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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 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: July 21, 2014
Last verified: July 2014
  Purpose

The primary 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 (AILD) up to at least Study Day 91, with follow-up Protocol VTI-208E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTI-208 study termination (after the last surviving enrolled subject completes Study Day 91).

Secondary objectives are to determine the proportion of survivors at Study Days 28 and 91.

Exploratory objectives are 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) up to Study Day 91, and the proportion of progression-free survivors (PFS) up to Study Days 28 and 91. Progression is defined as death or the first observed increase of at least 5 points from End of Study Day 1 MELD score (for both the ELAD and Control groups) until at least 24 hours after the ELAD Treatment Period is ended (end of Day 7 for Controls) and up to both End of Study Days 28 and 91 following 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 death or the first observed increase of at least 5 points from End of Study Day 1 MELD score (for both the ELAD and Control groups) until at least 24 hours after the ELAD Treatment Period is ended (end of Day 7 for Controls) and up to both End of Study Days 28 and 91 following Randomization.


Estimated Enrollment: 200
Study Start Date: February 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 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 of care treatment.

Subjects randomized to the Control group will receive standard of care treatment 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 meeting inclusion criteria 1 through 3 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 legally authorized 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. Bilirubin measurements must be taken at least 12 hours after any procedure known to artificially alter serum bilirubin (e.g., administration of packed red blood cells, plasma exchange);
  • Evidence of hemodynamic instability as defined by the following:

    1. Systolic blood pressure < 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
    2. Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
    3. Requirement for escalating doses of vasopressor support prior to Screening; OR
    4. Subject at maximum vasopressor dose at Screening;
  • Evidence of active bleeding or of major hemorrhage defined as requiring ≥ 2 units packed red blood cells to maintain stable hemoglobin occurring within 48 hours of Screening;
  • Clinical evidence of liver size reduction due to cirrhosis (liver size of the craniocaudal diameter (sagittal view) < 10 cm when measured on the mid clavicular line (or equivalent measurement) by ultrasound, or liver volume < 750 cc as determined by CT), unless Investigator interpretation of the clinical evidence indicates liver size of < 10 cm or volume < 750 cc is not considered reduced for the individual subject;
  • 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, including, but not limited to:

    1. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
    2. Cancer that has metastasized or has not yet been treated;
  • 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 (the observational study setting should not affect safety and/or efficacy of the VTI-208 clinical trial);
  • Previous liver transplant;
  • Previous enrollment in the treatment phase of another ELAD trial (e.g. a subject is not disqualified from enrollment in VTI-208 if they were screened for VTI-210 but did not qualify for enrollment in the treatment phase of the study and therefore did not receive ELAD or Control treatment;
  • 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 (the DNR/DNI criterion is not applicable in the UK);
  • Refusal to participate in the VTI-208E follow-up study;
  • Inability to provide an address for home visits.
  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: 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 51 Study Locations
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
Study Director: Jan Stange, MD Vital Therapies, Inc.
Principal Investigator: David J Reich, MD PA - Drexel University College of Medicine
Principal Investigator: Ram Subramanian, MD GA - Emory University Hospital
Principal Investigator: Lewis Teperman, MD NY - New York University Langone Medical Center
Principal Investigator: Robert Brown, MD NY - Columbia University Medical Center
Principal Investigator: Julie Thompson, MD MN - University of Minnesota Medical Center - Fairview
Principal Investigator: Paul Gaglio, MD NY - Montefiore Medical Center
Principal Investigator: Linda Sher, MD CA - Keck Hospital of University of Southern California
Principal Investigator: David Wolf, MD NY - Westchester Medical Center
Principal Investigator: Parvez Mantry, MD TX - Methodist Dallas Medical Center
Principal Investigator: Ali Al-Khafaji, MD PA - University of Pittsburgh Medical Center
Principal Investigator: Marquis E Hart, MD WA - Swedish Medical Center - Transplant Program
Principal Investigator: Samuel Ho, MD CA - VA San Diego Healthcare System
Principal Investigator: Anu Duddempudi, MD NY - North Shore University Hospital
Principal Investigator: Sumeet K Asrini, MD TX - Baylor University Medical Center
Principal Investigator: Thomas Ardiles, MD AZ - Maricopa Integrated Health System
Principal Investigator: Charles Landis, MD WA - University of Washington - Harborview Medical Center
Principal Investigator: Rohit Satoskar, MD DC - Georgetown University Hospital
Principal Investigator: Nikunj Shah, MD IL - Rush University Medical Center
Principal Investigator: Brian Borg, MD MS - University of Mississippi Medical Center
Principal Investigator: Alan Wigg, MD South Australia - Flinders Medical Centre - Bedford Park
Principal Investigator: Ross MacNicholas, MD Western Australia - Sir Charles Gairdner Hospital - Nedlands
Principal Investigator: Lance L Stein, MD GA - Piedmont Atlanta Hospital
Principal Investigator: Talal Adhami, MD OH - Cleveland Clinic Foundation
Principal Investigator: Rasheed Balogun, MD VA - University of Virginia Health System
Principal Investigator: Simona Rossi, MD PA - Albert Einstein Medical Center
Principal Investigator: Mark Jacob, MD NC - East Carolina University Brody School of Medicine
Principal Investigator: Santiago Munoz, MD NJ - Capital Health Medical Center - Hopewell Campus
Principal Investigator: Anne McCune, MD UK - Bristol - United Hospitals Bristol NHS Foundation Trust
Principal Investigator: Ahmed M Elsharkawy, MD UK - University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Principal Investigator: Andre Duarte-Rojo, MD AR - University of Arkansas for Medical Sciences
Principal Investigator: Adam Testro, MD Australia - Victoria - Austin Hospital
Principal Investigator: Angel Alsina, MD FL - Tampa General Hospital
Principal Investigator: Abdullah Al-Osaimi, MD PA - Temple University Hospital
Principal Investigator: Amay Parikh, MD NJ - Rutgers University Hospital
Principal Investigator: Geoffrey McCaughan, MD Australia - Royal Prince Alfred Hospital - New South Wales
Principal Investigator: Omer Junaidi, MD TX - Methodist Healthcare System of San Antonio
Principal Investigator: Willscott Naugler, MD OR - Oregon Health & Science University
Principal Investigator: Rahul Nanchal, MD WI - Medical College of Wisconsin - Froedtert Hospital
Principal Investigator: Raza Malik, MD MA - Beth Israel Deaconess Medical Center
Principal Investigator: Juan Gallegos-Orozco, MD UT - University of Utah Hospital
Principal Investigator: Tarek I Hassanein, MD CA - Sharp Coronado Hospital
Principal Investigator: Shahid Habib, MD AZ - University of Arizona Medical Center
Principal Investigator: Winfred W Williams, MD MA - Massachusetts General Hospital
Principal Investigator: Steven Colquhoun, MD CA - Cedars-Sinai Medical Center
Principal Investigator: Donald Hillebrand, MD IA - Unity Point Health-Methodist
Principal Investigator: Michael Allison, MD UK - England - Cambridge University Hospitals NHS Foundation Trust
Principal Investigator: Rajiv Jalan, MD UK - England - Royal Free Hospital
Principal Investigator: Heather Patton, MD CA - University of California San Diego Medical Center - Hillcrest
Principal Investigator: Alasdair Hay, MD UK - Scotland - Royal Infirmary of Edinburgh
Principal Investigator: Agustin Albillos, MD Spain - Madrid - Hospital Ramón y Cajal
Principal Investigator: Kalyan R Bhamidimarri, MD FL - University of Miami 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: July 21, 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 July 28, 2014