Brief 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).
Brief Title
To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Severe Acute Alcoholic Hepatitis
Eligibility Criteria
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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;
* 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
* 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.
Exclusion Criteria:
* 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;
* 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
Inclusion Criteria
Inclusion Criteria:
* 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.
inclusion/
* 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.
inclusion/
Gender
All
Gender Based
false
Keywords
liver failure
acute alcoholic hepatitis
patients failing steroid therapy
alcoholic hepatitis
steroid failure
Lille criteria
ELAD
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01829347
Org Class
Industry
Org Full Name
Vital Therapies, Inc.
Org Study Id
VTI-210
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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).
Outcome Measure
Overall Survival
Outcome 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
Secondary Outcomes
Outcome Description
Assess the proportion of survivors at Study Day 91.
Outcome Time Frame
Up to Study Day 91.
Outcome Measure
Proportion of Survivors at Study Day 91.
See Also Links
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kristina Chacko
Investigator Email
krchacko@montefiore.org
Investigator Phone