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

This study has been completed.
Sponsor:
Collaborator:
University of Texas
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00004467
First received: October 18, 1999
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Acute Liver Failure
Drug: acetylcysteine
Phase 3

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.  

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Overall survival rate [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Survival without liver transplantation (Spontaneous Survival [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  • Transplant rate [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  • Length of hospital stay [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  • Number of organ systems showing failure [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 173
Study Start Date: June 1998
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (BAL, 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, 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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004467

  Show 25 Study Locations
Sponsors and Collaborators
University of Texas
Investigators
Study Chair: William M. Lee, MD University of Texas
  More Information

Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00004467     History of Changes
Obsolete Identifiers: NCT00587366
Other Study ID Numbers: 199/13925 DK52827 (completed), UTSMC-1R03DK52827, UTSMC-IRB-0697-27200
Study First Received: October 18, 1999
Last Updated: January 12, 2010
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
acute liver failure
gastrointestinal disorders
rare disease

Additional relevant MeSH terms:
Liver Failure
Liver Failure, Acute
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on October 19, 2014