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Efficacy and Safety of Peginterferon a-2a in Patients of Chronic Hepatitis B With Spontaneous Decline of HBV DNA

Primary Purpose

Antiviral Treatment of Chronic Hepatitis B

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pegasys(Roche)
Entecavir
Sponsored by
Third Affiliated Hospital, Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antiviral Treatment of Chronic Hepatitis B focused on measuring Chronic hepatitis B,Spontaneous Decline of HBV DNA,Peginterferon a-2a, entecavir

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

This study focused on the subsequential antiviral therapeutic strategies for chronic hepatitis B patients with spontaneous decline of HBV DNA after acute exacerbation. Patients fullfilled the following criterias were chosen for screening: They were antiviral treatment naı¨ve and had been positive for hepatitis B surface antigen (HBsAg) for at least 6 months, were positive for HBeAg and had an HBV DNA Level of more than 500,000IU/ml. Their serum alanine aminotransferase level was greater than 2 but less than or equal to 30 times the upper limit of the normal range, their peak value of total bililubin ranged from 2mg/ml to 20mg/ml and the prothrombin time activity was greater than 60%.

ALL of these patients were hospitalized and pretreated with anti-inflammation and liver protection agents such as Stronger Neo-Minophagen C, Polyunsaturated phosphatidylcholine (Essentiale), Ursodeoxycholic Acid and L-Glutathione reduced, without any nuclutide of nucleoside. Their ALT、TBIL and PTA were monitor weekly and HBVDNA level were measured every two weeks. Patients were eligible if their HBVDNA declined spontaneously by 2 log(10) IU/mL while their ALT falled below 10 ULN and TBIL falled below 2mg/ml within 8 weeks of pretreatment.

Patients with advanced fibrosis, cirrhosis and hepatoma were excluded. Other cause of chronic liver disease should be systematically checked to exclude co-infection with HDV, HCV and HIV, comorbidities with alcoholism, autoimmune and metabolic liver disease. Serious medical or psychiatric illnesses that had usage of corticosteroid or immunosup-pressive agents at the time of study were excluded. All patients in this study lived in Guangdong, a province of 100,000,000 populations, with same demographics. Owing to patients fear or refusal of liver biopsy, no patients had the liver biopsy and the rest relied on other clinical methods to obtain equivalent information of patient conditions. In our cases, ultrasonorgraphy helped to filter out patients with advanced fibrosis.The liver sonar examination was performed by two experi-enced hepatologists at least three times on each patient.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    No Intervention

    Arm Label

    180µg of peginterferon alfa-2a

    Entecavir

    Control group

    Arm Description

    Cases in group A receive 180µg of peginterferon alfa-2a (Pegasys,Roche) once weekly for 48 weeks.

    cases in group B received an continual entecavir therapy(0.5 mg orally once daily)

    Those in group C didn't accept any antiviral regiment .

    Outcomes

    Primary Outcome Measures

    Complete viralogic response
    Complete viralogic response was defined as suppression of HBV DNA to the level below 60IU/mL(detected by Cobas Amplicor HBV Monitor Test, Roche Diagnostics).

    Secondary Outcome Measures

    HBsAg loss and seroconversion
    HBsAg loss was defined as HBsAg titre less than 0.05 IU/mL and the HBsAg seroconversion was defined as the loss of HBsAg and the presence of anti-HBs antibody. HBeAg seroconversion was defined as disappearance of HBeAg and appearance of anti-HBe antibody, while HBeAg loss was defined as disappearance of HBeAg only.
    ALT normalization
    ALT normalization was defined as ALT level less than 40 IU/L(determined by a sequential multiple autoanalyzer).
    Sick leave in patients in different groups

    Full Information

    First Posted
    August 22, 2012
    Last Updated
    September 28, 2013
    Sponsor
    Third Affiliated Hospital, Sun Yat-Sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01892241
    Brief Title
    Efficacy and Safety of Peginterferon a-2a in Patients of Chronic Hepatitis B With Spontaneous Decline of HBV DNA
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2010 (undefined)
    Primary Completion Date
    November 2012 (Actual)
    Study Completion Date
    February 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Third Affiliated Hospital, Sun Yat-Sen University

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Patients with spontaneous decline of HBV DNA were non-randomly assigned to accept peginterferon alfa-2a or entecavir therapy, or didn't accept any antiviral regiment.
    Detailed Description
    It was a prospective, non-randomized, open-label study that evaluated the efficacy and safety of pegasys treatment in chronic hepatitis B patients with spontaneous HBVDNA decline after acute exacerbation.Patients with spontaneous decline of HBV DNA(a decrease of HBV DNA levels of more than 2 log(10) IU/mL as compared to baseline before antiviral treatment) after acute exacerbation (ALT was 10-30ULN,TBIL was 2-20mg/ml,PTA>60%)were non-randomly divided into 3 groups: group A, B and C. Before treatment, the patients were counselled on the advantages and disadvantages of taking peginterferon or nucleos(t)ide analogue, and the subsequential treatment were decided by themselves. Cases in group A receive 180µg of peginterferon alfa-2a (Pegasys,Roche) once weekly for 48 weeks. Group B and C were control group, cases in group B received an continual entecavir therapy(0.5 mg orally once daily) and those in group C didn't accept any antiviral regiment.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Antiviral Treatment of Chronic Hepatitis B
    Keywords
    Chronic hepatitis B,Spontaneous Decline of HBV DNA,Peginterferon a-2a, entecavir

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    74 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    180µg of peginterferon alfa-2a
    Arm Type
    Experimental
    Arm Description
    Cases in group A receive 180µg of peginterferon alfa-2a (Pegasys,Roche) once weekly for 48 weeks.
    Arm Title
    Entecavir
    Arm Type
    Active Comparator
    Arm Description
    cases in group B received an continual entecavir therapy(0.5 mg orally once daily)
    Arm Title
    Control group
    Arm Type
    No Intervention
    Arm Description
    Those in group C didn't accept any antiviral regiment .
    Intervention Type
    Drug
    Intervention Name(s)
    Pegasys(Roche)
    Other Intervention Name(s)
    peginterferon alfa-2a
    Intervention Description
    180µg of peginterferon alfa-2a (Pegasys,Roche) once weekly for 48 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Entecavir
    Intervention Description
    continual entecavir therapy(0.5 mg orally once daily)
    Primary Outcome Measure Information:
    Title
    Complete viralogic response
    Description
    Complete viralogic response was defined as suppression of HBV DNA to the level below 60IU/mL(detected by Cobas Amplicor HBV Monitor Test, Roche Diagnostics).
    Time Frame
    week 96
    Secondary Outcome Measure Information:
    Title
    HBsAg loss and seroconversion
    Description
    HBsAg loss was defined as HBsAg titre less than 0.05 IU/mL and the HBsAg seroconversion was defined as the loss of HBsAg and the presence of anti-HBs antibody. HBeAg seroconversion was defined as disappearance of HBeAg and appearance of anti-HBe antibody, while HBeAg loss was defined as disappearance of HBeAg only.
    Time Frame
    week 24,48,72 and 96
    Title
    ALT normalization
    Description
    ALT normalization was defined as ALT level less than 40 IU/L(determined by a sequential multiple autoanalyzer).
    Time Frame
    week 24,48,72 and 96
    Title
    Sick leave in patients in different groups
    Time Frame
    week 48,72 and 96

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    This study focused on the subsequential antiviral therapeutic strategies for chronic hepatitis B patients with spontaneous decline of HBV DNA after acute exacerbation. Patients fullfilled the following criterias were chosen for screening: They were antiviral treatment naı¨ve and had been positive for hepatitis B surface antigen (HBsAg) for at least 6 months, were positive for HBeAg and had an HBV DNA Level of more than 500,000IU/ml. Their serum alanine aminotransferase level was greater than 2 but less than or equal to 30 times the upper limit of the normal range, their peak value of total bililubin ranged from 2mg/ml to 20mg/ml and the prothrombin time activity was greater than 60%. ALL of these patients were hospitalized and pretreated with anti-inflammation and liver protection agents such as Stronger Neo-Minophagen C, Polyunsaturated phosphatidylcholine (Essentiale), Ursodeoxycholic Acid and L-Glutathione reduced, without any nuclutide of nucleoside. Their ALT、TBIL and PTA were monitor weekly and HBVDNA level were measured every two weeks. Patients were eligible if their HBVDNA declined spontaneously by 2 log(10) IU/mL while their ALT falled below 10 ULN and TBIL falled below 2mg/ml within 8 weeks of pretreatment. Patients with advanced fibrosis, cirrhosis and hepatoma were excluded. Other cause of chronic liver disease should be systematically checked to exclude co-infection with HDV, HCV and HIV, comorbidities with alcoholism, autoimmune and metabolic liver disease. Serious medical or psychiatric illnesses that had usage of corticosteroid or immunosup-pressive agents at the time of study were excluded. All patients in this study lived in Guangdong, a province of 100,000,000 populations, with same demographics. Owing to patients fear or refusal of liver biopsy, no patients had the liver biopsy and the rest relied on other clinical methods to obtain equivalent information of patient conditions. In our cases, ultrasonorgraphy helped to filter out patients with advanced fibrosis.The liver sonar examination was performed by two experi-enced hepatologists at least three times on each patient.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gao Zhiliang, doctor
    Organizational Affiliation
    The Third Affliated Hospital of Sun Yat-sen University
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Zhao Zhixin, doctor
    Organizational Affiliation
    The Third Affliated Hospital of Sun Yat-sen University
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Efficacy and Safety of Peginterferon a-2a in Patients of Chronic Hepatitis B With Spontaneous Decline of HBV DNA

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