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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Vital Therapies, Inc.
Information provided by (Responsible Party):
Vital Therapies, Inc. Identifier:
First received: November 19, 2015
Last updated: October 6, 2016
Last verified: October 2016

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.

Condition Intervention Phase
Acute Alcoholic Hepatitis
Biological: ELAD System
Other: Standard of Care (Control)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multicenter, Controlled, Pivotal Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)

Further study details as provided by Vital Therapies, Inc.:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 91 days ] [ Designated as safety issue: Yes ]
    Overall survival will be assessed using a Kaplan-Meier analysis of the Intent-to-Treat population, utilizing a log-rank test

Secondary Outcome Measures:
  • Proportion of survivors [ Time Frame: 91 days ] [ Designated as safety issue: Yes ]
    A chi-square test will be used to evaluate the proportion of subjects who survived at end of study day 91

Estimated Enrollment: 150
Study Start Date: January 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ELAD System
This group will receive treatment with ELAD plus standard of care therapy.
Biological: ELAD System
An extracorporeal human hepatic cell-based liver treatment
Other Name: ELAD
Standard of Care (Control)
This group will receive standard of care therapy as defined in the protocol.
Other: Standard of Care (Control)
Standard medical treatment as defined by the protocol
Other Name: Standard of Care


Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02612428

Contact: Michael Stephens, PhD 858-924-1991
Contact: Brian Dempster 858-649-1814

  Show 26 Study Locations
Sponsors and Collaborators
Vital Therapies, Inc.
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: Alexander Kuo, MD CA - University of California, San Diego
Principal Investigator: Markus Busch, MD Germany - Medizinische Hochschule Hannover
Principal Investigator: Kristina Chacko, MD NY - Montefiore Medical Center
Principal Investigator: David E Bernstein, MD NY - Northwell Health / North Shore University Hospital
Principal Investigator: Brian Borg, MD MS - University of Mississippi Medical Center
Principal Investigator: Talal Adhami, MD OH - Cleveland Clinic Foundation
Principal Investigator: Sherilyn Gordon-Burroughs, MD 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: Xaralambos (Bobby) Zervos, DO FL - Cleveland Clinic Florida
  More Information

Responsible Party: Vital Therapies, Inc. Identifier: NCT02612428     History of Changes
Other Study ID Numbers: VTL-308 
Study First Received: November 19, 2015
Last Updated: October 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders processed this record on October 21, 2016