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

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ClinicalTrials.gov Identifier: NCT01471028
Recruitment Status : Completed
First Posted : November 11, 2011
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.

Tracking Information
First Submitted Date  ICMJE November 7, 2011
First Posted Date  ICMJE November 11, 2011
Results First Submitted Date  ICMJE July 24, 2018
Results First Posted Date  ICMJE February 15, 2019
Last Update Posted Date February 15, 2019
Study Start Date  ICMJE February 2013
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
Overall Survival [ Time Frame: Up to at least Study Day 91, with protocol VTI-208E providing additional survival data (at 6, 9, 12, 24 months) at the time of database lock (31 July 2015) ]
The primary endpoint of the study was a comparison of overall survival (OS) between the ELAD-treated and Control groups, with protocol VTI-208E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (31 July 2015).
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2011)
Overall Survival [ Time Frame: 91 days ]
Overall survival will be followed for all enrolled patients to determine whether ELAD treatment affects patient survival.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
Number of Survivors at Study Day 91. [ Time Frame: Up to Study Day 91. ]
Assess the proportion of survivors at Study Day 91.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: January 22, 2019)
Number of Progression-free Survivors at Study Day 91 [ Time Frame: Study Day 1 up to Study Day 91 ]
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure
Official Title  ICMJE A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)
Brief Summary

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.

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.

The ITT population includes all randomized subjects assigned to the group to which they were randomized, irrespective of actual treatment administered. Participant, Baseline Characteristics, and Outcome Measures used the ITT population. The safety population is defined as all subjects who are randomized based on actual treatment received. All serious adverse events and all non-serious adverse events analyses used the safety population.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Alcoholic Hepatitis
Intervention  ICMJE
  • Biological: ELAD treatment
    ELAD treatment consists of treatment with an extracorporeal liver assist system.
    Other Name: ELAD
  • Other: Standard of care (Control)
    Control receives standard medical treatment.
    Other Name: Standard of care as defined by the protocol
Study Arms  ICMJE
  • Experimental: ELAD Treatment
    This group will receive treatment with ELAD plus standard of care treatment.
    Intervention: Biological: ELAD treatment
  • Standard of care (Control)
    This group will receive standard of care treatment as defined in the protocol.
    Intervention: Other: Standard of care (Control)
Publications * Thompson J, Jones N, Al-Khafaji A, Malik S, Reich D, Munoz S, MacNicholas R, Hassanein T, Teperman L, Stein L, Duarte-Rojo A, Malik R, Adhami T, Asrani S, Shah N, Gaglio P, Duddempudi A, Borg B, Jalan R, Brown R, Patton H, Satoskar R, Rossi S, Parikh A, ElSharkawy A, Mantry P, Sher L, Wolf D, Hart M, Landis C, Wigg A, Habib S, McCaughan G, Colquhoun S, Henry A, Bedard P, Landeen L, Millis M, Ashley R, Frank W, Henry A, Stange J, Subramanian R; VTI-208 Study Group. Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial. Liver Transpl. 2018 Mar;24(3):380-393. doi: 10.1002/lt.24986.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 22, 2015)
203
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2011)
152
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01471028
Other Study ID Numbers  ICMJE VTI-208
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vital Therapies, Inc.
Study Sponsor  ICMJE Vital Therapies, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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 - Twin Cities Campus
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: David Bernstein, 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: Gary Jeffrey 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: Simona Rossi, MD PA - Albert Einstein Medical Center
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: Angel Alsina, MD FL - Tampa General Hospital
Principal Investigator: Jag Sunderram, MD NJ - Rutgers University Hospital
Principal Investigator: Geoffrey McCaughan, MD Australia - Royal Prince Alfred Hospital - New South Wales
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: Pedram Enayati, MD CA - Cedars-Sinai Medical Center
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: Alexander Kuo, 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
Principal Investigator: Xaralambos (Bobby) Zervos, DO FL - Cleveland Clinic Florida
Principal Investigator: Waldo Concepcion, MD CA - Stanford School of Medicine/Stanford University Medical Center
Principal Investigator: Julia A Wendon, MD UK - England - King's College Hospital
Principal Investigator: Fred Poordad, MD TX - The University of Texas Health Science Center - Texas Liver Institute
PRS Account Vital Therapies, Inc.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP