Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Acute on Chronic Hepatitis

Phase 2

Completed

• Conditions: Acute On Chronic Hepatitis
• Interventions: Biological: ELAD plus standard of care treatment; Other: Standard of care

• Registration Number: NCT00973817
• Lead Sponsor: Vital Therapies, Inc.

Brief Summary

The purpose of this study is to investigate the safety and efficacy of the use of ELAD in patients with diagnosed Acute On Chronic Hepatitis, including Acute Alcoholic Hepatitis.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-02
• Study First Submitted QC: 2009-09-07
• Study First Posted: 2009-09-09
• Primary Completion: 2011-04
• Study Completion: 2011-05
• Disposition First Submitted: 2012-07-24
• Disposition First Submitted QC: 2012-07-24
• Disposition First Posted: 2012-08-01
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-01
• Last Update Posted: 2013-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

• Age >/= 18</= 67 years; AND
• Acute decompensation of chronic liver disease over the preceding 30 days; AND
• MELD score between 18 and 35, inclusive; AND
• Subject or designated representative must provide Informed Consent

Exclusion Criteria

• Platelets <50,000mm at baseline; OR

• Evidence of chronic renal failure as defined by a serum creatinine >/= 2.5mg/dL as measured during the 1-6 month period prior to study entry. (Subject is not excluded with a creatinine >2.5 mg/dL if deemed to be type-1 hepato-renal syndrome); OR

• Contraindication to renal replacement therapy (hemodialysis or hemofiltration); OR

• International Normalization Ratio (INR) > 3.5; OR

• Septic shock as defined by a positive blood culture and two or more of the following:

  • Systolic blood pressure <90mmHg OR mean arterial pressure <60mmHg;
  • Tachypnea > 20 breaths per minute OR a PaCO2<32 mmHg;
  • White blood cell count < 4000 cell/mm3 OR > 12000 cell/mm3 (<4 x 10(9) or >12 x 10(9) cells/L).

• Evidence of major hemorrhage as indicated by:

  • requiring >/= 4 units packed red blood cells within a 48 hour period prior to Screening, OR
  • hemodynamic instability (sustained pulse > 120 beats/min AND systolic blood pressure < 100 mmHg over one hour)

Subjects with a recent history of gastrointestinal hemorrhage who have been successfully treated and remain hemodynamically stable for a period of 48 hours will then be eligible for the study if the investigator determines the subject to be at low risk for rebleeding; OR

• Evidence (by physical exam, history or lab evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome; OR
• Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis; OR
• Evidence of spontaneous bacterial peritonitis with uncontrolled infection; OR
• Evidence of brain death as determined by blood flow studies positive for herniation AND/OR absence of pupillary reflex; OR
• Systolic blood pressure <85 mmHg OR MAP <50mmHg at baseline; OR
• Requirement for escalating doses of vasopressor support OR of an alpha-adrenergic agent for one hour or longer AND evidence of hemodynamic instability; OR
• Subject at maximum vasopressor dose at Screen; OR
• Clinical or radiographic evidence of a new stroke or intracerebral bleeding; OR
• Seizures uncontrolled by medication; OR
• Acute myocardial infarction based on clinical and/or electrocardiographic evidence; OR
• Lung disease defined by a PaO2<60mmHg on room air, acute respiratory distress syndrome, or a history of severe COPD or interstitial lung disease; OR
• Pregnancy as determined by beta-HCG results or lactation; OR
• Participation in another investigational drug, biologic, or device study within 1 month of enrollment. Subjects enrolled in an observational study will be eligible for this trial.
• Previous liver transplant.
• Previous participation in a clinical trial involving ELAD.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ELAD	ELAD plus standard of care treatment	Use of ELAD for up to 6 days to stabilize liver function plus standard of care treatment plus standard of care treatment. Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)
ELAD	Standard of care	Use of ELAD for up to 6 days to stabilize liver function plus standard of care treatment plus standard of care treatment. Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)
Standard of care	Standard of care	Standard of care for acute on chronic hepatitis patients including medications and treatments typically given to patients admitted with acute hepatitis (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)

Primary Outcome Measures

Name	Time	Method
Time to progression at which a 5-point or greater Model for End stage Liver Disease (MELD) score is recorded relative to baseline	From Baseline up to Study Day 91	This is based on death or the first observed increase of at least 5 points from Baseline MELD score (whichever occurs earlier) at least 24 hours after the ELAD® Treatment Period is ended and up to Study Day 91 (90 days following Baseline).

Secondary Outcome Measures

Name	Time	Method
Time to progression at which a 5-point or greater MELD score is recorded relative to baseline	From Baseline up to Study Day 91	A secondary Overall Survival analysis will use the same methodology as the primary time to progression efficacy analysis, except that an event will be defined as death. Secondary efficacy analyses will evaluate the proportion of progression free survivors (MELD score increased less than 5 points relative to the Baseline MELD score).

Trial Locations

Locations (21)

University Hospitals Birmingham; 🇬🇧 Birmingham, England, United Kingdom

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Albert Einstein Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Univ. of Rochester, Strong Memorial Hospital; 🇺🇸 Rochester, New York, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

New York University Medical Center; 🇺🇸 New York, New York, United States

Drexel University College of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Westchester Medical Center; 🇺🇸 Valhalla, New York, United States

Temple University; 🇺🇸 Philadelphia, Pennsylvania, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

The Liver Institute at Methodist Dallas Medical Center; 🇺🇸 Dallas, Texas, United States

Royal Derby Hospital; 🇬🇧 Derby, United Kingdom

Edinburgh Royal Infirmary; 🇬🇧 Edinburgh, United Kingdom

St. James University Hospital; 🇬🇧 Leeds, United Kingdom

Royal Free Hospital London; 🇬🇧 London, United Kingdom

Kings College Hospital NHS Foundation Trust; 🇬🇧 London, England, United Kingdom

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States