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

Condition(s) targeted: Acute Liver Failure; Fulminant Hepatic Failure

Intervention: N-acetylcysteine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Texas Southwestern Medical Center

Official(s) and/or principal investigator(s):
William M Lee, MD, Principal Investigator, Affiliation: UT Southwestern Medical Center at Dallas

Overall contact:
William M Lee, MD, Phone: 214-645-6110, Email: william.lee@utsouthwestern.edu

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

Official title: A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study

Study design: Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome: 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).

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 200 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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

William M Lee, MD, Phone: 214-645-6110, Email: william.lee@utsouthwestern.edu

University of Alabama at Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Brendan McGuire, MD, Principal Investigator

University of California, Los Angeles, Los Angeles, California 90095, United States; Recruiting
Steven Han, MD, Principal Investigator

University of California, Davis, Sacramento, California 95817, United States; Recruiting
Lorenzo Rossaro, MD, Principal Investigator

University of California, San Francisco, San Francisco, California 94143, United States; Recruiting
Timothy Davern, MD, Principal Investigator

Mayo Clinic, Jacksonville, Jacksonville, Florida 32216, United States; Recruiting
Raj Satyanarayana, MD, Principal Investigator

Northwestern University Medical School, Chicago, Illinois 60611, United States; Recruiting
Daniel Ganger, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Raymond T Chung, MD, Principal Investigator

University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States; Recruiting
Robert Fontana, MD, Principal Investigator

Mayo Clinic, Rochester, Rochester, Minnesota 55905, United States; Recruiting
J. Eileen Hay, MB, ChB, Principal Investigator

University of Nebraska, Omaha, Nebraska 68198, United States; Recruiting
Timothy McCashland, MD, Principal Investigator

Mount Sinai School of Medicine, New York, New York 10029, United States; Recruiting
Lawrence Liu, MD, Principal Investigator

New York Presbyterian Hospital (Columbia and Cornel), New York, New York 10032, United States; Recruiting
Robert Brown, MD, Principal Investigator

Oregon Health Sciences University, Portland, Oregon 97239, United States; Recruiting
Kenneth Ingram, PA, Sub-Investigator
Jonathan Schwartz, MD, Principal Investigator
Atif Zaman, MD, MPH, Principal Investigator

Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, United States; Recruiting
Victor Araya, MD, Principal Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Rajender Reddy, MD, Principal Investigator
Mical Campbell, MD, Principal Investigator

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Obaid S Shaikh, MD, Principal Investigator

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Adrian Reuben, MBBS, Principal Investigator

Baylor University Medical Center, Dallas, Texas 75246, United States; Recruiting
Natalie G. Murray, MD, Principal Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
William M Lee, MD, Principal Investigator

Virginia Commonwealth University, Richmond, Virginia 23298, United States; Recruiting
R. Todd Stravitz, MD, Principal Investigator

University of Washington, Seattle, Washington 98195, United States; Recruiting
MD
Iris Liou, MD, Principal Investigator

Acute Liver Failure Website

Starting date: December 2008
Last updated: May 8, 2009