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Entecavir for Chronic Hepatitis B Patients With Persistently Normal ALT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01833611
Recruitment Status : Unknown
Verified April 2013 by Ting-Tsung Chang, National Cheng-Kung University Hospital.
Recruitment status was:  Active, not recruiting
First Posted : April 17, 2013
Last Update Posted : April 17, 2013
Information provided by (Responsible Party):
Ting-Tsung Chang, National Cheng-Kung University Hospital

Brief Summary:
Entecavir (ETV) has shown superior ability to suppress hepatitis B virus (HBV) replication, histology improvement as well as low rate of emergence of resistant mutants. Out of range of clinical recommendations for treatment of chronic hepatitis B (CHB), chronic HBV carriers with persistently normal ALT and viral load more than 10^5 copies/mL have progression of liver disease during long-term follow-up. In addition, certain proportions of these patients do have significant inflammation and fibrosis in liver histology. This study will be able to identify who are at risk of liver disease progression and evaluate efficacy of ETV regarding improvement of liver histology during short-term (1-year) and long-term ETV treatment (3-year).

Condition or disease Intervention/treatment Phase
Chronic Hepatitis Drug: Entecavir Drug: placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase IV Study of the Efficacy of Entecavir in Patients With Chronic Hepatitis B Virus Infection and Persistently Normal Alanine Aminotransferase
Study Start Date : September 2008
Estimated Primary Completion Date : November 2014
Estimated Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir

Arm Intervention/treatment
Experimental: ETV group
Entecavir 0.5mg at first year; then open with entecavir 0.5mg qd for 2nd, 3rd year
Drug: Entecavir
entecavir 0.5mg qd
Other Name: baraclude (generic name)

Placebo Comparator: Placebo group
Placebo at first year, then opne with entecavir 0.5mg qd for 2nd, 3rd year
Drug: placebo
placebo qd

Primary Outcome Measures :
  1. Improvement of liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT receiving entecavir. Please refer to "Description" section for the definiton of improvement of liver histology [ Time Frame: 1 year ]
    1. The ratio of liver histology improvement in two groups.
    2. Definition of improving liver histology is improvement in the necroinflammatory score (≥ 2 point decrease in Knodell necroinflammation score) and no worsening of fibrosis (≥ 1 point increase in the Knodell fibrosis score) at the week 52 liver biopsy compared to baseline.

Secondary Outcome Measures :
  1. Undetectable HBV DNA [ Time Frame: 1 year and 3 year ]
    1. The ratio of undetectable HBV DNA in two groups
    2. HBV DNA by the Roche TaqMan® HBV Test (limit of detection 60 IU/mL)

  2. the reduction of HBV DNA from baseline [ Time Frame: 1 year and 3 year ]
    1. expressed with Log 10 coipes/ml
    2. HBV DNA by the Roche TaqMan® HBV Test (limit of detection 60 IU/mL)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male and female subjects aged between 18 and 65 year-old with history of chronic hepatitis B virus infection;
  2. Detectable HBsAg at screening and for at least 24 weeks prior to screening or detectable HBsAg for < 24 week and negative for IgM core antibody and confirmation of chronic hepatitis on liver biopsy;
  3. ALT should be within normal range in recent one year and at least twice, which are at least 3 month apart;
  4. Normal ALT at screening;
  5. Screening HBV DNA of more than 10^5 copies/mL by Roche AmplicorTM PCR assay performed by the central laboratory;
  6. Evidence of chronic hepatitis on liver biopsy (Knodell HAI Score >= 4) performed ≤ 52 weeks prior to randomization;
  7. All women of childbearing potential must have a negative serum or urine pregnancy test.

Exclusion Criteria:

  1. Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV);
  2. Other forms of liver disease e.g., alcoholic, autoimmune, biliary disease;
  3. Patients with evidence of decompensation of liver disease;
  4. Therapy with interferon, thymosin alpha or antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir, lamivudine, and telbivudine) within 24 weeks of randomization into this study;
  5. More than 12 weeks of prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir lamivudine, and telbivudine);
  6. Prior therapy with entecavir;
  7. Known history of allergy to nucleoside analogues;
  8. Hemoglobin < 10.0 g/dL;
  9. Platelet count < 75,000/mm3;
  10. Absolute neutrophil count< 1500 cells/mm3;
  11. Creatinine > 1.5mg/dL (133 μmol/L);
  12. Anti-nuclear antibody (ANA) titer > l :160 unless attributable to non-hepatic disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01833611

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Buddhist Dalin Tzu-Chi General Hospital
Chia-Yi, Taiwan
Chia-Yi Christian Hospital
Chia-Yi, Taiwan
Chang-Gung Memorial Hospital, Kaohsiung
Kaohsiung, Taiwan
Kaohsiung Medical University Hospital
Kaohsiung, Taiwan
Sponsors and Collaborators
National Cheng-Kung University Hospital
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Principal Investigator: Ting-Tsung Chang, MD. PhD National Cheng-Kung University Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Ting-Tsung Chang, Clinical Professor, National Cheng-Kung University Hospital Identifier: NCT01833611     History of Changes
Other Study ID Numbers: ETV HR-96-23
First Posted: April 17, 2013    Key Record Dates
Last Update Posted: April 17, 2013
Last Verified: April 2013
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antiviral Agents
Anti-Infective Agents