Hepatitis B Research Network Pediatric Cohort Study (HBRN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01263600
First received: December 14, 2010
Last updated: March 12, 2013
Last verified: March 2013

December 14, 2010
March 12, 2013
December 2010
December 2016   (final data collection date for primary outcome measure)
Antigen loss: e and s [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
Loss of these viral markers may be associated with appearance of corresponding antibodies in serum (anti-HBe or anti-HBs). HBsAg loss appears to represent a "cure" of HBV infection and is associated with reduction, but not necessarily elimination, of the risk of future complications, such as Hepatocellular carcinoma (HCC) which may occur, particularly in those who lose HBsAg at an older age (after 50 years) or after the development of cirrhosis. When HBeAg or HBsAg loss occurs, participants will be followed more closely initially and then return to the regular follow-up schedule.
Antigen loss: e and s [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
Loss of these viral markers may be associated with appearance of corresponding antibodies in serum (anti-HBe or anti-HBs). HBsAg loss appears to represent a "cure" of HBV infection and is associated with reduction, but not necessarily elimination, of the risk of future complications, such as HCC which may occur, particularly in those who lose HBsAg at an older age (after 50 years) or after the development of cirrhosis. When HBeAg or HBsAg loss occurs, participants will be followed more closely initially and then return to the regular follow-up schedule.
Complete list of historical versions of study NCT01263600 on ClinicalTrials.gov Archive Site
  • Hepatitis exacerbation marked by alanine aminotransferase (ALT) Flare [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    A flare is defined as serum alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal which corresponds to (1 550 IU/L in females and 600 IU/L in males for 6 months - 18 months of age and 2) 350 IU/L in females and 400 IU/L in males for >18 months - < 18 years of age (12). Once a flare is detected, participants will be followed more closely until its resolution.
  • Cirrhosis [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

    The diagnosis of cirrhosis will be made by (1) liver histology, when available or In the absence of histological diagnosis, cirrhosis is defined as any one of the following

    • Presence of ascites or hepatic hydrothorax
    • Variceal or portal hypertensive bleeding
    • Hepatic encephalopathy
    • Child-Turcotte-Pugh (CTP) score of 7 or above

    or in the absence of hepatic decompensation (any two of the following):

    • Splenomegaly
    • Nodular liver
    • Platelet count below 120,000/mm3

    Once cirrhosis is diagnosed, patient follow-up should include Hepatocellular carcinoma(HCC)surveillance

  • Hepatic Decompensation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

    It is likely that the development of cirrhosis and subsequent hepatic decompensation will be preceded and foreseen by the progression of fibrosis. Development of hepatic decompensation will be defined by any of the following events:

    • Ascites or hepatic hydrothorax
    • Variceal bleeding or portal hypertensive bleeding
    • Hepatic encephalopathy
    • Child-Turcotte-Pugh (CTP) score of 7 or above

    It is anticipated that there will be a small number of patients that will develop decompensation during the follow-up.

  • Hepatocellular carcinoma (HCC) [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    HCC may be detected by routine surveillance or may become clinically apparent. The diagnosis of HCC will be made using the American Association for the Study of Liver Disease criteria.
  • Death [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Death may occur related to liver disease (typically hepatic decompensation or HCC) or may occur unrelated to hepatitis B or liver disease. Date and cause of death will be recorded.
  • Liver transplantation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Liver transplantation will be recorded upon notification. Date of transplantation, indication for transplantation, and occurrence of incidental HCC will be recorded. Follow-up ends with liver transplantation.
  • Reaching 18 years of Age [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Patients who reach 18 years of age and are within an adult HBRN clinical center will be offered participation in the adult cohort study and re-consented for the adult protocol.
  • Hepatitis exacerbation marked by ALT Flare [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    A flare is defined as serum ALT greater than or equal to 10 times the upper limit of normal which corresponds to 1) 550 IU/L in females and 600 IU/L in males for 6 months - 18 months of age and 2) 350 IU/L in females and 400 IU/L in males for >18 months - < 18 years of age (12). Once a flare is detected, participants will be followed more closely until its resolution.
  • Cirrhosis [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

    The diagnosis of cirrhosis will be made by (1) liver histology, when available or In the absence of histological diagnosis, cirrhosis is defined as any one of the following

    • Presence of ascites or hepatic hydrothorax
    • Variceal or portal hypertensive bleeding
    • Hepatic encephalopathy
    • Child-Turcotte-Pugh (CTP) score of 7 or above

    or in the absence of hepatic decompensation (any two of the following):

    • Splenomegaly
    • Nodular liver
    • Platelet count below 120,000/mm3

    Once cirrhosis is diagnosed, patient follow-up should include HCC surveillance

  • Hepatic Decompensation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

    It is likely that the development of cirrhosis and subsequent hepatic decompensation will be preceded and foreseen by the progression of fibrosis. Development of hepatic decompensation will be defined by any of the following events:

    • Ascites or hepatic hydrothorax
    • Variceal bleeding or portal hypertensive bleeding
    • Hepatic encephalopathy
    • Child-Turcotte-Pugh (CTP) score of 7 or above

    It is anticipated that there will be a small number of patients that will develop decompensation during the follow-up.

  • Hepatocellular carcinoma (HCC) [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    HCC may be detected by routine surveillance or may become clinically apparent. The diagnosis of HCC will be made using the American Association for the Study of Liver Disease criteria.
  • Death [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Death may occur related to liver disease (typically hepatic decompensation or HCC) or may occur unrelated to hepatitis B or liver disease. Date and cause of death will be recorded.
  • Liver transplantation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Liver transplantation will be recorded upon notification. Date of transplantation, indication for transplantation, and occurrence of incidental HCC will be recorded. Follow-up ends with liver transplantation.
  • Reaching 18 years of Age [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
    Patients who reach 18 years of age and are within an adult HBRN clinical center will be offered participation in the adult cohort study and re-consented for the adult protocol.
Not Provided
Not Provided
 
Hepatitis B Research Network Pediatric Cohort Study (HBRN)
Cohort Hepatitis B Virus (HBV) Pediatric Protocol

The purpose of this study is to describe participants 6 months to <18 years of age with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression.

•Primary Aim:

o To describe participants 6 months to <18 years of age with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression

Secondary Aims:

  • To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada.
  • To evaluate changes in HBV infection status and hepatitis B surface antigen (HBsAg) levels and factors associated with those changes.
  • To verify whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL is an accurate predictor of people who are, or who will become, inactive carriers, defined as people who are HBsAg positive, hepatitis B "e" antigen (HBeAg) negative, have normal alanine aminotransferase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months with HBV DNA under 1,000 IU/mL.
  • To assess the health related quality of life (HRQOL) of treatment naïve hepatitis B surface antigen (HBsAg) positive children and adolescents
  • To develop a bank of biospecimens (e.g., serum, plasma, DNA, liver tissue) obtained from participants with HBV infection.
  • To identify pediatric participants from 2 years to <18 years of age with chronic HBV infection for potential participation in treatment study to be conducted by the Hepatitis B Research Network (HBRN).
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Liver biopsy tissue, blood (serum, plasma, and DNA)

Non-Probability Sample

Pediatric patients from Children's Hospitals and university medical centers in the United States and Canada

Hepatitis B
Not Provided
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
December 2017
December 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Written informed consent/assent as appropriate
  • At least 6 months to <18 years of age
  • Hepatitis B surface antigen (HBsAg) positive

Exclusion Criteria:

  • Hepatic decompensation
  • Hepatocellular carcinoma (HCC)
  • Liver transplantation
  • Current Hepatitis B antiviral treatment (except pregnant females)
  • Known coinfection with HIV (patients with hepatitis D or hepatitis C coinfection are not excluded)
  • Medical or social condition which in the opinion of the principal investigator would interfere with or prevent regular follow up.
  • Unable or unwilling to return for regular follow-up
Both
6 Months to 17 Years
No
United States,   Canada
 
NCT01263600
DK082864Pediatric, U01DK082864
Yes
University of Pittsburgh
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Steven Belle, PhD University of Pittsburgh
University of Pittsburgh
March 2013

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