Clinical trial NCT01829347: To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Severe Acute Alcoholic Hepatitis
Keywords: liver failure
acute alcoholic hepatitis
patients failing steroid therapy
alcoholic hepatitis
steroid failure
Lille criteria
ELAD
Lead sponsor: Vital Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2013-04-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

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

Primary outcomes:
measure: Overall Survival
timeFrame: 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:
measure: Proportion of Survivors at Study Day 91.
timeFrame: Up to Study Day 91.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Bethesda
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center - Twin Cities Campus
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Rutgers University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center, San Antonio
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum Medizinische Klinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Baracaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario de Valme
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
city: Hampstead
country: United Kingdom
facility: Royal Free Hospital
state: London
city: Dundee
country: United Kingdom
facility: NHS Tayside
state: Scotland
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: South Yorkshire
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
Study officials:
affiliation: Vital Therapies, Inc.
name: Jan Stange, MD
role: STUDY_DIRECTOR
affiliation: UK - Royal Free Hospital
name: Rajiv Jalan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Clinic de Barcelona
name: Juan Caballeria, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Reina Sofia
name: José Luis Montero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Gregorio Marañon
name: Rafael Bañares, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: FL - University of Miami Hospital
name: Kalyan R Bhamidimarri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MN - University of Minnesota Medical Center - Twin Cities Campus
name: Julie Thompson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario Puerta de Hierro - Majadahonda
name: Valentin Cuervas-Mons Martinez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Clinico Universitario de Santiago de Compostela
name: Santiago Tome, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario y Politécnico La Fe
name: Martín Prieto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UK - Brighton & Sussex University Hospitals NHS Trust
name: Sumita Verma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NY - Montefiore Medical Center
name: Paul J Gaglio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario de Valme
name: Manuel Romero-Gomez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NC - Carolinas Medical Center
name: Andrew deLemos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UK - Doncaster Royal Infirmary
name: Joanna Sayer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: GA - Piedmont Atlanta Hospital
name: Lance Stein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario Marques de Valdecilla
name: Javier Crespo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: DC - Georgetown University Hospital
name: Rohit Satoskar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: WI - Aurora St. Luke's Medical Center
name: David J Kramer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PA - Drexel University College of Medicine
name: David Reich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: WA - Swedish Medical Center
name: Anne M Larson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: FL - Cleveland Clinic Florida
name: Xaralambos Zervos, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: MD - Johns Hopkins University Hospital
name: Kirti Shetty, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PA - Albert Einstein Medical Center
name: Simona Rossi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: GA - Emory University Hospital
name: Ram Subramanian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CA - University of California San Diego
name: Alexander Kuo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OH - Cleveland Clinic Foundation
name: Talal Adhami, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario de Cruces
name: Maria Jesús Suárez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NJ - Rutgers University Hospital
name: Nikolaos T Pyrsopoulos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: TX - University of Texas Health Science Center, San Antonio
name: Julio Gutierrez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AR - University of Arkansas for Medical Sciences
name: Andres Duarte-Rojo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Spain - Hospital Universitario Ramón y Cajal
name: Agustín Albillos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MA - Beth Israel Deaconess Medical Center
name: Raza Malik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germany - Medizinische Hochschule Hannover
name: Markus Busch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NY - North Shore University Hospital
name: Anupama Duddempudi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NE - University of Nebraska Medical Center
name: Marco Antonio Olivera-Martinez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germany - Charité Campus Virchow-Klinikum Medizinische Klinik
name: Eckart Schott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.