Comparison Between Lamivudine and Entecavir Treatment in Spontaneous Severe Acute Exacerbation

NCT01627223 | Terminated Phase 4

• 1 other identifier: NUC115132
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 8

Brief Summary

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 74 evaluable subjects, approximately 82 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, 85, and 180 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.

Conditions

Chronic Hepatitis B

Keywords

Spontaneous Severe Acute Exacerbation of Chronic Hepatitis B; Lamivudine (Zeffix®); Entecavir (Baraclude®)

Outcome Measures

Primary Outcomes (1)

• Change from baseline in HBV DNA level at each visit

  To compare the change from baseline in HBV DNA level at each visit during observational period between lamivudine and entecavir therapy.

  day 0、3、5、8±2、15±3、22±3、29±3、85±7、180±7

Secondary Outcomes (7)

• Overall survival (OS) rate during observational period

  Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3、85±7、180±7

• Proportion of subjects with HBV DNA response at each visit

  day 0、3、5、8±2、15±3、22±3、29±3、85±7、180±7

• Change from baseline in ALT and AST level at each visit

  Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3、85±7、180±7

• Change from baseline in bilirubin level at each visit

  Change from baseline (day0) to day 3、5、8±2、15±3、22±3、29±3、85±7、180±7

• Proportion of subjects with prolonged PT at each visit

  day 0、3、5、8±2、15±3、22±3、29±3、85±7、180±7

Study Arms (2)

Lamivudine 100 mg p.o. q.d.

EXPERIMENTAL

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

Entecavir 0.5 mg p.o. q.d

EXPERIMENTAL

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

Interventions

Lamivudine DRUG

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.

Also known as: Zeffix®

Lamivudine 100 mg p.o. q.d.

Entecavir DRUG

•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.

Also known as: Baraclude®

Entecavir 0.5 mg p.o. q.d

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 20 years of age
• 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
• 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
• Patient with sufficient renal function defined as SCr ≤ 1.5 x ULN or ClCr ≥ 50 mL/min
• Willing and able to sign a written informed consent

You may not qualify if:

• Female who is pregnant/lactating
• Patient with underlying liver cirrhosis classified as Child-Pugh class B or C
• Patients with documented hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) co-infection
• Patients with uncontrolled malignancy
• History or presence of alcohol or substance abuse within 1 year prior to the initiation of NRTI treatment
• History of hypersensitivity to any ingredient of observational drugs (Zeffix® or Baraclude®)
• Current use of medicine which may induce hepatotoxicity
• 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
• Use of any chemotherapy or immunosuppressive agents within 12 months prior to the initiation of NRTI treatment
• Use of any investigational product, including drug and invasive medical device, within 4 weeks prior to the initiation of NRTI treatment
• 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

Sponsors & Collaborators

• Taichung Veterans General Hospital: lead
• GlaxoSmithKline: collaborator

Study Sites (8)

Changhua Christian Hospital

Changhua, Taiwan, 500, Taiwan

Location

Chia-Yi Christian

Chiayi City, Taiwan, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, Taiwan, 40201, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan, 40447, Taiwan

Location

ChengChing Hospital

Taichung, Taiwan, 40764, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan, 407, Taiwan

Location

Tung's Taiching MetroHarbor Hospital

Taichung, Taiwan, 435, Taiwan

Location

National Taiwan University Hospital Yu-Lin Branch

YuLin, Taiwan, 640, Taiwan

Location

Related Publications (1)

• Lee TY, Chen CY, Lia HC, Hsu YC, Yang SS. The ultra-short virological dynamics in response to entecavir or lamivudine during chronic hepatitis B with spontaneous severe acute exacerbation. Antivir Ther. 2018;23(1):77-85. doi: 10.3851/IMP3183.

  PMID: 28671553 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Lamivudine; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• 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

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Division of Gastroenterology, Departmemt of Internal Medicine

Study Record Dates

• First Submitted: June 18, 2012
• First Posted: June 25, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: October 18, 2016

Record last verified: 2016-10

Locations

TW (8)