This study examines the safety and efficacy of using ELAD therapy as a continuous liver support in subjects with compromised liver function owing to severe acute alcoholic hepatitis (sAAH), allowing time for the subject's native liver to regenerate to a healthy state. The primary objective of the study is to evaluate safety and efficacy of ELAD with respect to overall survival (OS) of subjects through VTI-210 study termination (after the last surviving enrolled subject completes study day 91)
- Conditions
- Severe Acute Alcoholic Hepatitis (sAAH)MedDRA version: 17.0Level: PTClassification code 10019755Term: Hepatitis chronic activeSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2013-001884-21-DE
- Lead Sponsor
- VITAL THERAPIES, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
Subjects must meet ALL inclusion criteria to be eligible for the study:
1. Age = 18;
2. Total bilirubin = 8 mg/dL;
3. Medical history of alcohol abuse with evidence of causal and temporal (<6weeks) relationship to the use of alcohol and the onset of symptoms;
4. Maddrey score of = 32;
5. A clinical diagnosis of severe acute alcoholic hepatitis (sAAH) defined asmeeting two or more of the following:
a. Hepatomegaly
b. AST > ALT
c. Ascites
d. Leukocytosis (WBC count above lab normal at site);
6. Subject must have either:
a. a liver biopsy that, in the investigator's opinion, confirms a diagnosis of sAAH (stratum A)
OR
b. in the investigator's opinion, a liver biopsy is not justified due to the risk versus the diagnosis value, and no confirmatory liver biopsy is available, in which case the clinical diagnosis is sufficient (stratum B);
7. Subject must have failed steroid therapy according to the Lille protocol (Lille score >0.45) after completing 7 days of steroids;
8. Subject must be eligible for Standard of Care treatment as defined in the protocol;
9. Subject or legally authorized representative must provide Informed Consent for all phases of the study (Treatment, and 5-year Follow-Up Registry);
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 15
Subjects must NOT meet any of the following exclusion criteria:
1. Platelet count < 50,000/mm3;
2. International Normalization Ratio (INR) > 3.0;
3. MELD score > 35;
4. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom, etc.) indicated by any of the following:
a. Presence of sepsis or septic shock; OR
b. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Randomization; OR
c. Presence of spontaneous bacterial peritonitis during the 2 days prior to Randomization; OR
d. Clinical and radiological signs of pneumonia;
5. Evidence of more than one steroid regimen during this episode of liver failure;
6. Hospital admission for any other episodes of liver decompensation within the past 2 months;
7. Evidence of hemodynamic instability as defined by the following:
a. Systolic blood pressure < 90 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
b. Mean arterial pressure (MAP) < 60 mmHg with evidence of diminished perfusion unresponsive to fluid resuscitation and/or low-dose pressor support; OR
c. Requirement for escalating doses of vasopressor support prior to Screening; OR
d. Subject at maximum vasopressor dose at Screening or Randomization (low doses are allowed);
low dose vasopressor doses are defined as:
• Dobutamine: Low doses: 2.5 to 5.0 mcg/kg/min
• Dopamine: Low doses: 0.5 to 2 mcg/kg/min
• Norepinephrine: Low doses: 0.01 to 0.02 mcg/kg/min
• Phenylephrine: Low doses: 0.05 to 1 mcg/kg/min
• Vasopressin: Low doses: 0.01 to 0.02 U/min
8. Evidence of active bleeding or of major hemorrhage defined as requiring = 2 units packed red blood cells to maintain a stable hemoglobin occurring within 48 hours of Screening;
9. Evidence of occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;
10. 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:
a. Severe acute or chronic cardiovascular, central nervous system, or pulmonary disease;
b. Cancer that has metastasized or has not yet been treated;
11. 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 < 750cc is not considered reduced for the individual subject;
12. Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);
13. Uncontrolled seizures;
14. Positive serologies for viral hepatitis B (HBsAg) or hepatitis C indicating acute/chronic infection or a positive viral load for either hepatitis B or C;
15. Pregnancy as determined by ß-human chorionic gonadotropin (HCG) results;
16. 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);
17. Currently listed or scheduled for liver transplant during the 90-day study period;
18. Previous liver transplant;
19. Previous
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method