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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
  Purpose

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.


Condition Intervention Phase
Severe Acute Alcoholic Hepatitis
Biological: ELAD
Other: Standard of Care treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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 Severe Acute Alcoholic Hepatitis (AAH) Who Have Failed Steroid Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 150
Study Start Date: April 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
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 is predefined treatment for AAH complications (ascites, hepatic encephalopathy, varices, etc.)
Other Name: Usual treatment for the disease

Detailed Description:

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.

  Eligibility

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

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

  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: NCT01829347

Contacts
Contact: Andrew Henry 858-673-6840 ext 1844 ahenry@vitaltherapies.copm
Contact: Michael Stephens 858-924-1991 mstephens@vitaltherapies.com

Locations
United States, Florida
University of Miami Hospital Recruiting
Miami, Florida, United States, 33136
Contact: Eva Pavicic, BSN    305-243-2148      
Contact: Kalyan Bhamidimarri, MD    305-243-3333    kbhamidimari@med.miami.edu   
Principal Investigator: Kalyan Bhamidimarri, MD         
United States, Minnesota
University of Minnesota Medical Center - Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Melissa Cohen    612-624-6649    Cohen045@umn.edu   
Contact: Julie Thompson, MD    612-625-7498    Thom0235@umn.edu   
Principal Investigator: Julie Thompson, MD         
Spain
Hospital Clinico Universitario de Santiago de Compostela Recruiting
Santiago de Compostela, La Coruña, Spain, 15706
Contact: Santiago Tome, MD    +34 639868268    santiagotomemar@yahoo.es   
Principal Investigator: Santiago Tome, MD         
Hospital Universitario Puerta de Hierro - Majadahonda Recruiting
Majadahonda, Madrid, Spain, 28220
Contact: Valentin Cuervas-Mons Martinez, MD    +34911917341    valentin.cuervasmons@uam.es   
Principal Investigator: Valentin Cuervas-Mons Martinez, MD         
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Juan Caballeria, MD    +34 93 227 17 13    CABALLER@clinic.ub.es   
Principal Investigator: Juan Caballeria, MD         
Hospital Reina Sofia Recruiting
Cordoba, Spain, 14004
Contact: José Luís Montero, MD    +34 957 01 03 28    jlm14005623@gmail.com   
Principal Investigator: José Luís Montero, MD         
Hospital Gregorio Marañon Recruiting
Madrid, Spain, 28007
Contact: Rafael Bañares, MD    +34 91 586 86 99    rbanares@telefonica.net   
Principal Investigator: Rafael Bañares, MD         
Hospital Universitario y Politécnico La Fe Recruiting
Valencia, Spain, 46026
Contact: Martín Prieto, MD    +34 669.839.429    mprietoc@gmail.com   
Principal Investigator: Martín Prieto, MD         
United Kingdom
Royal Free Hospital Recruiting
Hampstead, London, United Kingdom, NW3 2QR
Contact: Melrose Browne-Morgan    +44 020 7794 0500 ext 22522    melrose.browne-morgan@nhs.net   
Contact: Nicola Childs, RN    +44 020 7794 0500 ext 22522    nicola.childs@nhs.net   
Principal Investigator: Rajiv Jalan, MD         
Sponsors and Collaborators
Vital Therapies, Inc.
Investigators
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
  More Information

Additional Information:
No publications provided by Vital Therapies, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vital Therapies, Inc.
ClinicalTrials.gov Identifier: NCT01829347     History of Changes
Other Study ID Numbers: VTI-210
Study First Received: April 8, 2013
Last Updated: October 29, 2014
Health Authority: United Kingdom: Research Ethics Committee
United States: Food and Drug Administration

Keywords provided by Vital Therapies, Inc.:
liver failure
acute alcoholic hepatitis
patients failing steroid therapy
alcoholic hepatitis
steroid failure
Lille criteria
ELAD

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

ClinicalTrials.gov processed this record on November 27, 2014