A Multi-Center Study of the Safety and Efficacy of N-Acetylcysteine in ALF
Information source: University of Texas Southwestern Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Liver Failure; Fulminant Hepatic Failure
Intervention: N-acetylcysteine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: University of Texas Southwestern Medical Center Official(s) and/or principal investigator(s):
William M Lee, MD, Principal Investigator, Affiliation: University of Southwestern Medical Center
Summary
The present proposal is to expand and continue the double blind, randomized trial of
N-acetylcysteine vs. placebo for the treatment of non-acetaminophen ALF, to test the safety
and efficacy of a short course (72 hours) of intravenous N-acetylcysteine in patients with
acute liver failure for whom no antidote or other specific treatment is available.
Clinical Details
Official title: A Multi-Center Study of the Safety and Efficacy of N-Acetylcysteine in the Treatment of Acute Liver Failure Not Caused by Acetaminophen in Adult Patients
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: The primary outcome is to compare all patients who survive (with or without
transplant) to those who die.
Secondary outcome: 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).
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 be stratified according to
coma grade (I-II vs. III-IV) and randomized to receive in blinded fashion by intravenous
route, either 5% dextrose in water or a solution of 5% dextrose in water containing
N-acetylcysteine, beginning at a dose of 150 mg/kg bodyweight in 200 ml 5% dextrose over one
hour, and in declining doses over a total of 72 hours (37). Patients randomized to placebo
will receive volume-matched 5% dextrose infusions. Care of patients and consideration of
transplantation or other clinical decisions will not be affected by the study or the use of
study drug or placebo.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Written Informed consent from patient's next of kin
- Altered mentation of any degree (encephalopathy)
- Evidence of moderately severe coagulopathy (INR ≥ 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 or the HELLP syndrome
- ALF thought secondary to intrahepatic malignancy
- Cerebral herniation
- Intractable arterial hypotension
- Severe sepsis (temperature >39º C and/or significant bacteremia) present at the time
of enrollment
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35294, United States
University of California, Davis, Sacramento, California 95817, United States
University of California, Los Angeles, Los Angeles, California 90095, United States
University of California, San Diego, San Diego, California 92103, United States
University of California, San Francisco, San Francisco, California 94143, United States
Mayo Clinic, Jacksonville, Jacksonville, Florida 32216, United States
Northwestern University Medical School, Chicago, Illinois 60611, United States
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States
Mayo Clinic, Rochester, Rochester, Minnesota 55905, United States
University of Nebraska, Omaha, Nebraska 68198, United States
Mount Sinai School of Medicine, New York, New York 10029, United States
New York Presbyterian Hospital (Columbia and Cornel), New York, New York 10032, United States
Duke University Medical Center, Durham, North Carolina 27710, United States
Oregon Health Sciences University, Portland, Oregon 97239, United States
Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, United States
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States
Medical University of South Carolina, Charleston, South Carolina 29425, United States
University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States
Baylor University Medical Center, Dallas, Texas 75246, United States
Virginia Commonwealth University, Richmond, Virginia 23298, United States
University of Washington, Seattle, Washington 98195, United States
Additional Information
Starting date: August 1998
Ending date: November 2006
Last updated: December 21, 2007
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