Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure

This study is currently recruiting participants.
Verified March 2014 by Vital Therapies, Inc.
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT01471028
First received: November 7, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The objective of the study is to evaluate safety and efficacy of ELAD® with respect to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver decompensation up to Study Day 91.

Secondary objectives are to evaluate the proportion of overall survival at Study Days 28 and 91.

An exploratory objective is to evaluate the ability of ELAD® to stabilize liver function, measured using the Model for End Stage Liver Disease (MELD) -based time to progression (TTP), with progression defined as the earlier of death or an increase of 5 points or more in MELD score at defined times post-randomization.


Condition Intervention Phase
Acute Alcoholic Hepatitis
Biological: ELAD treatment
Other: Standard of care (Control)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Time Frame: 91 days ] [ Designated as safety issue: Yes ]
    Overall survival will be followed for all enrolled patients to determine whether ELAD treatment affects patient survival.


Secondary Outcome Measures:
  • Overall survival at Study Days 28 and 91 [ Time Frame: 28 days and 91 days ] [ Designated as safety issue: Yes ]
    Secondary objectives are to evaluate the proportion of overall survival at Study Days 28 and 91


Other Outcome Measures:
  • Time to progression of disease [ Time Frame: Study Day 1 up to Study Day 91 ] [ Designated as safety issue: No ]
    An exploratory objective is to evaluate the ability of ELAD® to stabilize liver function, measured using the MELD-based time to progression (TTP), with progression defined as the earlier of death or an increase of 5 points or more in MELD score at defined times post-randomization.


Estimated Enrollment: 200
Study Start Date: February 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ELAD Treatment
This group will receive treatment with ELAD plus standard of care treatment.
Biological: ELAD treatment
ELAD treatment consists of treatment with an extracorporeal liver assist system.
Other Name: ELAD
Standard of care (Control)
This group will receive standard of care treatment as defined in the protocol.
Other: Standard of care (Control)
Control receives standard medical treatment.
Other Name: Standard of care as defined by the protocol

Detailed Description:

Subjects randomized to the ELAD® group will receive treatment with ELAD® for a maximum of five (5) 24 hour periods as well as standard medical therapy.

Subjects randomized to the Control group will receive standard medical therapy throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years;
  • Total bilirubin ≥ 8 mg/dL;
  • A clinical diagnosis of alcohol-induced liver decompensation (AILD), based upon evidence (by lab test, medical history, or family interview) of a clinical judgment of a temporal (6 weeks or less) and causal relationship between use of alcohol and this onset of symptoms;
  • Subjects will be classified as having either:

    a. Severe acute alcoholic hepatitis (AAH), with: i. Medical history of alcohol abuse; AND ii. Maddrey score of ≥ 32; AND iii. AAH documented by either:

    1. Confirmatory liver biopsy; OR 2. Two or more of the following:

    1. Hepatomegaly,
    2. AST > ALT,
    3. Ascites,
    4. Leukocytosis (WBC count above lab normal at site), OR

    b. Alcohol-induced decompensation of chronic liver disease that is not acute alcoholic hepatitis (as defined above), with: i. MELD score of 18-35; AND ii. Underlying chronic liver disease documented by:

    1. Liver biopsy, AND/OR
    2. Laboratory findings, AND/OR
    3. Medical history;
  • Not eligible for liver transplant during this hospitalization;
  • Subject or designated representative must provide Informed Consent;
  • Subject must be eligible for Standard of Care treatment as defined in the protocol.

Exclusion Criteria:

  • Platelet count < 40,000/mm3;
  • International Normalization Ratio (INR) > 3.5;
  • MELD Score > 35;
  • AST > 500 IU/L;
  • Evidence of infection unresponsive to antibiotics;
  • Evidence of reduction in total bilirubin of 20% or more in the previous 72 hours, if available:
  • Evidence of hemodynamic instability
  • Evidence of active bleeding or of major hemorrhage occurring within 48 hours of Screening;
  • Clinical evidence of liver size reduction due to cirrhosis ;
  • Occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;
  • Evidence by physical exam, history, or laboratory evaluation, of significant concomitant disease with expected life expectancy of less than 3 months;
  • Subject has chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
  • Subject has liver disease related to homozygous hemachromatosis, Wilson's Disease, has non-alcoholic fatty liver disease, or Budd-Chiari Syndrome;
  • Pregnancy as determined by β-human chorionic gonadotropin (HCG) results, or lactation;
  • Participation in another investigational drug, biologic, or device study within one month of enrollment, except for observational studies;
  • Previous liver transplant;
  • Previous participation in a clinical trial involving ELAD;
  • Have a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or such local equivalent) or any other Advanced Directive limiting Standard of Care in place;
  • Inability to provide an address for followup home health visits.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01471028

Contacts
Contact: Andrew Henry 858-673-6840 ext 1844 ahenry@vitaltherapies.com
Contact: Deborah Mongiovi 858-673-6840 ext 1987 dmongiovi@vitaltherapies.com

  Show 41 Study Locations
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Study Director: Jan Stange, MD Vital Therapies, Inc.
Principal Investigator: David J Reich, MD Drexel University College of Medicine
Principal Investigator: Ram Subramanian, MD Emory University
Principal Investigator: Lewis Teperman, MD New York University Langone Medical Center
Principal Investigator: Robert Brown, MD Columbia University Medical Center, New York
Principal Investigator: Julie Thompson, MD University of Minnesota, Minneapolis
Principal Investigator: Paul Gaglio, MD Montefiore Medical Center
Principal Investigator: Linda Sher, MD Keck Hospital of University of Southern California
Principal Investigator: David Wolf, MD Westchester Medical Center
Principal Investigator: Parvez Mantry, MD Methodist Dallas Medical Center
Principal Investigator: Brendan McGuire, MD University of Alabama at Birmingham Hospital
Principal Investigator: Ali Al-Khafaji, MD University of Pittsburgh
Principal Investigator: Marquis E Hart, MD Swedish Medical Center
Principal Investigator: Samuel Ho, MD San Diego Veterans Healthcare System
Principal Investigator: Anu Duddempudi, MD North Shore University Hospital, NY
Principal Investigator: Sumeet K Asrini, MD Baylor Health Care System
Principal Investigator: Thomas Ardiles, MD Maricopa Integrated Health System
Principal Investigator: Charles Landis, MD University of Washington
Principal Investigator: Rohit Satoskar, MD Georgetown University Hospital
Principal Investigator: Nikunj Shah, MD Rush University Medical Center
Principal Investigator: Brian Borg, MD University of Mississippi Medical Center
Principal Investigator: Alan Wigg, MD Flinders Medical Centre - South Australia
Principal Investigator: Ross MacNicholas, MD Sir Charles Gairdner Hospital, Nelands, Australia
Principal Investigator: Lance L Stein, MD Piedmont Atlanta Hospital, GA
Principal Investigator: Talal Adhami, MD The Cleveland Clinic
Principal Investigator: Rasheed Balogun, MD University of Virginia Health System
Principal Investigator: Simona Rossi, MD Albert Einstein Medical Center
Principal Investigator: Mark Jacob, MD East Carolina University Brody School of Medicine
Principal Investigator: Santiago Munoz, MD Capital Health Medical Center - Hopewell Campus
Principal Investigator: Anne McCune, MD United Hospitals Bristol NHS Foundation Trust
Principal Investigator: Ahmed M Elsharkawy, MD University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Principal Investigator: Andre Duarte-Rojo, MD University of Arkansas
Principal Investigator: Adam Testro, MD Austin Hospital, Melbourne Australia
Principal Investigator: Angel Alsina, MD Tampa General Hospital
Principal Investigator: Abdullah Al-Osaimi, MD Temple University Hospital
Principal Investigator: Amay Parikh, MD Rutgers University Hospital
Principal Investigator: Geoffrey McCaughan, MD Royal Prince Alfred Hospital, Sydney, Australia
Principal Investigator: Omer Junaidi, MD Methodist Healthcare System of San Antonio
Principal Investigator: Willscott Naugler, MD Oregon Health and Science University
Principal Investigator: Rahul Nanchal, MD Medical College of Wisconsin/Froedtert Hospital
Principal Investigator: Raza Malik, MD Beth Israel Deaconess Medical Center
Principal Investigator: Juan Gallegos-Orozco, MD University of Utah Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT01471028     History of Changes
Other Study ID Numbers: VTI-208
Study First Received: November 7, 2011
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vital Therapies, Inc.:
Acute alcoholic hepatitis
alcoholic
hepatitis
liver

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on April 15, 2014