N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure

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: NCT00248625
Recruitment Status : Completed
First Posted : November 4, 2005
Results First Posted : July 28, 2016
Last Update Posted : July 28, 2016
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Robert Squires, Jr., University of Pittsburgh

Brief Summary:
We have completed patient enrollment in the the double blind, randomized, placebo-controlled trial of intravenous (IV) N-acetylcysteine (NAC) vs. placebo for the treatment of non-acetaminophen ALF. The purpose of this study is to examine the safety and efficacy of intravenous NAC in children with ALF for whom no antidote or other specific treatment is available. Inclusion in the NAC Study required enrollment in the Pediatric Acute Liver Failure (PALF) Study Registry.

Condition or disease Intervention/treatment Phase
Acute Liver Failure Hepatic Encephalopathy Drug: N-acetylcysteine Drug: Placebo Phase 3

Detailed Description:

The Pediatric Acute Liver Failure (PALF) Study Group to identify, characterize, and develop management strategies for infants, children and adolescents who present with acute liver failure. The PALF study group includes 20 sites (17 in the United States, 2 in the United Kingdom, and 1 in Canada). The primary objective of the Pediatric Acute Liver Failure (PALF) study is to collect, maintain, analyze, and report clinical, epidemiological, and outcome data in children with ALF, including information derived from biospecimens.

Patients enrolled in the PALF study registry were able to enroll in the NAC study providing they met the additional required inclusion/exclusion criteria.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 184 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center Study of the Safety and Efficacy of N-acetylcysteine in the Treatment of Acute Liver Failure in Pediatric Patients Not Caused by Acetaminophen.
Study Start Date : January 2000
Actual Primary Completion Date : September 2009
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: N-acetylcysteine (NAC)
Eligible children were adaptively allocated by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive N-acetylcysteine (150 mg/kg/d) in 5% dextrose (D5W) infused over 24 hours for up to 7 consecutive days
Drug: N-acetylcysteine
The study drug is administered as a continuous infusion at a dose of 150 mg/kg/day for up to 7 days following entry into the study. The infusion is discontinued at the time of death, liver transplant or discharge.
Other Name: Mucomyst
Placebo Comparator: placebo
Eligible children were adaptively allocated within strata defined by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive 5% dextrose (D5W) infused over 24 hours for up to 7 consecutive
Drug: Placebo
Eligible children were adaptively allocated within strata defined by age (less than 2 years of age or at least 2 years old) and hepatic encephalopathy (grade 0-1 or 2-4) to receive N-acetylcysteine (150 mg/kg/d) in 5% dextrose (D5W) and water or placebo consisting of an equal volume of D5W alone. Volumes were adjusted for small children. Study medications were infused over 24 hours for up to 7 consecutive days in a dedicated line without other medications. Treatment was stopped earlier than 7 days in the case of hospital discharge, liver transplantation, or death within 7 days of randomization.
Other Name: dextrose in water

Primary Outcome Measures :
  1. Survival [ Time Frame: One year following randomization ]
    Spontaneous survival without transplant plus survival following transplantation

Secondary Outcome Measures :
  1. Spontaneous Recovery [ Time Frame: One year following randomization ]
    Survival without liver transplantation

  2. Cumulative Percent Incidence of Transplantation by 1 Year [ Time Frame: Within 1 year of randomization ]
  3. Length of Hospital Stay [ Time Frame: Randomization to hospital discharge ]
  4. Categorized Length of ICU Stay [ Time Frame: Within 7 days of randomization ]
    The length of ICU stay was categorized as number of days in ICU within 7 days of randomization, unless participant either died or received an LTx within this time period. Special categories were created for these cases.

  5. Number of Organ Systems Failing [ Time Frame: Within 7 days of randomization ]
  6. Highest Coma Grade of Hepatic Encephalopathy [ Time Frame: Within 7 days of randomization ]
    West Haven Criteria for hepatic encephalopathy (Grade 0 - IV ) is used for participants > 3 year of age. Coma grade IV indicates a participant who is comatose , with no reflexes, is decerebrate and has abnormal EEG changes with very slow delta activity. For participants less than 3 years the Whittington Scale was used. The Whittington scale does not use EEG changes and has only 3 levels, early (grades I and II), Mid (III) with somnolence, stupor, combativeness and Late (IV) for participants who are comatose with absent reflexes and decerebrate or decorticate posturing.

  7. Infectious Complication [ Time Frame: Within 7 days of randomization ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Meet entry criteria for and be enrolled in the Pediatric Acute Liver Failure prospective database.
  • Able to be evaluated and initiate treatment within the first 24 hours of hospitalization
  • Patients transferred from referring hospitals to the study site may be considered for enrollment, provided that no other treatment protocol has begun, and that no liver support device (BAL, extracorporeal liver assist device, transgenic pig perfusion) has been used or is contemplated.
  • Use of fresh frozen plasma infusions will not disqualify patients from participation.

Exclusion Criteria:

  • older than 18 years of age
  • pregnancy
  • ALF that is secondary to acute acetaminophen toxicity, mushroom poisoning, or a known malignancy.
  • Patients who exhibit signs of cerebral herniation, have intractable arterial hypotension, require inotropic drugs, or demonstrate signs of sepsis (temperature ≥ 39.5o C or bacteremia) at the time of enrollment
  • No exclusion will be made on the basis of race, ethnic group or gender.
  • Criteria for inclusion of females and minorities will be those established in the NIH guidelines

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): NCT00248625

  Hide Study Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado, Denver Children's Hospital
Denver, Colorado, United States, 80218
United States, Georgia
Emory University, Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Children's Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard University, Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
New York, New York, United States, 10032
United States, Ohio
University of Cincinnati, Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
University of Washington
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom, B4 6NH
King's College Hospital (London, UK)
London, United Kingdom, SE59RS
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Robert H Squires, M.D. Children's Hospital of Pittsburgh, University of Pittsburgh

Additional Information:

Responsible Party: Robert Squires, Jr., MD, University of Pittsburgh Identifier: NCT00248625     History of Changes
Other Study ID Numbers: IRB #: 0608007
U01DK072146 ( U.S. NIH Grant/Contract )
First Posted: November 4, 2005    Key Record Dates
Results First Posted: July 28, 2016
Last Update Posted: July 28, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Robert Squires, Jr., University of Pittsburgh:
acute liver failure
hepatic encephalopathy
acetaminophen toxicity

Additional relevant MeSH terms:
Brain Diseases
Liver Failure
Hepatic Encephalopathy
Liver Failure, Acute
Central Nervous System Diseases
Nervous System Diseases
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents