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

Primary Purpose

Acute Liver Failure, Fulminant Hepatic Failure

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
N-acetylcysteine
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Liver Failure focused on measuring Liver disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Alabama at Birmingham
  • University of California, Los Angeles
  • University of California, Davis
  • University of California, San Francisco
  • Mayo Clinic, Jacksonville
  • Northwestern University Medical School
  • Massachusetts General Hospital
  • University of Michigan Medical Center
  • Mayo Clinic, Rochester
  • University of Nebraska
  • Mount Sinai School of Medicine
  • New York Presbyterian Hospital (Columbia and Cornel)
  • Oregon Health Sciences University
  • University of Pennsylvania
  • Albert Einstein Medical Center
  • University of Pittsburgh Medical Center
  • Medical University of South Carolina
  • Baylor University Medical Center
  • University of Texas Southwestern Medical Center
  • Virginia Commonwealth University
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

N-acetycylcysteine

Standard of care

Arm 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.

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.

Outcomes

Primary Outcome Measures

Survival Rate With or Without Transplant
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Survival Rate With or Without Transplant
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Survival Rate With or Without Transplant
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
May 8, 2009
Last Updated
May 29, 2020
Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00896025
Brief Title
Study of N-Acetylcysteine in Acute Liver Failure (ALF)
Acronym
ONAC
Official Title
A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
This observational study was stopped after 140 patients were enrolled, no more funds available to continue.
Study Start Date
December 2008 (undefined)
Primary Completion Date
October 15, 2015 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Liver Failure, Fulminant Hepatic Failure
Keywords
Liver disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Open label-comparator is historical data.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N-acetycylcysteine
Arm Type
Active Comparator
Arm 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.
Arm Title
Standard of care
Arm Type
No Intervention
Arm 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.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine
Other Intervention Name(s)
Mucomyst
Intervention Description
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
Primary Outcome Measure Information:
Title
Survival Rate With or Without Transplant
Description
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Time Frame
3 Weeks
Title
Survival Rate With or Without Transplant
Description
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Time Frame
1-year follow-up
Title
Survival Rate With or Without Transplant
Description
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 Outcome Measure Information:
Title
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).
Description
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
Title
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).
Description
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.
Time Frame
1-year follow-up
Title
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).
Description
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.
Time Frame
2-year follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William M Lee, MD
Organizational Affiliation
UT Southwestern Medical Center at Dallas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Mayo Clinic, Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Northwestern University Medical School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic, Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
New York Presbyterian Hospital (Columbia and Cornel)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Albert Einstein Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.acuteliverfailure.org
Description
Acute Liver Failure Website

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

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