N-acetylcysteine in Non-Acetaminophen Pediatric Acute Liver Failure

University of Pittsburgh

Status and phase: Completed; Phase 3

Conditions: Hepatic Encephalopathy; Acute Liver Failure

Treatments: Drug: N-acetylcysteine; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00248625

U01DK072146 (U.S. NIH Grant/Contract)

IRB #: 0608007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 184 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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184 participants in 2 patient groups, including a placebo group

N-acetylcysteine (NAC)

Active Comparator group

Description:

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

Treatment:

Drug: N-acetylcysteine

placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo