Acute Liver Failure, Fulminant Hepatic Failure
Conditions
Keywords
Liver disease
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.
Interventions
DRUGN-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
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Texas Southwestern Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label-comparator is historical data.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate With or Without Transplant | 3 Weeks | The primary outcome is to compare all patients who survive (with or without transplant) to those who die. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 3 Week 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, therefore no data to analyze. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-acetycylcysteine 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 NAC infusion for a total of 72 hours. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | N-acetycylcysteine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 46 years |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
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.
Time frame: 3 Weeks
Population: 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 there was no data to analyze.
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.
Time frame: 1-year follow-up
Population: 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.
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.
Time frame: 2-year follow-up
Population: 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.
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.
Time frame: 3 Week follow-up
Population: Data was not collected since study was terminated, therefore there was no data to analyze.
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.
Time frame: 1-year follow-up
Population: Data was not collected since study was terminated, therefore there was no data to analyze.
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.
Time frame: 2-year follow-up
Population: Data was not collected since study was terminated, therefore there was no data to analyze.