Acute On Chronic HepatitisPhase 2/3SILVERNCT00973817
Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Acute on Chronic Hepatitis
A Phase 2/3 study of Acute On Chronic Hepatitis, run by Vital Therapies, Inc. at 21 sites in 2 countries.
Trial summary
The purpose of this study is to investigate the safety and efficacy of the use of ELAD in patients with diagnosed Acute On Chronic Hepatitis, including Acute Alcoholic Hepatitis. Read more about this study
- Who is it for?
- Ages 18 to 67 years
- Conditions the study is for
- Acute On Chronic Hepatitis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Sep 2009to May 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 to 67 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >/= 18</= 67 years; AND
- Acute decompensation of chronic liver disease over the preceding 30 days; AND
- MELD score between 18 and 35, inclusive; AND
- Subject or designated representative must provide Informed Consent
Who cannot join
- Platelets <50,000mm at baseline; OR
- Evidence of chronic renal failure as defined by a serum creatinine >/= 2.5mg/dL as measured during the 1-6 month period prior to study entry. (Subject is not excluded with a creatinine >2.5 mg/dL if deemed to be type-1 hepato-renal syndrome); OR
- Contraindication to renal replacement therapy (hemodialysis or hemofiltration); OR
- International Normalization Ratio (INR) > 3.5; OR
- Septic shock as defined by a positive blood culture and two or more of the following:
- Systolic blood pressure <90mmHg OR mean arterial pressure <60mmHg;
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- Tachypnea > 20 breaths per minute OR a PaCO2<32 mmHg;
- White blood cell count < 4000 cell/mm3 OR > 12000 cell/mm3 (<4 x 10(9) or >12 x 10(9) cells/L).
- Evidence of major hemorrhage as indicated by:
- requiring >/= 4 units packed red blood cells within a 48 hour period prior to Screening, OR
- hemodynamic instability (sustained pulse > 120 beats/min AND systolic blood pressure < 100 mmHg over one hour)
- Subjects with a recent history of gastrointestinal hemorrhage who have been successfully treated and remain hemodynamically stable for a period of 48 hours will then be eligible for the study if the investigator determines the subject to be at low risk for rebleeding; OR
- Evidence (by physical exam, history or lab evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome; OR
- Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis; OR
- Evidence of spontaneous bacterial peritonitis with uncontrolled infection; OR
- Evidence of brain death as determined by blood flow studies positive for herniation AND/OR absence of pupillary reflex; OR
- Systolic blood pressure <85 mmHg OR MAP <50mmHg at baseline; OR
- Requirement for escalating doses of vasopressor support OR of an alpha-adrenergic agent for one hour or longer AND evidence of hemodynamic instability; OR
- Subject at maximum vasopressor dose at Screen; OR
- Clinical or radiographic evidence of a new stroke or intracerebral bleeding; OR
- Seizures uncontrolled by medication; OR
- Acute myocardial infarction based on clinical and/or electrocardiographic evidence; OR
- Lung disease defined by a PaO2<60mmHg on room air, acute respiratory distress syndrome, or a history of severe COPD or interstitial lung disease; OR
- Pregnancy as determined by beta-HCG results or lactation; OR
- Participation in another investigational drug, biologic, or device study within 1 month of enrollment. Subjects enrolled in an observational study will be eligible for this trial.
- Previous liver transplant.
- Previous participation in a clinical trial involving ELAD.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States15 sites
University of Virginia
Charlottesville, Virginia, 22908
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
Baylor University Medical Center
Dallas, Texas, 75246
Indiana University
Indianapolis, Indiana, 46202
Cedars Sinai Medical Center
Los Angeles, California, 90048
New York University Medical Center
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
Temple University
Philadelphia, Pennsylvania, 19140
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Univ. of Rochester, Strong Memorial Hospital
Rochester, New York, 14642
California Pacific Medical Center
San Francisco, California, 94115
Westchester Medical Center
Valhalla, New York, 10595
United Kingdom6 sites
University Hospitals Birmingham
Birmingham, England, B15 2PR
Royal Derby Hospital
Derby, DE22 3NE
Edinburgh Royal Infirmary
Edinburgh, EH16 4SA
St. James University Hospital
Leeds, LS9 7TF
Kings College Hospital NHS Foundation Trust
London, England, SE5 9RS
Royal Free Hospital London
London, NW3 2QG
About this study
Official title: Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Subjects With Acute On Chronic Hepatitis (AOCH)
The purpose of this study is to investigate the safety and efficacy of the use of ELAD in patients with diagnosed Acute On Chronic Hepatitis, including Acute Alcoholic Hepatitis.
- Conditions
- Acute On Chronic Hepatitis
- Being tested
- ELAD plus standard of care treatment, Standard of care
- Keywords
- Hepatitis, AOCH
- Medical subject headings
- Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELAD plus standard of care treatmentBiological
Also called Extra corporeal liver assist system
Use of ELAD plus standard of care
Standard of careOther
Standard of care in the treatment of AOCH will be administered
| Study group | Role | What they receive |
|---|---|---|
| ELAD | Experimental | Use of ELAD for up to 6 days to stabilize liver function plus standard of care treatment plus standard of care treatment. Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated) Receives: Biological: ELAD plus standard of care treatment; Other: Standard of care |
| Standard of care | Other | Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated) Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression at which a 5-point or greater Model for End stage Liver Disease (MELD) score is recorded relative to baseline
This is based on death or the first observed increase of at least 5 points from Baseline MELD score (whichever occurs earlier) at least 24 hours after the ELAD® Treatment Period is ended and up to Study Day 91 (90 days following Baseline).
Measured: From Baseline up to Study Day 91
Secondary outcomes (1)
Time to progression at which a 5-point or greater MELD score is recorded relative to baseline
A secondary Overall Survival analysis will use the same methodology as the primary time to progression efficacy analysis, except that an event will be defined as death. Secondary efficacy analyses will evaluate the proportion of progression free survivors (MELD score increased less than 5 points relative to the Baseline MELD score).
Measured: From Baseline 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 posted9 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionApr 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute On Chronic 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vital Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Ashley, MS, Study director, Vital Therapies, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00973817
- Sponsor's protocol ID
- VTI-206
- Acronym
- SILVER
- Status last verified
- Apr 2013
- First submitted
- 2 Sep 2009
- Last updated
- 8 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Subjects With Acute On Chronic Hepatitis (AOCH)
- ClinicalTrials.gov ID
- NCT00973817
- Acronym / sponsor ID
- SILVER / VTI-206
- Conditions
- Acute On Chronic Hepatitis
- Keywords
- Hepatitis, AOCH
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Vital Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 9 Sep 2009 (estimated)
- Results
- Not posted in the source record
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 investigate the safety and efficacy of the use of ELAD in patients with diagnosed Acute On Chronic Hepatitis, including Acute Alcoholic Hepatitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ELAD | Experimental | Biological: ELAD plus standard of care treatment, Other: Standard of careUse of ELAD for up to 6 days to stabilize liver function plus standard of care treatment plus standard of care treatment. Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated) |
| Standard of care | Other | Other: Standard of careStandard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated) |
Who may qualify
- Ages
- 18 to 67 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age >/= 18</= 67 years; AND
- Acute decompensation of chronic liver disease over the preceding 30 days; AND
- MELD score between 18 and 35, inclusive; AND
- Subject or designated representative must provide Informed Consent
Key exclusion criteria (27 listed)
- Platelets <50,000mm at baseline; OR
- Evidence of chronic renal failure as defined by a serum creatinine >/= 2.5mg/dL as measured during the 1-6 month period prior to study entry. (Subject is not excluded with a creatinine >2.5 mg/dL if deemed to be type-1 hepato-renal syndrome); OR
- Contraindication to renal replacement therapy (hemodialysis or hemofiltration); OR
- International Normalization Ratio (INR) > 3.5; OR
- Septic shock as defined by a positive blood culture and two or more of the following:
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 plus standard of care treatmentAlso: Extra corporeal liver assist systemUse of ELAD plus standard of care | Biological | ELAD |
| Standard of careStandard of care in the treatment of AOCH will be administered | Other | ELAD, Standard of care |
Primary outcome
Time to progression at which a 5-point or greater Model for End stage Liver Disease (MELD) score is recorded relative to baseline
Time frame: From Baseline up to Study Day 91
This is based on death or the first observed increase of at least 5 points from Baseline MELD score (whichever occurs earlier) at least 24 hours after the ELAD® Treatment Period is ended and up to Study Day 91 (90 days following Baseline).
1 secondary outcome
Time to progression at which a 5-point or greater MELD score is recorded relative to baseline
Time frame: From Baseline up to Study Day 91
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2013.
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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.
Robert Ashley, MS study director
Vital Therapies, Inc.
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study of Acute On Chronic Hepatitis, run by Vital Therapies, Inc. at 21 sites in 2 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 4 inclusion and 27 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 8 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, United Kingdom. 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 combined 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to progression at which a 5-point or greater Model for End stage Liver Disease (MELD) score is recorded relative to baseline (time frame: From Baseline up to Study Day 91). 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 8 Apr 2013.