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

Acute Liver Failure Clinical Trial

— ONAC  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00896025
• Other study ID #: STU 012009-011
• Secondary ID: NIDDK U-01 05836
• Status: Terminated
• Phase: Phase 4
• Start date: December 2008
• Est. completion date: March 2016

Study information

• Verified date: May 2020
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 255
• Est. completion date: March 2016
• Est. primary completion date: October 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Liver Failure
• Fulminant Hepatic Failure
• Hepatic Insufficiency
• Liver Failure
• Liver Failure, Acute

Intervention

Drug:
• N-acetylcysteine
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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	3 Week follow-up
Secondary	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.	1-year follow-up
Secondary	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.	2-year follow-up

External Links

•   Acute Liver Failure Website