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

The University of Texas System (UT)

Status and phase: Terminated; Phase 4

Conditions: Acute Liver Failure; Fulminant Hepatic Failure

Treatments: Drug: N-acetylcysteine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00896025

NIDDK U-01 058369

STU 012009-011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 255 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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255 participants in 2 patient groups

N-acetycylcysteine

Active Comparator group

Description:

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.

Treatment:

Drug: N-acetylcysteine

Standard of care

No Intervention group

Description:

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.