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

NCT ID: NCT00896025

Last Updated: 2020-06-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 255 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2016-03-31

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.

Conditions

Acute Liver Failure; Fulminant Hepatic Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

N-acetylcysteine

Intervention Type: DRUG

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

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Mucomyst

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William M Lee, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center at Dallas

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California, Los Angeles

Los Angeles, California, United States

University of California, Davis

Sacramento, California, United States

University of California, San Francisco

San Francisco, California, United States

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Northwestern University Medical School

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Mayo Clinic, Rochester

Rochester, Minnesota, United States

University of Nebraska

Omaha, Nebraska, United States

Mount Sinai School of Medicine

New York, New York, United States

New York Presbyterian Hospital (Columbia and Cornel)

New York, New York, United States

Oregon Health Sciences University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

Stravitz 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.

Reference Type: DERIVED

PMID: 37183883 (View on PubMed)

Related Links

http://www.acuteliverfailure.org

Acute Liver Failure Website

Other Identifiers

NIDDK U-01 058369

Identifier Type: -

Identifier Source: secondary_id

STU 012009-011

Identifier Type: -

Identifier Source: org_study_id