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Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Acute on Chronic Hepatitis (SILVER)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT00973817
First received: September 2, 2009
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to investigate the safety and efficacy of the use of ELAD in patients with diagnosed Acute On Chronic Hepatitis, including Acute Alcoholic Hepatitis.


Condition Intervention Phase
Acute On Chronic Hepatitis
Biological: ELAD plus standard of care treatment
Other: Standard of care
Phase 2
Phase 3

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to progression at which a 5-point or greater Model for End stage Liver Disease (MELD) score is recorded relative to baseline [ Time Frame: From Baseline up to Study Day 91 ] [ Designated as safety issue: No ]
    This is based on death or the first observed increase of at least 5 points from Baseline MELD score (whichever occurs earlier) at least 24 hours after the ELAD® Treatment Period is ended and up to Study Day 91 (90 days following Baseline).


Secondary Outcome Measures:
  • Time to progression at which a 5-point or greater MELD score is recorded relative to baseline [ Time Frame: From Baseline up to Study Day 91 ] [ Designated as safety issue: No ]
    A secondary Overall Survival analysis will use the same methodology as the primary time to progression efficacy analysis, except that an event will be defined as death. Secondary efficacy analyses will evaluate the proportion of progression free survivors (MELD score increased less than 5 points relative to the Baseline MELD score).


Enrollment: 62
Study Start Date: September 2009
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ELAD
Use of ELAD for up to 6 days to stabilize liver function plus standard of care treatment plus standard of care treatment. Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)
Biological: ELAD plus standard of care treatment
Use of ELAD plus standard of care
Other Name: Extra corporeal liver assist system
Other: Standard of care
Standard of care in the treatment of AOCH will be administered
Standard of care
Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)
Other: Standard of care
Standard of care in the treatment of AOCH will be administered

  Eligibility

Ages Eligible for Study:   18 Years to 67 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/= 18</= 67 years; AND
  • Acute decompensation of chronic liver disease over the preceding 30 days; AND
  • MELD score between 18 and 35, inclusive; AND
  • Subject or designated representative must provide Informed Consent

Exclusion Criteria:

  • Platelets <50,000mm at baseline; OR
  • Evidence of chronic renal failure as defined by a serum creatinine >/= 2.5mg/dL as measured during the 1-6 month period prior to study entry. (Subject is not excluded with a creatinine >2.5 mg/dL if deemed to be type-1 hepato-renal syndrome); OR
  • Contraindication to renal replacement therapy (hemodialysis or hemofiltration); OR
  • International Normalization Ratio (INR) > 3.5; OR
  • Septic shock as defined by a positive blood culture and two or more of the following:

    • Systolic blood pressure <90mmHg OR mean arterial pressure <60mmHg;
    • Tachypnea > 20 breaths per minute OR a PaCO2<32 mmHg;
    • White blood cell count < 4000 cell/mm3 OR > 12000 cell/mm3 (<4 x 10(9) or >12 x 10(9) cells/L).
  • Evidence of major hemorrhage as indicated by:

    • requiring >/= 4 units packed red blood cells within a 48 hour period prior to Screening, 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 if the investigator determines the subject to be at low risk for rebleeding; OR

  • Evidence (by physical exam, history or lab evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome; OR
  • Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis; OR
  • Evidence of spontaneous bacterial peritonitis with uncontrolled infection; OR
  • Evidence of brain death as determined by blood flow studies positive for herniation AND/OR absence of pupillary reflex; OR
  • Systolic blood pressure <85 mmHg OR MAP <50mmHg at baseline; OR
  • Requirement for escalating doses of vasopressor support OR of an alpha-adrenergic agent for one hour or longer AND evidence of hemodynamic instability; OR
  • Subject at maximum vasopressor dose at Screen; OR
  • Clinical or radiographic evidence of a new stroke or intracerebral bleeding; OR
  • Seizures uncontrolled by medication; OR
  • Acute myocardial infarction based on clinical and/or electrocardiographic evidence; OR
  • Lung disease defined by a PaO2<60mmHg on room air, acute respiratory distress syndrome, or a history of severe COPD or interstitial lung disease; OR
  • Pregnancy as determined by beta-HCG results or lactation; OR
  • Participation in another investigational drug, biologic, or device study within 1 month of enrollment. Subjects enrolled in an observational study will be eligible for this trial.
  • Previous liver transplant.
  • Previous participation in a clinical trial involving ELAD.
  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: NCT00973817

Locations
United States, California
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
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, New York
New York University Medical Center
New York, New York, United States, 10016
Columbia University Medical Center
New York, New York, United States, 10032
Univ. of Rochester, Strong Memorial Hospital
Rochester, New York, United States, 14642
Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
United States, Pennsylvania
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
Temple University
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, United States, 75203
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United Kingdom
University Hospitals Birmingham
Birmingham, England, United Kingdom, B15 2PR
Kings College Hospital NHS Foundation Trust
London, England, United Kingdom, SE5 9RS
Royal Derby Hospital
Derby, United Kingdom, DE22 3NE
Edinburgh Royal Infirmary
Edinburgh, United Kingdom, EH16 4SA
St. James University Hospital
Leeds, United Kingdom, LS9 7TF
Royal Free Hospital London
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Study Director: Robert Ashley, MS Vital Therapies, Inc.
  More Information

No publications provided

Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT00973817     History of Changes
Other Study ID Numbers: VTI-206
Study First Received: September 2, 2009
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
European Union: European Medicines Agency
Denmark: Danish Medicines Agency

Keywords provided by Vital Therapies, Inc.:
Hepatitis
AOCH

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014