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N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure

This study has been completed.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Robert Squires, Jr., University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00248625
First received: November 3, 2005
Last updated: June 16, 2016
Last verified: June 2016
  Purpose
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 Intervention Phase
Acute Liver Failure
Hepatic Encephalopathy
Drug: N-acetylcysteine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Survival [ Time Frame: One year following randomization ] [ Designated as safety issue: Yes ]
    Spontaneous survival without transplant plus survival following transplantation


Secondary Outcome Measures:
  • Spontaneous Recovery [ Time Frame: One year following randomization ] [ Designated as safety issue: Yes ]
    Survival without liver transplantation

  • Cumulative Percent Incidence of Transplantation by 1 Year [ Time Frame: Within 1 year of randomization ] [ Designated as safety issue: Yes ]
  • Length of Hospital Stay [ Time Frame: Randomization to hospital discharge ] [ Designated as safety issue: Yes ]
  • Categorized Length of ICU Stay [ Time Frame: Within 7 days of randomization ] [ Designated as safety issue: Yes ]
    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.

  • Number of Organ Systems Failing [ Time Frame: Within 7 days of randomization ] [ Designated as safety issue: Yes ]
  • Highest Coma Grade of Hepatic Encephalopathy [ Time Frame: Within 7 days of randomization ] [ Designated as safety issue: Yes ]
    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.

  • Infectious Complication [ Time Frame: Within 7 days of randomization ] [ Designated as safety issue: Yes ]

Enrollment: 184
Study Start Date: January 2000
Study Completion Date: October 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00248625

  Show 20 Study Locations
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Robert H Squires, M.D. Children's Hospital of Pittsburgh, University of Pittsburgh
  More Information

Additional Information:
Publications:

Responsible Party: Robert Squires, Jr., MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00248625     History of Changes
Other Study ID Numbers: IRB #: 0608007  U01DK072146 
Study First Received: November 3, 2005
Results First Received: February 19, 2016
Last Updated: June 16, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of Pittsburgh:
acute liver failure
hepatic encephalopathy
acetaminophen toxicity
N-acetylcysteine

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
Acetaminophen
Acetylcysteine
N-monoacetylcystine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antidotes

ClinicalTrials.gov processed this record on December 02, 2016