Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects w/ AILD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02612428
Recruitment Status : Active, not recruiting
First Posted : November 23, 2015
Last Update Posted : June 12, 2018
Information provided by (Responsible Party):
Vital Therapies, Inc.

November 19, 2015
November 23, 2015
June 12, 2018
January 2016
March 2018   (Final data collection date for primary outcome measure)
Overall survival [ Time Frame: 91 days ]
Overall survival will be assessed using a Kaplan-Meier analysis of the Intent-to-Treat population, utilizing a log-rank test
Same as current
Complete list of historical versions of study NCT02612428 on Archive Site
Proportion of survivors [ Time Frame: 91 days ]
A chi-square test will be used to evaluate the proportion of subjects who survived at end of study day 91
Same as current
Not Provided
Not Provided
Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects w/ AILD
A Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)

The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival of subjects with a clinical diagnosis of alcohol-induced liver decompensation (AILD) through at least Study Day 91.

The secondary objective is to evaluate the proportion of survivors at Study Day 91 using a chi-squared test.

Not Provided
Phase 3
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Acute Alcoholic Hepatitis
  • Biological: ELAD System
    An extracorporeal human hepatic cell-based liver treatment
    Other Name: ELAD
  • Other: Standard of Care (Control)
    Standard medical treatment as defined by the protocol
    Other Name: Standard of Care
  • Experimental: ELAD System
    This group will receive treatment with ELAD plus standard of care therapy.
    Intervention: Biological: ELAD System
  • Standard of Care (Control)
    This group will receive standard of care therapy as defined in the protocol.
    Intervention: Other: Standard of Care (Control)
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
March 2023
March 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Subjects must meet ALL inclusion criteria to be eligible for the study:

  1. Age ≥18;
  2. Total bilirubin ≥16 mg/dL (≥273.6 µmol/L);
  3. A clinical diagnosis of alcohol-induced liver decompensation (AILD), based upon lab test or medical history or family interview with a causal relationship and temporal association (6 weeks or less) of alcohol use and hospital admission for this episode of AILD;
  4. Maddrey score ≥32;
  5. Subjects must have AILD that is severe acute alcoholic hepatitis (sAAH) diagnosed with either:

    a. A confirmatory liver biopsy, OR b. Two or more of the following: i. Hepatomegaly, ii. AST > ALT, iii. Ascites, iv. Leukocytosis (WBC count above lab normal at site);

    Note: Subjects will be classified as either:

    1. AILD that is sAAH with no underlying liver disease other than alcoholic liver disease, OR
    2. AILD that is sAAH with evidence of underlying liver disease other than alcoholic liver disease which must be documented by:

    i. Liver biopsy, AND/OR ii. Laboratory findings, AND/OR iii. Medical history;

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

Exclusion Criteria:

Subjects must NOT have any of the exclusion criteria to be eligible for the study:

  1. Age ≥50;
  2. Platelet count <40,000/mm3;
  3. International Normalization Ratio (INR) >2.5;
  4. Serum Creatinine ≥1.3 mg/dL (≥115.04 µmol/L);
  5. MELD score ≥30;
  6. AST >500 IU/L;
  7. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptoms, etc.) indicated by any of the following:

    1. Presence of sepsis or septic shock; OR
    2. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Randomization; OR
    3. Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization; OR
    4. Clinical and radiological signs of pneumonia;
  8. Evidence of reduction in total bilirubin of 20% or more in the previous 72 hours. 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);
  9. 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 on vasopressors, including but not limited to those listed below, at doses above the following at Screening or Randomization:

      • Dobutamine: 5.0 µg/kg/min
      • Dopamine: 2.0 µg/kg/min
      • Norepinephrine: 0.02 µg/kg/min
      • Phenylephrine: 1.0 µg/kg/min
      • Vasopressin: 0.02 U/min
  10. Evidence of active bleeding, major hemorrhage defined as requiring ≥2 units packed red blood cells to maintain a stable hemoglobin occurring within 48 hours prior to Randomization, or with banding of gastroesophageal varices during the 7 days immediately preceding screening;
  11. 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 <1200 cc as determined by CT or MRI], unless Investigator interpretation of the clinical evidence indicates liver size of <10 cm or volume <1200 cc is not considered reduced for the individual subject, and Sponsor agrees;
  12. Occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;
  13. Evidence by physical exam, history, or laboratory evaluation, of significant concomitant disease with a 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;
    3. Severe metabolic abnormalities that have not been corrected (See Section 5.1.3);
  14. Subject has chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
  15. Subject ventilated or intubated;
  16. Subject on hemodialysis;
  17. Subject has liver disease related to homozygous hemachromotosis, Wilson's disease, has non-alcoholic fatty liver disease, or Budd-Chiari Syndrome;
  18. Serological evidence (including viral titers) of active viral hepatitis A, B or C infection. If the investigator suspects that the subject may be at risk for viral hepatitis A, B or C, and no serology is available, then serologies must be obtained prior to Randomization, as a positive serology would be exclusionary;
  19. Pregnancy as determined by serum β-human chorionic gonadotropin (HCG) results, or subjects of child-bearing potential not willing to use effective means of contraception, without history of medical or surgical sterilization;
  20. 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 VTL-308 clinical trial);
  21. Previous liver transplant;
  22. Previous enrollment in the treatment phase of another ELAD trial;
  23. 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 Europe);
  24. Refusal to participate in the VTL-308E follow-up study;
  25. Inability to provide an address for home visits.
Sexes Eligible for Study: All
18 Years to 49 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
Austria,   Germany,   Ireland,   Spain,   United Kingdom,   United States
Not Provided
Not Provided
Vital Therapies, Inc.
Vital Therapies, Inc.
Not Provided
Study Director: Jan Stange, MD Vital Therapies, Inc.
Principal Investigator: David Reich, MD PA - Drexel University
Principal Investigator: Lance Stein, MD GA - Piedmont Atlanta Hospital
Principal Investigator: Nikolaos Pyrsopoulos, MD NJ - Rutgers University Hospital
Principal Investigator: Valentin Cuervas-Mons, MD Spain - Hospital Universitario Puerta de Hierro Majadahonda
Principal Investigator: Raza Malik, MD MA - Beth Israel Deaconess Medical Center
Principal Investigator: Nikunj Shah, MD IL - Rush University Medical Center
Principal Investigator: Simona Rossi, MD PA - Albert Einstein Medical Center
Principal Investigator: Juan Caballeria, MD Spain - Hospital Clinic de Barcelona
Principal Investigator: Ram Subramanian, MD GA - Emory University Hospital
Principal Investigator: Andres Duarte-Rojo, MD AR - University of Arkansas for Medical Sciences
Principal Investigator: Julie Thompson, MD MN - University of Minnesota
Principal Investigator: Peter R Galle, MD Germany - Universitätsmedizin Mainz
Principal Investigator: Hartmut H.-J. Schmidt, MD Germany - Universitätsklinikum Münster
Principal Investigator: Markus Busch, MD Germany - Medizinische Hochschule Hannover
Principal Investigator: Kristina Chacko, MD NY - Montefiore Medical Center
Principal Investigator: Talal Adhami, MD OH - Cleveland Clinic Foundation
Principal Investigator: Constance Mobley, MD, PhD TX - Houston Methodist Hospital
Principal Investigator: David J Kramer, MD WI - Aurora St. Luke's Medical Center
Principal Investigator: Stephen Caldwell, MD VA - University of Virginia Health System
Principal Investigator: Ali Al-Khafaji, MD PA - University of Pittsburgh Medical Center
Principal Investigator: Kalyan R Bhamidimarri, MD FL - Schiff Center for Liver Diseases/University of Miami
Principal Investigator: Manuel Romero-Gomez, MD Spain - Hospital Universitario Virgen del Rocío
Principal Investigator: Tarek Hassanein, MD CA - Sharp Coronado Hospital
Principal Investigator: Waldo Concepcion, MD CA - Stanford University Medical Center
Principal Investigator: Martin Prieto Castillo, MD Spain - Hospital Universitario y Politécnico La Fe
Principal Investigator: Rafael Bañares, MD Spain - Hospital Universitario Gregorio Marañón
Principal Investigator: Syed Naqvi, MD MO - University of Missouri Hospital
Principal Investigator: Matthias Dollinger, MD, PhD Germany - Klinikum Landshut gemeinnuetzige GmbH
Principal Investigator: Karen Krok, MD PA - The Pennsylvania State University and The Milton S. Hershey Medical Center
Principal Investigator: Rudolf Stauber, MD Austria - Medizinische Universität Graz
Principal Investigator: Christian Zauner, MD Austria - Medizinische Universität Klinik Für Innere Medizin III
Principal Investigator: Georg Lamprecht, MD Germany - Universitätsmedizin Rostock
Principal Investigator: Paul Thuluvath, MD MD - Mercy Medical Center
Principal Investigator: Trinidad Serrano Aullo, MD Spain - Hospital Clínico Universitario Lozano Blesa
Vital Therapies, Inc.
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP