A Study to Assess Safety and Efficacy of ELAD in Severe Acute Alcoholic Hepatitis Steroid Failures

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Vital Therapies, Inc.
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT01829347
First received: April 8, 2013
Last updated: October 29, 2014
Last verified: October 2014

April 8, 2013
October 29, 2014
April 2014
May 2016   (final data collection date for primary outcome measure)
Overall survival of sAAH subjects [ Time Frame: Study Day 1 through Study Day 91 ] [ Designated as safety issue: No ]
The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival (OS) in subjects with a clinical diagnosis of severe acute alcoholic hepatitis (sAAH) who have failed steroid therapy.
Overall survival at Day 91 [ Time Frame: Study Day 1 through Study Day 91 ] [ Designated as safety issue: Yes ]
Overall survival of subjects will be assessed from study randomization (Day 1) through Study Day 91.
Complete list of historical versions of study NCT01829347 on ClinicalTrials.gov Archive Site
To evaluate the proportion of survivors at End of Study Days 28 and 91. [ Time Frame: Study Days 28 and 91. ] [ Designated as safety issue: No ]
A chi-square test will be used to evaluate the proportion of subjects who survived at End of Study Day 28 and End of Study Day 91 based on the ITT population.
Not Provided
Not Provided
Not Provided
 
A Study to Assess Safety and Efficacy of ELAD in Severe Acute Alcoholic Hepatitis Steroid Failures
A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD® in Subjects With Severe Acute Alcoholic Hepatitis (AAH) Who Have Failed Steroid Therapy

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 who have failed steroid therapy.

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 where the steroid treatment has failed per the Lille criteria. 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Severe Acute Alcoholic Hepatitis
  • 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 Name: Human Cell-Based Bio-Artificial Liver Support System
  • Other: Standard of Care treatment
    Standard of care is predefined treatment for AAH complications (ascites, hepatic encephalopathy, varices, etc.)
    Other Name: Usual treatment for the disease
  • 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.
    Interventions:
    • Biological: ELAD
    • Other: Standard of Care treatment
  • Standard of Care (Control)
    Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD.EASL Guidelines.
    Intervention: Other: Standard of Care treatment
Parés 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
August 2016
May 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age ≥ 18 ;
  • Total bilirubin ≥ 8 mg/dL;
  • 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 have failed steroid therapy according to Lille protocol (Lille score > 0.45) after completing 7 days of steroid therapy.

Exclusion Criteria:

  • Platelet count < 50,000/mm3;
  • International Normalization Ratio (INR) > 3.0;
  • MELD score > 35;
  • Evidence of infection unresponsive to antibiotics;
  • Evidence of more than one steroid regimen during this episode of liver failure;
  • Hospital admission for any episodes of liver decompensation 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

Both
18 Years and older
No
Contact: Andrew Henry 858-673-6840 ext 1844 ahenry@vitaltherapies.copm
Contact: Michael Stephens 858-924-1991 mstephens@vitaltherapies.com
Spain,   United Kingdom,   United States
 
NCT01829347
VTI-210
Yes
Vital Therapies, Inc.
Vital Therapies, Inc.
Not Provided
Study Director: Jan Stange, MD Vital Therapies, Inc.
Principal Investigator: Rajiv Jalan, MD UK - Royal Free Hospital
Principal Investigator: Juan Caballeria, MD Spain - Hospital Clinic de Barcelona
Principal Investigator: José Luis Montero, MD Spain - Hospital Reina Sofia
Principal Investigator: Rafael Bañares, MD Spain - Hospital Gregorio Marañon
Principal Investigator: Kalyan R Bhamidimarri, MD FL - University of Miami Hospital
Principal Investigator: Julie Thompson, MD MN - University of Minnesota Medical Center - Fairview
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
Vital Therapies, Inc.
October 2014

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