Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00004467
Recruitment Status : Completed
First Posted : October 19, 1999
Last Update Posted : October 13, 2017
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:


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.

Condition or disease Intervention/treatment Phase
Acute Liver Failure Drug: N-acetylcysteine (NAC) Drug: Placebo Phase 3

Expanded Access : National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 173 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Study Start Date : June 1998
Actual Primary Completion Date : November 2006
Actual Study Completion Date : November 2006

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo Drug: Placebo
Infusion of 5% dextrose

Experimental: N-acetylcysteine (NAC) Drug: 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.
Other Name: Acetadote

Primary Outcome Measures :
  1. Overall survival rate [ Time Frame: 3 weeks ]

Secondary Outcome Measures :
  1. Survival without liver transplantation (Spontaneous Survival [ Time Frame: 3 weeks ]
  2. Transplant rate [ Time Frame: 3 weeks ]
  3. Length of hospital stay [ Time Frame: 3 weeks ]
  4. Number of organ systems showing failure [ Time Frame: 3 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00004467

Show Show 25 study locations
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Texas Southwestern Medical Center
Layout table for investigator information
Study Chair: William M. Lee, MD University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Additional Information:
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00004467    
Obsolete Identifiers: NCT00587366
Other Study ID Numbers: 199/13925 DK52827 (completed)
R03DK052827 ( U.S. NIH Grant/Contract )
UTSMC-IRB-0697-27200 ( Other Identifier: University of Texas Southwest Medical Center )
R01DK058369 ( U.S. NIH Grant/Contract )
U01DK058369 ( U.S. NIH Grant/Contract )
First Posted: October 19, 1999    Key Record Dates
Last Update Posted: October 13, 2017
Last Verified: October 2017

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
acute liver failure
gastrointestinal disorders
rare disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Failure
Hepatic Insufficiency
Liver Failure, Acute
Liver Diseases
Digestive System Diseases
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs