Randomized Study of Acetylcysteine in Patients With Acute Liver Failure Not Caused by Acetaminophen
5 other identifiers
interventional
173
1 country
25
Brief Summary
OBJECTIVES: I. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific treatment is available.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jun 1998
Longer than P75 for phase_3
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 1998
CompletedFirst Submitted
Initial submission to the registry
October 18, 1999
CompletedFirst Posted
Study publicly available on registry
October 19, 1999
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2006
CompletedOctober 13, 2017
October 1, 2017
8.4 years
October 18, 1999
October 11, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival rate
3 weeks
Secondary Outcomes (4)
Survival without liver transplantation (Spontaneous Survival
3 weeks
Transplant rate
3 weeks
Length of hospital stay
3 weeks
Number of organ systems showing failure
3 weeks
Study Arms (2)
Placebo
PLACEBO COMPARATORN-acetylcysteine (NAC)
EXPERIMENTALInterventions
Infusion of 5% dextrose with N-acetylcysteine with an initial loading dose of 150 mg/kg/h of NAC over 1 hour, followed by 12.5 mg/kg/h for 4 hours, then continuous infusions of 6.25 mg/kg/h for the remaining 67 hours.
Eligibility Criteria
You may qualify if:
- This is a phase III blinded study, which will involve approximately 200 patients. For this purpose, acute liver failure will be defined as onset of any mental status alteration and coagulopathy (INR \> 1.5) within 26 weeks of onset of a hepatitic illness, with no evidence of underlying chronic liver disease. Eligible patients will be those 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 or those who evolve to altered mentation if already in the hospital. All subjects will be between 18 and 70 years. Patients transferred from referring hospitals to a study site may be considered for enrollment, provided that no other specific treatment protocol has begun, and that no liver support device (bioartificial liver (BAL), extracorporeal liver assist device (ELAD), transgenic pig perfusion) has been used or is contemplated. Use of fresh frozen plasma infusions will not disqualify patients from participation.
You may not qualify if:
- Patients less than age 18 or over 70 years of age.
- ALF patients where acetaminophen or mushroom poisoning is assessed or Suspected to be a significant contributing or sole cause of the illness. Both these diagnoses require specific antidote therapy, including NAC in the case of acetaminophen, rather than randomized or non-specific treatment.
- Patients with a diagnosis of shock liver (ischemic hepatopathy), since the overall outcome for these patients in largely determined by the underlying etiology of the condition leading to shock. Heat stroke is not excluded.
- Acute liver failure of pregnancy or the HELLP syndrome (pregnancy associated hemolysis and coagulopathy). The effect of NAC on the fetus or the mother has not been determined; in addition, pregnancy-related liver diseases usually mandate rapid delivery of the infant.
- ALF thought secondary to intrahepatic malignancy. Patients with hepatic malignancy experiencing ALF have 100% mortality and are not transplant candidates.
- Patients who exhibit signs of cerebral herniation at the time of enrollment.
- Patients who demonstrate the presence of intractable arterial hypotension (arterial systolic blood pressure equal to or below 70 mmHg) present, or require inotropic drugs at the time of enrollment.
- Severe sepsis (temperature \>39o C and/or significant bacteremia) present at the time of enrollment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
University of Alabama at Birmingham
Birmingham, Alabama, 35294-0005, United States
Mayo Clinic
Scottsdale, Arizona, 85259, United States
University of California Los Angeles
Los Angeles, California, 90024, United States
University of California Davis
Sacramento, California, 95817, United States
University of California San Diego
San Diego, California, 92103-0707, United States
University of California San Francisco
San Francisco, California, 94115, United States
Mayo Clinic
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 Health Systems
Ann Arbor, Michigan, 48109, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198-3330, United States
Mount Sinai Medical Center, NY
New York, New York, 10029, United States
New York Presbyterian Hospital
New York, New York, 10032-3784, United States
Duke University Medical Center
Durham, North Carolina, 27715, United States
Oregon Health Sciences University
Portland, Oregon, 97201-3098, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, 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 at Dallas
Dallas, Texas, 75235-8897, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
Virginia Commonwealth University
Richmond, Virginia, 23298-0341, United States
University of Washington Medical Center
Seattle, Washington, 98195-6043, United States
Related Publications (3)
Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ 2nd, Murray NG, McCashland T, Reisch JS, Robuck PR; Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009 Sep;137(3):856-64, 864.e1. doi: 10.1053/j.gastro.2009.06.006. Epub 2009 Jun 12.
PMID: 19524577RESULTStravitz RT, Fontana RJ, Karvellas C, Durkalski V, McGuire B, Rule JA, Tujios S, Lee WM; Acute Liver Failure Study Group. Future directions in acute liver failure. Hepatology. 2023 Oct 1;78(4):1266-1289. doi: 10.1097/HEP.0000000000000458. Epub 2023 May 16.
PMID: 37183883DERIVEDSingh S, Hynan LS, Rule JA, Lee WM. Changes in alpha-foetoprotein and Gc-globulin in relation to outcomes in non-acetaminophen acute liver failure. Liver Int. 2019 Dec;39(12):2368-2373. doi: 10.1111/liv.14216. Epub 2019 Sep 10.
PMID: 31421008DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
William M. Lee, MD
University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
October 18, 1999
First Posted
October 19, 1999
Study Start
June 1, 1998
Primary Completion
November 1, 2006
Study Completion
November 1, 2006
Last Updated
October 13, 2017
Record last verified: 2017-10