TerminatedNCT01829347Updated Feb 19, 2019Results posted

To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

A Phase 3 interventional study of ELAD and Standard of Care treatment in Severe Acute Alcoholic Hepatitis, sponsored by Vital Therapies, Inc.. Terminated at 39 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-19.

Sponsored by Vital Therapies, Inc. · Phase 3, Interventional, and Treatment

Why this study was terminated

Due to results from the VTI-208 study, the ELAD plan is being re-evaluated.

Phase: Phase 3
Study type: Interventional
Enrollment: 18
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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).

Read the 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.

Conditions studied

Severe Acute Alcoholic Hepatitis

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Keywords

liver failure
acute alcoholic hepatitis
patients failing steroid therapy
alcoholic hepatitis
steroid failure
Lille criteria
ELAD

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 18 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Vital Therapies, Inc. is the lead sponsor of 8 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

Experimental
ELAD (plus Standard of Care)
ELAD is a human cell-based bio-artificial liver support system developed to improve survival of patients with acute liver failure and to provide liver support continuously to a subject with compromised liver function. Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.
Biological: ELAD · Other: Standard of Care treatment
Other
Standard of Care (Control)
Standard of care is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.
Other: Standard of Care treatment

Interventions

BiologicalELAD
ELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2.
Also known as: Human Cell-Based Bio-Artificial Liver Support System
OtherStandard of Care treatment
Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.
Also known as: Usual treatment for the disease

What researchers measure

Primary outcomes

Overall Survival
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).
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

Proportion of Survivors at Study Day 91.
Assess the proportion of survivors at Study Day 91.
Time frame: Up to Study Day 91.

Results

Posted Feb 19, 2019

Limitations and caveats

This study was terminated early after enrollment of only 18 out of 150 planned subjects due to findings from previous VTI-208 study. Thus, sample size of VTI-210 was very small leading to statistical analyses that cannot be meaningfully interpreted.

Participant flow

VTI-210

Participant flow — VTI-210
Milestone	ELAD (Plus Standard of Care)	Standard of Care (Control)
Started	9	9
Completed	3	6
Not completed	6	3
Withdrew: Death	5	3
Withdrew: Withdrawal by subject	1	0

VTI-210E

Participant flow — VTI-210E
Milestone	ELAD (Plus Standard of Care)	Standard of Care (Control)
Started	3	6
Completed	0	0
Not completed	3	6
Withdrew: Death	2	1
Withdrew: Study terminated prematurely	1	5

Outcome measures

PrimaryOverall Survival

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).

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
Reported as:: Count of participants · Participants

Overall Survival
Participants	ELAD (Plus Standard of Care)	Standard of Care (Control)
Overall Survival	2	5

Statistical analysis

ELAD (Plus Standard of Care) vs Standard of Care (Control) · Log Rank · p = 0.076 · Hazard ratio (hr): 0.310 · 95% CI 0.085 to 1.133

SecondaryProportion of Survivors at Study Day 91.

Assess the proportion of survivors at Study Day 91.

Time frame:: Up to Study Day 91.
Reported as:: Count of participants · Participants

Proportion of Survivors at Study Day 91.
Participants	ELAD (Plus Standard of Care)	Standard of Care (Control)
Proportion of Survivors at Study Day 91.	5	6

Statistical analysis

ELAD (Plus Standard of Care) vs Standard of Care (Control) · Fisher Exact · p = 1.000

Adverse events

Collected over Randomization through Study Day 91.. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
ELAD (Plus Standard of Care)	7/9 (77.8%)	6/9 (66.7%)	9/9 (100%)
Standard of Care (Control)	4/9 (44.4%)	5/9 (55.6%)	9/9 (100%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	ELAD (Plus Standard of Care)	Standard of Care (Control)
Cardiac arrestCardiac disorders	0/9	1/9
AscitesGastrointestinal disorders	0/9	1/9
Gastrointestinal haemorrhageGastrointestinal disorders	1/9	0/9
MelaenaGastrointestinal disorders	1/9	0/9
Alcoholic liver diseaseHepatobiliary disorders	0/9	1/9
Hepatitis alcoholicHepatobiliary disorders	1/9	1/9
Peritonitis bacterialInfections and infestations	0/9	1/9
SepsisInfections and infestations	1/9	0/9
Septic shockInfections and infestations	1/9	0/9
Fluid retentionMetabolism and nutrition disorders	1/9	0/9

Most frequent other events

Showing 10 of 104

Most frequent other events
Event	ELAD (Plus Standard of Care)	Standard of Care (Control)
AnaemiaBlood and lymphatic system disorders	7/9	2/9
HypotensionVascular disorders	6/9	1/9
AscitesGastrointestinal disorders	3/9	4/9
Abdominal painGastrointestinal disorders	3/9	1/9
Generalised oedemaGeneral disorders	3/9	0/9
Oedema peripheralGeneral disorders	3/9	3/9
BacteraemiaInfections and infestations	3/9	2/9
Hepatic encephalopathyNervous system disorders	3/9	1/9
DyspnoeaRespiratory, thoracic and mediastinal disorders	3/9	0/9
CoagulopathyBlood and lymphatic system disorders	2/9	1/9

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
<=18 years	0	0	0
Between 18 and 65 years	9	9	18
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
Mean	46.1 ± 7.29	50.0 ± 9.79	48.1 ± 8.61

Sex: Female, Male
Sex: Female, Male(Participants)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
Female	6	3	9
Male	3	6	9

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	9	9	18
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
United States	4	1	5
United Kingdom	2	2	4
Spain	3	6	9

Baseline MELD Score
Baseline MELD Score(MELD Score)	ELAD (Plus Standard of Care)	Standard of Care (Control)	Total
Mean	27.531 ± 2.8870	26.323 ± 2.8524	26.962 ± 2.8484

Study locations

39 sites

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205, United States
University of California San Diego
San Diego, California 92103, United States
Georgetown University Hospital
Washington, District of Columbia 20007, United States
University of Miami Hospital
Miami, Florida 33136, United States
Cleveland Clinic Florida
Weston, Florida 33331, United States
Piedmont Atlanta Hospital
Atlanta, Georgia 30309, United States
Emory University Hospital
Atlanta, Georgia 30322, United States
Johns Hopkins University Hospital
Bethesda, Maryland 20814, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215, United States
University of Minnesota Medical Center - Twin Cities Campus
Minneapolis, Minnesota 55455, United States
University of Nebraska Medical Center
Omaha, Nebraska 68198, United States
Rutgers University Hospital
Newark, New Jersey 07101, United States
Montefiore Medical Center
Bronx, New York 10467, United States
North Shore University Hospital
Manhasset, New York 11030, United States
Carolinas Medical Center
Charlotte, North Carolina 28204, United States
Cleveland Clinic Foundation
Cleveland, Ohio 44195, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania 19102, United States
Albert Einstein Medical Center
Philadelphia, Pennsylvania 19141, United States
University of Texas Health Science Center, San Antonio
San Antonio, Texas 78215, United States
Swedish Medical Center
Seattle, Washington 98104, United States
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin 53215, United States
Charité Campus Virchow-Klinikum Medizinische Klinik
Berlin, D-13353, Germany
Medizinische Hochschule Hannover
Hannover, D-30625, Germany
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, La Coruña 15706, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, Madrid 28220, Spain
Hospital Universitario de Cruces
Baracaldo, Vizcaya 48903, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Reina Sofia
Cordoba, 14004, Spain
Hospital Gregorio Marañon
Madrid, 28007, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Marques de Valdecilla
Santander, 39008, Spain
Hospital Universitario de Valme
Sevilla, 41014, Spain
Hospital Universitario y Politécnico La Fe
Valencia, 46026, Spain
Barts Health NHS Trust
London, England SE5 9RS, United Kingdom
King's College Hospital NHS Foundation Trust
London, England SE59RS, United Kingdom
Royal Free Hospital
Hampstead, London NW3 2QR, United Kingdom
NHS Tayside
Dundee, Scotland DD1 9SY, United Kingdom
Doncaster Royal Infirmary
Doncaster, South Yorkshire DN2 5LT, United Kingdom
Brighton & Sussex University Hospitals NHS Trust
Brighton, BN2 5BE, United Kingdom

References and documents

Publications

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. PubMed 25009371 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01829347
Lead sponsor: Vital Therapies, Inc.
Responsible party: Sponsor
First posted: Apr 11, 2013
Start date: Apr 2014
Primary completion: Oct 2015
Completion: Sep 2018
Results posted: Feb 19, 2019
Last update: Feb 19, 2019

Study contacts

Jan Stange, MD

study director · Vital Therapies, Inc.

Rajiv Jalan, MD

principal investigator · UK - Royal Free Hospital

Juan Caballeria, MD

principal investigator · Spain - Hospital Clinic de Barcelona

José Luis Montero, MD

principal investigator · Spain - Hospital Reina Sofia

Rafael Bañares, MD

principal investigator · Spain - Hospital Gregorio Marañon

Kalyan R Bhamidimarri, MD

principal investigator · FL - University of Miami Hospital

Julie Thompson, MD

principal investigator · MN - University of Minnesota Medical Center - Twin Cities Campus

Valentin Cuervas-Mons Martinez, MD

principal investigator · Spain - Hospital Universitario Puerta de Hierro - Majadahonda

Santiago Tome, MD

principal investigator · Spain - Hospital Clinico Universitario de Santiago de Compostela

Martín Prieto, MD

principal investigator · Spain - Hospital Universitario y Politécnico La Fe

Sumita Verma, MD

principal investigator · UK - Brighton & Sussex University Hospitals NHS Trust

Paul J Gaglio, MD

principal investigator · NY - Montefiore Medical Center

Manuel Romero-Gomez, MD

principal investigator · Spain - Hospital Universitario de Valme

Andrew deLemos, MD

principal investigator · NC - Carolinas Medical Center

Joanna Sayer, MD

principal investigator · UK - Doncaster Royal Infirmary

Lance Stein, MD

principal investigator · GA - Piedmont Atlanta Hospital

Javier Crespo, MD

principal investigator · Spain - Hospital Universitario Marques de Valdecilla

Rohit Satoskar, MD

principal investigator · DC - Georgetown University Hospital

David J Kramer, MD

principal investigator · WI - Aurora St. Luke's Medical Center

David Reich, MD

principal investigator · PA - Drexel University College of Medicine

Anne M Larson, MD

principal investigator · WA - Swedish Medical Center

Xaralambos Zervos, DO

principal investigator · FL - Cleveland Clinic Florida

Kirti Shetty, MD

principal investigator · MD - Johns Hopkins University Hospital

Simona Rossi, MD

principal investigator · PA - Albert Einstein Medical Center

Ram Subramanian, MD

principal investigator · GA - Emory University Hospital

Alexander Kuo, MD

principal investigator · CA - University of California San Diego

Talal Adhami, MD

principal investigator · OH - Cleveland Clinic Foundation

Maria Jesús Suárez, MD

principal investigator · Spain - Hospital Universitario de Cruces

Nikolaos T Pyrsopoulos, MD

principal investigator · NJ - Rutgers University Hospital

Julio Gutierrez, MD

principal investigator · TX - University of Texas Health Science Center, San Antonio

Andres Duarte-Rojo, MD

principal investigator · AR - University of Arkansas for Medical Sciences

Agustín Albillos, MD

principal investigator · Spain - Hospital Universitario Ramón y Cajal

Raza Malik, MD

principal investigator · MA - Beth Israel Deaconess Medical Center

Markus Busch, MD

principal investigator · Germany - Medizinische Hochschule Hannover

Anupama Duddempudi, MD

principal investigator · NY - North Shore University Hospital

Marco Antonio Olivera-Martinez, MD

principal investigator · NE - University of Nebraska Medical Center

Eckart Schott, MD

principal investigator · Germany - Charité Campus Virchow-Klinikum Medizinische Klinik

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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