Comparison Between Lamivudine and Entecavir Treatment in Patients
Information source: Taichung Veterans General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis B
Intervention: Lamivudine (Drug); Entecavir (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Taichung Veterans General Hospital Official(s) and/or principal investigator(s): Sheng-Shun Yang, M.D., Principal Investigator, Affiliation: Taichung Veterans General Hospital Yu-Chun Hsu, M.D., Principal Investigator, Affiliation: Changhua Christian Hospital Shih-Jer Hsu, M.D., Principal Investigator, Affiliation: National Taiwan University Hospital Yu-Lin Branch Hsueh-Chou Lai, M.D., Principal Investigator, Affiliation: China Medical University Hospital Chun-Che Lin, M.D., Principal Investigator, Affiliation: Chung Shan Medical University Jen-Chieh Huang, M.D., Principal Investigator, Affiliation: ChengChing Hospital Chi-Yi Chen, M.D., Principal Investigator, Affiliation: Chia-Yi Christian Tsung-Ming Chen, M.D., Principal Investigator, Affiliation: Tung's Taiching MetroHarbor Hospital
Overall contact: Sheng-Shun Yang, M.D., Phone: 886-4-23592525, Ext: 3309, Email: yansh@vghtc.gov.tw
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 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.
Clinical Details
Official title: Comparison Between Lamivudine and Entecavir Treatment in Patients With Spontaneous Severe Acute Exacerbation of Chronic Hepatitis B.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Overall survival (OS) rate during observational period
Secondary outcome: Change from baseline in HBV DNA level at each visitProportion of subjects with HBV DNA response at each visit Change from baseline in ALT and AST level at each visit Change from baseline in bilirubin level at each visit Proportion of subjects with prolonged PT at each visit Transplantation-free survival rate during observational period To assess the safety of lamivudine and entecavir treatments in patients with HBV-associated severe acute exacerbation.
Detailed description:
The study is to compare treatment response of lamivudine and entecavir in patients with
spontaneous severe acute exacerbation of chronic hepatitis B.
1. Primary objective:
• To compare the overall survival (OS) rate during observational period between lamivudine
and entecavir therapy.
2. Secondary objectives:
1. To compare the change from baseline in HBV DNA level at each visit between lamivudine
and entecavir therapy.
2. 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.
3. To compare the change from baseline in ALT and AST level at each visit between
lamivudine and entecavir therapy.
4. To compare the proportion of subjects with prolonged prothrombin time (PT) at each
visit between lamivudine and entecavir therapy.
5. To compare the change from baseline in bilirubin level at each visit between lamivudine
and entecavir therapy.
6. To compare the transplantation-free survival rate during observational period between
lamivudine and entecavir therapy.
7. To assess the safety of lamivudine and entecavir treatments in patients with
HBV-associated severe acute exacerbation.
Statistical method(s) for safety/efficacy evaluations:
1. The major analysis will be performed according to the principal of intent-to-treat
population; the safety evaluation will be performed according to the safety population.
2. For primary endpoint, the time to event will be analyzed by Kaplan-Meier method and
summarized as the number of observations, number of censored, median time point
estimate and the 95% CI for median.
3. Secondary efficacy endpoints:
1. Change from baseline in HBV DNA level at each visit 2. Proportion of subjects with HBV
DNA response* at each visit
- Defined as a ≥ 2 log10 decline from baseline HBV DNA level. 3. Change from baseline in
ALT level at each visit 4. Change from baseline in AST level at each visit 5.
Proportion of subjects with prolonged PT* at each visit
- PT at each visit will also be assessed. 6. Change from baseline in bilirubin level at
each visit 7. Transplantation-free survival rate during observational period Continuous
variables will be analyzed using two-sample t-test/ Wilcoxon Rank Sum test, and
categorical variables will be analyzed Chi-squared/ Fishers' exact test. Descriptive
statistics including mean, standard deviation, median, minimum, maximum, 95% confidence
interval will be also presented. Categorical variables will be summarized by counts and
percentage in frequency table. In addition, the time to event will be analyzed by
Kaplan-Meier method.
(4) The summary results of laboratory at the baseline and the end of study visit, the
change from baseline to end of study visit will be summarized by descriptive statistics
and paired t-test will be used under significant level 0. 05.
(5) Adverse events will be coded with MedDRA and a summary frequency table of adverse
events will be provided. The severity and relationship to study medication of adverse
events will be summarized as well. Furthermore, if any serious adverse event had
occurred, the brief summary about serious adverse event will be described and listed in
tables.
(6) All statistical tests will be two-side and evaluated at the 0. 05 level of
significance.
Eligibility
Minimum age: 20 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Sheng-Shun Yang, M.D., Phone: 886-4-23592525, Ext: 3309, Email: yansh@vghtc.gov.tw
Changhua Christian Hospital, Changhua 500, Taiwan; Recruiting Yu-Chun Hsu, M.D., Phone: 886-4-7238595, Ext: 5505, Email: 77149@cch.org.tw Yu-Chun Hsu, M.D., Principal 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., Sub-Investigator
Chia-Yi Christian, ChiaYi, Taiwan; Recruiting Chi-Yi Chen, M.D., Phone: 886-5-2765041, Ext: 2536, Email: chiyi.chen37@me.com Chi-Yi Chen, M.D., Principal Investigator
ChengChing Hospital, Taichung 40764, Taiwan; Not yet recruiting Jen-Chieh Huang, M.D., Phone: 886-4-24632000, Ext: 55144, Email: guthuang@yahoo.com.tw Jen-Chieh Huang, M.D., Principal Investigator Chi-Hung Chen, M.D., Sub-Investigator
China Medical University Hospital, Taichung 40447, Taiwan; Not yet recruiting Hsueh-Chou , Lai, Phone: 886-4-22052121, Ext: 2260, Email: t674233@ms54.hinet.net Hsueh-Chou Lai, M.D., Principal Investigator Jen-Wei Chou, M.D., Sub-Investigator Jung-Ta Kao, M.D., Sub-Investigator Wen-Pang Su, M.D., Sub-Investigator
Chung Shan Medical University Hospital, Taichung 40201, Taiwan; Not yet recruiting Chun-Che Lin, M.D., Phone: 886-4-24739595, Ext: 38315, Email: cshy333@csh.org.tw Chun-Che Lin, M.D., Principal Investigator
Taichung Veterans General Hospital, Taichung 407, Taiwan; Recruiting Sheng-Shun Yang, M.D., Phone: 886-4-23592525, Ext: 3309, Email: yansh@vghtc.gov.tw Teng-Yu Lee, M.D., Phone: 886-4-23592525, Ext: 3307, Email: tylee@vghtc.gov.tw Sheng-Shun Yang, M.D., Principal Investigator Teng Lee, M.D., Sub-Investigator
Tung's Taiching MetroHarbor Hospital, Taichung 435, Taiwan; Not yet recruiting Tsung-Ming Chen, M.D., Phone: 886-4-26581919, Ext: 4451, Email: t4696@ms.sltung.com.tw Tsung-Ming Chen, M.D., Principal Investigator
National Taiwan University Hospital Yu-Lin Branch, YuLin 640, Taiwan; Not yet recruiting Shih-Jer Hsu, M.D., Phone: 886-5-5323911, Ext: 2200, Email: shihjer.hsu@gmail.com Shih-Jer Hsu, M.D., Principal Investigator
Additional Information
Starting date: July 2012
Last updated: February 18, 2013
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