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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

November 3, 2005
June 16, 2016
January 2000
September 2009   (final data collection date for primary outcome measure)
Survival [ Time Frame: One year following randomization ] [ Designated as safety issue: Yes ]
Spontaneous survival without transplant plus survival following transplantation
overall survival rate (spontaneous survival without transplant plus survival following transplantation) at one year following entry into the study.
Complete list of historical versions of study NCT00248625 on ClinicalTrials.gov Archive Site
  • 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 ]
spontaneous recovery (survival without transplant), transplantation, length of hospital stay, number of organ systems failing, infectious complication, highest coma grade of hepatic ENC and the number of days until recovery or death.
Not Provided
Not Provided
 
N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure
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.
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Acute Liver Failure
  • Hepatic Encephalopathy
  • 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
  • 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
  • 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
    Intervention: Drug: N-acetylcysteine
  • 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
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
184
October 2010
September 2009   (final data collection date for primary outcome measure)

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
Both
up to 18 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   United Kingdom
 
NCT00248625
IRB #: 0608007, U01DK072146
Yes
No
Not Provided
Robert Squires, Jr., University of Pittsburgh
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
University of Pittsburgh
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP