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

Phase 4

Terminated

Conditions: Acute Liver Failure
Fulminant Hepatic Failure

Interventions: Drug: N-acetylcysteine

Registration Number: NCT00896025

Lead Sponsor: University of Texas Southwestern Medical Center

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 255

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
N-acetycylcysteine	N-acetylcysteine	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.

Primary Outcome Measures

Name	Time	Method
Survival Rate With or Without Transplant	2-year follow-up	The primary outcome is to compare all patients who survive (with or without transplant) to those who die.

Secondary Outcome Measures

Name	Time	Method
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	The estimated minimum enrollment for any statistical validity was 100 patients. Due to low enrollment (8 participants) and the likelihood of generating any meaningful study data moving forward, the DSMB recommended the early termination of the study. Data was not collected since study was terminated.

Trial Locations

Locations (21): Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Michigan Medical Center
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Ann Arbor, Michigan, United States
Northwestern University Medical School
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Chicago, Illinois, United States
Albert Einstein Medical Center
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Philadelphia, Pennsylvania, United States
Mayo Clinic, Rochester
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Rochester, Minnesota, United States
New York Presbyterian Hospital (Columbia and Cornel)
🇺🇸
New York, New York, United States
Oregon Health Sciences University
🇺🇸
Portland, Oregon, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
University of Nebraska
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Omaha, Nebraska, United States
University of California, Davis
🇺🇸
Sacramento, California, United States
Mayo Clinic, Jacksonville
🇺🇸
Jacksonville, Florida, United States
University of California, Los Angeles
🇺🇸
Los Angeles, California, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Washington
🇺🇸
Seattle, Washington, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States