Study of N-Acetylcysteine in Acute Liver Failure (ALF) (ONAC)

This study has been terminated.
(The low enrollment did not provide statistical power for any meaningful results.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
William Lee, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00896025
First received: May 8, 2009
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

This proposed study is a multi-center open label study to determine if N-acetylcysteine has any survival benefits in patients with ALF.


Condition Intervention Phase
Acute Liver Failure
Fulminant Hepatic Failure
Drug: N-acetylcysteine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • The Primary Outcome is to Compare All Patients Who Survive (With or Without Transplant) to Those Who Die. [ Time Frame: 3 Weeks, 1-year and 2-year follow-ups ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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). [ Time Frame: 3 Weeks, 1-year and 2-year follow-ups ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: December 2008
Study Completion Date: December 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
N-acetycylcysteine
Each eligible Acute Liver Failure patient will be given N-acetylcysteine (NAC), beginning at a dose of 150 mg/kg bodyweight in 250 ml 5% dextrose over one hour, followed by 50 mg/kg in 500 ml 5% dextrose over four hours, and 125 mg/kg in 1000 ml 5% dextrose over 19 hours, then 150 mg/kg in 1000 ml 5% dextrose per 24 hours for an additional 48 hours. The patient will be on continuous NAC infusion for a total of 72 hours.
Drug: N-acetylcysteine

Patients will be included in the trial from the onset of any hepatic coma grade and will receive NAC for the following 72 hrs.

NAC Solutions: The N-acetylcysteine will be added to 5% dextrose in defined concentrations according to the sequence of four specific doses required for the study.

i.Solution A: 150 mg/kg bodyweight in 250 ml 5% dextrose over one hour

ii.Solution B: 50 mg/kg in 500 ml 5% dextrose over four hours

iii.Solution C: 125 mg/kg in 1000 ml 5% dextrose over 19 hours

iv.Solution D: 150 mg/kg in 1000 ml 5% dextrose per 24 hours

v.Solution E: 150 mg/kg in 1000 ml 5% dextrose per 24 hours

Other Name: Mucomyst

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 or placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896025

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, Davis
Sacramento, California, United States, 95817
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
Mayo Clinic, Jacksonville
Jacksonville, Florida, United States, 32216
United States, Illinois
Northwestern University Medical School
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic, Rochester
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska
Omaha, Nebraska, United States, 68198
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
New York Presbyterian Hospital (Columbia and Cornel)
New York, New York, United States, 10032
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
William Lee
Investigators
Principal Investigator: William M Lee, MD UT Southwestern Medical Center at Dallas
  More Information

No publications provided

Responsible Party: William Lee, Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00896025     History of Changes
Other Study ID Numbers: 012009-011, NIDDK 058369
Study First Received: May 8, 2009
Results First Received: December 11, 2013
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Liver disease

Additional relevant MeSH terms:
Liver Failure
Liver Failure, Acute
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 18, 2014