N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure
Condition: Acute Liver Failure; Hepatic Encephalopathy
MeSH terms: Liver Failure; Hepatic Insufficiency; Hepatic Encephalopathy; Liver Failure, Acute; Brain Diseases
Intervention: N-acetylcysteine; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 184.0
Sex: All
Maximum age: 18 Years
Healthy volunteers: No
Keywords: acute liver failure; hepatic encephalopathy; acetaminophen toxicity; N-acetylcysteine

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.
    

Eligibility 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