A Multi-Center Group to Study Acute Liver Failure in Children

Hepatic Encephalopathy Clinical Trial

Official title:

A Multi-Center Group to Study Acute Liver Failure in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00986648
• Other study ID #: 1 UO1 DK072146-01
• Secondary ID: U01DK0721462U01D
• Status: Completed
• Phase: N/A
• First received: September 29, 2009
• Last updated: January 11, 2016
• Start date: January 2000
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

The PALF study group began with 20 sites and now continues with 12 sites (11 in the United States and 1 in Canada) in the new funding period. 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.

Description:

The PALF study group will collect clinical, epidemiological and outcome data on children with ALF. This information will be used to develop methods to predict whether a child will recover from the illness without the need for a liver transplant or other life-saving procedure. We believe the methods to predict survival will vary with different patient age groups, but that diagnosis, multi-system organ failure, degree of encephalopathy and level of coagulopathy will be important regardless of patient age. Biological samples, such as blood and liver tissue, will provide opportunities to identify subgroups of patients who have unique treatment requirements and outcomes. In addition, we hope to identify unrecognized mechanisms of liver injury resulting in ALF in children. Eligible study participants will be invited to participate in neurocognitive testing. Since patients that develop acute liver failure experience varying levels of hepatic encephalopathy and cerebral edema, we suspect that there may be residual sub-clinical neurological injury that compromises long-term neurocognitive function. Detailed neurocognitive testing has never been performed in a cohort of children that survive acute liver failure and this study seeks to close that information gap by defining the spectrum of neurocognitive outcomes in this population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Written informed consent/assent

• Birth through 17 years of age

• Biochemical evidence of acute liver injury

• Coagulopathy not corrected by vitamin K (or other intervention intended to correct coagulopathy)

• The presence of encephalopathy (ENC) is required if the INR is at least 1.5 and less than 2.0

• If INR is at least 2.0, the presence of ENC is not required

Exclusion Criteria:

• Known chronic underlying liver disease

• Multi-organ system failure following heart surgery or ECMO

• Solid organ or bone marrow transplantation

• Acute trauma

• Previously enrolled in the PALF Cohort Study

• Other severe illness, condition, or other reason in the opinion of the investigator that would make the patient unsuitable for the study

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Liver Failure
• Brain Diseases
• Hepatic Encephalopathy
• Liver Failure
• Liver Failure, Acute

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	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Harvard University, Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	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	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 (11)

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

Bucuvalas J, Filipovich L, Yazigi N, Narkewicz MR, Ng V, Belle SH, Zhang S, Squires RH. Immunophenotype predicts outcome in pediatric acute liver failure. J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):311-5. doi: 10.1097/MPG.0b013e31827a78b2. — 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

Leonis MA, Alonso EM, Im K, Belle SH, Squires RH; Pediatric Acute Liver Failure Study Group. Chronic acetaminophen exposure in pediatric acute liver failure. Pediatrics. 2013 Mar;131(3):e740-6. doi: 10.1542/peds.2011-3035. Epub 2013 Feb 25. — View Citation

Lu BR, Zhang S, Narkewicz MR, Belle SH, Squires RH, Sokol RJ; Pediatric Acute Liver Failure Study Group. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr. 2013 May; — 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 im — 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 — 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;4 — 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 — 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 20 — View Citation

Sundaram V, Shneider BL, Dhawan A, Ng VL, Im K, Belle S, Squires RH. King's College Hospital Criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr. 2013 Feb;162(2):319-23.e1. doi: 10.1016/j.jpeds.2012 — View Citation

* Note: There are 11 references in all — Click here to view all references