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

Phase 4TerminatedNCT00896025

University of Texas Southwestern Medical Center255 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

255

Conditions

Acute Liver Failure Fulminant Hepatic Failure

Interventions

N-acetylcysteineDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (21)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

Survival Rate With or Without Transplant

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

Time frame: 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.

Time frame: 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.

Time frame: 2-year follow-up

Secondary Outcomes

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).

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, therefore no data to analyze.

Time frame: 3 Week follow-up

Time frame: 1-year follow-up

Data from ClinicalTrials.gov

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