Acute Liver FailurePhase 2NCT01875874
Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)
A Phase 2 study testing ELAD in people with Acute Liver Failure and Fulminant Hepatic Failure, run by Vital Therapies, Inc. at 18 sites in United States.
Trial summary
This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Liver Failure, Fulminant Hepatic Failure, Primary Graft Non-Function
- What is being tested?
- ELAD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 18 sitesUnited States
- Study dates
- Oct 2014to Sep 2018
- Phase
- Phase 2
- 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
- Weight ≥ 40 kg;
- Age ≥ 18;
- Diagnosis of ALF attributed to one of the following:
- FHF (acute liver failure with no preexisting liver disease, see below);
- Primary Graft Non-Function (PNF);
- Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery);
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- Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours;
- Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E.
- Subjects with FHF must meet one of the following criteria:
- Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:
- Prothrombin time (PT) > 100 seconds [International Normalized Ratio (INR) > 6.5], OR
- Encephalopathy Grade 3 or 4 AND ARTERIAL AMMONIA >100 umol/liter and at least one of the following:
- Arterial pH < 7.30 at ≥ 24 hours after drug ingestion or volume resuscitation; ii. Renal failure documented by urine output < 0.5 mL/kg/hr over the preceding 12 hours; iii. Creatinine > 2.5 mg/dL; OR
- Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia >100 umol/liter, and at least two of the following:
- Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF
- Serum bilirubin > 17 mg/dL
- Subject > 40 years old
- PT > 50 seconds (INR > 3.5)
- Jaundice to encephalopathy time ≥ 7 days
Who cannot join
- Cerebral Perfusion Pressure ≤40 mm Hg for 1 hour or longer as measured by an intracranial pressure (ICP) monitor. (NOTE: In those cases where ICP monitor placement cannot be performed prior to study enrollment, this exclusion criterion will not apply);
- Chronic liver disease (e.g., compensated cirrhosis of any etiology, chronic hepatitis, nonalcoholic steatohepatitis, cholestatic liver disease, or metabolic liver disease) (NOTE: steatosis is not an exclusion criterion);
- Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;
- Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) indicated by any of the following:
- Presence of sepsis or septic shock; OR
- Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Enrollment; OR
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- Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR
- Clinical and radiological signs of pneumonia.
- Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer (except non-melanoma skin cancer), acute fatty-liver disease, hepatitis due to herpes virus or Budd-Chiari syndrome. (NOTE: in the case of subjects enrolled due to surgery-induced liver failure (SILF) then the original cause for the surgery will not be a criterion for exclusion);
- Portal hypertension;
- Liver dysfunction due to trauma;
- Irreversible brain death;
- Platelet count < 30,000/mm3 [NOTE: Subject may be included at the physician's discretion if platelet count exceeds 30,000/mm3 at time of initiation of therapy (even if the value is following platelet transfusion) and can be managed through the administration of blood products]
- Cardiovascular sepsis-related organ failure assessment score (SOFA score) >3;
- Stroke or intracranial hemorrhage;
- Seizures uncontrolled by medication;
- Acute myocardial infarction;
- Lung disease defined by a partial pressure of oxygen measurement (PaO2) ≤60 mmHg or a fraction of inspired oxygen (FiO2) ≥0.6, not corrected by medical management [including continuous venovenous hemofiltration (CVVH) if indicated] and ventilation with a Positive End Expiratory Pressure (PEEP) of >8cm H2O;
- Acute Respiratory Distress Syndrome;
- Pregnancy as determined by beta-human chorionic gonadotropin (β-hCG) results;
- ≤ 2 weeks postpartum;
- 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-212 clinical trial);
- Prior ELAD therapy;
- 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).
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Emory University Hospital
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rush University Medical Center
Chicago, Illinois, 60612
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Methodist Dallas Medical Center - The Liver Institute
Dallas, Texas, 75203
Keck Hospital of USC
Los Angeles, California, 90033
University of Miami Hospital
Miami, Florida, 33136
University of Minnesota Medical Center - Twin Cities Campus
Minneapolis, Minnesota, 55455
New York University Medical Center
New York, New York, 10016
Rutgers University Hospital
Newark, New Jersey, 07102
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
University of Utah
Salt Lake City, Utah, 84132
Swedish Medical Center
Seattle, Washington, 98104
Tampa General Hospital
Tampa, Florida, 33606
Montefiore Medical Center
The Bronx, New York, 10467
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Cleveland Clinic Floriday
Weston, Florida, 33331
About this study
Official title: An Open-Label, Multicenter, Historically-Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Acute Liver Failure (ALF)
This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls.
Read the detailed description
The VTI-212 study (VTI-212) is an open-label, multicenter, historically-controlled study of subjects with acute liver failure (ALF). Approximately 40 subjects who meet the eligibility requirements of the study will receive ELAD treatment in addition to standard of care treatment for ALF. The outcomes of these subjects will be compared with matched historical controls drawn from existing databases.
Subjects will undergo ELAD treatment for a minimum of 3 days (72 hours). It is recommended ELAD treatment be continued up to 10 days (240 hours).
Following ELAD treatment, subjects will continue standard medical therapy as defined by the institution and be followed through Study Day 28.
Subjects' diagnosis of ALF will be attributed to one of the following:
- Fulminant Hepatic Failure (FHF) (acute liver failure with no preexisting liver disease);
- Primary Graft Non-Function (PNF);
- Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery.
Screening evaluations and assessments will be completed for subjects and reviewed against inclusion/exclusion criteria.
Enrollment will define the time of study entry (Hour 0, Study Day 1, study baseline) and inclusion in the Intent-to-treat (ITT) population. Subjects will be evaluated throughout the 28-day study period.
If standard medical therapy, as defined by the institution and this protocol is consistent with discharging the subject home, then the subject should be discharged. Prior to discharge, the subject will be advised to attend all follow-up visits.
An extension of this study, the VTI-212E study (VTI-212E), will provide additional ELAD survival data, as available, through VTI-212 study termination (after the last surviving enrolled ELAD subject completes Study Day 28). This registry protocol segment of VTI-212 extends the safety monitoring period to 5 years to assess survival, incidence and characterization of tumor (in particular hepatocellular tumor), incidence of liver transplant, and assess quality of life using a standard, validated questionnaire.
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 Liver Failure, Fulminant Hepatic Failure, Primary Graft Non-Function, Surgically-Induced Liver Failure
- Being tested
- ELAD
- Keywords
- liver failure, acute liver failure, fulminant hepatic failure, primary graft non-function, surgically-induced liver failure, ELAD, ALF, FHF, PNF
- Medical subject headings
- Liver Failure, Acute, Liver Failure
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
Continuous treatment with the ELAD System for a minimum of 3 days to a maximum of 10 days. The subject's ultrafiltrated blood is circulated through 4 cartridges, each containing approximately 110 grams of C3A cells (approximately 440 grams total).
| Study group | Role | What they receive |
|---|---|---|
| ELAD plus standard of care | Experimental | Continuous ELAD treatment for a minimum of 3 days to a maximum of 10 days in addition to a standard of care for subjects with acute liver failure. Receives: Biological: ELAD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) of ALF Subjects
Measured: Study Day 1 through Study Day 28
Secondary outcomes (1)
Number of Subjects Who Survived at the End of Study Day 28 or Who Received Orthotopic Liver Transplantation on or Before That Study Day.
Measured: Study Day 1 through Study Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2013 (estimated)
- Study startOct 2014
- Primary completionSep 2015
- Study completionSep 2018
Why it stopped: Due to VTI-208 results, the ELAD clinical 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.
- Other trials for Acute Liver FailureStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vital Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jan Stange, MD, Ph.D., Study chair, Vital Therapies, Inc.Parvez Mantry, MD, Principal investigator, TX - Methodist Dallas Medical Center - The Liver InstituteDavid J Reich, MD, Principal investigator, PA - Drexel University College of MedicinePaul J Gaglio, MD, Principal investigator, NY - Montefiore Medical CenterJuan Gallegos-Orozco, MD, Principal investigator, UT - University of UtahAngel Alsina, MD, Principal investigator, FL - Tampa General HospitalLewis W Teperman, MD, Principal investigator, NY - New York University Medical CenterNikunj Shah, MD, Principal investigator, IL - Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01875874
- Sponsor's protocol ID
- VTI-212
- Status last verified
- Jan 2019
- First submitted
- 5 Jun 2013
- Last updated
- 12 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Historically-Controlled Study to Assess Safety and Efficacy of ELAD in Subjects With Acute Liver Failure (ALF)
- ClinicalTrials.gov ID
- NCT01875874
- Acronym / sponsor ID
- VTI-212
- Conditions
- Acute Liver Failure, Fulminant Hepatic Failure, Primary Graft Non-Function, Surgically-Induced Liver Failure
- Keywords
- liver failure, acute liver failure, fulminant hepatic failure, primary graft non-function, surgically-induced liver failure, ELAD, ALF, FHF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to VTI-208 results, the ELAD clinical plan is being re-evaluated.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Vital Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 12 Jun 2013 (estimated)
- Results
- Posted 22 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls.
Detailed description
The VTI-212 study (VTI-212) is an open-label, multicenter, historically-controlled study of subjects with acute liver failure (ALF). Approximately 40 subjects who meet the eligibility requirements of the study will receive ELAD treatment in addition to standard of care treatment for ALF. The outcomes of these subjects will be compared with matched historical controls drawn from existing databases.
Subjects will undergo ELAD treatment for a minimum of 3 days (72 hours). It is recommended ELAD treatment be continued up to 10 days (240 hours).
Following ELAD treatment, subjects will continue standard medical therapy as defined by the institution and be followed through Study Day 28.
Subjects' diagnosis of ALF will be attributed to one of the following:
- Fulminant Hepatic Failure (FHF) (acute liver failure with no preexisting liver disease);
- Primary Graft Non-Function (PNF);
- Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery.
Screening evaluations and assessments will be completed for subjects and reviewed against inclusion/exclusion criteria.
Enrollment will define the time of study entry (Hour 0, Study Day 1, study baseline) and inclusion in the Intent-to-treat (ITT) population. Subjects will be evaluated throughout the 28-day study period.
If standard medical therapy, as defined by the institution and this protocol is consistent with discharging the subject home, then the subject should be discharged. Prior to discharge, the subject will be advised to attend all follow-up visits.
An extension of this study, the VTI-212E study (VTI-212E), will provide additional ELAD survival data, as available, through VTI-212 study termination (after the last surviving enrolled ELAD subject completes Study Day 28). This registry protocol segment of VTI-212 extends the safety monitoring period to 5 years to assess survival, incidence and characterization of tumor (in particular hepatocellular tumor), incidence of liver transplant, and assess quality of life using a standard, validated questionnaire.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ELAD plus standard of care | Experimental | Biological: ELADContinuous ELAD treatment for a minimum of 3 days to a maximum of 10 days in addition to a standard of care for subjects with acute liver failure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Weight ≥ 40 kg;
- Age ≥ 18;
- Diagnosis of ALF attributed to one of the following:
- Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours;
- Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E.
Key exclusion criteria (24 listed)
- Cerebral Perfusion Pressure ≤40 mm Hg for 1 hour or longer as measured by an intracranial pressure (ICP) monitor. (NOTE: In those cases where ICP monitor placement cannot be performed prior to study enrollment, this exclusion criterion will not apply);
- Chronic liver disease (e.g., compensated cirrhosis of any etiology, chronic hepatitis, nonalcoholic steatohepatitis, cholestatic liver disease, or metabolic liver disease) (NOTE: steatosis is not an exclusion criterion);
- Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;
- Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) indicated by any of the following:
- Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer (except non-melanoma skin cancer), acute fatty-liver disease, hepatitis due to herpes virus or Budd-Chiari syndrome. (NOTE: in the case of subjects enrolled due to surgery-induced liver failure (SILF) then the original cause for the surgery will not be a criterion for exclusion);
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 SystemContinuous treatment with the ELAD System for a minimum of 3 days to a maximum of 10 days. The subject's ultrafiltrated blood is circulated through 4 cartridges, each containing approximately 110 grams of C3A cells (approximately 440 grams total). | Biological | ELAD plus standard of care |
Primary outcome
Overall Survival (OS) of ALF Subjects
Time frame: Study Day 1 through Study Day 28
1 secondary outcome
Number of Subjects Who Survived at the End of Study Day 28 or Who Received Orthotopic Liver Transplantation on or Before That Study Day.
Time frame: Study Day 1 through Study Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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, Ph.D. study chair
Vital Therapies, Inc.
Parvez Mantry, MD principal investigator
TX - Methodist Dallas Medical Center - The Liver Institute
David J Reich, MD principal investigator
PA - Drexel University College of Medicine
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ELAD in people with Acute Liver Failure and Fulminant Hepatic Failure, run by Vital Therapies, Inc. at 18 sites in United States.
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 19 inclusion and 24 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 12 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 18 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 22 Aug 2018). 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 (OS) of ALF Subjects (time frame: Study Day 1 through Study Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Feb 2019.