Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure

NCT ID: NCT01471028

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 203 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-08-31

Brief Summary

The primary objective of the study is to evaluate safety and efficacy of ELAD® with respect to overall survival (OS) of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) up to at least Study Day 91, with follow-up Protocol VTI-208E providing additional survival data up to a maximum of 5 years that will be included, as available, through VTI-208 study termination (after the last surviving enrolled subject completes Study Day 91).

Secondary objectives are to determine the proportion of survivors at Study Days 28 and 91.

Exploratory objectives are to evaluate the ability of ELAD to stabilize liver function, measured using the Model for End Stage Liver Disease (MELD)-based time to progression (TTP) up to Study Day 91, and the proportion of progression-free survivors (PFS) up to Study Days 28 and 91. Progression is defined as death or the first observed increase of at least 5 points from End of Study Day 1 MELD score (for both the ELAD and Control groups) until at least 24 hours after the ELAD Treatment Period is ended (end of Day 7 for Controls) and up to both End of Study Days 28 and 91 following Randomization.

Detailed Description

Subjects randomized to the ELAD® group will receive treatment with ELAD® for a maximum of five (5) 24 hour periods as well as standard of care treatment.

Subjects randomized to the Control group will receive standard of care treatment throughout the study.

The ITT population includes all randomized subjects assigned to the group to which they were randomized, irrespective of actual treatment administered. Participant, Baseline Characteristics, and Outcome Measures used the ITT population. The safety population is defined as all subjects who are randomized based on actual treatment received. All serious adverse events and all non-serious adverse events analyses used the safety population.

Conditions

Acute Alcoholic Hepatitis

Study Design

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

Study Groups

ELAD Treatment

This group will receive treatment with ELAD plus standard of care treatment.

Group Type: EXPERIMENTAL

ELAD treatment

Intervention Type: BIOLOGICAL

ELAD treatment consists of treatment with an extracorporeal liver assist system.

Standard of care (Control)

This group will receive standard of care treatment as defined in the protocol.

Group Type: OTHER

Standard of care (Control)

Intervention Type: OTHER

Control receives standard medical treatment.

Interventions

ELAD treatment

ELAD treatment consists of treatment with an extracorporeal liver assist system.

Intervention Type: BIOLOGICAL

Standard of care (Control)

Control receives standard medical treatment.

Intervention Type: OTHER

Other Intervention Names

ELAD; Standard of care as defined by the protocol

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years;
• Total bilirubin ≥ 8 mg/dL;
• A clinical diagnosis of alcohol-induced liver decompensation (AILD), based upon evidence (by lab test, medical history, or family interview) of a clinical judgment of a temporal (6 weeks or less) and causal relationship between use of alcohol and this onset of symptoms;

a. Severe acute alcoholic hepatitis (AAH), with: i. Medical history of alcohol abuse; AND ii. Maddrey score of ≥ 32; AND iii. AAH documented by either:

1. Confirmatory liver biopsy; OR 2. Two or more of the following:

1. Hepatomegaly,

2. AST > ALT,

3. Ascites,

4. Leukocytosis (WBC count above lab normal at site), OR

b. Alcohol-induced decompensation of chronic liver disease that is not acute alcoholic hepatitis (as defined above), with: i. MELD score of 18-35; AND ii. Underlying chronic liver disease documented by:

1. Liver biopsy, AND/OR

2. Laboratory findings, AND/OR

3. Medical history;

• Not eligible for liver transplant during this hospitalization;
• Subject or legally authorized representative must provide Informed Consent;
• Subject must be eligible for Standard of Care treatment as defined in the protocol.

Exclusion Criteria

• Platelet count < 40,000/mm3;
• International Normalization Ratio (INR) > 3.5;
• MELD Score > 35;
• AST > 500 IU/L;
• Evidence of infection unresponsive to antibiotics;
• Evidence of reduction in total bilirubin of 20% or more in the previous 72 hours, if available. Bilirubin measurements must be taken at least 12 hours after any procedure known to artificially alter serum bilirubin (e.g., administration of packed red blood cells, plasma exchange);
• Evidence of hemodynamic instability as defined by the following:

1. Systolic blood pressure < 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR

2. Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR

3. Requirement for escalating doses of vasopressor support prior to Screening; OR

4. Subject at maximum vasopressor dose at Screening;

• Evidence of active bleeding or of major hemorrhage defined as requiring ≥ 2 units packed red blood cells to maintain stable hemoglobin occurring within 48 hours of Screening;
• Clinical evidence of liver size reduction due to cirrhosis (liver size of the craniocaudal diameter (sagittal view) < 10 cm when measured on the mid clavicular line (or equivalent measurement) by ultrasound, or liver volume < 750 cc as determined by CT), unless Investigator interpretation of the clinical evidence indicates liver size of < 10 cm or volume < 750 cc is not considered reduced for the individual subject;
• 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, including, but not limited to:

1. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;

2. Cancer that has metastasized or has not yet been treated;

• Subject has chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
• Subject has liver disease related to homozygous hemachromatosis, Wilson's Disease, has non-alcoholic fatty liver disease, or Budd-Chiari Syndrome;
• Pregnancy as determined by β-human chorionic gonadotropin (HCG) results, or lactation;
• 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 safety and/or efficacy of the VTI-208 clinical trial);
• Previous liver transplant;
• Previous enrollment in the treatment phase of another ELAD trial (e.g. a subject is not disqualified from enrollment in VTI-208 if they were screened for VTI-210 but did not qualify for enrollment in the treatment phase of the study and therefore did not receive ELAD or Control treatment;
• Have a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or such 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-208E follow-up study;
• Inability to provide an address for 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.

David J Reich, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Drexel University College of Medicine

Ram Subramanian, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Emory University Hospital

Lewis Teperman, MD

Role: PRINCIPAL_INVESTIGATOR

NY - New York University Langone Medical Center

Robert Brown, MD

Role: PRINCIPAL_INVESTIGATOR

NY - Columbia University Medical Center

Julie Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

MN - University of Minnesota Medical Center - Twin Cities Campus

Paul Gaglio, MD

Role: PRINCIPAL_INVESTIGATOR

NY - Montefiore Medical Center

Linda Sher, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Keck Hospital of University of Southern California

David Wolf, MD

Role: PRINCIPAL_INVESTIGATOR

NY - Westchester Medical Center

Parvez Mantry, MD

Role: PRINCIPAL_INVESTIGATOR

TX - Methodist Dallas Medical Center

Ali Al-Khafaji, MD

Role: PRINCIPAL_INVESTIGATOR

PA - University of Pittsburgh Medical Center

Marquis E Hart, MD

Role: PRINCIPAL_INVESTIGATOR

WA - Swedish Medical Center - Transplant Program

David Bernstein, MD

Role: PRINCIPAL_INVESTIGATOR

NY - North Shore University Hospital

Sumeet K Asrini, MD

Role: PRINCIPAL_INVESTIGATOR

TX - Baylor University Medical Center

Thomas Ardiles, MD

Role: PRINCIPAL_INVESTIGATOR

AZ - Maricopa Integrated Health System

Charles Landis, MD

Role: PRINCIPAL_INVESTIGATOR

WA - University of Washington - Harborview Medical Center

Rohit Satoskar, MD

Role: PRINCIPAL_INVESTIGATOR

DC - Georgetown University Hospital

Nikunj Shah, MD

Role: PRINCIPAL_INVESTIGATOR

IL - Rush University Medical Center

Brian Borg, MD

Role: PRINCIPAL_INVESTIGATOR

MS - University of Mississippi Medical Center

Alan Wigg, MD

Role: PRINCIPAL_INVESTIGATOR

South Australia - Flinders Medical Centre - Bedford Park

Gary Jeffrey

Role: PRINCIPAL_INVESTIGATOR

Western Australia - Sir Charles Gairdner Hospital - Nedlands

Lance L Stein, MD

Role: PRINCIPAL_INVESTIGATOR

GA - Piedmont Atlanta Hospital

Talal Adhami, MD

Role: PRINCIPAL_INVESTIGATOR

OH - Cleveland Clinic Foundation

Simona Rossi, MD

Role: PRINCIPAL_INVESTIGATOR

PA - Albert Einstein Medical Center

Anne McCune, MD

Role: PRINCIPAL_INVESTIGATOR

UK - Bristol - United Hospitals Bristol NHS Foundation Trust

Ahmed M Elsharkawy, MD

Role: PRINCIPAL_INVESTIGATOR

UK - University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Andre Duarte-Rojo, MD

Role: PRINCIPAL_INVESTIGATOR

AR - University of Arkansas for Medical Sciences

Angel Alsina, MD

Role: PRINCIPAL_INVESTIGATOR

FL - Tampa General Hospital

Jag Sunderram, MD

Role: PRINCIPAL_INVESTIGATOR

NJ - Rutgers University Hospital

Geoffrey McCaughan, MD

Role: PRINCIPAL_INVESTIGATOR

Australia - Royal Prince Alfred Hospital - New South Wales

Raza Malik, MD

Role: PRINCIPAL_INVESTIGATOR

MA - Beth Israel Deaconess Medical Center

Juan Gallegos-Orozco, MD

Role: PRINCIPAL_INVESTIGATOR

UT - University of Utah Hospital

Tarek I Hassanein, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Sharp Coronado Hospital

Shahid Habib, MD

Role: PRINCIPAL_INVESTIGATOR

AZ - University of Arizona Medical Center

Winfred W Williams, MD

Role: PRINCIPAL_INVESTIGATOR

MA - Massachusetts General Hospital

Pedram Enayati, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Cedars-Sinai Medical Center

Michael Allison, MD

Role: PRINCIPAL_INVESTIGATOR

UK - England - Cambridge University Hospitals NHS Foundation Trust

Rajiv Jalan, MD

Role: PRINCIPAL_INVESTIGATOR

UK - England - Royal Free Hospital

Alexander Kuo, MD

Role: PRINCIPAL_INVESTIGATOR

CA - University of California San Diego Medical Center - Hillcrest

Alasdair Hay, MD

Role: PRINCIPAL_INVESTIGATOR

UK - Scotland - Royal Infirmary of Edinburgh

Agustin Albillos, MD

Role: PRINCIPAL_INVESTIGATOR

Spain - Madrid - Hospital Ramón y Cajal

Kalyan R Bhamidimarri, MD

Role: PRINCIPAL_INVESTIGATOR

FL - University of Miami Hospital

Xaralambos (Bobby) Zervos, DO

Role: PRINCIPAL_INVESTIGATOR

FL - Cleveland Clinic Florida

Waldo Concepcion, MD

Role: PRINCIPAL_INVESTIGATOR

CA - Stanford School of Medicine/Stanford University Medical Center

Julia A Wendon, MD

Role: PRINCIPAL_INVESTIGATOR

UK - England - King's College Hospital

Fred Poordad, MD

Role: PRINCIPAL_INVESTIGATOR

TX - The University of Texas Health Science Center - Texas Liver Institute

Locations

Maricopa Integrated Health System (MIHS)

Phoenix, Arizona, United States

University of Arizona Medical Center

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Sharp Coronado Hospital

Coronado, California, United States

Keck Hospital of University of Southern California

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Stanford School of Medicine/Stanford University Medical Center

Palo Alto, California, United States

University of California San Diego Medical Center - Hillcrest

San Diego, California, United States

Georgetown University Hospital

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

University of Miami Hospital

Miami, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota - Twin Cities Campus

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Rutgers University Hospital

New Brunswick, New Jersey, United States

North Shore University Hospital

Manhasset, New York, United States

New York University Langone Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Westchester Medical Center

Valhalla, New York, 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 Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Methodist Dallas Medical Center

Dallas, Texas, United States

Baylor University Medical Center

Dallas, Texas, United States

The University of Texas Health Science Center - Texas Liver Institute

San Antonio, Texas, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Swedish Medical Center - Transplant Program

Seattle, Washington, United States

University of Washington - Harborview Medical Center

Seattle, Washington, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Hospital Ramón y Cajal

Madrid, , Spain

King's College Hospital

London, England, United Kingdom

Royal Free Hospital

Hamstead, London, United Kingdom

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

United Hospitals Bristol NHS Foundation Trust

Bristol, , United Kingdom

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Countries

United States; Australia; Spain; United Kingdom

References

Thompson J, Jones N, Al-Khafaji A, Malik S, Reich D, Munoz S, MacNicholas R, Hassanein T, Teperman L, Stein L, Duarte-Rojo A, Malik R, Adhami T, Asrani S, Shah N, Gaglio P, Duddempudi A, Borg B, Jalan R, Brown R, Patton H, Satoskar R, Rossi S, Parikh A, ElSharkawy A, Mantry P, Sher L, Wolf D, Hart M, Landis C, Wigg A, Habib S, McCaughan G, Colquhoun S, Henry A, Bedard P, Landeen L, Millis M, Ashley R, Frank W, Henry A, Stange J, Subramanian R; VTI-208 Study Group. Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial. Liver Transpl. 2018 Mar;24(3):380-393. doi: 10.1002/lt.24986.

Reference Type: DERIVED

PMID: 29171941 (View on PubMed)

Related Links

http://www.vitaltherapies.com

Vital Therapies, Inc. website

Other Identifiers

VTI-208

Identifier Type: -

Identifier Source: org_study_id