Study to Assess Safety and Efficacy of ELAD in Subjects With Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Vital Therapies, Inc.
Sponsor:
Information provided by (Responsible Party):
Vital Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT01829347
First received: April 8, 2013
Last updated: August 7, 2015
Last verified: August 2015
  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 and Lille score failures (Lille score >0.45).


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 (sAAH) and Lille Score Failure

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 are Lille score failures (Lille score >0.45).


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 sAAH 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 sAAH complications (ascites, hepatic encephalopathy, varices, etc.)
Other Name: Usual treatment for the disease

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.

  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;
  • 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

  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

  Show 39 Study Locations
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 - Twin Cities Campus
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: Lance Stein, MD GA - Piedmont Atlanta Hospital
Principal Investigator: Javier Crespo, MD Spain - Hospital Universitario Marques de Valdecilla
Principal Investigator: Rohit Satoskar, MD DC - Georgetown University Hospital
Principal Investigator: David J Kramer, MD WI - Aurora St. Luke's Medical Center
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: Simona Rossi, MD PA - Albert Einstein Medical Center
Principal Investigator: Ram Subramanian, MD GA - Emory University Hospital
Principal Investigator: Alexander Kuo, MD CA - University of California San Diego
Principal Investigator: Talal Adhami, MD OH - Cleveland Clinic Foundation
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: Andres Duarte-Rojo, MD AR - University of Arkansas for Medical Sciences
Principal Investigator: Agustín Albillos, MD Spain - Hospital Universitario Ramón y Cajal
Principal Investigator: Raza Malik, MD MA - Beth Israel Deaconess Medical Center
Principal Investigator: Markus Busch, MD Germany - Medizinische Hochschule Hannover
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
  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: August 7, 2015
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 August 26, 2015