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NCT00248625 Clinical Trial

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.

Hepatic Encephalopathy Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT00248625
Other study ID # IRB #: 0608007
Secondary ID U01DK072146
Status Completed
Phase Phase 3
First received November 3, 2005
Last updated May 1, 2012
Start date January 2000
Est. completion date October 2010

Study information
Verified date April 2012
Source University of Pittsburgh
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Completed
Enrollment 184
Est. completion date October 2010
Est. primary completion date September 2009
Accepts healthy volunteers No
Gender Both
Age group N/A to 18 Years
Eligibility 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, ELAD, 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 APAP 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

Intervention

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.

Locations
Country Name City State
Canada Hospital for Sick Children Toronto Ontario
United Kingdom Birmingham Children's Hospital Birmingham
United Kingdom King's College Hospital (London, UK) London
United States University of Michigan Ann Arbor Michigan
United States Emory University, Children's Healthcare of Atlanta Atlanta Georgia
United States Johns Hopkins University Baltimore Maryland
United States Harvard University, Boston Children's Hospital Boston Massachusetts
United States Children's Memorial Hospital Chicago Illinois
United States University of Cincinnati, Cincinnati Children's Hospital Cincinnati Ohio
United States Children's Medical Center of Dallas Dallas Texas
United States University of Colorado, Denver Children's Hospital Denver Colorado
United States Baylor College of Medicine Houston Texas
United States Riley Children's Hospital Indianapolis Indiana
United States Columbia-Presbyterian New York New York
United States Mount Sinai Hospital New York New York
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States University of California, San Francisco San Francisco California
United States University of Washington Seattle Washington
United States St. Louis Children's Hospital St. Louis Missouri

Sponsors (2)
Lead Sponsor Collaborator
University of Pittsburgh National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (7)

Alonso EM. Acute liver failure in children: the role of defects in fatty acid oxidation. Hepatology. 2005 Apr;41(4):696-9. Review. — View Citation

James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM, Squires RH; Pediatric Acute Liver Failure Study Group. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics. 2006 Sep;118(3):e676-81. — View Citation

Narkewicz MR, Dell Olio D, Karpen SJ, Murray KF, Schwarz K, Yazigi N, Zhang S, Belle SH, Squires RH; Pediatric Acute Liver Failure Study Group. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement. J Pediatr. 2009 Dec;155(6):801-806.e1. doi: 10.1016/j.jpeds.2009.06.005. Epub 2009 Jul 29. — View Citation

Rudnick DA, Dietzen DJ, Turmelle YP, Shepherd R, Zhang S, Belle SH, Squires R; Pediatric Acute Liver Failure Study Group. Serum alpha-NH-butyric acid may predict spontaneous survival in pediatric acute liver failure. Pediatr Transplant. 2009 Mar;13(2):223-30. doi: 10.1111/j.1399-3046.2008.00998.x. Epub 2008 Jul 17. — View Citation

Shneider BL, Rinaldo P, Emre S, Bucuvalas J, Squires R, Narkewicz M, Gondolesi G, Magid M, Morotti R, Hynan LS. Abnormal concentrations of esterified carnitine in bile: a feature of pediatric acute liver failure with poor prognosis. Hepatology. 2005 Apr;41(4):717-21. — View Citation

Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, Dhawan A, Rosenthal P, Rodriguez-Baez N, Murray KF, Horslen S, Martin MG, Lopez MJ, Soriano H, McGuire BM, Jonas MM, Yazigi N, Shepherd RW, Schwarz K, Lobritto S, Thomas DW, Lavine JE, Karpen S, Ng V, Kelly D, Simonds N, Hynan LS. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006 May;148(5):652-658. — View Citation

Sundaram SS, Alonso EM, Narkewicz MR, Zhang S, Squires RH; Pediatric Acute Liver Failure Study Group. Characterization and outcomes of young infants with acute liver failure. J Pediatr. 2011 Nov;159(5):813-818.e1. doi: 10.1016/j.jpeds.2011.04.016. Epub 2011 May 31. — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary overall survival rate (spontaneous survival without transplant plus survival following transplantation) at one year following entry into the study. One year following entry into the study Yes
Secondary 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. One year following entry into the study Yes
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