Clinical trial NCT00896025: Study of N-Acetylcysteine in Acute Liver Failure (ALF)
Official title: A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Liver Failure
Fulminant Hepatic Failure
Keywords: Liver disease
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-05-11
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Open label-comparator is historical data.
Primary purpose: TREATMENT

Brief summary: This proposed study is a multi-center open label study to determine if N-acetylcysteine has any survival benefits in patients with acute liver failure.

Detailed description: Patients admitted to study sites with carefully defined criteria for acute liver failure and who are thought not to have acetaminophen toxicity, mushroom poisoning, pregnancy-related liver failure, or malignancy will be eligible. Each patient will receive intravenously in solution of 5% dextrose in water containing N-acetylcysteine, beginning at a dose of 150 mg/kg bodyweight in 250 ml 5% dextrose over one hour, and in declining doses over a total of 72 hours. Care of patients and consideration of transplantation or other clinical decisions will not be affected by the study or the use of study drug.

Eligibility criteria: Inclusion Criteria:

* Written Informed consent from patient's next of kin
* Altered mentation of any degree (encephalopathy)
* Evidence of moderately severe clotting abnormalities (international normalized ratio ≥ 1.5)
* A presumed acute illness onset of less than 26 weeks
* Admitted to study site hospital intensive care units with acute liver failure and who can be evaluated and started on treatment within the first 24 hours of hospitalization
* All subjects will be between 18 and 70 years
* The NIH guidelines on the inclusion of women and minorities as subjects will be observed

Exclusion Criteria:

* Patients less than age 18 or over 70 years of age
* Acetaminophen or mushroom poisoning induced liver failure
* Patients with a diagnosis of shock liver (ischemic hepatopathy)
* Acute liver failure of pregnancy
* Acute liver failure thought secondary to intra-hepatic malignancy
* Cerebral herniation
* Intractable arterial hypotension
* Severe sepsis (temperature \>39º C and/or significant bacteremia) present at the time of enrollment

Primary outcomes:
measure: Survival Rate With or Without Transplant
timeFrame: 3 Weeks
measure: Survival Rate With or Without Transplant
timeFrame: 1-year follow-up
measure: Survival Rate With or Without Transplant
timeFrame: 2-year follow-up
Secondary outcomes:
measure: To Compare Patients Who Survive Without Transplantation to All Other Patients Enrolled in This Study (Those Who Receive a Transplant and Live, Those Who Receive a Transplant and Die, or Those Who Die Before Transplantation).
timeFrame: 3 Week follow-up
measure: To Compare Patients Who Survive Without Transplantation to All Other Patients Enrolled in This Study (Those Who Receive a Transplant and Live, Those Who Receive a Transplant and Die, or Those Who Die Before Transplantation).
timeFrame: 1-year follow-up
measure: To Compare Patients Who Survive Without Transplantation to All Other Patients Enrolled in This Study (Those Who Receive a Transplant and Live, Those Who Receive a Transplant and Die, or Those Who Die Before Transplantation).
timeFrame: 2-year follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital (Columbia and Cornel)
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: UT Southwestern Medical Center at Dallas
name: William M Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: