To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD® in Subjects With Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

The purpose of this study is to determine if treatment with the ELAD System is safe and effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille score >0.45).

Study Overview

• Status: Terminated
• Conditions: Severe Acute Alcoholic Hepatitis
• Intervention / Treatment: Biological: ELAD; Other: Standard of Care treatment

Detailed Description

The Lille score will be used to identify subjects with an increased risk of mortality (Lille score failures). The Lille score is a prognostic model combining six reproducible variables at Day 0 and Day 7 of steroid treatment. The Lille score used in this protocol is being used independent of steroid administration during the 7 days of evaluation. A Lille score >0.45 (Lille score failure) indicates that the subject is at substantially increased risk of 30- and 90-day mortality. Subjects with severe acute alcoholic hepatitis (sAAH) are often treated with steroids as soon as their diagnosis is confirmed. This study is to assess treatment with the ELAD System in subjects who have failed per the Lille criteria, independent of steroid administration. ELAD treatment is done continuously for up to 10 days in addition to standard of care treatment. The Control group (those randomized not to receive ELAD treatment) will also get standard of care treatment. Standard of care is defined as the usual care for diet, medications, treatment of complications that may arise, etc. for sAAH patients.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, D-13353
    • Charité Campus Virchow-Klinikum Medizinische Klinik
  • Hannover, Germany, D-30625
    • Medizinische Hochschule Hannover
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Cordoba, Spain, 14004
    • Hospital Reina Sofía
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañon
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Sevilla, Spain, 41014
    • Hospital Universitario de Valme
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Hospital Clínico Universitario de Santiago de Compostela
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Hospital Universitario Puerta de Hierro - Majadahonda
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Hospital Universitario de Cruces
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Brighton & Sussex University Hospitals NHS Trust
  • England
    • London, England, United Kingdom, SE5 9RS
      • Barts Health NHS Trust
    • London, England, United Kingdom, SE59RS
      • King's College Hospital NHS Foundation Trust
  • London
    • Hampstead, London, United Kingdom, NW3 2QR
      • Royal Free Hospital
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • NHS Tayside
  • South Yorkshire
    • Doncaster, South Yorkshire, United Kingdom, DN2 5LT
      • Doncaster Royal Infirmary
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • San Diego, California, United States, 92103
      • University of California San Diego
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Johns Hopkins University Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center - Twin Cities Campus
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07101
      • Rutgers University Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
  • Texas
    • San Antonio, Texas, United States, 78215
      • University of Texas Health Science Center, San Antonio
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 ;
• Total bilirubin ≥8 mg/dL;
• Medical history of alcohol abuse with evidence of a causal and temporal (<6 weeks) relationship to the use of alcohol and hospital admission for this episode of sAAH;
• Maddrey score ≥32
• A clinical diagnosis of severe acute alcoholic hepatitis (sAAH);
• Subject must have liver biopsy or in investigator's opinion, if risk is too great to perform liver biopsy, then clinical diagnosis is sufficient;
• Subject must be a Lille score failure (Lille score >0.45) as defined in this study.

Exclusion Criteria:

• Platelet count <50,000/mm3;
• International Normalization Ratio (INR) >3.0;
• MELD score >35;
• Evidence of infection unresponsive to antibiotics;
• Evidence of jaundice for >3 months;
• Hospital admission for any episodes of liver decompensation not related to sAAH, (other than this episode of sAAH) within the past 2 months;
• Evidence of hemodynamic instability;
• Evidence of active bleeding or of major hemorrhage defined as requiring ≥2 units of packed red blood cells to maintain a stable hemoglobin occurring within 48 hours of Screening;
• Evidence of 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;
• Clinical evidence of liver size reduction due to cirrhosis, unless Investigator interpretation of the clinical evidence indicates liver size of <10 cm or volume of <750 cc is not considered reduced for the individual subject;
• Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
• Uncontrolled seizures;
• Positive serologies for viral hepatitis B or C;
• Pregnancy as determined by β-human chorionic gonadotropin (HCG) results;
• 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 the safety and/or efficacy of the VTI-210 clinical trial);
• Currently listed or scheduled for liver transplant during the 90-day study period;
• Previous liver transplant;
• Previous participation in a clinical trial involving ELAD;
• Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or 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-210E follow-up study;
• Is unable to provide an address for follow-up home visits.

And other inclusion/exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ELAD (plus Standard of Care); ELAD is a human cell-based bio-artificial liver support system developed to improve survival of patients with acute liver failure and to provide liver support continuously to a subject with compromised liver function. Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.	Biological: ELAD; ELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2.; Other Names: Human Cell-Based Bio-Artificial Liver Support System; Other: Standard of Care treatment; Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.; Other Names: Usual treatment for the disease
Other: Standard of Care (Control); Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.	Other: Standard of Care treatment; Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.; Other Names: Usual treatment for the disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The primary endpoint of the study was a comparison of overall survival (OS) between ELAD-treated and Control groups, with protocol VTI-210E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (11 July 2016).	Up to at least Study Day 91, with protocol VTI-208E providing additional survival data at the time of database lock (11 July 2016), approximately 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Survivors at Study Day 91.	Assess the proportion of survivors at Study Day 91.	Up to Study Day 91.

Collaborators and Investigators

• Sponsor: Vital Therapies, Inc.
• Investigators: Principal Investigator: Rajiv Jalan, MD, UK - Royal Free Hospital; Principal Investigator: José Luis Montero, MD, Spain - Hospital Reina Sofia; Principal Investigator: Rafael Bañares, MD, Spain - Hospital Gregorio Marañon; Principal Investigator: Valentin Cuervas-Mons Martinez, MD, Spain - Hospital Universitario Puerta de Hierro - Majadahonda; Principal Investigator: Santiago Tome, MD, Spain - Hospital Clinico Universitario de Santiago de Compostela; Principal Investigator: Martín Prieto, MD, Spain - Hospital Universitario y Politécnico La Fe; Principal Investigator: Sumita Verma, MD, UK - Brighton & Sussex University Hospitals NHS Trust; Principal Investigator: Paul J Gaglio, MD, NY - Montefiore Medical Center; Principal Investigator: Manuel Romero-Gomez, MD, Spain - Hospital Universitario de Valme; Principal Investigator: Andrew deLemos, MD, NC - Carolinas Medical Center; Principal Investigator: Joanna Sayer, MD, UK - Doncaster Royal Infirmary; Principal Investigator: Javier Crespo, MD, Spain - Hospital Universitario Marques de Valdecilla; Principal Investigator: David Reich, MD, PA - Drexel University College of Medicine; Principal Investigator: Anne M Larson, MD, WA - Swedish Medical Center; Principal Investigator: Xaralambos Zervos, DO, FL - Cleveland Clinic Florida; Principal Investigator: Kirti Shetty, MD, MD - Johns Hopkins University Hospital; Principal Investigator: Alexander Kuo, MD, CA - University of California San Diego; Principal Investigator: Maria Jesús Suárez, MD, Spain - Hospital Universitario de Cruces; Principal Investigator: Nikolaos T Pyrsopoulos, MD, NJ - Rutgers University Hospital; Principal Investigator: Julio Gutierrez, MD, TX - University of Texas Health Science Center, San Antonio; Principal Investigator: Agustín Albillos, MD, Spain - Hospital Universitario Ramón y Cajal; Principal Investigator: Anupama Duddempudi, MD, NY - North Shore University Hospital; Principal Investigator: Marco Antonio Olivera-Martinez, MD, NE - University of Nebraska Medical Center; Principal Investigator: Eckart Schott, MD, Germany - Charité Campus Virchow-Klinikum Medizinische Klinik

Publications and helpful links

General Publications

• Pares A, Mas A. Extracorporeal liver support in severe alcoholic hepatitis. World J Gastroenterol. 2014 Jul 7;20(25):8011-7. doi: 10.3748/wjg.v20.i25.8011.

Helpful Links

• Sponsor's website

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: April 8, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: liver failure; alcoholic hepatitis; acute alcoholic hepatitis; patients failing steroid therapy; steroid failure; Lille criteria; ELAD
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic
• Other Study ID Numbers: VTI-210