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

NCT ID: NCT00004467

Last Updated: 2017-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-06-30

Study Completion Date

2006-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Liver Failure

Keywords

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acute liver failure gastrointestinal disorders rare disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Infusion of 5% dextrose

N-acetylcysteine (NAC)

Group Type EXPERIMENTAL

N-acetylcysteine (NAC)

Intervention Type DRUG

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.

Interventions

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N-acetylcysteine (NAC)

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.

Intervention Type DRUG

Placebo

Infusion of 5% dextrose

Intervention Type DRUG

Other Intervention Names

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Acetadote

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

1. Patients less than age 18 or over 70 years of age.
2. 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.
3. 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.
4. 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.
5. ALF thought secondary to intrahepatic malignancy. Patients with hepatic malignancy experiencing ALF have 100% mortality and are not transplant candidates.
6. Patients who exhibit signs of cerebral herniation at the time of enrollment.
7. 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.
8. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William M. Lee, MD

Role: STUDY_CHAIR

University of Texas Southwestern Medical Center at Dallas, Dallas, TX

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

University of California Davis

Sacramento, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Northwestern University Medical School

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

New York Presbyterian Hospital

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 19524577 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37183883 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31421008 (View on PubMed)

Related Links

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http://www.acuteliverfailure.org

Acute Liver Failure Study Group

Other Identifiers

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R03DK052827

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UTSMC-IRB-0697-27200

Identifier Type: OTHER

Identifier Source: secondary_id

R01DK058369

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01DK058369

Identifier Type: NIH

Identifier Source: secondary_id

View Link

199/13925 DK52827 (completed)

Identifier Type: -

Identifier Source: org_study_id

NCT00587366

Identifier Type: -

Identifier Source: nct_alias