Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation (HBSAE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Kaohsiung Veterans General Hospital.
Sponsor:
Information provided by (Responsible Party):
Wei-Lun Tsai, Kaohsiung Veterans General Hospital.
ClinicalTrials.gov Identifier:
NCT01848743
First received: April 24, 2013
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

In Taiwan, 15% of general population had hepatitis B virus (HBV) infection, HBV is the leading cause of liver cirrhosis and hepatocellular carcinoma in Taiwan. After entering immune clearance, 10-30% of patients of chronic HBV develop acute exacerbation (AE) , some are mild but some developed hepatic decompensation or even death.

Previous study found that early use of lamivudine before bilirubin level is above 20 mg/dl can improve survival in chornic HBV with severe AE. From the study from Hongkong, lamivudine was found to have better survival than entecavir in chronic HBV with severe AE. Recent study from India found that tenofovir is able to improve survival in chronic HBV with severe AE. The aim of this study is to compare the effect of lamivudine and tenofovir for chronic HBV with severe AE.

The study aims to enroll 120 patients with chronic HBV defined as persistence of HBsAg for more than 6 months. Severe AE was defined as ALT > 400 U/L, prolongation of prothrombin time > 3 seconds, bilirubin > 2 mg/dl. Patients with hepatitis A, C, D or HIV infection, drug or alcoholic liver disease, hepatocellular carcinoma, under immuno-suppressive agents use, or previous use of anti-HBV agents are excluded. All enrolled patients are randomized into group A who received tenofovir 300 mg qd for 3 years and group B who received lamivuidne 100 mg qd for 6 months, followed by tenofovir 300mg qd for 30 months. Mortality rate and virological, biochemical and serological response were evaluated at 1,2,4,48,96 and 144 weeks. The values are expressed as mean + SD. Categorical variables were analyzed with Chi-square test or Fisher's exact test as appropriate and continuous variables were analyzed by Mann-Whitney test. Logistic regression test was applied to analyze the independent association of various variables with outcome. A p value < 0.05 was regarded as significant.


Condition Intervention Phase
Chronic HBV With Severe Exacerbation
Drug: Tenofovir
Drug: lamivudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tenofovir Versus Lamivudine for Patients of Chronic Hepatitis B With Severe Acute Exacerbation

Resource links provided by NLM:


Further study details as provided by Kaohsiung Veterans General Hospital.:

Primary Outcome Measures:
  • 6 months survival [ Time Frame: 6 months after treatment begins ] [ Designated as safety issue: No ]
    6 months survival after treatment begins


Secondary Outcome Measures:
  • rapid virological response [ Time Frame: 1,2 and 4 weeks after treatment ] [ Designated as safety issue: No ]
    Evaluate the relationship of rapid virological response ( at 1,2 and 4 weeks) and survival

  • HBeAg seroconversion and virological response 1, 2, and 3 years after treatment [ Time Frame: 1,2 and 3 years after treatment ] [ Designated as safety issue: No ]
    To evaluate the rate of HBeAg seroconversion and virological response 1, 2, and 3 years after treatment in the two arms

  • Safety profile [ Time Frame: during and 6 months after treatment ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events as a Measure of Safety and Tolerability


Estimated Enrollment: 120
Study Start Date: April 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tenofovir
All enrolled patients are randomized to tenofovir arm who receives tenofovir 300 mg qd for 36 months
Drug: Tenofovir
Other Name: viread
Placebo Comparator: lamivudine
All enrolled patients are randomized to lamivudine arm who received lamivudine 100 mg qd for 6 months, followed by tenofovir for another 30 months.
Drug: lamivudine
Other Name: zeffix

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HBsAg (+) > 6 months
  • ALT > 5X ULN
  • Prolongation of prothrombin time > 3 seconds and bilirubin level > 2 mg/dl
  • 20-75 years old

Exclusion Criteria:

  • HAV, HCV, HDV and HIV co-infection
  • Concurrent hepatocellular carcinoma
  • Drug, metabolic or alcohol as cause of hepatitis
  • Anti-viral treatment in recent 6 mnths
  • Pregnant woman
  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: NCT01848743

Contacts
Contact: Wei-Lun Tsai, M.D. 886-7-3422121 ext 2075 tsaiwl@yahoo.com.tw
Contact: Hoi-Hung Chnan, M.D. , PhD 886-7-3422121 ext 2074 hhchan@vghks.gov.tw

Locations
Taiwan
Kaohsiung Veterans General Hospigal Recruiting
Kaohsiung, Taiwan, 813
Contact: Wei-Lun Tsai, MD    886-7-3422121 ext 2075    tsaiwl@yahoo.com.tw   
Contact: Hi-Hung Chan, MD, PhD    886-7-3422121 ext 2074    hhchan@vghks.gov.tw   
Principal Investigator: Wei-Lun Tsai, MD         
Kaohsiung Veterans General Hospital Active, not recruiting
Kaohsiung, Taiwan, 813
Sponsors and Collaborators
Kaohsiung Veterans General Hospital.
  More Information

No publications provided

Responsible Party: Wei-Lun Tsai, Attending physician, Kaohsiung Veterans General Hospital.
ClinicalTrials.gov Identifier: NCT01848743     History of Changes
Other Study ID Numbers: Gilead IN-US-174-​0190
Study First Received: April 24, 2013
Last Updated: September 12, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Kaohsiung Veterans General Hospital.:
tenofovir, lamivudine, hepatitis B, acute exacerbation

Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Virus Diseases
Lamivudine
Tenofovir
Tenofovir disoproxil
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 22, 2014