Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)

NCT01875874 | Terminated Phase 2 Results DMC

• 1 other identifier: VTI-212
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 18

Brief Summary

This phase 2 study is developed to evaluate the effect of ELAD on overall survival (OS) in subjects with acute liver failure (ALF) compared to matched historical controls.

Conditions

Acute Liver Failure; Fulminant Hepatic Failure; Primary Graft Non-Function; Surgically-Induced Liver Failure

Keywords

liver failure; acute liver failure; fulminant hepatic failure; primary graft non-function; surgically-induced liver failure; ELAD; ALF; FHF; PNF

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) of ALF Subjects

  Study Day 1 through Study Day 28

Secondary Outcomes (1)

• Number of Subjects Who Survived at the End of Study Day 28 or Who Received Orthotopic Liver Transplantation on or Before That Study Day.

  Study Day 1 through Study Day 28

Study Arms (1)

ELAD plus standard of care

EXPERIMENTAL

Continuous ELAD treatment for a minimum of 3 days to a maximum of 10 days in addition to a standard of care for subjects with acute liver failure.

Biological: ELAD

Interventions

ELAD BIOLOGICAL

Continuous treatment with the ELAD System for a minimum of 3 days to a maximum of 10 days. The subject's ultrafiltrated blood is circulated through 4 cartridges, each containing approximately 110 grams of C3A cells (approximately 440 grams total).

Also known as: Human Cell-Based Bio-Artificial Liver Support System

ELAD plus standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight ≥ 40 kg;
• Age ≥ 18;
• Diagnosis of ALF attributed to one of the following:
• FHF (acute liver failure with no preexisting liver disease, see below);
• Primary Graft Non-Function (PNF);
• Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery);
• Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours;
• Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E.
• Subjects with FHF must meet one of the following criteria:
• Known acetaminophen ingestion or diagnostic serum level, and at least one of the following:
• Prothrombin time (PT) \> 100 seconds \[International Normalized Ratio (INR) \> 6.5\], OR
• Encephalopathy Grade 3 or 4 AND ARTERIAL AMMONIA \>100 umol/liter and at least one of the following:
• i. Arterial pH \< 7.30 at ≥ 24 hours after drug ingestion or volume resuscitation; ii. Renal failure documented by urine output \< 0.5 mL/kg/hr over the preceding 12 hours; iii. Creatinine \> 2.5 mg/dL; OR
• Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia \>100 umol/liter, and at least two of the following:
• Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF

You may not qualify if:

• Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment;
• Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) indicated by any of the following:
• Presence of sepsis or septic shock; OR
• Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Enrollment; OR
• Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR
• Clinical and radiological signs of pneumonia.
• Portal hypertension;
• Liver dysfunction due to trauma;
• Irreversible brain death;
• Platelet count \< 30,000/mm3 \[NOTE: Subject may be included at the physician's discretion if platelet count exceeds 30,000/mm3 at time of initiation of therapy (even if the value is following platelet transfusion) and can be managed through the administration of blood products\]
• Cardiovascular sepsis-related organ failure assessment score (SOFA score) \>3;
• Stroke or intracranial hemorrhage;
• Seizures uncontrolled by medication;
• Acute myocardial infarction;
• Lung disease defined by a partial pressure of oxygen measurement (PaO2) ≤60 mmHg or a fraction of inspired oxygen (FiO2) ≥0.6, not corrected by medical management \[including continuous venovenous hemofiltration (CVVH) if indicated\] and ventilation with a Positive End Expiratory Pressure (PEEP) of \>8cm H2O;

Sponsors & Collaborators

• Vital Therapies, Inc.: lead

Study Sites (18)

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Cleveland Clinic Floriday

Weston, Florida, 33331, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Medical Center - Twin Cities Campus

Minneapolis, Minnesota, 55455, United States

Location

Rutgers University Hospital

Newark, New Jersey, 07102, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Methodist Dallas Medical Center - The Liver Institute

Dallas, Texas, 75203, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Related Links

• Vital Therapies, Inc. website

MeSH Terms

Conditions

Liver Failure, Acute; Liver Failure

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Limitations and Caveats

This study was terminated early, after enrollment of only 8 out of 40 planned subjects, due to findings from previous VTI-208 study. Thus, sample size of VTI-212 was very small leading to statistical analyses that cannot be meaningfully interpreted.

Results Point of Contact

• Title: Robert Ashley
• Organization: Vital Therapies, Inc.

rashley@vitaltherapies.com

858-673-6840

Study Officials

• Jan Stange, MD, Ph.D.

  Vital Therapies, Inc.

  STUDY CHAIR

• Parvez Mantry, MD

  TX - Methodist Dallas Medical Center - The Liver Institute

  PRINCIPAL INVESTIGATOR

• David J Reich, MD

  PA - Drexel University College of Medicine

  PRINCIPAL INVESTIGATOR

• Paul J Gaglio, MD

  NY - Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Juan Gallegos-Orozco, MD

  UT - University of Utah

  PRINCIPAL INVESTIGATOR

• Angel Alsina, MD

  FL - Tampa General Hospital

  PRINCIPAL INVESTIGATOR

• Lewis W Teperman, MD

  NY - New York University Medical Center

  PRINCIPAL INVESTIGATOR

• Nikunj Shah, MD

  IL - Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• Julie Thompson, MD

  MN - University of Minnesota Medical Center - Twin Cities Campus

  PRINCIPAL INVESTIGATOR

• Winfred W Williams, Jr., MD

  MA - Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Lance Stein, MD

  GA - Piedmont Atlanta Hospital

  PRINCIPAL INVESTIGATOR

• Ram Subramanian, MD

  GA - Emory University Hospital

  PRINCIPAL INVESTIGATOR

• Nikolaos T Pyrsopoulos, MD

  NJ - Rutgers University Hospital

  PRINCIPAL INVESTIGATOR

• Marquis Hart, MD

  WA - Swedish Medical Center

  PRINCIPAL INVESTIGATOR

• Rohit Satoskar, MD

  DC - Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

• Talal Adhami, MD

  OH - Cleveland Clinic Foundation

  PRINCIPAL INVESTIGATOR

• Linda S Sher, MD

  CA - Keck Hospital of USC

  PRINCIPAL INVESTIGATOR

• Xaralambos Zervos, DO

  FL - Cleveland Clinic Florida

  PRINCIPAL INVESTIGATOR

• Kalyan R Bhamidimarri, MD

  FL - University of Miami Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2013
• First Posted: June 12, 2013
• Study Start: October 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2018
• Last Updated: February 12, 2019
• Results First Posted: August 22, 2018

Record last verified: 2019-01

Locations

US (18)