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

NCT01829347 | Terminated Phase 3 Results DMC

• 1 other identifier: VTI-210
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 39

Brief Summary

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).

Conditions

Severe Acute Alcoholic Hepatitis

Keywords

liver failure; acute alcoholic hepatitis; patients failing steroid therapy; alcoholic hepatitis; steroid failure; Lille criteria; ELAD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Proportion of Survivors at Study Day 91.

  Up to Study Day 91.

Study Arms (2)

ELAD (plus Standard of Care)

EXPERIMENTAL

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; Other: Standard of Care treatment

Standard of Care (Control)

OTHER

Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.

Other: Standard of Care treatment

Interventions

ELAD BIOLOGICAL

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.

Also known as: Human Cell-Based Bio-Artificial Liver Support System

ELAD (plus Standard of Care)

Standard of Care treatment OTHER

Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.

Also known as: Usual treatment for the disease

ELAD (plus Standard of Care); Standard of Care (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Vital Therapies, Inc.: lead

Study Sites (39)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University Hospital

Bethesda, Maryland, 20814, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota Medical Center - Twin Cities Campus

Minneapolis, Minnesota, 55455, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Rutgers University Hospital

Newark, New Jersey, 07101, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

University of Texas Health Science Center, San Antonio

San Antonio, Texas, 78215, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Charité Campus Virchow-Klinikum Medizinische Klinik

Berlin, D-13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, La Coruña, 15706, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, 28220, Spain

Location

Hospital Universitario de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario de Valme

Seville, 41014, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Barts Health NHS Trust

London, England, SE5 9RS, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE59RS, United Kingdom

Location

Royal Free Hospital

Hampstead, London, NW3 2QR, United Kingdom

Location

NHS Tayside

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, South Yorkshire, DN2 5LT, United Kingdom

Location

Brighton & Sussex University Hospitals NHS Trust

Brighton, BN2 5BE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25009371 DERIVED

Related Links

• Sponsor's website

MeSH Terms

Conditions

Liver Failure; Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Hepatitis; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Limitations and Caveats

This study was terminated early after enrollment of only 18 out of 150 planned subjects due to findings from previous VTI-208 study. Thus, sample size of VTI-210 was very small leading to statistical analyses that cannot be meaningfully interpreted.

Results Point of Contact

• Title: Robert Ashley
• Organization: Vital Therapies, Inc.

rashley@vitaltherapies.com

858-673-6840

Study Officials

• Jan Stange, MD

  Vital Therapies, Inc.

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2013
• First Posted: April 11, 2013
• Study Start: April 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: September 1, 2018
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2019-02

Locations

GB (6); DE (2); ES (10); US (21)