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

Acute Alcoholic Hepatitis Clinical Trial

Official title:

A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01471028
• Other study ID #: VTI-208
• Status: Completed
• Phase: Phase 3
• Start date: February 2013
• Est. completion date: August 2015

Study information

• Verified date: January 2019
• Source: Vital Therapies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: August 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

• Subjects meeting inclusion criteria 1 through 3 will be classified as having either:

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 ß-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.

Related Conditions & MeSH terms

• Acute Alcoholic Hepatitis
• Hepatitis
• Hepatitis, Alcoholic

Intervention

Biological:
• ELAD treatment
ELAD treatment consists of treatment with an extracorporeal liver assist system.

Other:
• Standard of care (Control)
Control receives standard medical treatment.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Spain	Hospital Ramón y Cajal	Madrid
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	Royal Free Hospital	Hamstead	London
United Kingdom	King's College Hospital	London	England
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Sharp Coronado Hospital	Coronado	California
United States	Baylor University Medical Center	Dallas	Texas
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Keck Hospital of University of Southern California	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	University of Miami Hospital	Miami	Florida
United States	University of Minnesota - Twin Cities Campus	Minneapolis	Minnesota
United States	Rutgers University Hospital	New Brunswick	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Stanford School of Medicine/Stanford University Medical Center	Palo Alto	California
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Maricopa Integrated Health System (MIHS)	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Utah Hospital	Salt Lake City	Utah
United States	The University of Texas Health Science Center - Texas Liver Institute	San Antonio	Texas
United States	University of California San Diego Medical Center - Hillcrest	San Diego	California
United States	Swedish Medical Center - Transplant Program	Seattle	Washington
United States	University of Washington - Harborview Medical Center	Seattle	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	University of Arizona Medical Center	Tucson	Arizona
United States	Westchester Medical Center	Valhalla	New York
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vital Therapies, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Progression-free Survivors at Study Day 91	An exploratory objective is to evaluate the ability of ELAD® to stabilize liver function, measured using the MELD-based time to progression (TTP), with progression 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.	Study Day 1 up to Study Day 91
Primary	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	Number of Survivors at Study Day 91.	Assess the proportion of survivors at Study Day 91.	Up to Study Day 91.

External Links

•   Vital Therapies, Inc. website