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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00896025
Recruitment Status : Terminated (The low enrollment did not provide statistical power for any meaningful results.)
First Posted : May 11, 2009
Results First Posted : January 29, 2014
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
William Lee, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE May 8, 2009
First Posted Date  ICMJE May 11, 2009
Results First Submitted Date December 11, 2013
Results First Posted Date January 29, 2014
Last Update Posted Date February 12, 2019
Study Start Date  ICMJE December 2008
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00896025 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2009)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of N-Acetylcysteine in Acute Liver Failure (ALF)
Official Title  ICMJE A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study
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.
Study Type  ICMJE Interventional
Study Phase Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Open label-comparator is historical data.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Liver Failure
  • Fulminant Hepatic Failure
Intervention  ICMJE 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
Study Arms
  • Active Comparator: 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 N-acetylcysteine infusion for a total of 72 hours.
    Intervention: Drug: N-acetylcysteine
  • No Intervention: Standard of care
    Each eligible Acute Liver Failure patient for whom the investigator chooses not to utilize N-acetylcysteine may serve as a control and receives standard of care.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 25, 2019)
255
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2009)
200
Actual Study Completion Date December 2010
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00896025
Other Study ID Numbers  ICMJE 012009-011
NIDDK U-01 058369
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party William Lee, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE William Lee
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: William M Lee, MD UT Southwestern Medical Center at Dallas
PRS Account University of Texas Southwestern Medical Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP