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

NCT01471028 | Completed Phase 3 Results DMC

• 1 other identifier: VTI-208
• Study Type: interventional
• Target: 203
• Locations: 4 countries
• Sites: 45

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.

Conditions

Acute Alcoholic Hepatitis

Keywords

Acute alcoholic hepatitis; alcoholic; hepatitis; liver

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The primary endpoint of the study was a comparison of overall survival (OS) between the ELAD-treated and Control groups, with protocol VTI-208E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (31 July 2015).

  Up to at least Study Day 91, with protocol VTI-208E providing additional survival data (at 6, 9, 12, 24 months) at the time of database lock (31 July 2015)

Secondary Outcomes (1)

• Number of Survivors at Study Day 91.

  Up to Study Day 91.

Other Outcomes (1)

• Number of Progression-free Survivors at Study Day 91

  Study Day 1 up to Study Day 91

Study Arms (2)

ELAD Treatment

EXPERIMENTAL

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

Biological: ELAD treatment

Standard of care (Control)

OTHER

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

Other: Standard of care (Control)

Interventions

ELAD treatment BIOLOGICAL

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

Also known as: ELAD

ELAD Treatment

Standard of care (Control) OTHER

Control receives standard medical treatment.

Also known as: Standard of care as defined by the protocol

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 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:
• \. Confirmatory liver biopsy; OR 2. Two or more of the following:
• Hepatomegaly,
• AST \> ALT,
• Ascites,
• 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:
• Liver biopsy, AND/OR
• Laboratory findings, AND/OR
• Medical history;
• Not eligible for liver transplant during this hospitalization;
• Subject or legally authorized representative must provide Informed Consent;

You may not qualify if:

• 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:
• Systolic blood pressure \< 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
• Mean arterial pressure (MAP) \< 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
• Requirement for escalating doses of vasopressor support prior to Screening; OR
• 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:

Sponsors & Collaborators

• Vital Therapies, Inc.: lead

Study Sites (45)

Maricopa Integrated Health System (MIHS)

Phoenix, Arizona, 85008, United States

Location

University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Sharp Coronado Hospital

Coronado, California, 92118, United States

Location

Keck Hospital of University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford School of Medicine/Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

University of California San Diego Medical Center - Hillcrest

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

Tampa General Hospital

Tampa, Florida, 33606, 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

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota - Twin Cities Campus

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Rutgers University Hospital

New Brunswick, New Jersey, 08903, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, 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 Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15216, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

The University of Texas Health Science Center - Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84108, United States

Location

Swedish Medical Center - Transplant Program

Seattle, Washington, 98104, United States

Location

University of Washington - Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

Royal Free Hospital

Hamstead, London, NW3 2QG, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, West Midlands, B152TH, United Kingdom

Location

United Hospitals Bristol NHS Foundation Trust

Bristol, BS2 8HW, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB20QQ, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29171941 DERIVED

Related Links

• Vital Therapies, Inc. website

MeSH Terms

Conditions

Hepatitis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

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

• David J Reich, MD

  PA - Drexel University College of Medicine

  PRINCIPAL INVESTIGATOR

• Ram Subramanian, MD

  GA - Emory University Hospital

  PRINCIPAL INVESTIGATOR

• Lewis Teperman, MD

  NY - New York University Langone Medical Center

  PRINCIPAL INVESTIGATOR

• Robert Brown, MD

  NY - Columbia University Medical Center

  PRINCIPAL INVESTIGATOR

• Julie Thompson, MD

  MN - University of Minnesota Medical Center - Twin Cities Campus

  PRINCIPAL INVESTIGATOR

• Paul Gaglio, MD

  NY - Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Linda Sher, MD

  CA - Keck Hospital of University of Southern California

  PRINCIPAL INVESTIGATOR

• David Wolf, MD

  NY - Westchester Medical Center

  PRINCIPAL INVESTIGATOR

• Parvez Mantry, MD

  TX - Methodist Dallas Medical Center

  PRINCIPAL INVESTIGATOR

• Ali Al-Khafaji, MD

  PA - University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Marquis E Hart, MD

  WA - Swedish Medical Center - Transplant Program

  PRINCIPAL INVESTIGATOR

• David Bernstein, MD

  NY - North Shore University Hospital

  PRINCIPAL INVESTIGATOR

• Sumeet K Asrini, MD

  TX - Baylor University Medical Center

  PRINCIPAL INVESTIGATOR

• Thomas Ardiles, MD

  AZ - Maricopa Integrated Health System

  PRINCIPAL INVESTIGATOR

• Charles Landis, MD

  WA - University of Washington - Harborview Medical Center

  PRINCIPAL INVESTIGATOR

• Rohit Satoskar, MD

  DC - Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

• Nikunj Shah, MD

  IL - Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• Brian Borg, MD

  MS - University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

• Alan Wigg, MD

  South Australia - Flinders Medical Centre - Bedford Park

  PRINCIPAL INVESTIGATOR

• Gary Jeffrey

  Western Australia - Sir Charles Gairdner Hospital - Nedlands

  PRINCIPAL INVESTIGATOR

• Lance L Stein, MD

  GA - Piedmont Atlanta Hospital

  PRINCIPAL INVESTIGATOR

• Talal Adhami, MD

  OH - Cleveland Clinic Foundation

  PRINCIPAL INVESTIGATOR

• Simona Rossi, MD

  PA - Albert Einstein Medical Center

  PRINCIPAL INVESTIGATOR

• Anne McCune, MD

  UK - Bristol - United Hospitals Bristol NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Ahmed M Elsharkawy, MD

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

  PRINCIPAL INVESTIGATOR

• Andre Duarte-Rojo, MD

  AR - University of Arkansas for Medical Sciences

  PRINCIPAL INVESTIGATOR

• Angel Alsina, MD

  FL - Tampa General Hospital

  PRINCIPAL INVESTIGATOR

• Jag Sunderram, MD

  NJ - Rutgers University Hospital

  PRINCIPAL INVESTIGATOR

• Geoffrey McCaughan, MD

  Australia - Royal Prince Alfred Hospital - New South Wales

  PRINCIPAL INVESTIGATOR

• Raza Malik, MD

  MA - Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Juan Gallegos-Orozco, MD

  UT - University of Utah Hospital

  PRINCIPAL INVESTIGATOR

• Tarek I Hassanein, MD

  CA - Sharp Coronado Hospital

  PRINCIPAL INVESTIGATOR

• Shahid Habib, MD

  AZ - University of Arizona Medical Center

  PRINCIPAL INVESTIGATOR

• Winfred W Williams, MD

  MA - Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Pedram Enayati, MD

  CA - Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Michael Allison, MD

  UK - England - Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Rajiv Jalan, MD

  UK - England - Royal Free Hospital

  PRINCIPAL INVESTIGATOR

• Alexander Kuo, MD

  CA - University of California San Diego Medical Center - Hillcrest

  PRINCIPAL INVESTIGATOR

• Alasdair Hay, MD

  UK - Scotland - Royal Infirmary of Edinburgh

  PRINCIPAL INVESTIGATOR

• Agustin Albillos, MD

  Spain - Madrid - Hospital Ramón y Cajal

  PRINCIPAL INVESTIGATOR

• Kalyan R Bhamidimarri, MD

  FL - University of Miami Hospital

  PRINCIPAL INVESTIGATOR

• Xaralambos (Bobby) Zervos, DO

  FL - Cleveland Clinic Florida

  PRINCIPAL INVESTIGATOR

• Waldo Concepcion, MD

  CA - Stanford School of Medicine/Stanford University Medical Center

  PRINCIPAL INVESTIGATOR

• Julia A Wendon, MD

  UK - England - King's College Hospital

  PRINCIPAL INVESTIGATOR

• Fred Poordad, MD

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

  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: November 7, 2011
• First Posted: November 11, 2011
• Study Start: February 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2019-01

Locations

GB (6); AU (3); US (35); ES (1)