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

NCT ID: NCT01829347

Last Updated: 2019-02-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2018-09-30

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).

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.

Conditions

Severe Acute Alcoholic Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ELAD

Intervention Type: 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.

Standard of Care treatment

Intervention Type: OTHER

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

Standard of Care (Control)

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

Group Type: OTHER

Standard of Care treatment

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: BIOLOGICAL

Standard of Care treatment

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

Intervention Type: OTHER

Other Intervention Names

Human Cell-Based Bio-Artificial Liver Support System; Usual treatment for the disease

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vital Therapies, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Stange, MD

Role: STUDY_DIRECTOR

Vital Therapies, Inc.

Rajiv Jalan, MD

Role: PRINCIPAL_INVESTIGATOR

UK - Royal Free Hospital

Juan Caballeria, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Clinic de Barcelona

José Luis Montero, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Reina Sofia

Rafael Bañares, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Gregorio Marañon

Kalyan R Bhamidimarri, MD

Role: PRINCIPAL_INVESTIGATOR

FL - University of Miami Hospital

Julie Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

MN - University of Minnesota Medical Center - Twin Cities Campus

Valentin Cuervas-Mons Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Puerta de Hierro - Majadahonda

Santiago Tome, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Clinico Universitario de Santiago de Compostela

Martín Prieto, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario y Politécnico La Fe

Sumita Verma, MD

Role: PRINCIPAL_INVESTIGATOR

UK - Brighton & Sussex University Hospitals NHS Trust

Paul J Gaglio, MD

Role: PRINCIPAL_INVESTIGATOR

NY - Montefiore Medical Center

Manuel Romero-Gomez, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario de Valme

Andrew deLemos, MD

Role: PRINCIPAL_INVESTIGATOR

NC - Carolinas Medical Center

Joanna Sayer, MD

Role: PRINCIPAL_INVESTIGATOR

UK - Doncaster Royal Infirmary

Lance Stein, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Piedmont Atlanta Hospital

Javier Crespo, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Marques de Valdecilla

Rohit Satoskar, MD

Role: PRINCIPAL_INVESTIGATOR

DC - Georgetown University Hospital

David J Kramer, MD

Role: PRINCIPAL_INVESTIGATOR

WI - Aurora St. Luke's Medical Center

David Reich, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Drexel University College of Medicine

Anne M Larson, MD

Role: PRINCIPAL_INVESTIGATOR

WA - Swedish Medical Center

Xaralambos Zervos, DO

Role: PRINCIPAL_INVESTIGATOR

FL - Cleveland Clinic Florida

Kirti Shetty, MD

Role: PRINCIPAL_INVESTIGATOR

MD - Johns Hopkins University Hospital

Simona Rossi, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Albert Einstein Medical Center

Ram Subramanian, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Emory University Hospital

Alexander Kuo, MD

Role: PRINCIPAL_INVESTIGATOR

CA - University of California San Diego

Talal Adhami, MD

Role: PRINCIPAL_INVESTIGATOR

OH - Cleveland Clinic Foundation

Maria Jesús Suárez, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario de Cruces

Nikolaos T Pyrsopoulos, MD

Role: PRINCIPAL_INVESTIGATOR

NJ - Rutgers University Hospital

Julio Gutierrez, MD

Role: PRINCIPAL_INVESTIGATOR

TX - University of Texas Health Science Center, San Antonio

Andres Duarte-Rojo, MD

Role: PRINCIPAL_INVESTIGATOR

AR - University of Arkansas for Medical Sciences

Agustín Albillos, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Hospital Universitario Ramón y Cajal

Raza Malik, MD

Role: PRINCIPAL_INVESTIGATOR

MA - Beth Israel Deaconess Medical Center

Markus Busch, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Medizinische Hochschule Hannover

Anupama Duddempudi, MD

Role: PRINCIPAL_INVESTIGATOR

NY - North Shore University Hospital

Marco Antonio Olivera-Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

NE - University of Nebraska Medical Center

Eckart Schott, MD

Role: PRINCIPAL_INVESTIGATOR

Germany - Charité Campus Virchow-Klinikum Medizinische Klinik

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California San Diego

San Diego, California, United States

Georgetown University Hospital

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

University of Miami Hospital

Miami, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Johns Hopkins University Hospital

Bethesda, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota Medical Center - Twin Cities Campus

Minneapolis, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Rutgers University Hospital

Newark, New Jersey, United States

North Shore University Hospital

Manhasset, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

University of Texas Health Science Center, San Antonio

San Antonio, Texas, United States

Swedish Medical Center

Seattle, Washington, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Charité Campus Virchow-Klinikum Medizinische Klinik

Berlin, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Hospital Clinico Universitario de Santiago de Compostela

Santiago de Compostela, La Coruña, Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario de Cruces

Barakaldo, Vizcaya, Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Reina Sofia

Córdoba, , Spain

Hospital Gregorio Marañon

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Universitario de Valme

Seville, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Barts Health NHS Trust

London, England, United Kingdom

King's College Hospital NHS Foundation Trust

London, England, United Kingdom

Royal Free Hospital

Hampstead, London, United Kingdom

NHS Tayside

Dundee, Scotland, United Kingdom

Doncaster Royal Infirmary

Doncaster, South Yorkshire, United Kingdom

Brighton & Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Countries

United States; Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25009371 (View on PubMed)

Related Links

http://www.vitaltherapies.com

Sponsor's website

Other Identifiers

VTI-210

Identifier Type: -

Identifier Source: org_study_id