Comparison Between Lamivudine and Entecavir Treatment in Patients (NUC115132)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Taichung Veterans General Hospital
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Sheng-Shun Yang, Taichung Veterans General Hospital
ClinicalTrials.gov Identifier:
NCT01627223
First received: June 18, 2012
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

This is a prospective, observational, open-label, 2-arm, parallel, multi-center study. Patients with HBV-associated severe acute exacerbation for whom the treatment with NRTI (such as lamivudine and entecavir) is medically recommended will be screened for eligibility. To target 88 evaluable subjects, approximately 98 patients should be recruited into this trial. After enrollment, all eligible subjects will be randomly assigned to one of the antiviral treatments below.

  • Cohort 1: Lamivudine 100 mg p.o. q.d.
  • Cohort 2: Entecavir 0.5 mg p.o. q.d. This process will be stratified by prolonged PT, < 4 sec / 4-6 sec / > 6 sec. Both lamivudine and entecavir will be taken once daily and the first dose of observational drug should be administered on Day 1. The observational period of individual subject will be 12 weeks; however, both treatments could be continued after the end of study based on physician's clinical judgment.

The efficacy and safety data will be collected at baseline, 3, 5, 8, 15, 22, 29 and 85 days after initiation of antiviral treatment. All assessments should be conducted based on routine practice of each hospital. Only the analysis of HBV DNA and anti-HDV will be performed in the central lab. For patients who are willing to provide the residual samples of HBV DNA assessment, the blood samples will be preserved appropriately. All AE(s) and SAE will be followed until resolution or the event is considered stable.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Lamivudine
Drug: Entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison Between Lamivudine and Entecavir Treatment in Patients With Spontaneous Severe Acute Exacerbation of Chronic Hepatitis B.

Resource links provided by NLM:


Further study details as provided by Taichung Veterans General Hospital:

Primary Outcome Measures:
  • Overall survival (OS) rate during observational period [ Time Frame: day 0、3、5、8±2、15±3、22±3、29±3、85±7 ] [ Designated as safety issue: No ]
    To compare the overall survival (OS) rate during observational period between lamivudine and entecavir therapy.


Secondary Outcome Measures:
  • Change from baseline in HBV DNA level at each visit [ Time Frame: Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3 ] [ Designated as safety issue: No ]
    To compare the change from baseline in HBV DNA level at each visit between lamivudine and entecavir therapy.

  • Proportion of subjects with HBV DNA response at each visit [ Time Frame: day 0、3、5、8±2、15±3、22±3、29±3 ] [ Designated as safety issue: No ]
    To compare the proportion of subjects who have a ≥ 2 log10 decline from baseline in HBV DNA level at each visit between lamivudine and entecavir therapy.

  • Change from baseline in ALT and AST level at each visit [ Time Frame: Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3 ] [ Designated as safety issue: No ]
    To compare the change from baseline in ALT and AST level at each visit between lamivudine and entecavir therapy.

  • Change from baseline in bilirubin level at each visit [ Time Frame: Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3 ] [ Designated as safety issue: No ]
    To compare the change from baseline in bilirubin level at each visit between lamivudine and entecavir therapy.

  • Proportion of subjects with prolonged PT at each visit [ Time Frame: day 0、3、5、8±2、15±3、22±3、29±3 ] [ Designated as safety issue: No ]
    To compare the proportion of subjects with prolonged prothrombin time (PT) at each visit between lamivudine and entecavir therapy.

  • Transplantation-free survival rate during observational period [ Time Frame: day 0、3、5、8±2、15±3、22±3、29±3、85±7 ] [ Designated as safety issue: No ]
    To compare the transplantation-free survival rate during observational period between lamivudine and entecavir therapy.

  • To assess the safety of lamivudine and entecavir treatments in patients with HBV-associated severe acute exacerbation. [ Time Frame: day 0 to day 85±7 ] [ Designated as safety issue: Yes ]
    1. Change in laboratory data
    2. Adverse events
    3. Serious adverse events (SAE)


Estimated Enrollment: 98
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lamivudine 100 mg p.o. q.d.

To target 88 evaluable subjects, approximately 98 patients should be recruited into this trial. After enrollment, all eligible subjects will be randomly assigned to one of the antiviral treatments below.

  • Cohort 1: Lamivudine 100 mg p.o. q.d.
  • Cohort 2: Entecavir 0.5 mg p.o. q.d.

This process will be stratified by prolonged PT, < 4 sec / 4-6 sec / > 6 sec. Both lamivudine and entecavir will be taken once daily and the first dose of observational drug should be administered on Day 1. The observational period of individual subject will be 12 weeks; however, both treatments could be continued after the end of study based on physician's clinical judgment.

Drug: Lamivudine

Lamivudine 100 mg p.o. q.d.

This process will be stratified by prolonged PT, < 4 sec / 4-6 sec / > 6 sec. Both lamivudine and entecavir will be taken once daily and the first dose of observational drug should be administered on Day 1. The observational period of individual subject will be 12 weeks; however, both treatments could be continued after the end of study based on physician's clinical judgment.

Other Name: Zeffix®
Experimental: Entecavir 0.5 mg p.o. q.d

To target 88 evaluable subjects, approximately 98 patients should be recruited into this trial. After enrollment, all eligible subjects will be randomly assigned to one of the antiviral treatments below.

  • Cohort 1: Lamivudine 100 mg p.o. q.d.
  • Cohort 2: Entecavir 0.5 mg p.o. q.d.

This process will be stratified by prolonged PT, < 4 sec / 4-6 sec / > 6 sec. Both lamivudine and entecavir will be taken once daily and the first dose of observational drug should be administered on Day 1. The observational period of individual subject will be 12 weeks; however, both treatments could be continued after the end of study based on physician's clinical judgment.

Drug: Entecavir

•Entecavir 0.5 mg p.o. q.d

This process will be stratified by prolonged PT, < 4 sec / 4-6 sec / > 6 sec. Both lamivudine and entecavir will be taken once daily and the first dose of observational drug should be administered on Day 1. The observational period of individual subject will be 12 weeks; however, both treatments could be continued after the end of study based on physician's clinical judgment.

Other Name: Baraclude®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 20 years of age
  2. HBsAg carrier with spontaneously severe acute exacerbation for whom the treatment with nucleoside and nucleotide reverse transcriptase inhibitor (NRTI) such as lamivudine and entecavir is medically recommended
  3. Patients who fulfills all of the following criteria at screening:

    • documented HBsAg positive for at least 6 months or anti-HBc IgM negative
    • HBV DNA ≥ 2,000 IU/mL*

      * The blood sample will be collected at screening visit, but this criterion will be checked after obtaining lab result. For patients fulfill all other criteria, they can be enrolled immediately.

    • total bilirubin ≥ 2 mg/dL or prolonged prothrombin time (PT) ≥ 3 sec
    • serum ALT ≥ 10 x ULN
  4. Patient with sufficient renal function defined as SCr ≤ 1.5 x ULN or ClCr ≥ 50 mL/min
  5. Willing and able to sign a written informed consent

Exclusion Criteria:

  1. Female who is pregnant/lactating
  2. Patient with underlying liver cirrhosis classified as Child-Pugh class B or C
  3. Patients with documented hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) co-infection
  4. Patients with uncontrolled malignancy
  5. History or presence of alcohol or substance abuse within 1 year prior to the initiation of NRTI treatment
  6. History of hypersensitivity to any ingredient of observational drugs (Zeffix® or Baraclude®)
  7. Current use of medicine which may induce hepatotoxicity
  8. Use of any antiviral therapy for HBV, such as interferon-α (IFN-α) and other nucleotide/nucleoside analogues, within 6 months prior to the initiation of NRTI treatment or exposure to any treatment for more than 3 months
  9. Use of any chemotherapy or immunosuppressive agents within 12 months prior to the initiation of NRTI treatment
  10. Use of any investigational product, including drug and invasive medical device, within 4 weeks prior to the initiation of NRTI treatment
  11. Patient with any medical or psychiatric condition, including the presence of significant abnormal laboratory values, which is considered not suitable for this study by investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627223

Contacts
Contact: Sheng-Shun Yang, M.D. 886-4-23592525 ext 3309 yansh@vghtc.gov.tw
Contact: Teng-Yu Lee, M.D. 886-4-23592525 ext 3301 tylee@vghtc.gov.tw

Locations
Taiwan
Changhua Christian Hospital Recruiting
Changhua, Taiwan, 500
Contact: Yu-Chun Hsu, M.D.    886-4-7238595 ext 5505    77149@cch.org.tw   
Principal Investigator: Yu-Chun Hsu, M.D.         
Sub-Investigator: Shun-Sheng Wu, M.D.         
Sub-Investigator: Kai-Lun Shih, M.D.         
Sub-Investigator: Hsu-Heng Yen, M.D.         
Sub-Investigator: Pei-Yuan Su, M.D.         
Sub-Investigator: Wei-Wen Su, M.D.         
Chia-Yi Christian Recruiting
ChiaYi, Taiwan
Contact: Chi-Yi Chen, M.D.    886-5-2765041 ext 2536    chiyi.chen37@me.com   
Principal Investigator: Chi-Yi Chen, M.D.         
ChengChing Hospital Not yet recruiting
Taichung, Taiwan, 40764
Contact: Jen-Chieh Huang, M.D.    886-4-24632000 ext 55144    guthuang@yahoo.com.tw   
Principal Investigator: Jen-Chieh Huang, M.D.         
Sub-Investigator: Chi-Hung Chen, M.D.         
China Medical University Hospital Not yet recruiting
Taichung, Taiwan, 40447
Contact: Hsueh-Chou , Lai    886-4-22052121 ext 2260    t674233@ms54.hinet.net   
Principal Investigator: Hsueh-Chou Lai, M.D.         
Sub-Investigator: Jen-Wei Chou, M.D.         
Sub-Investigator: Jung-Ta Kao, M.D.         
Sub-Investigator: Wen-Pang Su, M.D.         
Chung Shan Medical University Hospital Not yet recruiting
Taichung, Taiwan, 40201
Contact: Chun-Che Lin, M.D.    886-4-24739595 ext 38315    cshy333@csh.org.tw   
Principal Investigator: Chun-Che Lin, M.D.         
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 407
Contact: Sheng-Shun Yang, M.D.    886-4-23592525 ext 3309    yansh@vghtc.gov.tw   
Contact: Teng-Yu Lee, M.D.    886-4-23592525 ext 3307    tylee@vghtc.gov.tw   
Principal Investigator: Sheng-Shun Yang, M.D.         
Sub-Investigator: Teng Lee, M.D.         
Tung's Taiching MetroHarbor Hospital Not yet recruiting
Taichung, Taiwan, 435
Contact: Tsung-Ming Chen, M.D.    886-4-26581919 ext 4451    t4696@ms.sltung.com.tw   
Principal Investigator: Tsung-Ming Chen, M.D.         
National Taiwan University Hospital Yu-Lin Branch Not yet recruiting
YuLin, Taiwan, 640
Contact: Shih-Jer Hsu, M.D.    886-5-5323911 ext 2200    shihjer.hsu@gmail.com   
Principal Investigator: Shih-Jer Hsu, M.D.         
Sponsors and Collaborators
Taichung Veterans General Hospital
GlaxoSmithKline
Investigators
Principal Investigator: Sheng-Shun Yang, M.D. Taichung Veterans General Hospital
Principal Investigator: Yu-Chun Hsu, M.D. Changhua Christian Hospital
Principal Investigator: Shih-Jer Hsu, M.D. National Taiwan University Hospital Yu-Lin Branch
Principal Investigator: Hsueh-Chou Lai, M.D. China Medical University Hospital
Principal Investigator: Chun-Che Lin, M.D. Chung Shan Medical University Hospital
Principal Investigator: Jen-Chieh Huang, M.D. ChengChing Hospital
Principal Investigator: Chi-Yi Chen, M.D. Chia-Yi Christian
Principal Investigator: Tsung-Ming Chen, M.D. Tung's Taiching MetroHarbor Hospital
  More Information

No publications provided

Responsible Party: Sheng-Shun Yang, M.D. Division of Gastroenterology, Departmemt of Internal Medicine, Taichung Veterans General Hospital
ClinicalTrials.gov Identifier: NCT01627223     History of Changes
Other Study ID Numbers: NUC115132
Study First Received: June 18, 2012
Last Updated: February 18, 2013
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Taichung Veterans General Hospital:
Spontaneous Severe Acute Exacerbation of Chronic Hepatitis B
Lamivudine (Zeffix®)
Entecavir (Baraclude®)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Lamivudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014