Acute Liver FailurePhase 4ONACNCT00896025
Study of N-Acetylcysteine in Acute Liver Failure (ALF)
A Phase 4 study testing N-acetylcysteine in people with Acute Liver Failure and Fulminant Hepatic Failure, run by University of Texas Southwestern Medical Center at 21 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Liver Failure, Fulminant Hepatic Failure
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 255 participants
- Where
- 21 sitesUnited States
- Study dates
- Dec 2008to Mar 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University Medical School
Chicago, Illinois, 60611
Baylor University Medical Center
Dallas, Texas, 75246
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32216
University of California, Los Angeles
Los Angeles, California, 90095
Mount Sinai School of Medicine
New York, New York, 10029
New York Presbyterian Hospital (Columbia and Cornel)
New York, New York, 10032
University of Nebraska
Omaha, Nebraska, 68198
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Albert Einstein Medical Center
Philadelphia, Pennsylvania, 19141
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Oregon Health Sciences University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23298
Mayo Clinic, Rochester
Rochester, Minnesota, 55905
University of California, Davis
Sacramento, California, 95817
University of California, San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
About this study
Official title: A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study
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.
Read the 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.
- Conditions
- Acute Liver Failure, Fulminant Hepatic Failure
- Being tested
- N-acetylcysteine
- Keywords
- Liver disease
- Medical subject headings
- Liver Failure, Acute, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called Mucomyst
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
| Study group | Role | What they receive |
|---|---|---|
| N-acetycylcysteine | Active comparator | 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. Receives: Drug: N-acetylcysteine |
| Standard of care | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival Rate With or Without Transplant
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Measured: 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.
Measured: 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.
Measured: 2-year follow-up
Secondary outcomes (3)
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.
Measured: 3 Week follow-up
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.
Measured: 1-year follow-up
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.
Measured: 2-year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2009 (estimated)
- Study startDec 2008
- Primary completion15 Oct 2015
- Study completionMar 2016
Why it stopped: This observational study was stopped after 140 patients were enrolled, no more funds available to continue.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Liver FailureStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Open label-comparator is historical data.
- Masking
- None (open label)
- Enrolment
- 255 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William M Lee, MD, Principal investigator, UT Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00896025
- Sponsor's protocol ID
- STU 012009-011
- Other IDs
- NIDDK U-01 058369
- Acronym
- ONAC
- Status last verified
- May 2020
- First submitted
- 8 May 2009
- Last updated
- 1 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Stravitz RT, Fontana RJ, Karvellas C, Durkalski V, McGuire B, Rule JA, Tujios S, Lee WM; Acute Liver Failure Study Group. Future directions in acute liver failure. Hepatology. 2023 Oct 1;78(4):1266-1289. doi: 10.1097/HEP.0000000000000458. Epub 2023 May 16.
PubMed 37183883
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study
- ClinicalTrials.gov ID
- NCT00896025
- Acronym / sponsor ID
- ONAC / STU 012009-011
- Conditions
- Acute Liver Failure, Fulminant Hepatic Failure
- Keywords
- Liver disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This observational study was stopped after 140 patients were enrolled, no more funds available to continue.
- Enrolment
- 255 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Dec 2008
- Primary completion
- 15 Oct 2015 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 11 May 2009 (estimated)
- Results
- Posted 29 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label-comparator is historical data.
| Arm | Type | Receives |
|---|---|---|
| N-acetycylcysteine | Active comparator | Drug: N-acetylcysteineEach 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. |
| Standard of care | No intervention | –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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: MucomystPatients 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 | Drug | N-acetycylcysteine |
Primary outcome
Survival Rate With or Without Transplant
Time frame: 3 Weeks
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Survival Rate With or Without Transplant
Time frame: 1-year follow-up
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
Survival Rate With or Without Transplant
Time frame: 2-year follow-up
The primary outcome is to compare all patients who survive (with or without transplant) to those who die.
3 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).
Time frame: 3 Week follow-up
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).
Time frame: 1-year follow-up
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).
Time frame: 2-year follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37183883Stravitz RT, Fontana RJ, Karvellas C, Durkalski V, McGuire B, Rule JA, Tujios S, Lee WM; Acute Liver Failure Study Group. Future directions in acute liver failure. Hepatology. 2023 Oct 1;78(4):1266-1289. doi: 10.1097/HEP.0000000000000458. Epub 2023 May 16.
- Acute Liver Failure WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Acute Liver Failure
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
RecruitingObservational study
Establishing a Reference Framework for Outcomes After Machine-Preserved Liver Transplantation in Europe
End-stage Liver Disease (ESLD), Acute Liver Failure
Recruiting
Evaluation of Fibroscan® Performance in Diagnosing Acute Heart Failure in Patients Presenting to the Emergency Department
Acute Heart Failure (AHF)
RecruitingObservational study
CytOSorb TreatMent Of Critically Ill PatientS Registry
Septic Shock, Acute Respiratory Distress Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William M Lee, MD principal investigator
UT Southwestern Medical Center at Dallas
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing N-acetylcysteine in people with Acute Liver Failure and Fulminant Hepatic Failure, run by University of Texas Southwestern Medical Center at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival Rate With or Without Transplant (time frame: 3 Weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00896025, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2020.