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

NCT00896025 | Terminated Phase 4 Results DMC

• 2 other identifiers: STU 012009-011NIDDK U-01 058369
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 21

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.

Conditions

Acute Liver Failure; Fulminant Hepatic Failure

Keywords

Liver disease

Outcome Measures

Primary Outcomes (3)

• Survival Rate With or Without Transplant

  The primary outcome is to compare all patients who survive (with or without transplant) to those who die.

  3 Weeks

• Survival Rate With or Without Transplant

  The primary outcome is to compare all patients who survive (with or without transplant) to those who die.

  1-year follow-up

• Survival Rate With or Without Transplant

  The primary outcome is to compare all patients who survive (with or without transplant) to those who die.

  2-year follow-up

Secondary Outcomes (3)

• 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).

  3 Week follow-up

• 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).

  1-year follow-up

• 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).

  2-year follow-up

Study Arms (2)

N-acetycylcysteine

ACTIVE COMPARATOR

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.

Drug: N-acetylcysteine

Standard of care

NO INTERVENTION

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.

Interventions

N-acetylcysteine 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

Also known as: Mucomyst

N-acetycylcysteine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32216, United States

Location

Northwestern University Medical School

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

New York Presbyterian Hospital (Columbia and Cornel)

New York, New York, 10032, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• 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.

  PMID: 37183883 DERIVED

Related Links

• Acute Liver Failure Website

MeSH Terms

Conditions

Liver Failure, Acute; Liver Diseases

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Early termination lead to zero subjects analyzed.

Results Point of Contact

• Title: William M. Lee, MD
• Organization: University of Texas Southwestern Medical Center

william.lee@utsouthwestern.edu

214-645-6111

Study Officials

• William M Lee, MD

  UT Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label-comparator is historical data.

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 11, 2009
• Study Start: December 1, 2008
• Primary Completion: October 15, 2015
• Study Completion: March 1, 2016
• Last Updated: June 1, 2020
• Results First Posted: January 29, 2014

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)