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Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) System in Patients With Hepatic Insufficiency (ELAD)

Primary Purpose

Acute Hepatitis, Chronic Hepatitis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ELAD plus standard of care treatment

Standard of care treatment

About this trial

This is an interventional treatment trial for Acute Hepatitis focused on measuring Hepatitis, acute, Acute Hepatitis OR Chronic Hepatitis

Eligibility Criteria

19 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Weight >40 kilograms
Age >18 and <70 years
Acute decompensation of cirrhosis over the preceding 48-72 hour period
Up to 4 weeks from symptom onset to presentation
Presence of a precipitating event
Either a MELD score of ≥32, or ≥24 with one or more of the following
- Severe encephalopathy of grade 3 or 4 on the Westhaven scale
- Renal dysfunction typical of type-1 hepato-renal syndrome, i.e. acute renal failure without evidence of elevated serum creatinine (>2.5mg/dL) during the 1 to 6 months prior to study entry. Serum creatinine at study entry >2.5mg/dL does not exclude the subject from enrolment
SOFA score ≥9 at the initial Screening Visit

Exclusion Criteria:

Platelets <50,000 or reducing to <80,000 over a 72 hour period
Renal failure: Serum creatinine ≥2.5 mg/dL as measured during the 1 - 6 month period prior to study entry. If a subject has a contraindication to renal replacement therapy (hemodialysis or hemofiltration), then the subject should be excluded from entry into the study
Active sepsis. Sepsis will be defined as positive microbiological culture, ascitic white cell count >450 cells/mm³ (or ascitic neutrophil count >250 cells/mm³), or clinical signs and chest x-ray appearances for at least 48 hours without clinical improvement prior to randomization, or other evidence of infection not under control
Evidence of major hemorrhage indicated by requiring ≥ 4 unit blood transfusion within a 24 hour period, 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
Evidence (by physical exam, history, or laboratory evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, fatty-liver disease of non-alcoholic origin, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome;
Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis
Evidence of Small Bowel Perforation within 48 hours of treatment;
Evidence of brain death as determined by blood flow studies positive for herniation and/or absence of pupillary reflex
Mean Arterial Pressures (MAP) < 50 mm Hg for one hour or longer;
Requirement for escalating doses of vasopressor support of an alpha-adrenergic agent for one hour or longer and evidence of hemodynamic instability;
Clinical or radiographic evidence of a new stroke or intracerebral bleeding
Seizures uncontrolled by medication
Acute myocardial infarction based on clinical and/or electrocardiographic evidence
Lung disease defined by a PaO2 <60 mm Hg or a history of severe COPD or interstitial lung disease
Pregnancy as determined by βHCG results, or lactation
Participation in another investigational drug, biologic, or device study within one month of enrollment

Sites / Locations

Scripps Clinic
California Pacific Medical Center
University of Chicago Medical Center
Massachusetts General Hospital
University of Michigan Hospital
Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

ELAD (plus Standard of Care)

Standard of Care (Control)

Arm Description

Treatment with ELAD in addition to standard of care therapy Standard of care therapy defines uniform treatment for ascites, esophageal varices, dietary recommendations, etc.

Standard of care treatment Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)

Outcomes

Primary Outcome Measures

To provide evidence that (1) subjects treated with ELAD have a higher 30-day transplant-free survival in subjects with AOCH than those not treated with ELAD, and (2) it is safe when used for 3 to 10 days of treatment.

Secondary Outcome Measures

Full Information

NCT ID

NCT00771446

First Posted

October 9, 2008

Last Updated

April 5, 2013

Sponsor

Vital Therapies, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00771446

Brief Title

Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) System in Patients With Hepatic Insufficiency

Acronym

ELAD

Official Title

Safety & Efficacy of the Extracorporeal Liver Assist Device (ELAD) in Patients With Acute on Chronic Hepatitis (AOCH)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2013

Overall Recruitment Status

Completed

Study Start Date

October 2008 (undefined)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vital Therapies, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Evaluate on how well the ELAD system works in treating people with liver failure.

Detailed Description

This is a multicenter, open-label, randomized, concurrent control study of subjects with acute on chronic hepatitis. Subjects meeting the eligibility requirements of the study will be randomly assigned in a 2:1 ratio to receive either standard medical therapy for acute liver failure plus the ELAD system, or standard medical therapy alone, with the latter defined as conventional therapy for acute on chronic hepatitis determined to be clinically appropriate by the treating physician. Immediately prior to treatment initiation, subject eligibility will be confirmed. Treatment with ELAD will continue for a minimum of 3 days and up to a maximum of 10 days or until clinical status improves relative to study entry. Subjects will be followed until 30 days has elapsed since study enrollment (control) or 30 days has elapsed since cessation of ELAD therapy (ELAD group), whichever comes first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Hepatitis, Chronic Hepatitis

Keywords

Hepatitis, acute, Acute Hepatitis OR Chronic Hepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ELAD (plus Standard of Care)

Arm Type

Experimental

Arm Description

Treatment with ELAD in addition to standard of care therapy Standard of care therapy defines uniform treatment for ascites, esophageal varices, dietary recommendations, etc.

Arm Title

Standard of Care (Control)

Arm Type

Other

Arm Description

Intervention Type

Biological

Intervention Name(s)

ELAD plus standard of care treatment

Intervention Description

ELAD is a liver assist system - Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)

Intervention Type

Other

Intervention Name(s)

Standard of care treatment

Intervention Description

Standard of care for acute liver failure patients including medications and treatments typically given to these patients (Pentoxifylline, corticosteroids, abdominal paracentesis, nutritional therapy, etc., if indicated)

Primary Outcome Measure Information:

Title

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Weight >40 kilograms Age >18 and <70 years Acute decompensation of cirrhosis over the preceding 48-72 hour period Up to 4 weeks from symptom onset to presentation Presence of a precipitating event Either a MELD score of ≥32, or ≥24 with one or more of the following Severe encephalopathy of grade 3 or 4 on the Westhaven scale Renal dysfunction typical of type-1 hepato-renal syndrome, i.e. acute renal failure without evidence of elevated serum creatinine (>2.5mg/dL) during the 1 to 6 months prior to study entry. Serum creatinine at study entry >2.5mg/dL does not exclude the subject from enrolment SOFA score ≥9 at the initial Screening Visit Exclusion Criteria: Platelets <50,000 or reducing to <80,000 over a 72 hour period Renal failure: Serum creatinine ≥2.5 mg/dL as measured during the 1 - 6 month period prior to study entry. If a subject has a contraindication to renal replacement therapy (hemodialysis or hemofiltration), then the subject should be excluded from entry into the study Active sepsis. Sepsis will be defined as positive microbiological culture, ascitic white cell count >450 cells/mm³ (or ascitic neutrophil count >250 cells/mm³), or clinical signs and chest x-ray appearances for at least 48 hours without clinical improvement prior to randomization, or other evidence of infection not under control Evidence of major hemorrhage indicated by requiring ≥ 4 unit blood transfusion within a 24 hour period, 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 Evidence (by physical exam, history, or laboratory evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, fatty-liver disease of non-alcoholic origin, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome; Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis Evidence of Small Bowel Perforation within 48 hours of treatment; Evidence of brain death as determined by blood flow studies positive for herniation and/or absence of pupillary reflex Mean Arterial Pressures (MAP) < 50 mm Hg for one hour or longer; Requirement for escalating doses of vasopressor support of an alpha-adrenergic agent for one hour or longer and evidence of hemodynamic instability; Clinical or radiographic evidence of a new stroke or intracerebral bleeding Seizures uncontrolled by medication Acute myocardial infarction based on clinical and/or electrocardiographic evidence Lung disease defined by a PaO2 <60 mm Hg or a history of severe COPD or interstitial lung disease Pregnancy as determined by βHCG results, or lactation Participation in another investigational drug, biologic, or device study within one month of enrollment

Overall Study Officials: