( i.e. blood flow studies positive for herniation and/or pupillary reflex absent);
  7. Platelet count <50,000/mm3 or reducing to <80,000/mm3 over a 72 hr. period. (NOTE: Patient may be included at the physician's discretion if platelet count exceeds 50,000mm3 at time of initiation of therapy and can be managed through the administration of blood products);
  8. Mean Arterial Pressures (MAP) ≤50 mm Hg for one hour or longer as measured by an indwelling arterial line, OR; patients ≤18 years old and whose MAP is ≤40 mm Hg for one hour or longer;
  9. Vasopressor support exceeding 1.0 µg/kg/min of an alpha-adrenergic agent for one hour or longer;
  10. Clinical or radiographic evidence of stroke or intracerebral bleeding;
  11. Seizures uncontrolled by medication;
  12. Acute myocardial infarction based on clinical and/or electrocardiographic evidence;
  13. Lung disease defined by a PaO2 ≤ 60mm Hg or an FiO2 ≥0.6, not corrected by medical management (including CVVH if indicated);
  14. Pregnancy as determined by βhCG results;
  15. ≤2 weeks postpartum;
  16. Participation in another investigational study within 30 days of enrollment;
  17. Prior ELAD® therapy.
  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: NCT00832728

Locations
United States, California
Scripps Green Hospital
La Jolla, California, United States, 92037
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Loyola University Medical Center
Chicago, Illinois, United States, 60153
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Louisiana State University Health Sciences Center-Shreveport
Shreveport, Louisiana, United States, 71103
United States, New York
New York University Medical Center
New York, New York, United States, 10016
University of Rochester, Strong Memorial
Rochester, New York, United States, 14642
United States, Pennsylvania
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Study Director: Robert A Ashley Vital Therapies, Inc.
  More Information

No publications provided

Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT00832728     History of Changes
Other Study ID Numbers: VTI-202
Study First Received: January 29, 2009
Last Updated: July 24, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Failure
Liver Failure, Acute
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 19, 2014