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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01471028




Registration number
NCT01471028
Ethics application status
Date submitted
7/11/2011
Date registered
11/11/2011
Date last updated
15/02/2019

Titles & IDs
Public title
Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure
Scientific title
A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)
Secondary ID [1] 0 0
VTI-208
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Alcoholic Hepatitis 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - ELAD treatment
Other interventions - Standard of care (Control)

Experimental: ELAD Treatment - This group will receive treatment with ELAD plus standard of care treatment.

Other: Standard of care (Control) - This group will receive standard of care treatment as defined in the protocol.


Other interventions: ELAD treatment
ELAD treatment consists of treatment with an extracorporeal liver assist system.

Other interventions: Standard of care (Control)
Control receives standard medical treatment.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
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 outcome [1] 0 0
Number of Survivors at Study Day 91.
Timepoint [1] 0 0
Up to Study Day 91.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2015
Sample size
Target
Accrual to date
Final
203
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Mississippi
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
United Kingdom
State/province [19] 0 0
England
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London
Country [21] 0 0
United Kingdom
State/province [21] 0 0
West Midlands
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Bristol
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Cambridge
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Vital Therapies, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01471028
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jan Stange, MD
Address 0 0
Vital Therapies, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01471028