Acute Alcoholic HepatitisPhase 3NCT01471028
Assess Safety and Efficacy of ELAD (Extracorporeal Liver Assist System) in Subjects With Alcohol-Induced Liver Failure
A Phase 3 study testing ELAD treatment in people with Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 45 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Alcoholic Hepatitis
- What is being tested?
- ELAD treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 203 participants
- Where
- 45 sitesin 4 countries
- Study dates
- Feb 2013to Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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:
Show all 17Show fewer
- Hepatomegaly,
- AST > ALT,
- Ascites,
- Leukocytosis (WBC count above lab normal at site), OR
- 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;
- Subject must be eligible for Standard of Care treatment as defined in the protocol.
Who cannot join
- 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);
Show all 26Show fewer
- 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:
- Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
- 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 β-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.
Trial locations and contacts
45 sites in 4 countries.
45 sites in 4 countries
United States35 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Emory University Hospital
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Rush University Medical Center
Chicago, Illinois, 60612
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Sharp Coronado Hospital
Coronado, California, 92118
Methodist Dallas Medical Center
Dallas, Texas, 75203
Baylor University Medical Center
Dallas, Texas, 75246
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Keck Hospital of University of Southern California
Los Angeles, California, 90033
Cedars-Sinai Medical Center
Los Angeles, California, 90048
North Shore University Hospital
Manhasset, New York, 11030
University of Miami Hospital
Miami, Florida, 33136
University of Minnesota - Twin Cities Campus
Minneapolis, Minnesota, 55455
Rutgers University Hospital
New Brunswick, New Jersey, 08903
New York University Langone Medical Center
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Stanford School of Medicine/Stanford University Medical Center
Palo Alto, California, 94304
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Maricopa Integrated Health System (MIHS)
Phoenix, Arizona, 85008
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15216
University of Utah Hospital
Salt Lake City, Utah, 84108
The University of Texas Health Science Center - Texas Liver Institute
San Antonio, Texas, 78215
University of California San Diego Medical Center - Hillcrest
San Diego, California, 92103
Swedish Medical Center - Transplant Program
Seattle, Washington, 98104
University of Washington - Harborview Medical Center
Seattle, Washington, 98104
Tampa General Hospital
Tampa, Florida, 33606
Montefiore Medical Center
The Bronx, New York, 10467
University of Arizona Medical Center
Tucson, Arizona, 85724
Westchester Medical Center
Valhalla, New York, 10595
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Cleveland Clinic Florida
Weston, Florida, 33331
United Kingdom6 sites
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Birmingham, West Midlands, B152TH
United Hospitals Bristol NHS Foundation Trust
Bristol, BS2 8HW
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB20QQ
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Royal Free Hospital
Hamstead, London, NW3 2QG
King's College Hospital
London, England, SE5 9RS
Australia3 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009
About this study
Official title: A Randomized, Open-Label, Multicenter, Controlled 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 (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.
Read the detailed 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.
- Conditions
- Acute Alcoholic Hepatitis
- Being tested
- ELAD treatment, Standard of care (Control)
- Keywords
- Acute alcoholic hepatitis, alcoholic, hepatitis, liver
- Medical subject headings
- Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELAD treatmentBiological
Also called ELAD
ELAD treatment consists of treatment with an extracorporeal liver assist system.
Standard of care (Control)Other
Also called Standard of care as defined by the protocol
Control receives standard medical treatment.
| Study group | Role | What they receive |
|---|---|---|
| ELAD Treatment | Experimental | This group will receive treatment with ELAD plus standard of care treatment. Receives: Biological: ELAD treatment |
| Standard of care (Control) | Other | This group will receive standard of care treatment as defined in the protocol. Receives: Other: Standard of care (Control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Assess the proportion of survivors at Study Day 91.
Measured: Up to Study Day 91.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startFeb 2013
- Primary completionJan 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vital Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jan Stange, MD, Study director, Vital Therapies, Inc.David J Reich, MD, Principal investigator, PA - Drexel University College of MedicineRam Subramanian, MD, Principal investigator, GA - Emory University HospitalLewis Teperman, MD, Principal investigator, NY - New York University Langone Medical CenterRobert Brown, MD, Principal investigator, NY - Columbia University Medical CenterJulie Thompson, MD, Principal investigator, MN - University of Minnesota Medical Center - Twin Cities CampusPaul Gaglio, MD, Principal investigator, NY - Montefiore Medical CenterLinda Sher, MD, Principal investigator, CA - Keck Hospital of University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01471028
- Sponsor's protocol ID
- VTI-208
- Status last verified
- Jan 2019
- First submitted
- 7 Nov 2011
- Last updated
- 15 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29171941
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Alcohol-Induced Liver Decompensation (AILD)
- ClinicalTrials.gov ID
- NCT01471028
- Acronym / sponsor ID
- VTI-208
- Conditions
- Acute Alcoholic Hepatitis
- Keywords
- Acute alcoholic hepatitis, alcoholic, hepatitis, liver
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 203 participants (actual)
- Lead sponsor
- Vital Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 11 Nov 2011 (estimated)
- Results
- Posted 15 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ELAD Treatment | Experimental | Biological: ELAD treatmentThis group will receive treatment with ELAD plus standard of care treatment. |
| Standard of care (Control) | Other | Other: Standard of care (Control)This group will receive standard of care treatment as defined in the protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- Not eligible for liver transplant during this hospitalization;
Key exclusion criteria (26 listed)
- Platelet count < 40,000/mm3;
- International Normalization Ratio (INR) > 3.5;
- MELD Score > 35;
- AST > 500 IU/L;
- Evidence of infection unresponsive to antibiotics;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ELAD treatmentAlso: ELADELAD treatment consists of treatment with an extracorporeal liver assist system. | Biological | ELAD Treatment |
| Standard of care (Control)Also: Standard of care as defined by the protocolControl receives standard medical treatment. | Other | Standard of care (Control) |
Primary outcome
Overall Survival
Time frame: 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)
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).
1 secondary outcome
Number of Survivors at Study Day 91.
Time frame: Up to Study Day 91.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29171941Thompson 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.
- Vital Therapies, Inc. websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Stange, MD study director
Vital Therapies, Inc.
David J Reich, MD principal investigator
PA - Drexel University College of Medicine
Ram Subramanian, MD principal investigator
GA - Emory University Hospital
45 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ELAD treatment in people with Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 45 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, United Kingdom, Australia, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01471028, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.