Severe Acute Alcoholic HepatitisPhase 3NCT01829347
To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
A Phase 3 study testing ELAD in people with Severe Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 39 sites in 4 countries.
Trial summary
The purpose of this study is to determine if treatment with the ELAD System is safe and effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille score >0.45). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Acute Alcoholic Hepatitis
- What is being tested?
- ELAD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 39 sitesin 4 countries
- Study dates
- Apr 2014to Sep 2018
- 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 ;
- Total bilirubin ≥8 mg/dL;
- Medical history of alcohol abuse with evidence of a causal and temporal (<6 weeks) relationship to the use of alcohol and hospital admission for this episode of sAAH;
- Maddrey score ≥32
- A clinical diagnosis of severe acute alcoholic hepatitis (sAAH);
- Subject must have liver biopsy or in investigator's opinion, if risk is too great to perform liver biopsy, then clinical diagnosis is sufficient;
- Subject must be a Lille score failure (Lille score >0.45) as defined in this study.
Who cannot join
- Platelet count <50,000/mm3;
- International Normalization Ratio (INR) >3.0;
- MELD score >35;
- Evidence of infection unresponsive to antibiotics;
- Evidence of jaundice for >3 months;
- Hospital admission for any episodes of liver decompensation not related to sAAH, (other than this episode of sAAH) within the past 2 months;
Show all 23Show fewer
- Evidence of hemodynamic instability;
- Evidence of active bleeding or of major hemorrhage defined as requiring ≥2 units of packed red blood cells to maintain a stable hemoglobin occurring within 48 hours of Screening;
- Evidence of 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;
- Clinical evidence of liver size reduction due to cirrhosis, unless Investigator interpretation of the clinical evidence indicates liver size of <10 cm or volume of <750 cc is not considered reduced for the individual subject;
- Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
- Uncontrolled seizures;
- Positive serologies for viral hepatitis B or C;
- Pregnancy as determined by β-human chorionic gonadotropin (HCG) results;
- 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 VTI-210 clinical trial);
- Currently listed or scheduled for liver transplant during the 90-day study period;
- Previous liver transplant;
- Previous participation in a clinical trial involving ELAD;
- Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or 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-210E follow-up study;
- Is unable to provide an address for follow-up home visits.
- And other inclusion/exclusion criteria
Trial locations and contacts
39 sites in 4 countries.
39 sites in 4 countries
United States21 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Emory University Hospital
Atlanta, Georgia, 30322
Johns Hopkins University Hospital
Bethesda, Maryland, 20814
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Carolinas Medical Center
Charlotte, North Carolina, 28204
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
North Shore University Hospital
Manhasset, New York, 11030
University of Miami Hospital
Miami, Florida, 33136
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
University of Minnesota Medical Center - Twin Cities Campus
Minneapolis, Minnesota, 55455
Rutgers University Hospital
Newark, New Jersey, 07101
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
University of Texas Health Science Center, San Antonio
San Antonio, Texas, 78215
University of California San Diego
San Diego, California, 92103
Swedish Medical Center
Seattle, Washington, 98104
Montefiore Medical Center
The Bronx, New York, 10467
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Cleveland Clinic Florida
Weston, Florida, 33331
Spain10 sites
Hospital Universitario de Cruces
Barakaldo, Vizcaya, 48903
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Reina Sofia
Córdoba, 14004
Hospital Gregorio Marañon
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid, 28220
Hospital Universitario Marques de Valdecilla
Santander, 39008
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, La Coruña, 15706
Hospital Universitario de Valme
Seville, 41014
Hospital Universitario y Politécnico La Fe
Valencia, 46026
United Kingdom6 sites
Brighton & Sussex University Hospitals NHS Trust
Brighton, BN2 5BE
Doncaster Royal Infirmary
Doncaster, South Yorkshire, DN2 5LT
NHS Tayside
Dundee, Scotland, DD1 9SY
Royal Free Hospital
Hampstead, London, NW3 2QR
Barts Health NHS Trust
London, England, SE5 9RS
King's College Hospital NHS Foundation Trust
London, England, SE59RS
Germany2 sites
Charité Campus Virchow-Klinikum Medizinische Klinik
Berlin, D-13353
Medizinische Hochschule Hannover
Hanover, D-30625
About this study
Official title: A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD® in Subjects With Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
The purpose of this study is to determine if treatment with the ELAD System is safe and effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille score >0.45).
Read the detailed description
The Lille score will be used to identify subjects with an increased risk of mortality (Lille score failures). The Lille score is a prognostic model combining six reproducible variables at Day 0 and Day 7 of steroid treatment. The Lille score used in this protocol is being used independent of steroid administration during the 7 days of evaluation. A Lille score >0.45 (Lille score failure) indicates that the subject is at substantially increased risk of 30- and 90-day mortality. Subjects with severe acute alcoholic hepatitis (sAAH) are often treated with steroids as soon as their diagnosis is confirmed. This study is to assess treatment with the ELAD System in subjects who have failed per the Lille criteria, independent of steroid administration. ELAD treatment is done continuously for up to 10 days in addition to standard of care treatment. The Control group (those randomized not to receive ELAD treatment) will also get standard of care treatment. Standard of care is defined as the usual care for diet, medications, treatment of complications that may arise, etc. for sAAH patients.
- Conditions
- Severe Acute Alcoholic Hepatitis
- Being tested
- ELAD, Standard of Care treatment
- Keywords
- liver failure, acute alcoholic hepatitis, patients failing steroid therapy, alcoholic hepatitis, steroid failure, Lille criteria, ELAD
- Medical subject headings
- Liver Failure, Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELADBiological
Also called Human Cell-Based Bio-Artificial Liver Support System
ELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2.
Standard of Care treatmentOther
Also called Usual treatment for the disease
Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.
| Study group | Role | What they receive |
|---|---|---|
| ELAD (plus Standard of Care) | Experimental | ELAD is a human cell-based bio-artificial liver support system developed to improve survival of patients with acute liver failure and to provide liver support continuously to a subject with compromised liver function. Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines. Receives: Biological: ELAD; Other: Standard of Care treatment |
| Standard of Care (Control) | Other | Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines. Receives: Other: Standard of Care treatment |
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 ELAD-treated and Control groups, with protocol VTI-210E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (11 July 2016).
Measured: Up to at least Study Day 91, with protocol VTI-208E providing additional survival data at the time of database lock (11 July 2016), approximately 27 months
Secondary outcomes (1)
Proportion 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 Apr 2013 (estimated)
- Study startApr 2014
- Primary completionOct 2015
- Study completionSep 2018
Why it stopped: Due to results from the VTI-208 study, the ELAD plan is being re-evaluated.
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 Severe 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
- 18 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.Rajiv Jalan, MD, Principal investigator, UK - Royal Free HospitalJuan Caballeria, MD, Principal investigator, Spain - Hospital Clinic de BarcelonaJosé Luis Montero, MD, Principal investigator, Spain - Hospital Reina SofiaRafael Bañares, MD, Principal investigator, Spain - Hospital Gregorio MarañonKalyan R Bhamidimarri, MD, Principal investigator, FL - University of Miami HospitalJulie Thompson, MD, Principal investigator, MN - University of Minnesota Medical Center - Twin Cities CampusValentin Cuervas-Mons Martinez, MD, Principal investigator, Spain - Hospital Universitario Puerta de Hierro - Majadahonda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01829347
- Sponsor's protocol ID
- VTI-210
- Status last verified
- Feb 2019
- First submitted
- 8 Apr 2013
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pares A, Mas A. Extracorporeal liver support in severe alcoholic hepatitis. World J Gastroenterol. 2014 Jul 7;20(25):8011-7. doi: 10.3748/wjg.v20.i25.8011.
PubMed 25009371
Study at a glance
From the registry record, last updated by the sponsor on 19 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 Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
- ClinicalTrials.gov ID
- NCT01829347
- Acronym / sponsor ID
- VTI-210
- Conditions
- Severe Acute Alcoholic Hepatitis
- Keywords
- liver failure, acute alcoholic hepatitis, patients failing steroid therapy, alcoholic hepatitis, steroid failure, Lille criteria, ELAD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to results from the VTI-208 study, the ELAD plan is being re-evaluated.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vital Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 11 Apr 2013 (estimated)
- Results
- Posted 19 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 purpose of this study is to determine if treatment with the ELAD System is safe and effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille score >0.45).
Detailed description
The Lille score will be used to identify subjects with an increased risk of mortality (Lille score failures). The Lille score is a prognostic model combining six reproducible variables at Day 0 and Day 7 of steroid treatment. The Lille score used in this protocol is being used independent of steroid administration during the 7 days of evaluation. A Lille score >0.45 (Lille score failure) indicates that the subject is at substantially increased risk of 30- and 90-day mortality. Subjects with severe acute alcoholic hepatitis (sAAH) are often treated with steroids as soon as their diagnosis is confirmed. This study is to assess treatment with the ELAD System in subjects who have failed per the Lille criteria, independent of steroid administration. ELAD treatment is done continuously for up to 10 days in addition to standard of care treatment. The Control group (those randomized not to receive ELAD treatment) will also get standard of care treatment. Standard of care is defined as the usual care for diet, medications, treatment of complications that may arise, etc. for sAAH patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ELAD (plus Standard of Care) | Experimental | Biological: ELAD, Other: Standard of Care treatmentELAD is a human cell-based bio-artificial liver support system developed to improve survival of patients with acute liver failure and to provide liver support continuously to a subject with compromised liver function. Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines. |
| Standard of Care (Control) | Other | Other: Standard of Care treatmentStandard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 ;
- Total bilirubin ≥8 mg/dL;
- Medical history of alcohol abuse with evidence of a causal and temporal (<6 weeks) relationship to the use of alcohol and hospital admission for this episode of sAAH;
- Maddrey score ≥32
- A clinical diagnosis of severe acute alcoholic hepatitis (sAAH);
Key exclusion criteria (23 listed)
- Platelet count <50,000/mm3;
- International Normalization Ratio (INR) >3.0;
- MELD score >35;
- Evidence of infection unresponsive to antibiotics;
- Evidence of jaundice for >3 months;
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 |
|---|---|---|
| ELADAlso: Human Cell-Based Bio-Artificial Liver Support SystemELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2. | Biological | ELAD (plus Standard of Care) |
| Standard of Care treatmentAlso: Usual treatment for the diseaseStandard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines. | Other | ELAD (plus Standard of Care), 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 the time of database lock (11 July 2016), approximately 27 months
The primary endpoint of the study was a comparison of overall survival (OS) between ELAD-treated and Control groups, with protocol VTI-210E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (11 July 2016).
1 secondary outcome
Proportion 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 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25009371Pares A, Mas A. Extracorporeal liver support in severe alcoholic hepatitis. World J Gastroenterol. 2014 Jul 7;20(25):8011-7. doi: 10.3748/wjg.v20.i25.8011.
- Sponsor's websiteLink provided by the sponsor.
Related trials for Severe Acute Alcoholic Hepatitis
Recruiting
Intestinal Microbiota Profiling in Severe Acute Alcoholic Hepatitis Patients
Severe Acute Alcoholic Hepatitis, Alcohol
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.
Rajiv Jalan, MD principal investigator
UK - Royal Free Hospital
Juan Caballeria, MD principal investigator
Spain - Hospital Clinic de Barcelona
39 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 in people with Severe Acute Alcoholic Hepatitis, run by Vital Therapies, Inc. at 39 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 7 inclusion and 23 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: stopped early, as of the sponsor's last update on 19 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 39 sites in United States, Spain, United Kingdom, Germany. 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 19 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 the time of database lock (11 July 2016), approximately 27 months). 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 NCT01829347, 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 19 Feb 2019.