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Acute Liver FailurePhase 3NCT00004467

Randomized Study of Acetylcysteine in Patients With Acute Liver Failure Not Caused by Acetaminophen

A Phase 3 study testing N-acetylcysteine (NAC) in people with Acute Liver Failure, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

OBJECTIVES: I. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific treatment is available. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Liver Failure
What is being tested?
N-acetylcysteine (NAC)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
173 participants
Where
25 sitesUnited States
Study dates
Jun 1998to Nov 2006
Phase
Phase 3
Are there results?
None posted in the registry

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

  • This is a phase III blinded study, which will involve approximately 200 patients. For this purpose, acute liver failure will be defined as onset of any mental status alteration and coagulopathy (INR > 1.5) within 26 weeks of onset of a hepatitic illness, with no evidence of underlying chronic liver disease. Eligible patients will be those 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 or those who evolve to altered mentation if already in the hospital. All subjects will be between 18 and 70 years. Patients transferred from referring hospitals to a study site may be considered for enrollment, provided that no other specific treatment protocol has begun, and that no liver support device (bioartificial liver (BAL), extracorporeal liver assist device (ELAD), transgenic pig perfusion) has been used or is contemplated. Use of fresh frozen plasma infusions will not disqualify patients from participation.

Who cannot join

  • Patients less than age 18 or over 70 years of age.
  • ALF patients where acetaminophen or mushroom poisoning is assessed or Suspected to be a significant contributing or sole cause of the illness. Both these diagnoses require specific antidote therapy, including NAC in the case of acetaminophen, rather than randomized or non-specific treatment.
  • Patients with a diagnosis of shock liver (ischemic hepatopathy), since the overall outcome for these patients in largely determined by the underlying etiology of the condition leading to shock. Heat stroke is not excluded.
  • Acute liver failure of pregnancy or the HELLP syndrome (pregnancy associated hemolysis and coagulopathy). The effect of NAC on the fetus or the mother has not been determined; in addition, pregnancy-related liver diseases usually mandate rapid delivery of the infant.
  • ALF thought secondary to intrahepatic malignancy. Patients with hepatic malignancy experiencing ALF have 100% mortality and are not transplant candidates.
  • Patients who exhibit signs of cerebral herniation at the time of enrollment.
Show all 9Show fewer
  • Patients who demonstrate the presence of intractable arterial hypotension (arterial systolic blood pressure equal to or below 70 mmHg) present, or require inotropic drugs at the time of enrollment.
  • Severe sepsis (temperature >39o C and/or significant bacteremia) present at the time of enrollment.
  • In general, acute liver failure (ALF) patients comprise somewhat more women than men, but there is no preponderance of any racial group, other than that expected on the basis of geographic differences. No exclusion will be made on the basis of race, ethnic group or gender. Criteria for inclusion of women and minorities will be those established in the NIH guidelines. Each study site will provide for review a log of patients considered for the NAC study with no identifiers, yielding only gender and age, race and reason for not participating as a check on gender or ethnic bias.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • University of Michigan Health Systems

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-0005

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University Medical School

    Chicago, Illinois, 60611

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235-8897

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Duke University Medical Center

    Durham, North Carolina, 27715

  • Mayo Clinic

    Jacksonville, Florida, 32216

  • University of California Los Angeles

    Los Angeles, California, 90024

  • Mount Sinai Medical Center, NY

    New York, New York, 10029

  • New York Presbyterian Hospital

    New York, New York, 10032-3784

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-3330

  • 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, 97201-3098

  • Virginia Commonwealth University

    Richmond, Virginia, 23298-0341

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis

    Sacramento, California, 95817

  • University of California San Diego

    San Diego, California, 92103-0707

  • University of California San Francisco

    San Francisco, California, 94115

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • University of Washington Medical Center

    Seattle, Washington, 98195-6043

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

OBJECTIVES:

  1. Determine the safety and efficacy of a short course (72 hours) of intravenous acetylcysteine in patients with acute liver failure for whom no antidote or specific treatment is available.
Read the detailed description

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to receive intravenous acetylcysteine or placebo for 72 hours. Treatment must begin within 12 hours of hospitalization. Patients who advance to grade III or IV encephalopathy are eligible for liver transplantation.

Patients are followed at 3 weeks.

Being tested
N-acetylcysteine (NAC), Placebo
Keywords
acute liver failure, gastrointestinal disorders, rare disease
Medical subject headings
Liver Failure, Acute, Gastrointestinal Diseases, Rare Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • N-acetylcysteine (NAC)Drug

    Also called Acetadote

    Infusion of 5% dextrose with N-acetylcysteine with an initial loading dose of 150 mg/kg/h of NAC over 1 hour, followed by 12.5 mg/kg/h for 4 hours, then continuous infusions of 6.25 mg/kg/h for the remaining 67 hours.

  • PlaceboDrug

    Infusion of 5% dextrose

Study groups in NCT00004467
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
N-acetylcysteine (NAC)ExperimentalNot described
Receives: Drug: N-acetylcysteine (NAC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival rate

    Measured: 3 weeks

Secondary outcomes (4)

  1. Survival without liver transplantation (Spontaneous Survival

    Measured: 3 weeks

  2. Transplant rate

    Measured: 3 weeks

  3. Length of hospital stay

    Measured: 3 weeks

  4. Number of organ systems showing failure

    Measured: 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 1999 (estimated)
  2. Study startJun 1998
  3. Primary completionNov 2006
  4. Study completionNov 2006

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
173 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004467
Sponsor's protocol ID
199/13925 DK52827 (completed)
Other IDs
R03DK052827, UTSMC-IRB-0697-27200, R01DK058369, U01DK058369
Status last verified
Oct 2017
First submitted
18 Oct 1999
Last updated
13 Oct 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Publications

  • Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ 2nd, Murray NG, McCashland T, Reisch JS, Robuck PR; Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009 Sep;137(3):856-64, 864.e1. doi: 10.1053/j.gastro.2009.06.006. Epub 2009 Jun 12.

    PubMed 19524577

  • 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

  • Singh S, Hynan LS, Rule JA, Lee WM. Changes in alpha-foetoprotein and Gc-globulin in relation to outcomes in non-acetaminophen acute liver failure. Liver Int. 2019 Dec;39(12):2368-2373. doi: 10.1111/liv.14216. Epub 2019 Sep 10.

    PubMed 31421008

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing N-acetylcysteine (NAC) in people with Acute Liver Failure, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 25 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 1 inclusion and 9 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: finished, as of the sponsor's last update on 13 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Overall survival rate (time frame: 3 weeks). 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 NCT00004467, which also lists 3 linked publications.

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 13 Oct 2017.

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